Exosome-mediated secretion of miR-127-3p regulated by RAB27A accelerates metastasis in renal cell carcinoma.

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.

Perilipin1 Expression as a Prognostic Factor in Patients with Squamous Cell Carcinoma of the Lung.

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.

Intravascular NK/T-cell lymphoma: a case report and literature review.

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.

Fc Receptor Expression as a Prognostic Factor in Patients With Non-small-cell Lung Cancer.

BACKGROUND/AIM: The neonatal Fc receptor (FcRn) is a major histocompatibility class I-like molecule responsible for the transfer of passive humoral immunity from a mother to her newborn. Recent research revealed that FcRn is involved in antigen-presentation, humoral immunity and antitumor immunity of various types of cancer, such as lung, colon and breast. Lung cancer is the leading cause of cancer-related death and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer. NSCLC is a highly heterogeneous disease and this affects the prognosis. Therefore, many studies have tried to identify factors that are associated with prognosis. The lungs are a major organ expressing FcRn. We aimed to evaluate FcRn expression in surgical specimens of NSCLC and determine its correlation with patient prognosis. MATERIALS AND METHODS: We analyzed 140 NSCLC surgical specimens for FcRn expression using immunohistochemistry and correlated positivity with clinicopathology and survival of these patients. A chi-squared test and Kaplan-Meier analysis with log-rank tests were performed for statistical evaluation. RESULTS: The FcRn-positive group had a significantly higher disease-free survival and a tendency towards increased disease-specific survival in patients with tumor-node-metastasis stage I NSCLC. CONCLUSION: Our study supports the hypothesis that FcRn down-regulation is associated with NSCLC progression.

RAB27A and RAB27B Expression May Predict Lymph Node Metastasis and Survival in Patients With Gastric Cancer.

BACKGROUND/AIM: RAB27A and RAB27B are involved in exosome secretion. To date, there have been many attempts to elucidate the roles of RAB27A and RAB27B in the prognosis of various cancer types. The association of RAB27A and RAB27B expression with the clinical and pathological features was evaluated in patients with stomach cancer. MATERIALS AND METHODS: A total of 360 patients who had undergone surgery for stomach cancer between January 1999 and December 2007 at Gyeongsang National University were enrolled in the study. Disease-free survival (DFS) and disease-specific survival (DSS) were compared according to immunohistochemistry of tumor samples. RAB27A and RAB27B mRNA and protein were also extracted from four stomach cancer cell lines using quantitative polymerase chain reaction and western blotting. RESULTS: Strong nuclear RAB27A expression in tumor samples was statistically significantly correlated with lymph node metastasis. Cytoplasmic RAB27B expression was related to poor disease-free survival and its combined cytoplasmic and membranous expression was related to disease-specific survival of patients with different histopathological types of stomach cancer. High RAB27A expression and high RAB27B expression was found in four stomach cancer cell blocks. Among the four cell lines, NCI-N87 exhibited the lowest relative mRNA density and HS746T exhibited the highest relative protein density for both RAB27A and RAB27B. CONCLUSION: RAB27A and RAB27B expression may help predict lymph node metastasis and survival of patients with gastric cancer.

Correlation between myoferlin expression and lymph node metastasis in papillary thyroid carcinoma.

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.

Cardiac Calcified Amorphous Tumor in the Left Atrium: A Case Report.

A cardiac calcified amorphous tumor (CAT) is a rare non-neoplastic mass of the heart with histological characteristics comprising calcification and amorphous fibrous material. Little is known regarding the incidence, symptoms, and therapeutic strategies for CAT. Echocardiography and computed tomography were performed on a 48-year-old man who had a cardiac mass that was accidentally discovered on admission to a local hospital for a fracture related to a trauma that occurred 1 month prior. After surgery, a histological examination resulted in the diagnosis of a cardiac CAT. The patient was discharged without postoperative complications on the 12th day after surgery.

PD-1 Expression and its Correlation With Prognosis in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Programmed death ligand-1 (PD-L1) and programmed death protein 1 (PD-1) expression levels in many tumors and their correlation with prognosis have been actively studied. However, studies on PD-1 expression and its prognostic value in clear cell renal cell carcinoma (ccRCC) are limited and controversial. In this study, we describe the expression of PD-1 and its prognostic significance and association with clinical features in patients with ccRCC. MATERIALS AND METHODS: We obtained clinicopathological data from 166 patients with ccRCC who were treated at Gyeongsang National University Hospital, Jinju, Korea between January 2000 and December 2009. Tissue microarray blocks were made using representative paraffin blocks of ccRCC specimens. Two pathologists analyzed PD-L1 and PD-1 expression in both tumor and inflammatory cells. RESULTS: PD-1 expression in tumor-infiltrating inflammatory cells was significantly correlated with unfavorable disease-free survival (DFS) (p<0.001) and disease-specific survival (DSS) (p=0.002) in the univariate analysis. A statistically significant correlation between PD-1 expression and unfavorable DFS (p=0.025) was observed in the multivariate analysis. CONCLUSION: PD-1 expression in tumor-infiltrating inflammatory cells serves as an independent prognostic factor for unfavorable DSS in patients with ccRCC.

Diagnostic Utility of p62 Expression in Intranuclear Inclusions in Thyroid Core Needle Biopsy Specimens.

BACKGROUND/AIM: Core needle biopsy (CNB) has been widely used as an alternative method to ultrasound-guided fine-needle aspiration cytology for histological diagnosis of thyroid specimens. However, nuclear artifactual vacuoles (NuVas) produced during tissue processing can be very difficult and sometimes impossible to distinguish from intranuclear inclusions (NuIns). P62 is an autophagy receptor that recognizes, targets, and eliminates toxic cellular materials during autophagy. Herein, we examined the utility of p62 immunohistochemical staining to detect NuIns in thyroid core needle biopsy specimens. PATIENTS AND METHODS: Thirty-five thyroid CNB slides from 32 patients and corresponding resection specimens stained with hematoxylin and eosin were reviewed by two pathologists. The immunohistochemical staining pattern of p62 was used to differentiate NuIns from NuVas. The diameter of each nucleus (A) and NuIn (B) was measured, and the number of p62-expressing NuIn-positive (p62In) cells was counted using 1/2 (B/A) and 1/3 (B/A) criteria. The criterion of 1/3 includes NuIns larger than 1/3 and smaller than 1/2 of the nuclear diameter. The criteria of 1/2 includes NuIns larger than 1/2 of the nuclear diameter. RESULTS: By applying the 1/2 criterion, there were no p62In cells in follicular adenoma (FA) samples. However, in papillary thyroid carcinoma (PTC) samples, 22 of 25 specimens exhibited p62In cells. The sensitivity and specificity to distinguish FA from PTC using the 1/2 criterion were 0.88 and 1.00, respectively. By applying the 1/3 criterion, there was one p62In cell hit in FA samples. However, 23 of 25 PTC specimens showed p62In cells. The sensitivity and specificity to distinguish FA from PTC using the 1/3 criterion were 1.00 and 0.90, respectively. CONCLUSION: P62 is a useful marker for distinguishing FA and PTC based on CNB specimens. We suggest the 1/2 criteria for identifying p62In cells.

Characteristics of Gastric Carcinomas With High ERCC1 Expression and the Prognostic Value of ERCC1 Expression.

BACKGROUND/AIM: We aimed to evaluate the characteristics of gastric carcinoma with high excision repair cross complementing 1 (ERCC1) expression and the prognostic value of ERCC1 expression. MATERIALS AND METHODS: ERCC1 expression was evaluated by immunohistochemistry in 309 surgically resected gastric carcinoma specimens using a tissue microarray. Cancer-related survival was analysed using competing risk analysis. RESULTS: Compared to ERCC1-low gastric carcinomas, ERCC1-high gastric carcinomas showed less local invasion (p=0.0013), lower N stage (p=0.0302), earlier pTNM stage (p=0.0003), and less frequent recurrence (p=0002). Patients with ERCC1-high gastric carcinoma showed lower cumulative incidence function estimate of cancer-related death [3.37; 95% confidence intervaI (CI)=0.89-8.75] than did those with ERCC1-low gastric carcinoma (17.12; 95% CI=12.24-22.69; p-value by Gray's test=0.0012). Adjusted proportional sub-distribution hazard ratio for cancer-related death in the patients with ERCC1-high tumour was 0.272 (95% CI=0.084-0.878; p=0.0295). CONCLUSION: High ERCC1 expression may be an independent positive prognostic marker for gastric carcinoma.