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Introduction: Cervical cancer was the seventh most common malignant tumor among women in the Podlaskie Voivodeship in 2016. The development of this cancer is preceded by the occurrence of cervical intraepithelial neoplasia (CIN). Pap smear is still the basic method of secondary prevention of cervical cancer. If the result of the Pap test is positive, further diagnosis is necessary (colposcopy, histopathological examination). Aim: The aim of the study was to assess the incidence of intraepithelial cervical lesions and its correlation with the results of histopathological examination in the female population of the Podlaskie Voivodeship. Material and methods: 51,136 Pap smear tests were analyzed (retrospectively). The tests were performed in the Podlaskie Voivodeship from January 2012 to December 2019. Of this group, 134 patients had a histopathological examination. The results of both studies were compared. Results: Among the cytological tests performed in private offices, incorrect results accounted for 1.35%. The value is two times lower than in the case of tests carried out in the prevention program in Podlaskie Voivodeship. The results were consistent in 77% of patients diagnosed with HSIL and in 35% of patients diagnosed with LSIL. Conclusions: The obtained congruence of cytological and histopathological results is comparable to the data in the literature. The creation of a central registry of pap smears would be helpful in the quality monitoring and the number of abnormal results.

Histopathological evaluation plays a key role in the diagnosis of colorectal cancer (CRC). Tumor-related local inflammation is regarded as a novel prognostic parameter. Neutrophils constitute one of the main types of inflammatory cells. The aim of the present study was to evaluate the prognostic value of intratumoral tumor-associated neutrophils (intraTANs), stromal TANs (stromaTANs) and necrosis, as well as their combined parametric value in formalin-fixed paraffin-embedded tissue sections from patients with CRC. For this purpose, a retrospective study of 160 patients with CRC who underwent surgery was conducted. The association of intraTANs, stromaTANs, necrosis and their combined parametric value with the clinicopathological features of patients with CRC was examined. The Kaplan-Meier method and the log-rank test were used to compare survival curves. To identify independent prognostic factors, uni- and multivariate Cox proportional hazards regression models were used. StromaTANs were associated with lymph node metastasis (P=0.049) and tumor deposits (P=0.041). In addition, necrosis was found to be associated with venous (P=0.003), lymphatic (P=0.007) and perineural (P=0.015) invasion, as well as with lymph node metastasis (P=0.033), the number of invaded lymph nodes (P=0.012), and lymph node pouch invasion (P=0.043). Furthermore, necrosis was found to be associated with the white blood cell count (P=0.030), neutrophil count (P=0.011), the combined neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (NLR-PLR) (P=0.038), and the combined platelet and NLR (PLT-NLR status) (P=0.030), as well as with the serum carcinoembryonic antigen (CEA) levels following surgery (P=0.011) and the monocyte-to-lymphocyte ratio (P=0.023). The combined parametric value was found to be associated with pT stage (P=0.049), venous (P=0.034) and lymphatic (P=0.026) invasion, and with serum CEA levels prior to surgery (P=0.029). The analysis of the 3-year disease-free survival (DFS) time revealed that tumor growth [hazard ratio (HR), 2.070; 95% CI, 1.837-3.808; P=0.003] and the combined parametric value (intraTANs, stromaTANs and necrosis, HR, 1.577; 95% CI, 1.372-3.032; P=0.028) were independent factors for patients with CRC. Taken together, the findings of the present study demonstrated that the combined value of neutrophils and necrosis examined in the cancerous tissue may be used as a prognostic factor for the 3-year DFS time in patients with CRC.

BACKGROUND Despite effective prevention and screening methods, the incidence and mortality rates associated with colorectal cancer (CRC) are still high. Insulin receptor substrate 1 (IRS-1), a signaling molecule involved in cell proliferation, survival and metabolic responses has been implicated in carcinogenic processes in various cellular and animal models. However, the role of IRS-1 in CRC biology and its value as a clinical CRC biomarker has not been well defined. AIM To evaluate if and how IRS-1 expression and its associations with the apoptotic and proliferation tumor markers, Bax, Bcl-xL and Ki-67 are related to clinicopathological features in human CRC. METHODS The expression of IRS-1, Bax, Bcl-xL and Ki-67 proteins was assessed in tissue samples obtained from 127 patients with primary CRC using immunohistochemical methods. The assays were performed using specific antibodies against IRS-1, Bax, Bcl-xL, Ki-67. The associations between the expression of IRS-1, Bax, Bcl-xL, Ki-67 were analyzed in relation to clinicopathological parameters, i.e., patient age, sex, primary localization of tumor, histopathological type, grading, staging and lymph node spread. Correlations between variables were examined by Spearman rank correlation test and Fisher exact test with a level of significance at P < 0.05. RESULTS Immunohistochemical analysis of 127 CRC tissue samples revealed weak cytoplasmatic staining for IRS-1 in 66 CRC sections and strong cytoplasmatic staining in 61 cases. IRS-1 expression at any level in primary CRC was associated with tumor grade (69% in moderately differentiated tumors, G2 vs 31% in poorly differentiated tumors, G3) and with histological type (81.9% in adenocarcinoma vs 18.1% in adenocarcinoma with mucosal component cases). Strong IRS-1 positivity was observed more frequently in adenocarcinoma cases (95.1%) and in moderately differentiated tumors (85.2%). We also found statistically significant correlations between expression of IRS-1 and both Bax and Bcl-xL in all CRC cases examined. The relationships between studied proteins were related to clinicopathological parameters of CRC. No significant correlation between the expression of IRS-1 and proliferation marker Ki-67, excluding early stage tumors, where the correlation was positive and on a high level (P = 0.043, r = 0.723). CONCLUSION This study suggests that IRS-1 is co-expressed with both pro- and antiapoptotic markers and all these proteins are more prevalent in more differentiated CRC than in poorly differentiated CRC.

Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide. At every phase of cancer development, the inflammatory process has an important impact. Accurate assessment inflammatory cells in the tumour environment in conjunction with clinico-pathologic features can be a relevant prognostic or predictive parameter. Purpose: To analyse inflammatory cell infiltration in CRC tumour mass and correlate with chosen clinico-pathologic parameters. Materials and methods: The study group consisted of 160 patients (64 women, 96 men) diagnosed with colorectal cancer who underwent surgery. Tissue material obtained from routine histopathological diagnosis was stained with H&E and used to assess the type of inflammatory cells in the invasive front and centre of the tumour. Results were subjected to statistical analysis with the age and gender of patients, tumour localization, tumour growth and size, TNM stage, adenocarcinoma type, fibrosis, necrosis, metastasis and tumour invasion (by the Spearman’s correlation coefficient test). Results: The presence of neutrophils in the invasive front of tumour mass was associated with fibrosis and inflammatory cell infiltration in the invasive front of tumour. Macrophages in the invasive front of tumour were found to correlate with tumour growth (expanding and infiltrate). Macrophages and eosinophils were associated with inflammatory cell infiltration in the invasive front and in the centre of tumour. Conclusions: The type of inflammatory cells in the invasive front or centre of the tumour may be useful to prognoses clinical features of colorectal cancer

Introduction: Colorectal cancer (CRC) is one of the most common cancers in Poland. The aim of this study was to investigate the clinical significance of absolute monocyte count, neutrophil-to-monocyte ratio (NMR) and monocyte­to­lymphocyte ratio (MLR) in pre- and postoperative blood samples of patients with CRC. Materials and Methods: We retrospectively reviewed medical records of 160 patients diagnosed with CRC who underwent surgery. Blood samples were obtained within 3 days before and after the surgical treatment. Venous blood samples were also obtained from 42 healthy controls. Results: Pre- and postoperative NMR were significantly higher than healthy controls (p

Molecular next gene sequencing was used to evaluate mutations in 409 common mutated cancer-related genes in malignant mesothelioma of tunica vaginalis testis (MMTVT) of 81-year-old man. Multifocal papillary-solid areas contained necrosis among highly cellular fields with multiple mitoses. It was positive for WT1, CKAE1/AE3, calretinin, CK7 with negativity for CK5, PSA, TTF-1. Following mutations were revealed in PARP1 (NM_001618: c.2285TC p.V762A), RNF213 (NM_001256071: c.3121GA, p.A1041T), PAX8 (NM_013992: c.404AG, p.K135R), MTRR (NM_024010: c.147AG, p.I49M) and two sorts of mutations in structure of KMT2C gene (NM_170606: c.2447_2448insA (c.2447dupA), p.Y816fs and NM_170606: c.1042GA, p.D348N) for the first time in MMTVT.

Diagnosis of acute coronary syndrome (ACS) based on copeptin level may enable one to confirm or rule-out acute myocardial infarction (AMI) with higher sensitivity and specificity, which may in turn further reduce mortality rate and decrease the economic costs of ACS treatment. We conducted a systematic review and meta-analysis to investigate the relationship between copeptin levels and type of ACS. We searched Scopus, PubMed, Web of Science, Embase, and Cochrane to locate all articles published up to 10 October 2021. We evaluated a meta-analysis with random-effects models to evaluate differences in copeptin levels. A total of 14,139 patients (4565 with ACS) were included from twenty-seven studies. Copeptin levels in AMI and non-AMI groups varied and amounted to 68.7 ± 74.7 versus 14.8 ± 19.9 pmol/L (SMD = 2.63; 95% CI: 2.02 to 3.24; p < 0.001). Copeptin levels in the AMI group was higher than in the unstable angina (UAP) group, at 51.9 ± 52.5 versus 12.8 ± 19.7 pmol/L (SMD = 1.53; 95% CI: 0.86 to 2.20; p < 0.001). Copeptin levels in ST-elevation myocardial infarction (STEMI) versus non-ST elevation myocardial infarction (NSTEMI) patient groups were 54.8 ± 53.0 versus 28.7 ± 46.8 pmol/L, respectively (SMD = 1.69; 95% CI: = 0.70 to 4.09; p = 0.17). In summary, elevated copeptin levels were observed in patients with ACS compared with patients without ACS. Given its clinical value, copeptin levels may be included in the assessment of patients with ACS as well as for the initial differentiation of ACS.

The presence of tumor cells in the large intestine stimulates hypoxia and local inflammatory mediators that activate numerous inflammatory cells, including a diverse lymphoid tumor cell population. The aim of the present study was to evaluate tumor-infiltrating lymphocytes (TILs) located in the invasive primary tumor, surrounding deposits of tumor cells and those present in distal metastatic cells in the liver of patients with colorectal cancer. Furthermore, the correlation of TILs with anatomical parameters was assessed. The study group included 123 patients with primary tumor colorectal cancer without distant metastasis, 25 cases with deposits of colorectal cancer cells and 15 cases of colorectal cancer liver metastasis. TILs were assessed in tissues stained with hematoxylin-eosin using light microscopy and evaluated by two independent pathologists blinded to the clinical information. Infiltration of TILs in the invasive front of primary tumor was stronger compared with those surrounding deposits of cancer cells and liver metastases (P

Introduction: Expression of Epo, a glycoprotein secreted by the fetal liver and the adult kidney in response to cellular hypoxia and its receptor have been described in human solid tumors, such as colon and breast cancer. Purpose: Since activation of Epo-EpoR signaling pathway in erythroid progenitor and precursor cells leads to promotion of proliferation and differentiation or prevention of programmed cell death through Bcl-xl and Bcl-2 it was of interest to investigate expression of Epo, EpoR, apoptosis regulator – Bax and marker of proliferating cells - Ki-67 and assess correlation between them, with regard to clinicopathological variables of colorectal cancer. Materials and methods: The correlations between expression of Epo, EpoR, Bax and Ki-67 in colorectal cancer were analyzed in regard to patient age, sex, primary localization, histopathological type, grading, staging and lymph node invasion. Statistical analyses were performed by using the Spearman rank correlation test applying a significance level of p60, male, female , primary localization in rectum, primary localization in colon, adenocarcinoma, G2, G3. Statistical analysis revealed no significant correlations between expression of neither Ki-67 with Epo nor Ki-67 with EpoR in all groups of patients. Conclusions: Epo seems to be a pleiotropic cytokine, which can exert its biological effect on several cell types, including neoplastic cells. The effect of Epo-EpoR signaling can differ in various cells and conditions.

Nowadays, Hepatitis B X interacting protein (HBXIP) is an object of scientists’ interest worldwide. It is a protein with significant involvement in the development of malignant tumors like breast or ovarian cancer. One of the most important functions of HBXIP is the regulation of cell proliferation, which is related to the progression of a cell cycle. Many studies provide the growing number of evidence that HBXIP plays various important roles, including the regulation of a cell cycle through complexes with survivin, belonging to the inhibitors of apoptosis and interactions with transcriptional factors like STAT4, SP1, TFIID or E2F1. It also has the influence on the promotion of tumor angiogenesis thanks to the association with VEGF and FGF8. Another important role of HBXIP is a reprogramming of glucose metabolism to conditions favorable to growing cancerous cells due to regulating the activation of SCO2 and PDHA1. Furthermore, it impacts on the complement-dependent cytotoxicity, also, HBXIP affects on lipid metabolism through disturbing of metabolic pathways of FAS. According to recent studies, HBXIP can be used as a prognostic biomarker in many tumors, including cervical cancer, ovarian cancer, and esophageal squamous cell carcinoma thanks to the high expression of this protein noted exclusively in these tumor tissues. What is even more interesting, it significantly correlates with clinical attributes like metastasis to lymph nodes or grading and in some cases can potentially be used as the indicator of prognosis of treatment effectiveness. The paper is review through main functions of HBXIP and its possible applications.

The efficacy of cancer immunotherapy has been actively explored in the treatment of various malignant neoplasms of the gastrointestinal tract. In light of recent reports, the present study aimed to investigate the combination of the absolute lymphocyte count (ALC), percentage of tumor-infiltrating lymphocyte (TILs) and tumor progression status in patients with colorectal cancer (CRC) who underwent surgery. The medical records of 160 patients diagnosed with CRC were retrospectively reviewed. TILs were determined as a percentage of mononuclear inflammatory cells in the total intratumoral or stromal area as determined in five high power fields (magnification, x200-400), at the invasive front and in the centre of the tumour. Blood samples were obtained within 3 days prior to and 7 days following the surgical treatment. The assessment of the TIL percentage was performed in the tissue at the invasive front and in the centre of the primary tumour mass in combination with the determination of ALC in whole blood samples. The samples were obtained prior to and after surgery from patients with CRC, and the tumour progression status was also assessed (TILs/ALC/tumour progression status). A significant association was observed between the percentage of TILs in the main mass of tumour and the tumour size (P=0.031), the pT stage (P=0.049) and the incidence of necrosis (P=0.037) following surgery. The histological type was associated with the evaluated combined parameters prior to surgery (P=0.046). Lymph node pouch invasion was associated with TILs at the invasive front of tumour and with ALC prior to and after surgery (P=0.006 and P=0.037). Furthermore, the data indicated that the percentage of TILs located on the invasive front and centre of the tumour, and the ALC prior to and following surgery correlated with the treatment status (P=0.032, P=0.018, P≤0.001 and P≤0.001). A significant association was noted between eight features and evaluated combined parameters following surgery. These included the tumour size (P=0.021), TNM stage (P

Out-of-hospital cardiac arrest (OHCA) is a challenge for medical staff, especially in the COVID-19 period. The COVID-19 disease caused by the SARS-CoV-2 coronavirus is highly infectious, thus requiring additional measures during cardiopulmonary resuscitation (CPR). Since CPR is a highly aerosol-generating procedure, it carries a substantial risk of viral transmission. We hypothesized that patients with diagnosed or suspected COVID-19 might have worse outcomes following OHCA outcomes compared to non-COVID-19 patients. To raise awareness of this potential problem, we performed a systematic review and meta-analysis of studies that reported OHCA in the pandemic period, comparing COVID-19 suspected or diagnosed patients vs. COVID-19 not suspected or diagnosed group. The primary outcome was survival to hospital discharge (SHD). Secondary outcomes were the return of spontaneous circulation (ROSC), survival to hospital admission or survival with favorable neurological outcomes. Data including 4210 patients included in five studies were analyzed. SHD in COVID-19 and non-COVID-19 patients were 0.5% and 2.6%, respectively (odds ratio, OR = 0.25, 95% confidence interval, CI: 0.12, 0.53, p &lt, 0.001). Bystander CPR rate was comparable in the COVID-19 vs. not COVID-19 group (OR = 0.88, 95% CI: 0.63, 1.22, p = 0.43). Shockable rhythms were observed in 5.7% in COVID-19 patients compared with 37.4% in the non-COVID-19 group (OR = 0.19, 95% CI: 0.04, 0.96, p = 0.04, I2 = 95%). ROSC in the COVID-19 and non-COVID-19 patients were 13.3% vs. 26.5%, respectively (OR = 0.67, 95% CI: 0.55, 0.81, 0.001). SHD with favorable neurological outcome was observed in 0% in COVID-19 vs. 3.1% in non-COVID-19 patients (OR = 1.35, 95% CI: 0.07, 26.19, p = 0.84). Our meta-analysis suggests that suspected or diagnosed COVID-19 reduces the SHD rate after OHCA, which seems to be due to the lower rate of shockable rhythms in COVID-19 patients, but not due to reluctance to bystander CPR. Future trials are needed to confirm these preliminary results and determine the optimal procedures to increase survival after OHCA in COVID-19 patients.

Recombinant human erythropoietin (Epo) is an effective and convenient treatment for cancer-related anaemia. In our study for the first time, we evaluated the effect of simultaneous use of Epo and Bruton’s tyrosine kinase (BTK) inhibitor LFM-A13 on the viability and tumour development of breast cancer cells. The results demonstrated that Epo significantly intensifies the anticancer activity of LFM-A13 in MCF-7 and MDA-MB-231. The featured therapeutic scheme efficiently blocked the tumour development in zebrafish experimental cancer model. Epo and LFM-A13 administered together resulted in effective cell killing, accompanied by attenuation of the BTK signalling pathways, loss of mitochondrial membrane potential (MMP), accumulation of apoptotic breast cancer cells with externalised PS, a slight increase in phase G0/G1 and a reduction in cyclin D1 expression. Simultaneous use of Epo with LFM-A13 inhibited early stages of tumour progression. This therapeutic scheme may be rationale for further possible research.

BACKGROUND Colorectal cancer is the third most common malignancy worldwide. Therefore, it is critically important to identify new useful markers that can be easily obtained in routine practice. Inflammation is a crucial issue in the pathogenesis and development of cancer. AIM To evaluate the prognostic value of absolute monocyte count, monocyte to lymphocyte ratio (MLR), the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (NLR-PLR), and combined platelet and neutrophil-to-lymphocyte ratio (PLT-NLR) in peripheral blood samples of patients with colorectal cancer undergoing surgery. METHODS We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery, and 42 healthy controls. The status of absolute monocyte count, MLR, NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery. Haematologic factors were examined in correlation with the type of tumour growth, tumour size, histological type, percentage of mucinous component, grade of malignancy, Tumour-Node-Metastasis stage, venous, lymphatic and perineural invasion of cancer cells, status of lymph node invasion and the presence of cancer cell deposits. The Kaplan-Meier method and the long-rank test were used to compare survival curves. To determine independent prognostic factors, univariate and multivariate Cox proportional hazards regression models were applied. RESULTS The PLT-NLR status was correlated with tumour size and the presence of perineural invasion (P = 0.015; P = -0.174, P = 0.037). Moreover, high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component (NLR-PLR: P = 0.002; P = 0.009; PLR-NLR status: P = 0.002; P = 0.007). The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery [HR = 2.903, 95%CI: (1.368-6.158), P = 0.005] and the status of lymph node metastasis [HR = 0.813, 95%CI: (0.653-1.013), P = 0.050] were independent prognostic factors in colorectal cancer patients. CONCLUSION The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.

We examined a status of fibrosarcoma arising in dermatofibrosarcoma protuberans of 64-year-old male patient. A dermal, solid, grayish-yellow, desmin-negative trichrome-bluish tumor measured 1.5 cm in diameter pT1a (edition 8 pTNM). It was composed of spindle cells. It was consistent with dermatofibrosarcoma protuberans (ICD-O3: 8832/3) in areas of low mitotic activity, low atypia and sustained CD34 positivity. CD34-negative texture with high mitotic index and atypia was consistent with the high grade sarcoma apparently of fibrous origin, given category of poorly differentiated fibrosarcoma. The high grade component was graded (G3) and scored according to French Federation of Cancer Centers Sarcoma Group (FNCLCC): total score of 6 points: tumor differentiation: 3 points + Mitotic count: 3 points (up to 26 mitoses/ 10HPF in high-grade fields), + no necrosis: 0 points. In low grade sarcomatous component ADAMTS20 (NM_025003: c.1661CT, p.P554L) NF1 (NM_001042492: c. 2173GT, p.E725X) and PKHD1 (NM_138694: c. 11074CT, p.R3692X) were revealed with following allelic frequencies: 25%, 27% and 17%. In high grade component allelic frequencies of the same mentioned mutations were 30%, 30% and 14% respectively. In the light of our findings, none of detected mutations can be regarded as a mutation that would definitely induce phenotype of high malignancy, because ADAMTS20, NF1 and PKHD1 mutations were detected both in high grade sarcoma and in low grade areas of dermatofibrosarcoma protuberans. It also points that these mutations appeared on early stages of tumor development.

This paper presents a review on retinal gliosis illustrated by series of three cases of patients (a 39-year-old man and a 35-year-old woman with massive retinal gliosis (MRG) and a 51-year-old man with truly focal nodular gliosis of retina) with intraocular tumor-like masses and loss of vision, who recently suffered from painful inflammation of eyeball and who classically had a history of remote ocular trauma, onset of blindness early in lifetime or gradual but progressive loss of sight. The diagnosis of this pathological entity is given for the lesions that are composed of GFAP strongly positive, elongated, fusiform cells consistent with fibrillary astrocytes. As illustrated in cases from our pathological practice, PAS gave positive patchy disseminated reaction in form of cellular densely purplish granules in minority of cells representing glycogen storing. This feature could be consistent with PAS-positive Müller cells that also constitute retinal gliosis as one of cellular components of normal retina that is induced to reactive proliferation. Thus, the paper presents histological background and differential diagnosis of the entity.

Bisphenol A (BPA), one of the most common endocrine disrupting chemicals, is a carbon-based synthetic compound used in the production of water bottles, cans, food packaging, dental materials, medical equipment, thermal paper, toys and articles for children. Bisphenol A has been associated with serious health effects in humans. It elicits several disorders and plays a role in the pathogenesis of several tumors such as breast, ovarian, prostate and colorectal cancer. The aim of the research is to review the latest literature assessing participation of BPA in the process of neoplasia. There is not much research on this subject and the role of BPA in the carcinogenesis is still not understood. The present review summarizes the current knowledge of the role of BPA in carcinogenesis.

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide. Patients with CRC are diagnosed based on various predictors, including performance status, clinicopathological factors and TNM classification. The aim of the present study was to analyze the neutrophil and lymphocyte counts, as well as the neutrophil-to-lymphocyte ratio (NLR) in pre- and postoperative blood samples of patients with CRC in correlation with specific anatomical variables and disease- free survival (DFS). The variables pre- and postoperative neutrophil count (preNEU and postNEU, respectively), lymphocyte count and NLR were significantly higher in cancer patients than those noted in healthy subjects (all P

Cancer cells are characterized by a low antigenic immunogenicity, a rapid growth and an immunosuppressive effect on the extracellular matrix. These properties induce a weak immune response in colorectal cancer (CRC) carcinogenesis. It is therefore crucial to determine the composition of the inflammatory mass, including neutrophils, macrophages and eosinophils in the tumor tissue of patients with CRC, and to analyze other clinicopathological parameters. The present study included 144 patients diagnosed with CRC. Tissue samples obtained from routine histopathological diagnosis were stained with hematoxylin and eosin. Inflammatory cells were assessed in the invasive front and in the center of the tumor by light microscopy under a high-power magnification. The percentage of neutrophils in the invasive front was significantly higher compared with that in the center of the tumor mass (P

Mutations in the X-linked androgen receptor (AR) gene cause complete androgen insensitivity syndrome (CAIS). CAIS may cause congenital sexual development disorder, which frequently develops into testicular tumors. Here, we describe a novel splice-site intron 1 mutation in AR leading to improper splicing and AR protein absence in CAIS gonads. We characterized a patient's postpubertal gonadal steroidogenic enzyme expression profile. Localization of both CYP11A1 and CYP17A1 enzymes was restricted to both Leydig tumor cells and adjacent to tumor gonadal tissues. Sertoli cells of the CAIS gonad showed abundant HSD17B3 protein, which is an adult Leydig cell marker that enables the conversion of androstenedione to testosterone. Such HSD17B3 expression is typical for fetal-type Sertoli cells in rodents. The postpubertal CAIS gonad of our patient was completely devoid of androgen signaling pathway activity. Plausibly, the postpubertal Leydig cells consisted of two distinct cell populations: postpubertal fetal-type Leydig cells that persisted as androgen-independent cells and immature adult Leydig cells that failed to differentiate. Taken together, in this CAIS postpubertal testis, both Leydig and fetal-type Sertoli cells participated in testosterone production. Our results indicate the importance of molecular analysis as well as the characterization of steroidogenic enzyme profiling in the CAIS patient's gonad.

Introduction Fallopian tube carcinoma is a rare neoplasm derived from mucous tissue located inside fallopian tubes. The disease is most prevalent in women in 4th to 6th decade. The early stages are asymptomatic, advanced stages can be diagnosed based on Latzko's triad: serous, amber-colored discharges, pathological resistance during abdominal physical examination, colic abdominal pain alleviating when the discharge is released. Aim To present a case of an uncommon neoplasm found by mistake. Case study We present a case of a 60-year-old asymptomatic woman admitted to gynecological–oncological department with a suspicion of a neoplasm in the left ovarian cyst. The surgery performed excluded the possibility of malignancy of the ovary, but the histopathological examination afterwards revealed the presence of a high-grade serous carcinoma in the right fallopian tube. In CT imaging enlarged, paraaortic lymph nodes were revealed. The patient underwent a surgery and received postoperative adjuvant chemotherapy. Results and discussion The fallopian tube cancer may be related to ovarian cancer. It can be found on one side or bilaterally. There is a need for further diagnostic proceedings in order to confirm diagnosis and to select optimal treatment. Main negative prognostic factors are stage and the lack of optimal cytoreduction. Depending on the staging appropriate treatment is chosen with surgery being the basic procedure. Adjuvant chemotherapy is used. Radiotherapy is only justified as a palliative procedure. Conclusions The fallopian tube carcinoma if often found either during or after the surgery. The optimal treatment is the excision of the reproductive organs with lymphadenectomy.

Squamous cell carcinoma (SqCC) of the breast should be differentiated between the primary skin keratinizing squamous carcinoma and squamous metaplastic cancer. In the current study, the cases of two patients who were diagnosed with SqCC originated from skin and the breast were discussed. A fine-needle aspiration biopsy confirmed the presence of atypical squamous cells. In both cases, the microscopic examination of the surgical specimen revealed a malignant neoplasm differentiated into SqCC characterized by keratinizing cancer cells with abundant eosiphilic cytoplasm with large, hyperchromatic vesicular nuclei. Immunohistochemical studies showed negative for progesterone and estrogen receptors and human epidermal growth factor receptor 2. Moreover, negative expression of cytokeratin 7 and 20 was confirmed. The diagnosis of the both tumors was established based on the detailed analysis of clinical, macroscopical and microscopical information. SqCC localized in the breast is a great diagnostic challenge in pathomorphology and more attention should be paid for analysis of such lesions in daily practice.

1Department of Oncology, Faculty of Medicine, University of Warmia and Mazury, Olsztyn, Poland Head of Department: prof. Sergiusz Nawrocki, MD, PhD 2Department of Surgical Oncology, Hospital Ministry of Internal Affairs with Warmia and Mazury Oncology Centre, Olsztyn, Poland Head of Department: Andrzej Lachowski, MD 3Department of Internal Diseases, Gastroenterology, Cardiology and Infectiology Faculty of Medicine, University of Warmia and Mazury, Olsztyn, Poland Head of Department: prof. Piotr Zaborowski, MD, PhD 4Department of Gynecology and Gynecologic Oncology, Hospital Ministry of Internal Affairs with Warmia and Mazury Oncology Centre, Olsztyn, Poland Head of Department: Leszek Frąckowiak, MD, PhD 5Department of Pathomorphology, Bialystok Oncology Centre, Poland Head of Department: prof. Waldemar Famulski, MD, PhD, DSc

The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC). In addition, the correlation between cellular inflammatory infiltration, and anatomoclinical and histopathological features of patients was evaluated. The study involved 160 patients diagnosed with primary operable CRC. The local inflammatory infiltrate was assessed in the invasive front and center of the tumor using light microscopy with hematoxylin and eosin (H&E) staining, according to the Klintrup-Makinen criteria, tumor stroma percentage, and Glasgow microenvironment score. The inflammatory infiltrate in the invasive front of the tumor was correlated with gender (P=0.018), the invasion of blood vessels (P=0.020) and lymph vessels (P=0.038), the presence of tumor-infiltrating lymphocytes in the invasive front (P=0.033) and center (P

The local mechanisms of antitumor immune defense determine the development and organization of the tumor microenvironment, and the composition and relative proportions of the inflammatory cell population affect the quality and characteristics of the immune response. The aim of the present study was to conduct a quantitative morphological evaluation of two types of tumor-infiltrating lymphocyte (TILs) populations, including those located in the stroma and intraepithelial cancer structures, in the invasive front and the center of the tumor in patients with colorectal cancer (CRC). The study included 160 patients with CRC who had undergone surgery. The tissue material was stained with hematoxylin and eosin, as used in routine histopathological diagnosis, and the two TIL populations were observed and counted with light microscopy. The relative extent of infiltration of stromal and intraepithelial TILs into the front and center of the primary tumors was similar. The extent of infiltration by stromal TILs was negatively correlated with the morphological features of tumor progression including the cancer infiltration of blood vessels (P=0.016), the invasion of lymph vessels (P=0.007), perineural invasion (P=0.036), lymph node involvement (P=0.047) and distant metastases (P=0.032). The infiltration by intraepithelial TILs was positively correlated with a desmoplastic reaction (P=0.002). Disease-free survival time was statistically shorter in patients without intraepithelial TILs in the center of the primary tumor mass (P=0.049; hazard ratio = 1.45). These results confirm that the infiltration of TILs into the invasive front and center of the tumor in patients with CRC serves an important role in the invasion and progression of the disease, and should be considered in routine histopathological examinations.

Periostin, also known as osteoblast-specific factor 2, is a cell-adhesion protein with pleiotropic properties. The protein serves a vital role in the maintenance and development of tooth and bone tissue, in addition to cardiac development and healing. Periostin levels are increased in several forms of cancer, including pancreatic, ovarian, colon, lung, breast, gastric, thyroid, and esophageal head and neck carcinomas. The present review highlights the key role of periostin in tumorigenesis, particularly in increasing cell survival, invasion, angiogenesis, epithelial-mesenchymal transition and metastasis of carcinoma cells by interacting with numerous cell-surface receptors, including integrins, in the phosphoinositide 3-kinase-Akt pathway. In addition, periostin actively affects the canonical Wnt signaling pathway of colorectal tumorigenesis. The current review focused on the involvement of periostin in the development of colorectal, esophageal and gastric cancer.

Estrogen receptor (ER) is a major feature of endometrioid adenocarcinoma. It has a significant impact on constitution of estrogen-responsiveness of this endometrial malignancy, in which STAT3 (signal transducer and activator of transcription) becomes hyperactivated. The aim of our study was to detect immunohistochemically and compare expressions of STAT3 with apoptosis regulators (Bak and Bcl-xL) in regard to different pathological features and variably pronounced ER-α immunoprofile in 78 endometrioid adenocarcinomas. STAT3 was abundantly detected in nuclei of cancer cells in 54 cases, thus pointing at its activation as an universal nuclear transcriptional factor. Bcl-xL and Bak were expressed in cytoplasm of malignant cells in 62 and 20 cancers, respectively. STAT3 correlated both with Bcl-xL (p = 0.001, r = 0.365) and Bak (p 0.001, r = 0.436) in all of endometrioid adenocarcinomas and variably in different subgroups of these tumours segregated in regard to grading, staging and patients' age. Remarkably, only ER-α positive cancers retained these correlations in opposition to ER-α negative tumours with negativity defined as an immunoreactivity below 10%. ER-α receptor probably enhances interactions between STAT3 and Bcl-xL to be present in statistically significant manner. Presence of ER-α receptor seems to be crucial for relationships among Bcl-xL and STAT3 to occur in endometrioid adenocarcinomas.

Introduction Splenic rupture is a rare postoperative complication in gynecological practice. In the literature, there are only isolated reported cases of ruptured spleen after gynecological procedures. Splenic rupture has been reported following hysterectomy, cesarean section, laparoscopy, and ruptured ectopic pregnancy. Aim Presentation of splenic rupture as a complication of gynecological surgery. Case study A case of 68-year-old patient operated for giant ovarian tumor with spontaneous splenic rupture following total abdominal hysterectomy with bilateral salpingo-oophorectomy is described. Internal hemorrhage was a main clinical presentation. Diagnosis was made intraoperatively. Splenectomy was performed in cooperation with a surgical oncologist. Results and discussion Diagnosis of splenic rupture as a postoperative complication after gynecological surgery is frequently established intraoperatively due to the suddenness of symptoms of shock and the need for immediate surgical intervention. Conclusions Possibility of complications such as splenic rupture in the postoperative period needs to be taken into account by gynecologists in the case of postoperative intra-abdominal hemorrhage. Cooperation between gynecologist and general surgeon is advisable for management of splenic rupture.

During carcinogenesis, loss of intracellular cohesion is observed among cancer cells with altered expression of such adhesion molecules as E-cadherin and beta-catenin, and aberrant expression and cellular location of intercellular gap junction proteins-connexins. The aim of this study was to evaluate immunohistochemically the expression and relationship between E-cadherin and beta-catenin, and the connexins Cx26 and Cx43 in 86 endometrioid adenocarcinomas. The aberrant cytoplasmic translocation of the studied proteins was a predominant finding, whereas only a minority of cases showed normal, nuclear beta-catenin labeling or membranous distribution of the remaining molecules. E-cadherin was positively and significantly associated with beta-catenin (P=0.001, r=0.366), as was Cx26 with Cx43 (P0.001, r=0.719), E-cadherin with Cx26 (P0.001, r=0.413), and E-cadherin and Cx43 (P0.001, r=0.434) in all cancers. A subgroup of endometrioid adenocarcinomas (FIGO IB+II) exclusively showed a positive significant association between the expression of beta-catenin and Cx26 (P=0.038, r=0.339). In addition, there were significantly more beta-catenin-positive carcinomas among superficially spreading cancers (FIGO IA) than among deeper invading neoplasms (FIGO IB+II) (P=0.056). The altered location of the studied proteins indicates impairment of their physiological functions. In particular, normal membranous distribution of E-cadherin and connexins is lost and replaced by abnormal cytoplasmic accumulation in most cancers, and thus intercellular ties are expected to be weakened and loosened as a consequence. In contrast, the lack of relationship between beta-catenin and connexins, E-cadherin seems to be closely associated with the expression of Cx26 and Cx43 in endometrioid adenocarcinomas.

Beta-catenin accumulation is suppressed by TGF-beta1 (transforming growth factor beta1) in intestinal epithelium suggesting negative feedback between these two factors. Besides that, beta-catenin interacts with HIF-1alpha (hypoxia-inducible factor-1alpha) at the promoter region of HIF-1 target genes. Our study was aimed at comparison of beta-catenin with HIF-1alpha, TGF-beta1, Ki67 and survival of sporadic colorectal cancer patients. Expressions of beta-catenin, TGF-beta1, HIF-1alpha, Ki67 were evaluated in triads of specimens of each primary tumor of 72 sporadic colorectal cancers with immunohistochemistry due to limited availability of tissue material. Disease-free survival was analyzed in case of all 100 beta-catenin stained tumors, in 85 cancers stained for HIF-1 and in 72 neoplasms with TGFbeta1 staining. Beta-catenin, TGF-beta1 and HIF-1alpha accumulated in 72 colorectal cancer cells. Beta-catenin correlated both with HIF-1alpha and TGF-beta1 in all colorectal cancers (p < 0.009, r = 0.307 and p = 0.003, r = 0.342, respectively) and in subgroups of different clinico-pathological profile. Beta-catenin failed to correlate with Ki67. In case of beta-catenin, TGF-beta1 and HIF-1alpha, disease-free survival curves failed to show any statistically significant differences between groups of marker negative tumors, cancers with low expression and neoplasms with higher protein expression. Positive correlations between beta-catenin and TGF-beta1 may indicate ineffective attempts of TGF-beta1 to reduce intracellular level of beta-catenin in colorectal cancer. Associations between beta-catenin and HIF-1alpha reflect previously detected interactions between HIF-1alpha with beta-catenin and are confirmative for presence of such reactions in human colorectal cancer.

Progression of numerous neoplasms could involve alterations of gap junction channels composed of connexins (Cxs). Disorders of expression and cellular displacement of Cxs were also found in endometrial cancer. Gap junctional intercellular communication can be regulated by wide array of agents, for instance, growth factors, oncogenes, and steroid hormones. Nevertheless, expressions of Cxs and progesterone receptor (PR) were not compared in human tissues. This study focused on assessment of expression of estrogen receptor alpha (ERalpha) and PRs in relation to the expression of Cx26 and Cx43 in 88 cases of endometrial cancer and analysis of these proteins' expression in comparison with anatomoclinical features. Positive ERalpha and PR nuclear staining was present in 66 (75%) and 60 (68.2%) of all studied tumors, respectively. Positive correlation was found between expression of PR and histopathologic type of tumor (P = 0.026), and negative correlation was drawn with grading (G) (P = 0.002). There were positive reactions to Cx26 and Cx43 of mainly cytoplasmic location in 60 (68.2%) and 66 (75%) of studied cancers, respectively. Progesterone receptor expression correlated negatively with Cx26 in endometrial cancers (P = 0.016, r = -0.256). Moreover, ERalpha expression positively correlated with PR expression (P < 0.001, r = 0.678). On the ground of our findings, disorders of Cx expression and altered distribution pattern occur during endometrial carcinogenesis, and it seems that PR could participate in this fact. Loss of functional gap junctions may occur because of the aberrant expression and localization of Cx26 and Cx43 in endometrial cancer.

Growth inhibitory function of transforming growth factor-beta1 (TGF-beta1) is abolished in colorectal cancer cells as a consequence of mutations of various downstream signaling agents, such as p53, which fail to respond to TGF-beta1 stimulation. TGF-beta1 could also suppress T-cell-mediated anticancer immunity. We aimed at a comparison between cancer expressions of apoptosis regulators, such as p53, BCL-2-associated X protein (Bax), and B-cell leukemia/lymphoma extra-long protein (Bcl-xL), with TGF-beta1 in malignant and adjacent inflammatory cells in immunohistochemical evaluations of 108 colorectal cancers. Cytoplasm compartment of cancer cells was overloaded with TGF-beta1, and 87% of all cancers were TGF-beta1 positive (94/108). A very strong pattern of staining was detected for TGF-beta1 in cytoplasm of inflammatory cells at tumor margins. TGF-beta1 correlated with Bcl-xL and Bax in all colorectal cancers (P < 0.001, r= 0.473 and P < 0.001, r= 0.435, respectively) and subgroups of different clinicopathological features, especially in deeply invading cancers (pT3+pT4) instead of superficially growing tumors (pT1+pT2). Expression of TGF-beta1 in inflammatory infiltrates correlated with immunoreactivities to Bcl-xL of cancer cells (P= 0.024, r= 0.217). TGF-beta1 did not associate with p53, nor did TGF-beta1 of inflammatory cells correlate with Bax expression in cancer cells. Lack of correlations between TGF-beta1 and p53 proteins could indicate mutations at the TGF-beta1-dependent apoptotic pathway. Dominant positive linkage between TGF-beta1 and Bcl-xL and selective lack of association with Bax suggest TGF-beta1 could support colorectal cancer cell survival. The pattern of correlations seems to confirm a remarkable shift from TGF-beta1-dependent suppression of cancer growth by apoptosis to inhibition of anticancer immunity by TGF-beta1.