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Introduction: Levels of the human epidermal growth factor receptor 2 (HER2) gene are low in normal breast tissue, but half of the patients with breast cancer exhibit higher levels of this receptor. The differential expression of the HER2 gene in normal and malignant cells makes it an excellent biomarker for therapeutic purposes. In this study, we evaluated the degree of HER2 overexpression in patients and its relationship with age and the occurrence of metastases. Materials & Methods: In this retrospective, registry-based, two-center cohort study, information on 1500 breast cancer patients recruited from Shahid Mostafa Khomeini Hospital in Ilam Province was collected from 2020 to 2023. Results: The likelihood of metastasis in cancer patients with HER2 gene expression was three times higher (adjusted OR: 2.82; 95% CI: 1.79-3.29; P=0.001). Additionally, the involvement of lymph nodes (adjusted OR: 2.01; 95% CI: 0.87-3.79; P=0.03) was significantly associated with increased metastasis. Conclusion: This study demonstrates that HER2 gene expression and the number of involved lymph nodes are significant prognostic factors that increase the risk of metastasis. Therefore, implementing comprehensive breast cancer screenings can play an important role in the treatment and prevention of metastasis in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background. Fascin is a protein that is increased in many epithelial cancers, and this increased expression is related to the more aggressive behavior and metastasis of many of these cancers. Considering the relatively high prevalence of oral lichen planus (OLP) and the inconsistencies regarding its malignant transformation potential, this study aimed to investigate the expression level of fascin in OLP and oral squamous cell carcinoma (OSCC). Methods. In this experimental study, 27 samples of erosive OLP and 30 samples of OSCC were immunohistochemically stained with fascin. The extent of fascin expression (epithelial cells with cytoplasmic immunoreactivity) in OLP was categorized into 4 scores based on the extent of epithelial staining. SCC specimens were scored according to the intensity and percentage of staining, and the sum of these two numbers was finally considered the total score, which ranged from 0 to 7. Fascin expression in two groups was compared using the Kruskal-Wallis test. Results. About half of the lichen planus samples (48.15%) received a score of 3. Most of the SCC samples received a score of 5 or 6. The comparison of the expression of fascin between the two groups demonstrated a statistically significant difference (P<0.001). Conclusion. The increased expression of fascin in lichen planus and SCC may indicate the role of fascin in carcinogenesis. Practical Implications. Overexpression of fascin in lichen planus and SCC may be a diagnostic marker for malignant transformation and a prognostic marker, respectively. [ABSTRACT FROM AUTHOR]

Background: Odontogenic cysts and tumors develop from the dental follicle of asymptomatic impacted teeth. Odontogenic tissues express the epidermal growth factor receptor family (EGFR), which mediates cell proliferation, survival, and neoplastic differentiation. The present study aimed to compare the immunohistochemical expression of EGFR and human epidermal growth factor receptor 2 (HER2) in the dental follicle of impacted wisdom teeth with normal and abnormal radiographic size. Methods: In this analytical study, immunohistochemical staining of EGFR and HER2 was performed on 30 normal and 30 abnormal follicles of impacted third molars. Follicles with a width of <2.5 mm were considered normal, whereas those with a width of ≥2.5 mm were regarded as abnormal. The immunoreactive score (IRS) was used to report the expression levels of EGFR and HER2. The obtained data were analyzed using SPSS software. Age and sex were compared in normal and abnormal groups with independent t test and Chi square test, respectively. P<0.05 was considered statistically significant. Results: The EGFR and HER2 overall expression was high in all normal and abnormal follicles. The comparison of the percentage of stained cells and intensity of EGFR and HER2 staining in normal and abnormal follicles were not significantly different (P=0.73, P=0.63, P=0.95, respectively). Conclusion: Due to the high expression of EGFR and HER2 in normal and abnormal follicles, as well as the lack of significant differences in these two groups, the radiographic size of dental follicles might not indicate the potential capabilities of their cells, and more research in this field is recommended. [ABSTRACT FROM AUTHOR]

Background: Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that is classified as a premalignant condition. Epithelial growth factor receptor (EGFR) is associated with tumorigenesis and tumor progression and is overexpressed in several oral malignant disorders. Despite the association of EGFR overexpression with oral potentially malignant lesions, few studies have analyzed its expression in OLP, showing controversial results. This study aimed to compare the expression of EGFR as a protein marker in Reticular and Erosive OLP. Methods: This descriptive-analytical cross-sectional was conducted on 15 paraffin blocks of reticular lichen planus lesions, 16 paraffin blocks of erosive OLP lesions, and 8 paraffin blocks of inflammatory fibrous hyperplasia lesions as the control group (39 in total). After immunohistochemical staining for EGFR, samples were simultaneously observed by two maxillofacial pathologist, and the percentage of stained cells, intensity of staining, pattern of staining, and the location of stained cells were obtained. Results: The Mann-Whitney-U test showed that there was no significant difference in the mean percentage of stained cells between erosive OLP and reticular OLP (P-value = 0.213) and between reticular OLP and control group (P-value = 0.137), but there was a significant difference between erosive OLP and control group (P-value = 0.035). Fisher's exact test showed that there was no significant difference between the frequency distribution of staining patterns in three types of lesions (P-value = 0.90). Kruskal-Wallis test showed that there was no significant difference between the intensity of staining in the three groups (P-value = 0.19) and also there was no significant difference between the location of stained cells in different layers of the epithelium in the three groups (P-value = 0.90). Conclusions: The results of this study showed that in comparison of reticular OLP, erosive OLP, and the control group there was a significant difference just between erosive OLP and control group in the percentage of stained cells. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is a severe life-threatening condition in which many women are involved yearly. One factor that has recently been noticed and investigated as a diagnostic predictor of this type of cancer is the number of tumor buds and the relation of this factor with a patient's survival rate. Materials and methods: This study includes 150 female patients over 18 years old with a mean age of 53.99 ± 12.56 years old with breast cancer, which was diagnosed at various medical centers, including Rouhani Hospital itself, and referred to Rouhani Hospital Medical Center, Babol, Iran. The number of intratumoral and peritumoral buds in patients' microscopic slides were archived and evaluated along with tumor microenvironment on hematoxylin and eosin (H&E) slides and compared to other clinicopathological findings. This article precisely investigated the relationship between the number of intratumoral and peritumoral buds with patients' 5-year survival rate. Also, the relationship between age, tumor stage, grade, size, the number of lymph nodes involved, and the presence of metastasis with the number of intratumoral and peritumoral buds was studied. Results and discussion: The result showed a significant statistical association between the number of intratumoral and peritumoral buds with tumor size, tumor stage, presence of metastasis, the number of lymph nodes involved, and 5-year survival rate. On the other hand, there is not a significant statistical association between the number of intratumoral and peritumoral buds with age and tumor grade. Conclusion: Our investigation revealed a significant statistical relationship between the number of tumor buds and patients' survival rate. So, this factor should be considered significant to help those patients increase their survival ratio. [ABSTRACT FROM AUTHOR]

Background: High-risk Human Papillomavirus (HPV) genotypes are found in malignant oral epithelial lesions, and HPV infection is proposed as a risk factor for initiating Squamous cell carcinoma (SCC) in the head and neck region. This study suggests a practical approach to detect HPV in HPVassociated oral epithelial dysplasia (HAOED). Methods: Fifty-four oral epithelial dysplasia specimens were examined, comprising twenty-seven cases diagnosed with highgrade dysplasia and twenty-seven cases diagnosed with lowgrade dysplasia using a binary grading system. To assess the cases for HPV, the specimens were examined for p16 protein using an immunohistochemical (IHC) study, and then, the Chromatin In Situ Hybridization (CISH) test was performed for all positive cases. Chromatin Immunoprecipitation-Polymerase Chain Reaction (ChIP-PCR) was performed on CISH-positive specimens to assess the outcome. This cross-sectional study was conducted in 2020 at Tehran University of Medical Science. SPSS software version 22.0 was used to perform the Chi square or Fisher's exact test to examine the relationship between variables (statistically significant level P<0.05). Results: The expression of p16 protein was not associated with the severity of epithelial dysplasia (81.5% in low-grade and 59.2% in high-grade cases) (P=0.16). Moreover, according to the CISH test result, 9.25% of all specimens were positive (P>0.99), and in the nine cases, undergone the ChIP-PCR study, two cases (22.2%) showed positivity for HPV-16, while one case (11.1%) demonstrated positivity for HPV-51. Conclusion: Regarding HAOED, here, we proposed a step-bystep combination approach using different diagnostic methods, including IHC for p16 protein, CISH, and ChIP-PCR based on a complementary algorithm. [ABSTRACT FROM AUTHOR]

Background: The aggregation of clonal plasma cells causes plasma cell neoplasms, which vary in severity and clinical outcomes. The present research focused on the epidemiological, clinical, immunologic, and cytogenetic characteristics of plasma cell neoplasms. Methods: In this five-year retrospective cross-sectional study, demographic information such as age and sex, calcium elevation, renal insufficiency, anemia, and bone lesion (CRAB) characteristics, as well as laboratory data including bone marrow and peripheral blood film results, immunohistochemistry, flow cytometry, and cytogenetic study outcomes were collected at Shiraz University of Medical Sciences, Shiraz, Iran. The collected data were analyzed using SPSS Statistics software (version 20.0). Descriptive statistics were reported as numbers, percentages, and mean±SD. Results: 417 newly diagnosed plasma cell neoplasm patients were confirmed by bone marrow or other tissue biopsy tests. 279 patients were men (66.9%). The most prevalent age group was 60-64 years old (18.46%). Plasma cell myeloma (PCM) affected 355 (85.13%) patients, while monoclonal gammopathy of undetermined significance (MGUS) affected 6 (1.43%) patients. Solitary plasmacytoma was seen in 56 (13.42%) patients. At the time of diagnosis, 119 (33.52%) of 355 PCM patients were asymptomatic, whereas 236 (66.47%) patients had at least one CRAB symptom, 55 (15.49%) had two or more, and 14 (3.94%) had three or more. There were 7 (1.97%) cases of amyloidosis. Cytogenetic abnormalities were found in 51.28% (40/78) of the patients. Twenty-one individuals (52.5%) were hyperdiploid with multiple trisomy, while 19 (47.50%) were not. Conclusion: When diagnosed, Iranian PCM patients might have more advanced disease. PCM was more prevalent in young adults, and hyperdiploid was the most common cytogenetic finding in this investigation. [ABSTRACT FROM AUTHOR]

Background: Three main cell signaling pathways including the endoplasmic reticulum stress (ERS) response, autophagy, and apoptosis play critical roles in both cell survival and death. They were found to crosstalk with one another during tumorigenesis and cancer progression. This study aimed to investigate the expression of the spliced form of X-box binding protein 1 (XBP1s), p62, and caspase-3, as the essential biomarkers of ERS, autophagy, and apoptosis in patients with colorectal cancer (CRC), as well as the correlation between their expression and clinicopathological data. Methods: This retrospective study was conducted on formalinfixed paraffin-embedded (FFPE) blocks, which were collected from patients and their tumor margins, from the tumor bank of Imam Khomeini Hospital (Tehran, Iran) from 2017 to 2019. Tissue microarray (TMA) was used to measure the XBP1s, p62, and caspase-3 biomarkers. Data were analyzed using SPSS software version 20, and P≤0.05 was considered statistically significant. Results: Evaluating the total of 91 patients, a significant relationship was found between XBP1s expression and TNM stage (P=0.003), primary tumor (pT) (P=0.054), and the degree of differentiation (P=0.006); and between caspase-3 with pT (P=0.004), and lymphovascular invasion (P=0.02). However, no significant correlation was found between p62 and clinicopathological data. Furthermore, a positive relationship between XBP1s and p62 was confirmed (correlation coefficient: 22.2% and P=0.05). Conclusion: Our findings indicated that XBP1s could be considered as a target for therapy in personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Due to the close association of CD31 marker positivity and tumor microvessel density, the relationship between this marker and the pathophysiological behavior of the tumor, such as the ability to invade the surrounding tissues and organ damage, is also quite probable. Objectives: We aimed at evaluating the association of CD3l expression with the likelihood of microvascular invasion and other abnormal histopathological findings in patients with colorectal cancer. Methods: In our cross-sectional study, the pathology numbers of 50 samples that were diagnosed with colorectal cancer in their pathology report during 202l and 2022 were identified by searching our hospital information system. Immunohistochemical staining (IHC) using CD31 monoclonal antibody was performed for assessing CD31 positivity. Results: CD31 positivity was found in 34.0% of cases, 35.5% in colon masses, and 31.6% in rectal masses. The patients with positive CD31 had significantly higher tumor grades (P< 0.045). The prevalence rate of vascular invasion was significantly higher in patients with positive CD31 compared to those with negative CD31 states (47.1% versus 12.1%, P = 0.006). Also, the rate of lymph node involvement in the groups with positive and negative CD31 was 58.8% and 24.2%, respectively, indicating a significant difference (P = 0.016). In multivariable logistic regression models, CD31 positivity was shown to be associated with the risk for vascular invasion (OR = 6.211, P = 0.020) and lymph node involvement (OR= 6.535, P = 0.011). Conclusions: CD31 positivity in patients with colorectal cancer can effectively predict invasive behavior of the tumor including vascular invasion, lymph node involvement, and high tumor grades. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PC) is one of the most common cancers worldwide. Recently, multiparametric magnetic resonance imaging (mpMRI) has been used to diagnose PC in suspected patients. Prostate Imaging Reporting & Data System (PI-RADS) was developed and applied as a criterion for detecting lesions suspicious of PC. Various studies have been conducted to determine the negative predictive value of non-suspicious mpMRI (PI-RADS 1 or 2). However, the results of these studies have been limited and different. Objectives: This study was conducted to determine the PC rate in patients with PI-RADS 2 lesions in mpMRI and the factors related to clinically significant prostate cancer (CsPC) diagnosis in these lesions. Methods: By referring to the archive department of Shahada-e-Tajrish, Rasul-e-Akram, Treata, and Payambaran hospitals, among the patients suspected of PC who underwent biopsy and had elevated prostate-specific antigen (PSA) serum levels, the prostate biopsy samples of 330 patients were consecutively included in the study. Frequency of samples diagnosed with PC and its histological characteristics, including mass location, Gleason score (GS), Gleason group (GG), percentage of G4 and G5 cells, sample size, percentage of involvement of sample with cancer tissue, and invasion to the surrounding tissues were examined. Adenocarcinoma samples were divided into low-risk, intermediate-to-high-risk groups based on D'Amico criteria and the relationship between age, PSA total (PSAt), PSA density (PSAd), prostate volume, and the presence of a PI-RADS 3 or 4 lesion at the same time with the rate of diagnosed CsPCs were reviewed. Results: The data from 709 tissue samples were collected, among which 249 were from the right inner part, 249 were from the left inner part, and 211 biopsy samples were from the peripheral portion of the prostate. Among these, 390 tissue samples in mpMRI studies were PI-RADS 2, and 319 were PI-RADS 3 or 4. The mean age of the patients was 64.78 ± 37.55. The mean PSAd, PSAt, and prostate volume were 0.15 ± 0.11, 8.73 ± 6.43, and 61.18 ± 25.76, respectively. Seventy-five samples were diagnosed with adenocarcinoma, of which 48% are in PI-RADS group 2, and 52% are in PI-RADS group 3 - 4 (P-value = 0.263). Comparing the histological characteristics of adenocarcinoma samples between the two groups showed that only the amount of GG was significantly higher in the samples with PI-RADS 3 and 4 (P-value = 0.035). Adenocarcinomas diagnosed in 72.2% of cases in PI-RADS 2 samples and 84.6% of PI-RADS 3 and 4 samples were clinically significant, and no significant difference was seen between the two groups (P-value = 0.38). The amount of PSAt in PI-RADS 2 adenocarcinoma samples was significantly higher in clinically significant carcinomas than in low-risk carcinomas (P-value = 0.045). Conclusions: The results of the present study showed that PI-RADS 2 lesions should be considered for biopsy when there is clinical suspicion of PC. PSA levels can effectively determine the need for biopsy in PI-RADS 2 lesions. [ABSTRACT FROM AUTHOR]

Introduction: Epithelioid type inflammatory myofibroblastic sarcoma (EIMS) is a subtype of inflammatory myofibroblastic tumor (IMT). It consists of round or epithelioid cells, and almost all types of EIMS contain rearrangements of the anaplastic lymphoma kinase (ALK) gene. Case presentation: We describe a 20-year-old female presenting with abdominal pain and a rapidly growing intraabdominal mass who underwent surgical tumor resection. She was diagnosed with EIMS. ALK and ki-67 expressions were detected in immunohistochemistry assessment. She was started with Crizotinib 200 mg twice a day, and chemotherapy was also initiated due to the recurrence of the disease 4 months after the initial treatment. She was unresponsive to all the medical regimens and died in 8 months. Conclusion: Approach to patients with EIMS is really challenging in terms of both diagnosis and treatment. Patients with combined surgical and non-surgical treatment regimen were seen to have a more favorable outcome in some EIMS cases. Therefore, it is essential to implement a multidisciplinary approach to diagnose and treat patients suspicious of EIMS. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor among oral cancers. Cyclin D1 and Ki-67 have associated with cell division. The aim of this study was to compare the expression of these markers in OSCC with and without cervical lymph node (LN) metastasis. Materials and Methods: This cross-sectional study was performed on 40 OSCCs with and without cervical LN metastasis (20 in each group) that was recorded in the pathology archive of Ayatollah Kashani Hospital in Isfahan. Clinical information including age, gender, and location was collected. Some histopathological parameters including depth of invasion, lymphovascular invasion (LVI), perineural invasion (PNI), number of LN metastases, histopathological grade, and stage of disease were evaluated. Immunohistochemical staining was performed for cyclin D1 and Ki-67. All data were entered into SPSS24 software and were analyzed by Mann--Whitney, Kruskal--Wallis, Chi-square, Fisher's exact, and t-tests. P < 0.05 was considered statistically significant. Results: Based on LVI and stage of disease, a significant correlation was found between the two groups (P < 0.001). There was a significant difference between the two groups based on cyclin D1 expression (P = 0.05). The expression of the Ki-67 showed a significant difference based on tumor location (P = 0.026) and PNI (P = 0.033). Conclusion: The use of markers should be considered in determining the prognosis of OSCC, and the cyclin D1 marker is one of the useful markers for predictors of cervical LN metastasis. [ABSTRACT FROM AUTHOR]

Background: The association between metabolic syndrome (MetS) and breast cancer may significantly impact the mortality and incidence of breast cancer. This study aimed to assess the association between MetS risk factors and immunohistochemical (IHC) profiles in women with breast cancer. Methods: This cross-sectional study used the medical records of 300 breast cancer patients with an average age of 53.11±12.97 years in the Chemotherapy and Radiation Therapy Clinic of Dr. Anbiai, Tehran, Iran (2020-2021). The cases were divided into five subgroups including luminal A, luminal B (HER-2-), luminal B (HER-2+), HER-2 overexpressing, and triple negative. Results: There was no difference in the prognostic indicators between the presence and absence of MetS in women with breast cancer. A higher proportion of luminal A tumors (39.3%), luminal B (HER-2+) (25%), triple-negative (17%), luminal B (HER-2-) (10.7%), HER-2 overexpression (8%) was observed in women with MetS than those without MetS. Multivariate logistic regression analysis showed that patients with MetS had a 41% higher chance of developing luminal A than those without MetS, and patients with a BMI≥30 Kg/m² had an 80% higher chance of developing luminal B (HER-2+) than those with a BMI<30 Kg/m². Moreover, women with a waist circumference higher than 88 cm had a 14 % lower chance of developing Luminal B (HER-2+) than those with a waist circumference less than 88 cm. Conclusion: There was no difference in prognostic indicators and IHC profile in patients with and without MetS. [ABSTRACT FROM AUTHOR]

Background & Objective: Leptin is an adipocyte-derived hormone with a critical role in energy balance. As demonstrated by previous investigations, leptin acts as a proliferative and angiogenic factor in cancer cells. However, results regarding its role in colorectal cancer are still inconclusive. We aimed to evaluate serum leptin and tissue expression of leptin receptor (Ob-R) in normal and malignant samples of colorectal. Methods: Serum and tissue samples from pathology-confirmed colorectal cancer patients and normal controls referring to a university hospital of Mazandaran were obtained during 2019-21. ELISA and immunohistochemistry were applied to determine leptin and Ob-R expression respectively. Results: A total of 90 samples belonging to 46 normal and 44 CRC patients were enrolled. Normal and CRC groups included 32 (69.56%) and 21 (47.72%) female subjects respectively. The average leptin concentration in the normal group was 115.80 and, in the patient, group was 124.47 ng/mL (P=0.897). CRC cases showed an insignificantly higher Ob-R detection rate (P=0.086). Conclusion: There was no significant difference in leptin and Ob-R expression between CRC patients and normal subjects. Thus, leptin and its receptor may not be useful as a biomarker of CRC. [ABSTRACT FROM AUTHOR]

Background: Lipocalin-2 (LCN2) deregulation has been reported in several types of cancer and is implicated in the proliferation, migration, angiogenesis, and progression of tumors. However, its aberrant expression has been rarely studied in nasopharyngeal carcinoma (NPC). In the present study, we investigated the expression of LCN2 in NPC patients. Methods: In this descriptive cross-sectional study, 29 NPC and 20 non-cancerous control paraffin pathology blocks were obtained from the seven-year (2011 to 2018) archive of Razi Laboratory in Rasht, Iran. LCN2 mRNA expression was evaluated through quantitative real-time PCR. In addition, immunohistochemistry was performed to evaluate LCN2 expression at the protein level. The fold change value and total immunostaining score (TIS) were applied for quantitative evaluation. The nonparametric Mann-Whitney U test and Fisher's exact test were used through GraphPad Prism 8.3.0 software. P<0.05 was considered statistically significant. Results: Our results revealed that LCN2 mRNA and protein levels in NPC tissues were significantly higher than control tissues (P=0.028 and P=0.002, respectively). At the protein level, 65.51% (19/29) of NPC patients were categorized as having high LCN2 expression (TIS>3) and 34.47% (10/29) as low expression (TIS≤3). While in the control group, 25% (5/20) of subjects represented a high expression of LCN2 (TIS>3), and 75% (15/20) showed no or weak expression (TIS≤3). No significant correlation was found between the overexpression of LCN2 at the protein level and the demographic features of the patients. Conclusion: Our findings suggest that LCN2 might be considered a potential new diagnostic marker for NPC. However, this warrants further studies. [ABSTRACT FROM AUTHOR]

Background&Objective:The platelet-derived growth factor receptor (PDGFR) signaling pathway has a vital function as a regulator of glioma development. PDGFRA alterations have been observed in a variety of cancers and have been important clinical targets for tyrosine kinase inhibitors like Imatinib. The aim of this study was to evaluate the role of PDGFRA and PDGFA in the pathogenesis of GBM and to determine whether the constitutive activation of PDGFRA is driven by gene mutations or protein expression. Materials&Methods:PDGFRA-activating gene mutations (exons 12, 18) were assessed in a subset of 75 samples, of which 65 were GBM and 10 were pilocytic astrocytoma, using PCR followed by direct sequencing. PDGFA expression was evaluated by immunohistochemistry in a series of 20 cases including 15 cases of glioblastoma multiforme and 5 cases of pilocytic astrocytoma. Results:No PDGFRA-activating mutations were found by Sanger sequencing. In addition, this study found polymorphism in PDGFRA exon 12, c.1701A> G, which was a silent mutation. Immunohistochemical analysis showed elevated PDGFA expression in 25% (5 out of 20) of glioma cases. PDGFA expression was not detected in any pilocytic astrocytoma; however, 33.33% (5 out of 15) of GBM samples showed increased PDGFA expression. Conclusion:Consistent with previous studies, the findings of the present study underline the importance of PDGFA and PDGFRA alterations as a possible potential predictive biomarker and a therapeutic target in GBM. Further research is needed to better understand the underlying genetic mechanisms driving abnormal PDGFRA activity in gliomas. [ABSTRACT FROM AUTHOR]

Background: Lymphatic neoplasia may occur in various types, such as lymphoma, lymphosarcoma, lympholeukemia, and plasmacytoid leukemia. Lymphoma, defined as a malignant tumour of lymphoid tissue, has been found in a number of fish families including Esocidae and Salmonidae. However, the occurrence of lymphoma is rare in those belonging to the Cyprinidae. A final diagnosis of ocular and testicular T-cell lymphoma in the present study was based on the clinical signs, morphology, and texture of the tumour masses in the macroscopic and microscopic examinations. In addition, histopathological and immunohistochemical findings corresponded to T-cell lymphoma characteristics. Case presentation: A 2-year-old hermaphrodite koi carp (Cyprinus carpio Linnaeus 1758) with a large ocular mass and severe exophthalmia in the right eye was referred to the Ornamental Fish Clinic in October 2020. Under anesthesia, enucleation was performed. 57 days after enucleation of the right eye, exophthalmia in the left eye was discovered. 221 days after surgery, the fish was discovered to be dead. At necropsy, a large soft tissue mass attached to the left testis was discovered. There were also small whitish nodules on the surface of the liver. Histopathology revealed a hypercellular ocular mass with scant connective tissue. The sections also revealed multifocal hemorrhages, round to ovoid neoplastic cells, mild-to-moderate anisokaryosis and anisocytosis, and mitotic figures. Basophilic neoplastic cells were found in blood vessels within the testicular mass, raising the possibility of systemic spread. The liver showed microscopic metastasis with morphologic similarities to the ocular and testicular tumors. The neoplastic cells infiltrating the left and right eyes as well as the testicular mass were immunohistochemically positive for CD3 but negative for CD20. The masses were diagnosed as T-cell lymphoma based on histopathological and immunohistochemical findings. Conclusions: This case report provides the first evidence of clinical, histopathological, morphological, and immunohistochemical findings of an ocular and testicular T-cell lymphoma in a hermaphrodite koi carp (Cyprinus carpio) in Iran. [ABSTRACT FROM AUTHOR]

Background: Due to the increasing prevalence of oral squamous cell carcinoma (OSCC) in Iran and especially in young people, this study aimed to identify human papillomavirus (HPV) using p16 in OSCC. Materials and Methods: In this descriptive-analytical cross-sectional study, 40 samples from the archives of the Pathology Department of Kashani Hospital were selected by a definitive diagnosis of OSCC with neck dissection. Demographic information including age, gender, location, and size of the lesion was obtained. Samples were divided into two groups based on lymph node (LN) metastasis. Immunohistochemical staining was performed for p16. Data were entered into SPSS 24 software and statistically analyzed by t-test, ANOVA, and Spearman nonparametric test. P <0.05 was statistically significant. Results: The mean age of patients was 59.7 ± 17.11 which in terms of age and gender there was no significant difference between the two groups including with and without cervical LN metastasis (P > 0.05). There was no significant difference between the two groups based on the grade of tumor, perninural invasion, tumor size and location (P > 0.05). The only significant difference between the two groups was based on lymphovascular invasion and disease stage (P < 0.05). The p16 expression also showed a significant difference between the two groups (P < 0.05). Conclusion: In OSCCs without cervical LN metastasis, a significant increase in p16 expression was observed compared to samples with cervical LNs metastasis. The presence of HPV was higher in samples with less LNs metastasis and possibly a better prognosis. [ABSTRACT FROM AUTHOR]

The protozoan parasite Neospora caninum infects carnivores as definitive and a wide range of mammals as intermediate hosts. This parasite is regarded as an important cause of abortion in cattle worldwide, causing significant economic losses. Although there is serological evidence of infection in Old World camelids, the significance of N. caninum in these animal species is still poorly understood. The aim of this study was to use molecular and histological methods to detect N. caninum in the blood and tissues of 100 slaughtered one-humped camels (Camelus dromedarius) in Iran. For this, genomic DNA was extracted from blood, brain, portal lymph node and liver of the camels, and nested-PCR assay followed by sequencing were performed. Besides, paraffin-embedded tissue sections were stained with hematoxylin and eosin (H&E) and studied microscopically. In addition, immunohistochemical staining for N. caninum was attempted on brain samples with positive PCR results. All animals were tested for antibodies against N. caninum and Toxoplasma gondii by whole tachyzoite-agglutination tests. N. caninum DNA was detected in blood, brain, and portal lymph node, but not in the liver of two (2%) camels. Histopathological examination revealed cysts resembling N. caninum in brain samples of one of these camels; however, immunohistochemical staining for N. caninum and T. gondii did not allow a morphological identification. IgG antibodies to N. caninum and T. gondii were detected in 36% and 35% of the camels, respectively. This study provides the first insight into direct detection of N. caninum in C. dromedarius in Iran. Further molecular studies on aborted fetuses, stillborn animals and cases of perinatal mortality are needed to understand the possible involvement of N. caninum in cases of reproductive failure. As the definitive hosts of N. caninum are domestic and wild canids, producers should be advised to monitor and limit exposure of their camelids to these species and their feces. Highlights: First direct detection of N. caninum DNA in blood and tissues of one-humped camels (Camelus dromedarius) in Iran. N. caninum DNA was detected in blood, brain, portal lymph node, but not liver tissue. Tissue cysts were observed in histological sections of the brain in one camel. [ABSTRACT FROM AUTHOR]

Background and Aim: Gastric cancer (GC) is a major health problem worldwide. Several studies have shown the virus's role in cancer pathogenesis. Therefore, the aim of this study was to evaluate the presence of human papillomavirus (HPV) in GC by immunohistochemistry (IHC) and polymerase chain reaction (PCR) in hospitals in the East Azerbaijan province, Iran. Materials and Methods: In this descriptive cross-sectional study, 100 tissue samples of paraffin-embedded, including GC (50 samples), benign gastric hyperplasia (25 samples), and a control group (25 samples) were collected from the archives of laboratories in East Azerbaijan province from April to October 2021. The IHC and PCR were used to detect the HPV virus. SPSS software version 22 and t-test and Chi-Square statistical tests were used for data analysis. Results: 8 out of 50 cancer samples were HPV positive by IHC and PCR. HPV-positive samples had a mean age of 62.87 ± 9.67. Men had the highest number of HPV-positive samples compared to women (5 samples vs. 3 samples). However, no viral genomes were observed in non-malignant and control samples. There was a significant relationship between HPV infection and GC (P=0.03). Conclusion: According to the present study's findings, the presence of HPV infection in GC plays an important role in the development of GC in the hospitals of East Azerbaijan province. Also, the results showed that PCR and IHC are both more sensitive and reliable in detecting HPV because the results of both IHC and PCR were the same. Hence IHC method can be used as an alternative to the PCR method to detect HPV oncoproteins. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the etiology and contributing factors of cavitary pulmonary lesions in HIV infected patients. Methods: In this study, 844 HIV infected patients with a total of 1000 admissions were investigated at Masih Daneshvari Hospital from Aug 2010 to Oct 2019. After excluding the missing data and distorted documentation, 746 cases and 878 admission episodes finally underwent statistical analysis. The CXRs were observed thoroughly and the cavitary lesions were identified. Eventually, demographic data, diagnostic information, and laboratory findings were extracted and analyzed. Results: Of the 878 episodes of hospitalization, cavitary pulmonary lesions were observed in 145 documents. The most prevalent etiology was TB with 105 cases (72.5%). After that, Pneumocystis jiroveci and septic embolism were responsible for a further 7.6% and 5.6% of the total lung cavities, respectively. 58.5% of the cavities were present in a single lobe, with men being affected in 90.2% of the cases. The upper lobes were the most common site of involvement in the lungs [42.9% for Left Upper Lobe (LUL) and 52.3% for Right Upper Lobe (RUL)]. The rate of definitive diagnosis was significantly higher in patients affected with cavitary lesions (82.8%) in comparison with the unaffected (74.8%) (p=0.001). No significant difference in demographics, HIV and ART status, CD4+ cell count, viral load, and mortality was evident between the two groups. Conclusion: The most common etiology of cavitary lesions in HIV positive patients was attributable to TB, PJP, and septic embolism respectively. Cavitary lesions were more prevalent in males and mainly tend to involve the upper zones of pulmonary parenchyma. [ABSTRACT FROM AUTHOR]

Introduction: Today, colon cancer is one of the most common types of gastrointestinal cancer worldwide. CD133 as a known cancer stem cell marker has been found effective in cell proliferation and differentiation in various cancers, including colon cancer. We aimed to investigate the relationship between CD133 expression in colon cancer with prognostic factors and survival rate of patients with colon cancer by immunohistochemistry. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue was taken from patients with colon cancer. Histopathology examination was done using hematoxylin and eosin staining. Immunohistochemistry was performed to determine CD133 expression. Association between CD133 expression and clinicopathological profile was then assessed. Results: There was a statistically significant association between CD133 protein expression and sex , cancer stage, and lymphatic invasion (p = 0.044, p = 0.131, and p = 0.002, respectively). However, no significant correlation was identified between CD133 expression and other factors, including age of patients with colorectal cancer (CRC) (p = 0.267), tumor location (p = 0.494), tumor differentiation grade (p = 0.263), neural tissue invasion, and 5-year survival (p = 0.054). Conclusion: CD133 is a useful predictive or prognostic biomarker for CRC in clinical assessment and may serve as a potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

Background: Amplification of HER2 is an important factor in the diagnosis and treatment of breast cancer. Fluorescence in situ hybridization (FISH) is the gold standard for the detection of HER2-positive tumors. However, the Immunohistochemistry (IHC) assay for the detection of HER2 is more popular in the preclinical laboratory since it is faster and more economical compared to the FISH test. Materials and Methods: In this study, the status of HER2 amplification is determined by the FISH test using 44 formalin-fixed paraffin-embedded tissue samples and comparing the results with the IHC test to determine the reliability of the IHC test. Also, the relationship between HER2 amplification and estrogen, progesterone receptors, P53, age, menopausal status, family history of breast cancer, tumor size, and histological grade were determined. Results: Examination of HER2 in 44 samples by IHC showed 3 (6.8%) and 5 (11.4%) samples were positive (IHC 3+) and negative (IHC 0, 1+), respectively, and 36 (81.8%) samples were ambiguous (IHC 2 +), but examination by FISH showed 21 samples (47, 7%) were positive and 23 samples (52, 3%) were negative. There was a significant difference between IHC and FISH in the detection of HER2 amplification (P=0.019). Also, there was a significant difference between HER2 amplification and menopause in patients (P=0.035). Conclusion: This result demonstrated that the IHC test is not a reliable test to determine HER2 amplification. This study represented that FISH analysis is more reliable than IHC and must be preferentially performed for all cases, especially for HER2 +2 cases for whom the IHC result is 2+. [ABSTRACT FROM AUTHOR]

Background and Aim: Bartonella quintana is an aerobic, gram-negative, rod-shaped, and polar bacterium. Detection of this bacterium is done through blood culture in an agar medium, and the longtime of detection by culture has made molecular methods such as PCR important for more accurate and faster detection. Materials and Methods: For this reason, 100 cultured negative endocarditis specimens were collected in this study. DNA extraction was performed from B. quintana, and the concentration and quality of the obtained DNA were measured. PCR reaction was performed on the genome of negative control samples. To clone a portion of the amplified gene in PUC 18 plasmid, the PCR product was first purified. After ligation, JM107 E. coli susceptible to calcium chloride was used. Transformed bacteria were cultured on LB Broth medium containing Ampicillin antibiotic. Then 2 to 3 white colonies were selected, and PCR was performed. Plasmid extraction was performed after confirming the presence of recombinant and inserted plasmids. Results: The last dilution of PUC18 plasmid for B. quintana with an initial concentration of 780 ng/μL, which formed a detectable band on the gel, was calculated to be 10-7, and the minimum number of detectable copies in a 25 μL PCR reaction equal to 24 copies. . In quantitative DNA analysis, its amount was calculated between 1.69 and 1.8. Conclusion: The collected samples were then examined for the presence of B. quintana in patients. Of the 60 samples collected, none were positive. [ABSTRACT FROM AUTHOR]

Statement of the Problem: Oral epithelial dysplasia (OED) is a common potentially malignant lesion of oral cavity that should be managed to prevent likely malignant transformation. Purpose: Here, we present a combination of binary grading system with complementary immunohistochemical (IHC) staining for Ki67 biomarker to provide a reproducible OED grading system. Materials and Method: In this cross-sectional study, seventy out of one hundred OED specimens, which were accompanied by IHC stained microscopic slides for Ki67 antigen were evaluated by four independent oral pathologists. Both three-tier and binary grading systems based on WHO microscopic criteria were employed, blindly in a four-step method with at least twoweek interval between each observation. Intra- and inter-observational reliability was assessed using Kappa statistical analysis. Results: OED diagnosis based on binary system showed significant intra-observer reliability comparing to three-tier system without biomarker. Moreover, OED diagnosis based on binary system using Ki67 biomarker showed significant inter-observer reliability comparing to diagnosis in three tier system and based on binary system without Ki67 biomarker showed significant inter-observer reliability comparing to diagnosis based on three-tier system without Ki67. Conclusion: Here, we found that application of IHC staining for Ki67 biomarker in binary system might provide a more reliable grading method for oral pathologist form different educational background. [ABSTRACT FROM AUTHOR]

Background: Gestational trophoblastic disease (GTD) is a general term that includes several types of pathologically different diseases, which range from hydatidiform mole to choriocarcinoma. Early differentiation of these types is important to determine treatment strategy and prognosis. Objectives: Genetic markers such as TP53 and HER-2/neu expression are recently shown to have diagnostic and prognostic values. The aim of this study was to evaluate its significance. Methods: We enrolled 62 patients diagnosed with GTD referred to Imam Hossein Hospital in Tehran, Iran between 2012 and 2017. Endometrial pathologic specimens were stained, using the immunohistochemistry (IHC) method for the expression of TP53 and HER-2/neu genes. Expression levels determined by IHC were compared between final pathologic diagnoses, using one-way ANOVA test (analysis of variances), which detects significant differences between the means of 3 or more independent groups. Results: Out of 62 participants, 32 and 24 cases were diagnosed as partial and complete hydatidiform mole, respectively. Four cases had invasive hydatidiform mole and only 2 cases were diagnosed as choriocarcinoma. Analysis using ANOVA demonstrated that expression levels of both TP53 and HER-2/neu genes are significantly higher among patients with invasive form and choriocarcinoma compared with non-invasive hydatidiform mole (P< 0.05 for both genes). The receiver operating characteristic (ROC) curve for each gene showed that more than 55% positive staining for the TP53 gene can differentiate non-invasive hydatidiform mole from invasive form and choriocarcinoma with 100% sensitivity, and 92.9% specificity. Conclusions: TP53 expression might serve as a potential diagnostic aid to differentiate benign and malignant GTDs and a future target for adjusting treatment based on the expression levels. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer (EC) is known as the most common malignancy of the female reproductive system, suggested to be associated with hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome (LS). Objectives: Therefore, the aim of the present study was to screen for LS in patients with EC using immunohistochemistry (IHC). Methods: In this retrospective cross-sectional study, the patients with EC, referred to Qaem Hospital, Mashhad, Iran, from 2015 - 2019, were enrolled. Paraffin-embedded tissue blocks were then examined via IHC for the expression of four mismatch repair (MMR) proteins, includingMLH1,MSH2,MSH6, andPMS2. The demographic and tumor-related data were also extracted from medical records and pathology reports. The data were consequently analyzed at the significance level of P < 0.05. Results: A total number of 100 patients with EC were evaluated using IHC, and 12 (12%) cases were found suspected. As well, no significant relationship was observed between LS and age, tumor site, tumor histology, tumor size, tumor grade, tumor-infiltrating lymphocytes (TILs), and a family/personal history of malignancies. Conclusions: The prevalence of LS based on the IHC expression of the MMR proteins (MLH1, MSH2, MSH6, and PMS2) was 12% in the patients with EC. There was also no significant relationship between the cases suspected and the demographic and tumor-related data. [ABSTRACT FROM AUTHOR]

Background: Ductal carcinoma in situ (DCIS) is widely recognized as the precursor of invasive ductal carcinoma (IDC). We aimed to compare clinicopathological characteristics and prognosis between IDC with and without coexisting DCIS stratified by biological subtypes to evaluate the clinical outcome of these two groups. Method: Data from 5814 patients with IDC (32.4) and IDC/DCIS (67.6%), who underwent surgery from December 1993 through December 2019, were retrospectively assessed. We evaluated the prognosis of IDC with coexisting DCIS in different molecular subtypes. Results: IDC/DCIS patients were younger (P < 0.001). They also presented with a low tumor grade and had less lymph node involvement compared with the pure IDC patients. Compared with the patients with IDC, luminal B subtype was more frequent in those with IDC/DCIS, with 19.4% versus 13.2 %; human epidermal growth factor receptor-2 enriched subtype was also more frequently observed, with 12.2 vs. 8.7%. The 5-year disease-free survival (DFS) was higher in the IDC/DCIS patients (P = 0.036). The survival outcomes significantly improved in the cases with a higher amount of DCIS. The presence of coexisting DCIS (P =0.038), tumor size (P < 0.001), lymph node status (P = 0.005), lymph vascular invasion (P = 0.02), and molecular subtypes (P < 0.001) were found to be DFS-associated independent prognostic factors. Conclusion: DCIS along with IDC were associated with improved prognosis. The presence of DCIS may be a marker of lower aggressiveness, and could be noticed as a prognostic factor in future treatment algorithms. [ABSTRACT FROM AUTHOR]

Rosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive. The aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats. Gas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results. REO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1 , LOC729197 , ATP8A2 , NDST4 , and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT 2 A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects. This study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil. [Display omitted] • The antidepressant mechanism of action of Rosa damascena essential oil may involve the modulation of the serotonergic synapse signaling pathway, which regulates the expression relevant proteins in the ERK-CREB-BDNF pathway. • Joint transcriptomics and metabolomics analyses validated that Rosa damascena essential oil regulates the tryptophan metabolic pathway. • Rosa damascena essential oil ameliorates hippocampal neuronal damage induced by CUMS and modulates neurotransmitter levels. • The key active components in Rosa damascena essential oil responsible for its antidepressant effects may include citronellol, geraniol and (E,E)-farnesol. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is one of the lethal cancers and there is no effective treatment for these patients and still, 5-year survival rate is about 25% to 30%. Finding reliable biomarkers for early-stage diagnosis, targeted therapy, and survival prediction is a priority in this cancer. Objectives: In this study we were trying to know about the molecular classification of gastric cancers in a group of patients from the South of Iran. Patients and Methods: In a cross sectional study, 50 specimens of gastric cancer were selected that have enough tissue to be stained by immunohistochemistry (IHC). IHC was performed for Her-2, mismatch repair genes (MLH-1, MSH-2, MSH-6, and PMS-2), and PDL-1. Frequency of positive makers was compared with survival and outcome. Results and Conclusion: In our study, deficient MMR (dMMR) was detected in 4 patients (8.0%). PD-L1 expression in tumor cells (TC) was observed in 1 of 4 cases (25%) with PMS2 loss. However, PD-L1 in TCs and TILs (tumor infiltrating lymphocytes) was negative in 1 case with MLH1 loss and in 3 of 4 cases with PMS2 loss, which was not statistically significant. All of our 50 cases were positive for MSH2 and MSH6, 24% of which showed TCs with PDL-1 expression and 32% of them in TIL. HER2 was positive in 2 (2/50, 4.0%) cases, among which all of the cases were positive for PD-L1 expression in TCs and TILs, respectively. However, in HER2-negative group, 26.2% (11/42) and 28.6% (12/42) of tumors were positive for PD-L1 in TCs and TILs, respectively. The expression rate of PD-L1 in HER2 negative TCs was significantly higher than that in HER2 positive TCs (P =.033). Immunohistochemistry for Her-2 was equivocal in 6 cases (12.0%) none of which expressed PD-L1 in tumor cells. In our study minimum and maximum survival times from detection of gastric cancer were 1 and 87 months, respectively. The mean ± SD and median ± SD of overall survival time were 30.69 ± 4.88 and 18 ± 1.45 months, respectively. One and 3-year survival rates of 40% and 24%, respectively. PD-L1 expression was not associated with survival, but its expression was associated with intestinal type Lauren classification and negative HER-2. PD-L1 positivity in tumor cells or tumor infiltrating lymphocytes was not an independent prognostic factor in gastric cancer. [ABSTRACT FROM AUTHOR]

Synovial Sarcoma (SS) is a rare soft-tissue malignancy. Only about 15% of SS originates from the retroperitoneum. Retroperitoneal SS (RSS) is usually diagnosed incidentally due to the anatomy of the retroperitoneum. The most common complaints of patients are abdominal and low back pain. Other common symptoms of RSS are palpable abdominal mass, weight loss, and anemia. In this study, we will describe a 29-year-old white Asian man with a diagnosis of RSS after radical nephrectomy. He was admitted to the Urology Department of Shohada-e Tajrish hospital, Tehran, Iran in March 2019. The distinguishing feature of this case is the size of the mass, which has never been reported so much for retroperitoneal synovial sarcoma. Radiologic imaging showed a huge retroperitoneal mass originating from the kidney. Based on the pathologic features and immunohistochemistry (IHC) study, the diagnosis was consistent with synovial sarcoma. Accurate diagnosis of RSS is usually based on the pathological findings. Therefore, in case of doubt, a biopsy can be employed. Surgical resection of the tumor and lymph nodes dissection is the main and most important part of the treatment. Aggressive resection with free margin is recommended. The role of adjuvant and neoadjuvant chemotherapy in RSS is not certain to date, but it is recommended according to the patient's condition. [ABSTRACT FROM AUTHOR]

Objective The most important tumor characteristic of Lynch syndrome (LS) is microsatellite instability (MSI). In the current study, BAT34c4 and BAT26 mononucleotide markers were evaluated as part of efforts to test a cost-effective panel for MSI testing in Iranian patients, comparing it with the Promega kit. Methods Amsterdam II clinical criteria were used to identify patients at risk for LS. The MSI status of these patients was determined using BAT34c4 and BAT26 markers, as well as the Promega kit. The results of both methods were compared, and the sensitivity and specificity of new short tandem repeat (STR) markers were estimated using statistical formulas. Results Of the 37 patients we studied who were at risk for LS, 27% showed MSI-high results, via the Promega kit. The same results were achieved for BAT34c4 and BAT26 separately. Conclusions The novel 2-marker kit for MSI testing has similar accuracy as the Promega kit at a lower cost, due to fewer markers and a more economical labeling method. [ABSTRACT FROM AUTHOR]

Statement of the Problem: E-cadherin and N-cadherin are two types of cell adhesion molecules that are involved in organ development, wound healing, and pathological conditions through the process of epithelial-mesenchymal transition (EMT). However, their role has not yet been fully elucidated in the pathogenesis of periodontal diseases. Purpose: To determine the expression level of proteins associated with the EMT process (E-cadherin and N-cadherin) in chronic periodontitis. Materials and Method: In this cross-sectional study, 37 samples (19 cases with healthy gingival tissue and 18 cases with severe chronic periodontitis) that referred to the Periodontology Department of Zahedan Dental School, Zahedan, Iran, in 2018 were included. The samples were immunohistochemically stained with E-cadherin and N-cadherin monoclonal antibodies. Afterward, the percentage of stained cells and the staining intensity of the cells were evaluated. Finally, the obtained data were analyzed using by IBM© SPSS© Statistics version 21 using Mann-Whitney statistical test. Results: In this study, 89.5% of the healthy gingival tissue samples and 61.1% of samples with chronic periodontitis showed E-cadherin expression in more than 50% of cells. This difference between the two groups was not significant (p= 0.13); however, the E-cadherin staining intensity of the healthy gingival tissue was strong while that of the samples with chronic periodontitis was moderate (p= 0.002). The N-cadherin expression was negative in 68.4% of healthy gingival cases, while 50% of the cases with chronic periodontitis showed a high expression of N-cadherin. This difference was statistically significant (p= 0.04). Moreover, the N-cadherin staining intensity also had a significant difference between the two groups (p= 0.004). Conclusion: Based on the results of the present study, the increased expression of N-cadherin and reduction of staining intensity of E-cadherin was found in chronic periodontitis compared to healthy gingival tissues. Therefore, EMT process may be involved in the pathogenesis of severe chronic periodontitis. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is considered themostcommonmalignant disease in the female population. It isknownasanemerging epidemy with a great burden on women's health, which can be associated with poor outcomes. Some factors including histological type, immunohistochemistry (IHC), tumor grade, and tumor size can have effects on breast cancer. Objectives: This study aimed at assessing the effects of mentioned factors on IHC type of breast cancer. Methods: This retrospective cross-sectional study was conducted on 142 patients, who were referred to one of the referral centers for breast cancer in Mashhad. Information including age, histological type, familial history, menopause status, tumor grade, tumor size, and IHC properties was collected from the patient's medical records. Allred score was used for reporting hormonal status. The data were analyzed by version 26 of SPSS software. Results: The mean age of patient was 50.2 - 12.7. The frequency of luminal A and luminal B type was calculated as 29.7 and 18.9%, respectively. In addition, triple-negative IHC type has a prevalence of 24.3% and HER2 had a prevalence of 27%. There were no signifi- cant differences between age (P = 0.34), familial history (P = 0.42), menopause (P = 0.36), histological type (invasive: P = 0.11, in situ: P = 0.45), and IHC properties. However, tumor diameter (P = 0.0001) and tumor grading (P = 0.002) had significant association with IHC properties. Conclusions: Factors including tumor size and pathological grade can have effects on the gene expression properties of breast cancers. Luminal IHC type A is more common in breast cancer and is associated with better outcomes. However, age, histological type, familial history, and menopause status had no effects on the IHC properties of breast cancer. [ABSTRACT FROM AUTHOR]

Background: The use of biomarkers has become increasingly important in the diagnosis and treatment of several malignancies, including breast cancer. Among the established biomarkers, receptor tyrosine-protein kinase erbB-2 (HER-2/ neu) has been found to be of a predictive and prognostic role in breast cancer patients. Method: 94 patients with primary breast cancer were enrolled in our prospective study between 2016 and 2017. 5 cc clot blood samples were taken for serum HER- 2/neu testing at the time of diagnosis of breast cancer. The patients' demographic data, tumor characteristics, including tumor size, tumor grade, presence of lymph node involvement, and stage, hormone receptor, and tissue HER-2/neu status of the subjects were recorded following tumor removal. Results: All of the patients were female with the age range of 27 to 80 years (the mean of age was 49.66. 36 patients (38.3%) had positive tissue HER-2 results and 58 (61.7%) had negative results. In those with high level serum HER-2 ECD, 28(77.7%) had positive tissue HER-2 and 8(22.2%) had negative results. Moreover, in the patients with low level serum HER-2 ECD, 8(13.7%) had positive tissue HER-2 and 50(86.2%) had negative results with the sensitivity of 77.7% and specificity of 86.2%. HER2 ECD levels were highly concordant with tissue HER2 status, with a P value of less than 0.001, which was considered to be statistically significant. Among different clinicopathologic variables, serum and tissue HER-2/nu were significantly correlated with only tumor grade. Conclusion: A significantly increased release of HER2 ECD levels may accurately predict tumor HER2 status as detected with immunohistochemistry and/or in situ hybridizations studies. [ABSTRACT FROM AUTHOR]

Background: Solitary fibrous tumor (SFT) is a fibroblastic tumor that has been originally reported as a pleural tumor but now has been defined as a tumor that can be seen everywhere in the human body. Histopathologically, many of the fibroblastic tumors can mimic SFT, and immunohistochemistry is necessary for differential diagnosis. Several markers have been used, and recently, STAT6 has been introduced as a diagnostic marker. No research study has been reported from Iran. Objectives: In this report, we are trying to introduce our experience about the clinicopathologic findings of 35 cases of SFT during the last 10 years from our center with an emphasis on the diagnostic role of STAT6 in this tumor. Patients and methods: During the last 10 years, we confirmed the diagnosis of 35 cases of SFT in the pathology archives of Shiraz University of Medical Sciences. These 35 cases were considered as cases. All the clinicopathologic findings were also extracted from the clinical charts of the patients. To evaluate the diagnostic role of STAT6, another 35 cases of spindle cell tumors were also extracted from the pathology archives as mimickers of SFT. STAT6 was stained in all of the 70 cases and controls. Results and discussion: Our experience showed that SFT is more common in middle-aged men with a wide age range, although it is very rare in children. It can be present in every location with a wide size range from less than 1 cm to more than 15 cm. The presence of abnormal staghorn vessels is one of the main diagnostic histopathologic characteristics. STAT6 showed a sensitivity and specificity of 91% and 86% in the diagnosis of SFT. Other markers such as CD99, CD34, and BCL2 have also been considered useful in the differential diagnosis of this tumor, although the diagnostic accuracy seems to be lower than STAT6. High mitosis, presence of necrosis, and atypia are important criteria for predicting malignant and aggressive behavior in SFT. Among 35 cases in our study, 17% showed malignant behavior as recurrent or metastatic tumors. Conclusion: Solitary fibrous tumor is a common soft tissue tumor that can be seen everywhere and needs careful histopathologic and immunohistochemical evaluation for the correct diagnosis and prediction of aggressive or benign behavior. [ABSTRACT FROM AUTHOR]

Background: Considering the great variations in the reported prevalence of prostate cancer across the world possibly due to different genetic and environmental backgrounds, we aimed to determine the expression pattern and the diagnostic utility of α-methylacyl coenzyme A racemase (AMACR) among Iranian patients with prostate adenocarcinoma. Materials and Methods: In this cross-sectional study, formalin-fixed paraffin-embedded tissues of 58 patients with a definitive pathologic diagnosis of prostatic adenocarcinoma were evaluated. The expression of AMACR, intensity, and extensity of its staining was determined in selected samples by immunohistochemical technique. Results: AMACR expression was significantly higher in neoplastic compared to normal tissue (P < 0.05). The expression of AMACR was significantly associated with the age of the patients (P = 0.04). The intensity of the staining was associated with the grade of the prostate adenocarcinoma (P = 0.04). There was no significant relationship between AMACR expression and perineural invasion. The sensitivity, specificity, positive predictive value, and negative predictive value of AMACR were 90%, 96%, 96%, and 90%, respectively. Conclusion: Findings from our study indicate that AMACR could be used as a diagnostic tool for the diagnosis of prostate adenocarcinoma. However, due to false-positive staining in the mimicker of prostatic adenocarcinoma, it is recommended to use it in combination with basal cell markers. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is an acquired depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. Although the etiology of vitiligo is unknown, over the last few years, substantial data from clinical research have greatly supported the "Autoimmune theory." Vitiligo has two major forms: progressive and stable. As cytokines are important mediators of immunity, the most important of them are IL-2, IL-6, and tumor necrosis factor-α (TNF-α). Objectives: We aimed to study the serum level of IL-2, IL-6, and TNF-α in stable and progressive vitiligo and compared them to find a useful lab test to determine the form of vitiligo for diagnose and treatment. Materials and Methods: Serum IL-2, IL-6, and TNF-α were done by the indirect enzyme-linked immunosorbent assay (ELISA) in 40 cases of stable and progressive vitiligo. Results: Twenty patients had progressive vitiligo and 20 patients were stable vitiligo. In every group, there were seven male patients. Twenty-one patients had a positive family history of vitiligo and four patients had other autoimmune diseases. The average age and familial history between two groups and two genders were not meaningful. The mean serum TNF-α level was significantly higher in progressive than stable vitiligo. No significant difference was observed in the serum levels of IL-2, IL-6 between stable and progressive vitiligo. The mean serum IL-6 and TNF-α had higher levels in male patients. Conclusion: Analysis of TNF-α levels in every age or gender can show us the type of vitiligo, stable or progressive and we can choose the best form of treatment for patients. [ABSTRACT FROM AUTHOR]

Background & Objective: Microsatellite instability is common in familial colorectal cancers. It can be tested by the molecular and immunohistochemical methods. There are very few studies which address comparing the clinicopathological characteristics of microsatellite stable (MSS) and microsatellite unstable (MSI) colorectal cancers from Iran. In this study, we aimed to evaluate the clinicopathological and immunohistochemical findings of MSS and MSI colorectal cancers in our Center as the largest Center of gastrointestinal surgery and oncology in the South of Iran. We also compared the immunohistochemical method vs. molecular study using DNA sequencing. Methods: For 5 years (2015-2019), 34 patients who underwent operation in the affiliated Hospitals of Shiraz University of Medical Sciences were clinically suspected to microsatellite instability (MSI). The molecular diagnostic tests with DNA sequencing were performed. Clinicopathological and immunohistochemical findings of MSI colorectal cancers were compared with those who were stable. Results: In the South of Iran, MSI colorectal cancers were more common in males. These tumors were more common in the right side with more tendencies to produce mucin with lymphocytic infiltration. Conclusion: Immunohistochemistry would be a specific method for diagnosis of MSI colorectal cancers but may be associated with high rate of false negative results and of low sensitivity. Therefore, we recommend performing molecular studies by DNA sequencing in those colon cancers with clinical suspicion for MSI and negative immunohistochemical findings. [ABSTRACT FROM AUTHOR]

Background: Undifferentiated embryonal sarcoma of liver (UESL) and hepatic mesenchymal hamartoma (HMH) are two rare entities which mainly affect the pediatric population. The aim of this investigation was to provide a comprehensive overview of the clinicopathologic characteristics of the patients diagnosed with these two conditions in a tertiary referral center in Iran. Methods: In this retrospective study patients diagnosed with UESL or HMH between 2012 and 2020 were studied. A comprehensive histopathologic evaluation of the cases along with immunohistochemistry evaluation using a panel of antibodies was conducted. Furthermore, clinical, paraclinical, and treatment data and follow up information was collected. Results: A total of 16 patients (8 UESL, 8 HMH) were studied in this investigation. Patients with UESL had a significantly (p = 0.002) higher age at diagnosis compared with those with HMH. Histologically, UESL cases were characterized by anaplastic cells with eosinophilic cytoplasm and bizarre nuclei and frequent atypical mitosis and spindling in a myxoid stroma while disordered arrangement of hepatic parenchyma, bile ducts, and primitive mesenchyme was seen in HMH. Furthermore, small round cells and extramedullary hematopoiesis were seen in 2 UESL and 3 HMH cases, respectively. Concurrent HMH was also seen in two UESL cases. Immunohistochemistry panel showed positive staining for Vimentin, Glypican-3, Desmin, CD56, CD10, and BCL2 in UESL cases and immunoreactivity for Vimentin, HepPar 1, Glypican-3, SMA, CD56, BCL2, and CD34 in various components of HMH. Conclusions: In this study, the clinicopathologic features of UESL and HMH cases are presented. We also evaluated the utility of an immunohistochemistry panel in the diagnosis of these two rare entities and suggested novel markers. Our study corroborated the findings of previous investigations and expanded the clinicopathologic features of these two rare entities with diagnostic and potential therapeutic implications. [ABSTRACT FROM AUTHOR]

Background: Iran is one of the high-risk countries for esophageal squamous cell carcinoma (ESCC). Human papillomavirus (HPV) has been reported as one of the etiologic, pathogenetic, and prognostic factors in this tumor, especially in high-risk geographic areas. Previous reports from our geographic area, that is, the South of Iran failed to show any evidence of HPV in the cases of ESCC by molecular methods. Objectives: In this study, we evaluated P16 and P53 immunohistochemistry (IHC) expression in the cases of esophageal ESCC from Fars province in the South of Iran to find the presence of any correlation between clinicopathologic findings with P16 and P53 expression by IHC as etiologic and prognostic biomarkers. We also tried to compare the results from other geographic areas of Iran and the world. Results: P16 and P53 expression were found in 42.9% and 66.12% of ESCCs, respectively. No statistically significant correlation was found between clinicopathologic findings and P16 pr P53 expression. Conclusion: Although P16 and P53 expression in ESCC in the South of Iran is significant, there is no statistically significant correlation between clinicopathologic findings and outcome in ESCC and expression of these 2 proteins to be considered as biomarkers. Results from other geographic areas of Iran and the world are also very controversial and inconsistent. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of the COVID19 pandemic, that has killed one million nine hundred people and infected more the 90 million until end of 2020, has been studied by many researchers. Here, we try to explain its biological behavior based on our recent autopsy information and review of literature. Methods: In this study, patients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result were considered eligible for enrollment. Histopathological examinations were done on 13 people who were hospitalized in Afzalipour hospital, Kerman, Iran. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry and electron microscopy. Results: The most frequent co-morbidity in the patients was cardiovascular disease. The common initial symptoms of COVID-19 infection were dyspnea and cough. In all cases, the number of white blood cells was higher than the normal range. Common histopathological findings were variable degrees of vasculitis as degenerative to necrotic changes of endothelium and trafficking of inflammatory cells in the vessel wall with fibrinoid necrosis. Tissue damage included interstitial acute inflammatory cells reaction with degenerative to necrotic changes of the parenchymal cells. CD34 and Factor VIII immunohistochemistry staining showed endothelial cell degeneration to necrosis at the vessel wall and infiltration by inflammatory cells. Electron microscopic features confirmed the degenerative damages in the endothelial cells. Conclusion: Our histopathological studies suggest that the main focus of the viral damage is the endothelial cells (endotheliopathica) in involved organs. Also, our findings suggest that degeneration of leukocytes occurs at the site of inflammation and release of cytokines (leukocytoclastica) resulting in a cytokine storm. [ABSTRACT FROM AUTHOR]

Background: Identifying Lynch syndrome (LS) in patients with colorectal cancer (CRC) and monitoring their relatives can increase the life expectancy of these patients. Objectives: The aim of this study was to analyze the cost-effectiveness of 5 molecular testing strategies to screen LS among patients with newly diagnosed CRC and to conduct preventive surveillance in their first-degree relatives. Methods: A decision tree model was designed to identify the number of LS mutations and the related costs in the CRC patients. Five strategies were modeled, i.e., Amsterdam II criteria, microsatellite instability (MSI) testing, immunohistochemistry (IHC), and next-generation sequencing (NGS). A Marko model was also used to estimate the long-term outcome of monitoring (including colonoscopy and taking aspirin) among relatives of those patients with CRC who carried LS. Results: All strategies were cost-effective compared with no testing condition. The 2 most cost-effective strategies were strategy 2 (IHC testing followed by NGS testing) and strategy 4 (MSI testing followed by NGS testing), with the ICER of 4,604$ and 4,748$ per quality-adjusted life year (QALY), respectively. Based on one-way sensitivity analysis of IHC sensitivity, the Cost of colonoscopy, MSI sensitivity, and the number of families who inherited LS had the most effect on the results. Conclusions: The findings suggested that from an Iranian health care system perspective, IHC testing followed byNGStesting could be regarded as the most cost-effective strategy compared to the other strategies. These results can be useful in offering to screen LS in newly diagnosed CRC patients. [ABSTRACT FROM AUTHOR]

Background: The study aimed at evaluating steroid biomarker genes (ERα, PGR, ERβ) and determining the expression level of estrogen-regulated genes (SCUB2 and BCL2) and growth factors receptors (HER2 and IGFR1) in cancer tissue samples obtained from Iranian patients with breast cancer. Moreover, relationships with clinicopathologic aspects of tumor and response to treatment were studied. Methods: The current study was conducted on 246 breast tissue samples. The expression levels of these genes and their relationships with clinicopathologic aspects and treatment response were evaluated. Results: Based on immunohistochemistry (IHC) results, 12% of the ER negative patients expressed ERα. Comparing the effects of ERα and coexpression of BCL2 and SCUBE2 on the survival of the patients demonstrated remarkably poorer survival in ERα positive, SCUBE2, and BCL2 negative groups in comparison with other patients, which was statistically significant in the logrank analysis (P = 0.01). Evaluation of the effects of coexpression of HER2 and IGFR1 on patients' survival demonstrated a worse survival rate in patients with positive expression of both receptors, which was insignificant. Conclusion: Many studies suggest that PGR alone is not enough for the functional evaluation of ERα. Evaluation of the progesterone receptor expression as well as other genes such as BLC2, SCUBE2, and IGFR1, seems necessary to evaluate functionality. [ABSTRACT FROM AUTHOR]

Canalicular adenoma (CA) is a rare, benign salivary gland tumor that has special tendency to occur in the upper lip. Buccal mucosa is the second most common site. It occurs more often in older patients with peak prevalence in the seventh decade of life. A definitive female predominance has been reported. According to the latest English published literature, 531 cases of CA have been reported. We present a case of CA of the hard palate that presented in a 29-year-old female patient. The histopathological and immunohistochemical findings showed typical features of CA and intense expression of pan-cytokeratin and S-100 protein. We also review its differential diagnosis from other salivary gland tumors. [ABSTRACT FROM AUTHOR]

Background: The DNA mismatch repair (MMR) system is one of the molecular pathways involved in colorectal cancer (CRC) carcinogenesis that consists of several genes, including MLH1 (MutL homolog 1), MSH6 (MutS homolog 6), MSH2 (MutS homolog 2), and MSH3 (MutS homolog 3). The protein encoded by PMS2 (post-meiotic segregation 2) is also essential for MMR. Here, we address the correlation between immunohistochemical and transcriptional expression of PMS2 with the tumor grade and clinical stage of non-hereditary/sporadic CRC disease. Methods: This study retrospectively analyzed 67 colorectal resections performed for 38 male and 29 female patients. Random biopsies were taken by a gastroenterologist from patients referring to three hospitals in the cities of Zanjan, Urmia and Qazvin (Iran) during 2017-2019. All specimens were examined and classified for localization of tumor, pathological stage and grade. The PMS2 protein expression was studied immunohistochemically and analysis of mRNA expression was performed in the same tissue sections. Results: Immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analysis showed a decrease in PMS2 expression compared with paracancerous tissue (P < 0.001), which correlated with tumor stage. In addition, reduced PMS2 expression was correlated with the tumor differentiation grade, underlining a connection between downregulation of PMS2 and progression of CRC. Comparing the PMS2 mRNA levels in different groups showed the following results: 0.92 ± 0.18 in patients with Stage I CRC tumor, 0.86 ± 0.38 in Stage II, 0.50 ± 0.29 in Stage III, and 0.47 ± 0.23 in Stage IV. Conclusion: These findings suggest that PMS2 may provide a potential reliable biomarker for CRC classification by combined immunohistochemical and mRNA analysis. [ABSTRACT FROM AUTHOR]

Aims: Cervical cancer (CC) is a common malignancy in women, predominantly caused by human papillomavirus. The most subtypes are adenocarcinomas (AC) and squamous cell carcinomas (SCC), which show various features and treatment responses. Programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) as Immune checkpoint molecules, play a role in immune evasion. We investigated PD-L1 expression in AC and SCC of the cervix and explored its link to clinical characteristics., Methods and Results: The present cross-sectional research was done between 2016 and 2022 on samples in Shahid Beheshti University of Medical Sciences-affiliated hospitals in Iran. Histological tissue samples of CCs (16 AC and 48 SCC) were assessed, and clinical information was obtained by reviewing their medical documents. PD-L1 expression was evaluated by immunohistochemistry and we used the combined positive score. SCC cases showed a higher (not significant) PD-L1 expression. The PD-L1 expression and clinical characteristics were not significantly correlated in both subgroups., Conclusion: Although SCC cases exhibited higher PD-L1 expression, this difference was non-significant. More investigations should highlight the role of PD-L1 in CC and the potential benefits of immunotherapy., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Gastric cancer is a common cancer developed in a carcinogenesis process from precancerous lesions including chronic gastritis, intestinal metaplasia, and dysplasia. Survivin, an inhibitor-of-apoptosis protein, is associated with the initiation and progression of gastric cancer. The present study aimed to evaluate the immunohistochemical expression patterns of survivin and its relationship with early diagnosis of gastric cancer in Iranian patients., Methods: In this retrospective case-control study, immunoexpression of survivin was investigated on sections obtained from formalin-fixed paraffin-embedded tissue blocks of 38 chronic gastritis, 32 intestinal metaplasia, 20 dysplasia, 28 gastric adenocarcinoma, and 22 controls., Results: Survivin immunoexpression in chronic gastritis was higher than controls, but this difference was not statistically significant ( P  > 0.05). However, survivin immunoexpression had a steady significant increase from control and chronic gastritis to intestinal metaplasia to dysplasia to gastric adenocarcinoma ( P  < 0.05). Sensitivity, specificity, and area under the curve of survivin immunohistochemical test for the diagnosis of gastric cancer were 87.5%, 74.4%, and 0.85, respectively. Males had a significantly higher survivin expression than females ( P  < 0.001). Also, survivin expression was significantly higher in older patients than in younger ones ( P  < 0.001)., Conclusion: It seems that the steady increase in survivin expression from different precancerous lesions to gastric adenocarcinoma suggests that survivin can be used as a potential biomarker for the prevention and early diagnosis of gastric cancer., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Increasing numbers of pregnant women with coronavirus disease 2019 are being reported around the world. The majority of neonates delivered to pregnant women infected with severe acute respiratory syndrome coronavirus 2 have been negative for the virus, but a small number have tested positive for infection. It is important to determine whether vertical transmission of coronavirus disease 2019 occurs and the mechanisms for its development. Based on a number of clinical and laboratory findings, it has been suggested that transplacental transmission may be occurring, but a method to confirm this is necessary. This communication analyzes and evaluates the covariables that have been discussed as potential indicators of vertical and, specifically, intrauterine transmission, including the timing of onset of neonatal illness, neonatal viral test positivity, neonatal antibody testing for immunoglobulin (Ig) G and IgM, and viral analysis of swabs of whole specimens of placental tissue. None of these methods can provide confirmatory evidence that infection developed prior to labor and delivery, or that transplacental transmission occurred. This commentary proposes that diagnosis of early-onset neonatal coronavirus disease 2019 infection should be limited to neonates with positive reverse transcription polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 within the initial 72 hours of life. It also proposes that the occurrence of intrauterine transplacental severe acute respiratory syndrome coronavirus 2 among infected mother-infant dyads be based upon identification of severe acute respiratory syndrome coronavirus 2 in chorionic villus cells using immunohistochemistry or nucleic acid methods such as in situ hybridization. Evaluating placentas from neonates with coronavirus disease 2019 using these methods will be instrumental in determining the potential role and prevalence of transplacental transmission of the coronavirus. [ABSTRACT FROM AUTHOR]