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Abstract Background The exosome-mediated extracellular secretion of miRNAs occurs in many cancers, and RAB27A is a potent regulator of exosome secretion. For metastatic renal cell carcinoma (RCC), this study examines the mechanisms of cancer metastasis via the RAB27A-regulated secretion of specific miRNAs. Methods RAB27A knockdown (KD) and overexpressing (OE) RCC cells were used to examine cell migration and adhesion. The particle counts and sizes of exosomes in RAB27A OE cells were analyzed using Exoview, and those of intraluminal vesicles (ILV) and multivesicular bodies (MVB) were measured using an electron microscope. Analysis of RNA sequences, protein–protein interaction networks, and the competing endogenous RNA (ceRNA) network were used to identify representative downregulated miRNAs that are likely to undergo cargo-sorting into exosomes and subsequent secretion. A molecular beacon of miR-137-3p, one of the most representatively downregulated genes with a fold change of 339, was produced, and its secretion was analyzed using Exoview. RAB27A OE and control cells were incubated in an exosome-containing media to determine the uptake of tumor suppressor miRNAs that affect cancer cell metastasis. Results Migration and cell adhesion were higher in RAB27A OE cells than in RAB27A KD cells. Electron microscopy revealed that the numbers of multivesicular bodies and intraluminal vesicles per cell were higher in RAB27A OE cells than in control cells, suggesting their secretion. The finding revealed that miR-127-3p was sorted into exosomes and disposed of extracellularly. Protein–protein interaction analysis revealed MYCN to be the most significant hub for RAB27A-OE RCC cells. ceRNA network analysis revealed that MAPK4 interacted strongly with miR-127-3p. Conclusion The disposal of miR-127-3p through exosome secretion in RAB27A overexpressing cells may not inhibit the MAPK pathway to gain metastatic potential by activating MYCN. The exosomes containing miRNAs are valuable therapeutic targets for cancer treatment.

Intravascular lymphoma is characterized by an exclusively intravascular distribution of tumor cells. Intravascular natural killer/T-cell lymphoma (IVNKTL) is extremely rare, highly aggressive, commonly Epstein-Barr virus (EBV)–positive, and predominantly affects the skin and central nervous system. Here we report a case of IVNKTL diagnosed in a 67-year-old female, presenting with persistent intermittent fever and skin rashes throughout the body. Incisional biopsy of an erythematous lesion on the chest exhibited aggregation of medium to large-sized atypical lymphoid cells confined to the lumen of small vessels that were positive for CD3, granzyme B, and CD56 on immunohistochemistry and EBV-encoded RNA in situ hybridization. EBV DNA was also detected in serum after diagnosis. With a review of 26 cases of IVNKTL to date, we suggest that active biopsy based on EBV DNA detection may facilitate early diagnosis of IVNKTL.

Background: Hypoxia-regulated proteins (HIF-1α and GLUT-1) have been identified as prognostic markers in various cancers; however, their role in endometrial cancer remains unclear. This study aimed to evaluate HIF-1α and GLUT-1 expression in endometrial cancer and correlate their expression with clinicopathological features. Materials and Methods: A tissue microarray (TMA) was constructed using specimens from a retrospective cohort of 51 endometrial cancer patients who underwent hysterectomy at the Gyeongsang National University Hospital between 2002 and 2009. Clinicopathologic data were collected from electronic medical records, and HIF-1α and GLUT-1 expressions were assessed in the tumor tissue. Results: GLUT-1 expression in endometrial cancer was categorized as mosaic, central, or diffuse. Most patients (56.0%) exhibited a central pattern, followed by diffuse (32.0%) and mosaic (12.0%) patterns. GLUT-1 expression was not significantly associated with histologic grade (p = 0.365). HIF-1α expression in immune cells, but not tumor cells, was significantly associated with a higher histologic grade. A higher proportion of HIF-1α-positive immune cells, using both thresholds (≤1% vs. >1% and ≤5% vs. >5%), was significantly associated with higher histologic grade (p = 0.032 and p = 0.048, respectively). In addition, a higher proportion of HIF-1α-positive immune cells was significantly associated with a diffuse GLUT-1 expression pattern using >5% as a threshold. There were no significant differences in the proportion of HIF-1α-positive immune cells between groups stratified by age, tumor size, or invasion depth, regardless of whether the 1% or 5% threshold for HIF-1α positivity was used. Conclusions: A higher proportion of HIF-1α-positive immune cells is associated with endometrial cancers with higher histologic grade and diffuse GLUT1 expression patterns. These findings suggest a potential role for HIF-1α as a prognostic marker and highlight the need for further studies into the role of HIF-1α in the tumor microenvironment.

Background: Endometrial cancer (EC) has robust molecular diagnostic evidence that correlates well with prognosis. In various types of cancers, FcRn has been identified as an early marker for prognosis. This study aims to assess FcRn expression and its association with clinicopathological features in endometrial cancer. Materials and Methods: We employed a tissue microarray (TMA) from a retrospective cohort of 41 patients diagnosed with endometrioid endometrial cancer post hysterectomy between January 2002 and December 2009 at Gyeongsang National University Hospital. Relevant clinical data collection for the cohort involved reviewing patients’ electronic medical charts. FcRn expression in microarrays of patient EC tissue was examined in conjunction with clinicopathologic data. Experiments, including siRNA knock-down, PCR mRNA semiquantification, Western blot, and confluence change tests, were conducted on the Ishikawa cell line. Results: The overall FcRn expression rate in EC patients was 41.8%. FIGO stage showed a statistically significant relationship with FcRn expression, while age, lymphovascular invasion, myometrial invasion, and tumor size had no effect. In endometrioid cancer cells of FIGO stage IA, FcRn was less frequently expressed than in other high-staged EC patients (p = 0.021). In experiments on the Ishikawa cell line, the siRNA knock-down group exhibited quantitatively lower FCGRT mRNA expression and lower FcRn protein signal compared to the scrambled RNA control group. The change in confluence over time measured at three hotspots did not show a significant difference between groups. Conclusions: To the best of our knowledge, this study represents the initial assessment of FcRn expression in endometrioid EC samples. FcRn expression was significantly associated with the FIGO stage. Ishikawa cell line proliferation did not significantly change in response to decreased FcRn expression. Further studies are needed to elucidate FcRn expression in EC as a potential molecular parameter.

Abstract We aimed to quantitatively analyze the exosome and its cargo in individual aqueous humor (AH) samples from pseudoexfoliation (PEX) glaucoma patients compared to controls using a novel detection platform. We investigated the size distribution and measured the quantitative exosome particle counts in each AH sample. AH (80–120 µL) was obtained during cataract surgery or glaucoma filtering surgery from 12 Korean subjects (six with PEX glaucoma and six age-matched controls). The mean size of the exosomes was 58.9 ± 18.5 nm measured by a tangential flow filtration system using single-particle interferometric reflectance imaging sensor. Exosome particle count in each CD 63, CD 81, and CD9 spot was significantly greater in PEX glaucoma than in controls in total, CD 63, CD9, syntenin, and scattering(all p

Background Myoferlin is a multifunctional protein expressed in various normal and cancer cells, with novel oncogenic roles being newly discovered. Recently, correlations have been found between myoferlin expression and unfavorable prognosis in various carcinomas. This study investigated the prognostic role of myoferlin expression in papillary thyroid carcinoma (PTC), specifically that associated with nodal metastasis. Methods We collected clinicopathological data and PTC tissues from 116 patients who had been admitted to Gyeongsang National University Hospital in 2010. Immunohistochemical analysis was performed on surgical specimen-derived tissue microarray blocks. Myoferlin expression was graded, and the relationship between expression level and pathological features of tumors based on the American Joint Committee on Cancer staging system was evaluated. Results Of the 116 patient samples, 100 cases exhibited positive myoferlin expression. Higher grade of myoferlin expression was correlated with lower T category group (p = .010). Presence of lymph node metastasis was determined to be significantly correlated with low-grade myoferlin expression (p = .019), with no significant difference between pN1a and pN1b tumors. Conclusions Our study revealed an adverse correlation between myoferlin expression and pathological features of PTC, evidence of the potential prognostic role of myoferlin in PTC lymph node metastasis.

Abstract We aimed to obtain microRNA (miRNA) profiles of patients with pseudoexfoliation (PEX) glaucoma or normal-tension glaucoma (NTG) compared to normal controls using individual aqueous humor (AH) samples and investigate the role of miRNAs in the pathogenesis of PEX glaucoma compared to NTG in Korean. AH (80-120 µl) was collected before cataract surgery or trabeculectomy from 26 Korean subjects (eleven with PEX glaucoma, age-matched eight NTG, and seven controls). RNA sequencing was conducted for RNA samples extracted from 26 AH samples. Bioinformatics analysis was performed for targets and related pathways. A total of 334 and 291 discrete miRNAs were detected in AH samples of PEX glaucoma and NTG patients, respectively. Two significantly upregulated miRNAs (hsa-miR-30d-5p and hsa-miR-320a) and ten significantly downregulated miRNAs (hsa-miR-3156-5p, hsa-miR-4458, hsa-miR-6717-5p, hsa-miR-6728-5p, hsa-miR-6834-5p, hsa-miR-6864-5p, hsa-miR-6879-5p, hsa-miR-877-3p, hsa-miR-548e-3p, and hsa-miR-6777-5p) in PEX glaucoma patients compared to control (fold-change > 2, p

Perilipin (PLIN) is a major structural protein located on the surface of lipid droplets. PLIN plays an important role in human metabolism and is associated with metabolic diseases, such as obesity, diabetes, hypertension, and endocrine disorders. The dysregulation of lipid metabolism is one of the most prominent metabolic changes observed in cancers. Therefore, the PLIN protein family has recently attracted attention owing to its role in lipid metabolism and cancer. To date, no studies have addressed the association between the prognosis of lung cancer and PLIN1 expression. For the first time, we found that high PLIN1 expression was significantly correlated with worse disease-free survival (DFS) in lung squamous cell carcinoma (SCC). We examined PLIN1 expression by the immunohistochemical analysis of surgical lung SCC specimens obtained from 94 patients. We analyzed the correlation between PLIN1 expression, clinicopathological data, and patient survival, using a chi-squared test, Kaplan–Meier analysis with log-rank tests, and the multivariate Cox proportional hazards regression test. High PLIN1 expression was significantly correlated with lower DFS in the Kaplan–Meier analysis and the multivariate Cox proportional hazards regression model. High PLIN1 expression was significantly correlated with worse prognosis in lung SCC.

Abstract Identifying the lung carcinoma subtype in small biopsy specimens is an important part of determining a suitable treatment plan but is often challenging without the help of special and/or immunohistochemical stains. Pathology image analysis that tackles this issue would be helpful for diagnoses and subtyping of lung carcinoma. In this study, we developed AI models to classify multinomial patterns of lung carcinoma; ADC, LCNEC, SCC, SCLC, and non-neoplastic lung tissue based on convolutional neural networks (CNN or ConvNet). Four CNNs that were pre-trained using transfer learning and one CNN built from scratch were used to classify patch images from pathology whole-slide images (WSIs). We first evaluated the diagnostic performance of each model in the test sets. The Xception model and the CNN built from scratch both achieved the highest performance with a macro average AUC of 0.90. The CNN built from scratch model obtained a macro average AUC of 0.97 on the dataset of four classes excluding LCNEC, and 0.95 on the dataset of three subtypes of lung carcinomas; NSCLC, SCLC, and non-tumor, respectively. Of particular note is that the relatively simple CNN built from scratch may be an approach for pathological image analysis.

Abstract The mechanism of nonalcoholic fatty liver disease (NAFLD) has not been completely revealed. In this study, we investigated the association of liver histological changes and long noncoding RNAs (lncRNAs) in the NAFLD zebrafish model. Forty zebrafish were fed a high-cholesterol diet (1.5 g per day) for 8 weeks. We measured fatty liver changes in the zebrafish liver using oil red O staining and divided them into two groups based on high and low scores. We pooled each group of zebrafish livers and identified lncRNAs, miRNAs, and mRNAs using Next-generation sequencing. Human homologs of lncRNAs were identified using ZFLNC, Ensembl, and NONCODE. We found several significant genes, including 32 lncRNAs, 5 miRNA genes, and 8 protein-coding genes, that were associated with liver metabolism and NAFLD-related functions in zebrafish. In particular, eight conserved human homologs of lncRNAs were found. We discovered the human homologs of eight lncRNA candidates from fatty liver zebrafish for the first time. The spectrum of biological mechanisms by which lncRNAs mediate their functional roles in NAFLD in a high cholesterol diet adult zebrafish model remains to be uncovered.

Abstract We aimed to identify and compare microRNAs (miRNAs) from individual aqueous humor samples between normal-tension glaucoma (NTG) patients and normal controls. Aqueous humor (80 to 120 µl) was collected before cataract surgery. Six stable NTG patients and seven age-matched controls were included in the final analysis. RNA sequencing was conducted for RNA samples extracted from the 13 aqueous humor samples, and bioinformatics analysis was employed for the miRNA targets and related pathways. Two hundred and twenty-eight discrete miRNAs were detected in the aqueous humor and consistently expressed in all samples. Eight significantly upregulated miRNAs were found in the NTG patients compared to the controls (fold-change > 2, p

Abstract Background Smoking‐ and nonsmoking‐associated lung cancers have different mechanisms of carcinogenesis. We divided non‐small cell lung cancer (NSCLC) patients into nonsmoking and smoking groups with the aim of trying to understand the utility of brain‐specific angiogenesis inhibitor 1 (BAI1) expression in the separate groups. Methods Clinicopathological data were obtained from 148 patients who had undergone surgery for NSCLC of the lung. Tissue microarray blocks were made of samples from NSCLC patients. Two pathologists graded the intensity of BAI1 expression as high or low expression in the cancer cells of patients in the smoking and nonsmoking groups. Results NSCLC nonsmokers with higher BAI1 nuclear expression had poor disease‐specific survival (DSS) (hazard ratio: 2.679; 95% confidence interval [CI]:1.022–7.022, p = 0.045). The Kaplan–Meier survival curve confirmed that higher BAI1 expression was significantly associated with poor DSS (p = 0.034) in the nonsmoking group. Conclusions We divided NSCLC patients into nonsmoking and smoking groups and found that nuclear BAI1 expression was related to patient survival in nonsmoking NSCLC patients. We suggest BAI1 expression as a predictive marker of nonsmoking‐associated NSCLC and recommend that it be evaluated as an AJCC staging criterion in the future.

Abstract. Introduction:. Waldenström's macroglobulinemia is a lymphoplasmacytic lymphoma (LPL) associated with a monoclonal immunoglobulin M protein. Although acute kidney injury (AKI) due to immunoglobulin M paraprotein infiltration into the renal interstitium has been reported, there has been no report of AKI with invasion of the immunoglobulin G paraprotein into the renal interstitium in a patient with LPL. Patient concerns:. A 65-year-old male was admitted to our hospital with fatigue and decreased renal function. He complained of a 3-kg weight loss in the last 3 months. Diagnosis:. The initial blood urea nitrogen and serum creatinine levels were 55.9 and 1.83 mg/dL, respectively. Serum protein electrophoresis revealed a monoclonal component (3.5 g/dL) in the gamma region and immunofixation electrophoresis showed an immunoglobulin G kappa monoclonal protein. Renal pathology revealed that CD3–CD20+ CD138+ lymphoid cells had infiltrated the renal interstitium. A bone marrow biopsy was compatible with LPL. Interventions:. Intravenous methylprednisolone (1 mg/kg) was administered after confirming the renal pathological findings. Outcomes:. Serum creatinine decreased to 0.8 mg/dL 14 days after treatment Conclusions:. Physicians should recognize LPL secreting various immunoglobulins as a possible cause of AKI when renal failure of unknown etiology and serum immunoglobulin paraprotein is present. A kidney biopsy should be performed for definitive diagnosis and appropriate management.

Abstract Background Research on diagnosing recurrent non‐small cell lung cancer (NSCLC) and applying target gene treatment using exosomes in a less invasive way is very important. Recently, however, it has been argued that exosomes do not contain double‐stranded DNA (dsDNA) or histones. In this study, we describe the expression of extracellular vesicle (EV) markers in specimens from squamous cell carcinoma (SCC) of the lung and analyze their relationship with the prognosis of patients. Methods Clinical and pathological data were obtained from 96 patients who had undergone surgery for SCC of the lung. Tissue microarray blocks were made using representative paraffin blocks of samples from patients with SCC of the lung. Two pathologists graded the intensity of CD63, CD9, LC3A/B, P62, and ANXA1 expression as high or low expression. In addition, the authors designated the combined expression of these five independent markers as “positive EV expression” in this article. Results SCCs with low CD63 and SCCs with low EV expression showed unfavorable disease‐free survival (DFS) (P‐value = 0.037 and 0.006, respectively) in the survival analysis. The Kaplan‐Meier survival curve confirmed that the low EV expression showed a statistically significant relationship with unfavorable DFS (P‐value = 0.004). There were no statistically significant differences in DFS and disease‐specific survival in each low and high expression group for CD9, LC3A/B, ANXA1, and P62 in the Cox regression analysis. Conclusions As EV expression was related to the prognosis of lung SCC patients, a broader approach using different extracellular vesicles rather than a conventional exosome‐dependent one is needed.

Background Macrophage migration inhibitory factor (MIF) has been shown to play an important role in the inflammatory and immune response in squamous cell carcinoma (SCC). Recent studies have reported that MIF is involved in the tumorigenesis and overexpressed in various cancers. In this study, we assessed the prognostic role of MIF expression in SCC of the lung, and demonstrated the effect of knockdown of MIF on the migration in lung SCC cell lines. Methods The relationship between MIF expression and clinicopathological parameters and the prognostic role of MIF expression were evaluated with immunohistochemical staining in 96 patients with SCC of the lung. The expression of MIF mRNA and protein was analyzed by semi‐quantitative polymerase chain reaction and Western blot in lung SCC cell. The effect of knockdown of MIF was assessed by wound healing assay. Results The high percentage of MIF‐positive cells was significantly associated with lymph node metastasis (P = 0.004), and was a poor prognostic factor of disease‐free survival (DFS) (hazard ratio [HR]: 3.125; 95% confidence interval [CI], 1.628–5.998; P = 0.001) and disease‐specific survival (DSS) (HR: 2.303; 95% CI, 1.172–4.525; P = 0.016). Moreover, Kaplan‐Meier analysis showed that SCC patients with a high percentage of MIF‐positive cells had a significantly lower DFS (P = 0.001) and DSS (P = 0.014) than those with a low percentage. Furthermore, wound healing assay revealed that knockdown of MIF resulted in decreased cellular migration. Conclusion MIF is closely associated with tumor progression and could be a prognostic factor in SCC of the lung.

Background: The Hippo signaling pathway has a key role in tumorigenesis. This study aimed to evaluate the relationship between the expression of core components of the Hippo signaling pathway and its association with clinicopathological features in endometrial cancer. Materials and Methods: We retrospectively collected endometrioid endometrial cancer specimens from 60 patients between January 2002 and December 2009 at Gyeongsang National University Hospital. Relevant clinicopathological data were obtained through electronic medical records of patients. The expression patterns of six core components (YAP, p-YAP, LATS1/2, MST1/2, KIBRA, and Merlin) were identified by immunohistochemistry on tissue microarray sections. Results: The positive expression ratio was 75.0% for YAP, 73.3% for p-YAP, 26.7% for MST1/2, 16.7% for KIBRA, 15.0% for Merlin, and 15.0% for LATS1/2. YAP expression was negatively correlated with MST 1/2 kinases (p = 0.045) and positively correlated with p-YAP (p = 0.012). Merlin, and MST 1/2 kinases (p = 0.043) showed a positive correlation. A subgroup of patients aged below 60 years (p = 0.004) and with myometrial invasion depth of less than 1/2 (p = 0.041) showed a positive association with YAP expression. p-YAP expression was negatively associated with a subset of patients with primary tumour size ≥4 cm (p = 0.03). Logistic regression analysis showed a significant association between age and YAP expression. The odds ratio of p-YAP expression was significantly lower in the group with tumour size ≥4 cm. Conclusion: Two prognostic factors, age and tumour size, were significantly associated with the expression of YAP and p-YAP in endometrial cancer. Further research should focus on their expression as a marker for prediction of clinicopathological implications in endometrial cancer.

The purpose of this paper is to evaluate the association of maternal clinical and laboratory features and placental histopathological changes with disease severity in pregnancy-related hypertensive disorders. From January 2021 to December 2021, clinical and laboratory data at the time of delivery and histopathological features of the placenta were collected from pregnant women with pregnancy-related hypertensive disorders at a single institution. The women were classified according to the pregnancy-related hypertensive disorder clinical severity, and each variable was compared accordingly. Gestational age-matched normotensive groups were also compared. Univariate and multivariate regression analyses were used to identify factors influencing pregnancy-related hypertensive disorder severity. Fifty-eight pregnancies were analyzed. Maternal albumin levels before delivery (beta coefficient −0.83, p = 0.043) and increased placental syncytial knots (beta coefficient 0.71, p = 0.026) are important parameters that are closely related to disease severity in women with pregnancy-related hypertensive disorders. The combination of albumin, PAPP-A, total bilirubin, and eGFR levels appears to be optimal for predicting pregnancy-related hypertensive disorder severity.

Background Rab27A and Rab27B are the major components of vesicle fusion and trafficking in exosome secretion and play important roles in tumor progression and metastasis. In addition, Rab27A and Rab27B are associated with tumor prognosis. This study investigated the prognostic roles of Rab27A and Rab27B expression in patients with non‐small cell lung cancer (NSCLC). Methods Rab27A and Rab27B expression was assessed in 133 cases of NSCLC by immunohistochemistry. We evaluated the correlations between Rab27A and Rab27B expression and clinicopathological data and determined their prognostic role in NSCLC. Results Rab27A and Rab27B expression were significantly related to patient gender (P = 0.007 and 0.002, respectively) and histologic type (P = 0.009 and < 0.001, respectively), but not to patient age, smoking history, surgical method, or tumor node metastasis stage. The multivariate Cox proportional hazards regression model verified that high Rab27B expression is a prognostic factor for unfavorable disease‐specific survival (hazard ratio 2.680, 95% confidence interval 1.116–6.437; P = 0.027) in squamous cell carcinoma (SQCC). Kaplan–Meier analysis revealed significantly poorer prognosis in SQCC patients with high Rab27B expression compared to patients with low Rab27B expression (P = 0.030). Conclusion High Rab27B expression could be an unfavorable prognostic factor in patients with SQCC of the lung.

Background S100A8 and S100A9 have been gaining recognition for modulating tumor growthand metastasis. This study aimed at evaluating the clinical significance of S100A8 and S100A9 innon-small cell lung cancer (NSCLC). Methods We analyzed the relationship between S100A8and S100A9 expressions, clinicopathological characteristics, and prognostic significance in tumorcells and peritumoral inflammatory cells. Results The positive staining of S100A8 in tumorcells was significantly increased in male (p < .001), smoker (p = .034), surgical method other thanlobectomy (p = .024), squamous cell carcinoma (SQCC) (p < .001) and higher TNM stage (p = .022)compared with female, non-smoker, lobectomy, adenocarcinoma (ADC), and lower stage. Theproportion of tumor cells stained for S100A8 was related to histologic type (p < .001) and patientsex (p = .027). The proportion of inflammatory cells stained for S100A8 was correlated with patientage (p = .022), whereas the proportion of inflammatory cells stained for S100A9 was correlatedwith patient sex (p < .001) and smoking history (p = .031). Moreover, positive staining in tumorcells, more than 50% of the tumor cells stained and less than 30% of the inflammatory cellsstained for S100A8 and S100A9 suggested a tendency towards increased survivability in SQCCbut towards decreased survivability in ADC. Conclusions S100A8 and S100A9 expressions might be potential prognostic markers in patients with NSCLC.

Nonsecretory multiple myeloma is a rare variant of multiple myeloma characterized by the proliferation of clonal plasma cells in the bone marrow. It is difficult to establish an early and accurate diagnosis of nonsecretory multiple myeloma because in nonsecretory myeloma cases, monoclonal immunoglobulin cannot be detected in the serum or urine via electrophoresis. In this report, we describe a case of nonsecretory multiple myeloma presenting as recurrent vertebral compression fractures in a 70-year-old male patient and suggest that nonsecretory multiple myeloma can be included in the differential diagnosis of multiple and recurrent vertebral compression fractures, despite the lack of detectable monoclonal immunoglobulin in the serum or urine by electrophoresis.

Carcinosarcoma of the salivary gland is an extremely rare tumor that is composed of both malignant epithelial and mesenchymal components. Diagnosing carcinosarcoma with fine-needle aspiration cytology is challenging because of its overlapping cytomorphologic characteristics with other high-grade malignant salivary gland tumors. Among the many features, including pleomorphic oncocytoid epithelial components, necrotic background, and mitoses, recognizing the singly scattered atypical spindle cells is most essential in carcinosarcoma. We present a case of a 66-year-old male patient with characteristic features of carcinosarcoma, who was successfully treated by wide local excision and subsequent radiation therapy.

Background For endometrioid carcinoma patients, International Federation of Gynecologists and Obstetricians (FIGO) histologic grading is very important for identifying the appropriate treatment method. However, the interobserver discrepancy with this three-tiered grading system is a serious potential problem. In this study, we used immunohistochemistry to analyze the relationship between FIGO histologic grading score and myoferlin expression. Methods We studied the endometrioid carcinoma tissues of 60 patients from Gyeongsang National University Hospital between January 2002 and December 2009. Immunohistochemical analysis of myoferlin was performed on tissue microarray blocks from surgical specimens. Results Myoferlin expression was observed in 58 of 60 patients. Moderate and strong myoferlin expression was observed in low-grade endometrioid carcinoma, while there was a tendency toward loss of myoferlin expression in high-grade endometrioid carcinoma (p

Background The immunotherapeutic role of programmed death-ligand 1 (PD-L1) in life expectancy in many cancers has been highlighted. However, data regarding PD-L1 expression in papillary thyroid carcinoma (PTC) are limited. In this study, we describe the PD-L1 and programmed cell death protein 1 (PD-1) expressions in PTC and analyze their correlation with lymph node (LN) metastasis. Methods Clinicopathological data were obtained from 116 patients with PTC who were treated in Gyeongsang National University Hospital, Jinju, Korea in 2009. Tissue microarray blocks were made using representative paraffin blocks of classical PTCs excluding follicular variants. Two pathologists graded the proportion and intensity of PD-L1 and PD-1 expression in both tumor and inflammatory cells. According to their proportions, positive PTC cells were scored as negative (0%), grade 1 (1%–50%), and grade 2 (51%–100%). Similarly, positive inflammatory cells were graded as negative (0%), grade 1 (1%–10%), and grade 2 (11%–20%). The intensity of each protein expression was simplified as positive or negative. Results A statistically significant correlation exists between the proportions of PD-1 and PD-L1 expression both in papillary carcinoma (p=.001) and peritumoral lymphoid cells in the thyroid (p

Thymoma is the most common neoplasm of the anterior mediastinum and has malignant potential. Germ cell tumors (GCTs) found in the anterior mediastinum are usually benign, and malignant GCTs, such as seminomas, are rare. Histologically, mediastinal seminoma is indistinguishable from testicular seminoma except for site-associated morphological features such as lymphoid follicular hyperplasia. Therefore, excluding metastasis is very important. Recently, we treated a young adult patient with multiple thymic masses that occurred simultaneously. The patient underwent a thymectomy for the removal of the mediastinal masses, one of which was diagnosed as type B2 invasive thymoma, and two of which were diagnosed as primary mediastinal seminomas with massive follicular hyperplasia. The patient received adjuvant chemotherapy after surgical resection. To our knowledge, this is the first description of a thymoma and a mediastinal seminoma occurring simultaneously in the thymus. We present this case along with a literature review.

Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.

Primary hepatic neuroendocrine carcinoma (PHNEC) is rare and its origin is not clearly understood. The coexistence of PHNEC and hepaotcellular carcinoma has been reported in only a few cases. We report a rare case of combined PHNEC and hepaotcellular carcinoma in a patient with liver cirrhosis caused by chronic hepatitis B that resulted in aggressive behavior and poor prognosis. (Korean J Gastroenterol 2016;68:109-113)

Background and Objectives: To investigate the diagnostic performance of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and subsequent ultrasonography (US) for determining cervical nodal metastasis in oncology patients. Materials and Methods: Fifty-nine cervical lymph nodes (LNs) initially detected by PET/CT with subsequent neck US were included in this retrospective study. All LNs were subjected to US-guided fine-needle aspiration or core needle biopsy. The maximum standardized uptake value (SUVmax) and sonographic features were assessed. Results: Forty-three of 59 cervical LNs detected by PET/CT were malignant. PET/CT alone showed a highest diagnostic value for metastatic LNs with 81.4% sensitivity, 68.8% specificity, and 78% accuracy when SUVmax ≥5.8 was applied as an optimal cut-off value. Combined PET/CT and subsequent US diagnoses for determining nodal metastasis showed the following diagnostic performance: 81.4% sensitivity, 87.5% specificity, and 83.1% accuracy. There was a significant difference in the diagnostic performance between the two diagnostic imaging approaches (p = 0.006). Conclusions: Combined diagnosis using subsequent US showed a significantly higher diagnostic performance for determining nodal metastasis in the neck. Therefore, we believe that our proposed diagnostic strategy using subsequent US can be helpful in evaluating cervical LNs on PET/CT. Moreover, our results clarify the need for US-guided tissue sampling in oncology patients.

Radiation-induced lung injury (RILI) is a common and unavoidable complication of thoracic radiotherapy. The current study was conducted to evaluate the ability of clarithromycin (CLA) to prevent radiation-induced pneumonitis, oxidative stress, and lung fibrosis in an animal model. C57BL/6J mice were assigned to control, irradiation only, irradiation plus CLA, and CLA only groups. Test mice received single thoracic exposures to radiation and/or oral CLA (100 mg/kg/day). Histopathologic findings and markers of inflammation, fibrosis, and oxidative stress were compared by group. On a microscopic level, CLA inhibited macrophage influx, alveolar fibrosis, parenchymal collapse, consolidation, and epithelial cell changes. The concentration of collagen in lung tissue was lower in irradiation plus CLA mice. Radiation-induced expression of tumor necrosis factor (TNF)-α, TNF receptor 1, acetylated nuclear factor kappa B, cyclooxygenase 2, vascular cell adhesion molecule 1, and matrix metallopeptidase 9 were also attenuated by CLA. Expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, transforming growth factor-β1, connective tissue growth factor, and type I collagen in radiation-treated lungs were also attenuated by CLA. These findings indicate that CLA ameliorates the deleterious effects of thoracic irradiation in mice by reducing pulmonary inflammation, oxidative damage, and fibrosis.

Background/Aim: Immune checkpoint inhibitors (ICI) and tumor-infiltrating lymphocytes (TILs) for cancer treatment in clinical oncology have revolutionized patient care. However, no gold standard exists for the criteria of analytical validity of TILs of different types of cancer. Materials and Methods: Clinicopathological data from 60 patients with endometrioid carcinoma (EC) who had undergone surgical treatment at the Gyeongsang National University Hospital between January 2002 and December 2009, were investigated. The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PDL1) expression levels were characterized by immunohistochemical staining patterns, and the interpretations derived from machine learning morphometric analysis (Genie) and the pathologists' assessments were compared. In solid tumors, pathologists assessed the proportion of positive cells in each core of the tissue microarray. For Genie, the proportion of positive cells in the entire core and the number of positive cells per 1 mm² were used. Results: Both the pathologists and Genie identified the same trend in association with tumor size, with significant differences (p=0.026, p=0.033). Genie expression showed a significant association with PD1 expression, and pathologists identified a significant association with PDL1 expression in immune cells. Conclusion: The PD1 expression levels identified in immune cells of EC specimens were similar between the pathologists and Genie, suggesting that there is little resistance to the introduction of morphometric analysis. To our knowledge, this is the first study to introduce and validate machine learning as an integrated method for predicting prognosis and treatment based on PD1 expression in EC tumor microenvironments. [ABSTRACT FROM AUTHOR]