Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

BACKGROUND: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs). METHODS: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0), mild (1+), moderate (2+), and strong (3+). RESULTS: TG2 staining intensity was negative in 8.5% of CCRCC (n=54), 1+ in 32.6% (n=208), 2+ in 50.5% (n=322), and 3+ in 8.5% (n=54). Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011), high T category (p=.049), metastasis (p=.043) and male sex (p<.001) but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively). On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054). CONCLUSIONS: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.

Histologic Variations and Immunohistochemical Features of Metastatic Clear Cell Renal Cell Carcinoma

BACKGROUND: Due to advancements in treatment of metastatic and advanced renal cell carcinoma (RCC), it has become increasingly important to diagnose metastatic RCC and the specific subtype. In this study, we investigated the diverse histologic features of metastatic clear cell renal cell carcinoma (CCRCC) cases in comparison with corresponding primary lesions. METHODS: We identified 119 metastatic CCRCC cases from 81 corresponding primary lesions diagnosed between 1995 and 2010 and evaluated the diverse histologic and immunohistochemical features of these lesions. RESULTS: A total of 44 primary lesions (54.3%) had a non-clear cell component in addition to a typical clear cell component. Of the 119 metastatic lesions, 63 lesions (52.9%) contained a non-clear cell component, and 29 metastatic lesions were composed of a non-clear cell component only. Rhabdoid features were the most frequent non-clear cell histology among the metastatic lesions. Metastatic CCRCCs mainly showed positive CD10 and epithelial membrane antigen staining and negative cytokeratin 7 staining. CONCLUSIONS: Metastatic CCRCC commonly showed a variety of histologic features. If there is a difficulty to diagnose metastatic CCRCC due to a variety of histologic features or small biopsy specimen, histologic review of the primary lesion and immunohistochemical analysis can help determine the correct diagnosis.

ALK-Positive Renal Cell Carcinoma in a Large Series of Consecutively Resected Korean Renal Cell Carcinoma Patients

BACKGROUND: Recently, there have been a few reports of renal cell carcinoma (RCC) cases with anaplastic lymphoma kinase (ALK) gene fusion. In this study, we screened consecutively resected RCCs from a single institution for ALK protein expression by immunohistochemistry, and then we performed fluorescence in situ hybridization to confirm the ALK gene alteration in ALK immunohistochemistry-positive cases. METHODS: We screened 829 RCCs by ALK immunohistochemistry, and performed fluorescence in situ hybridization analysis using ALK dual-color break-apart rearrangement probe. Histological review and additional immunohistochemistry analyses were done in positive cases. RESULTS: One ALK-positive case was found. Initial diagnosis of this case was papillary RCC type 2. This comprises 0.12% of all RCCs (1/829) and 1.9% of papillary RCCs (1/53). This patient was a 44-year-old male with RCC found during routine health check-up. He was alive without evidence of disease 12 years after surgery. The tumor showed a papillary and tubular pattern, and showed positivity for CD10 (focal), epithelial membrane antigen, cytokeratin 7, pan-cytokeratin, PAX-2, and vimentin. CONCLUSIONS: We found the first RCC case with ALK gene rearrangement in Korean patients by ALK immunohistochemistry among 829 RCCs. This case showed similar histological and immunohistochemical features to those of previous adult cases with ALK rearrangement, and showed relatively good prognosis.

ERG Immunohistochemistry and Clinicopathologic Characteristics in Korean Prostate Adenocarcinoma Patients

BACKGROUND: Transmembrane protease serine 2-ETS related gene (TMPRSS2-ERG) gene fusion, the most common genetic alternation in prostate cancer, is associated with protein expression of the oncogene ERG. Recently, an immunohistochemical staining method using an anti-ERG antibody was shown to have a strong correlation with altered ERG protein expression. METHODS: We analyzed a total of 303 radical prostatectomy specimens (obtained from Korean prostate cancer cases) using a constructed tissue microarray and ERG immunohistochemical staining. Thereafter, we evaluated the association between ERG expression and clinicopathological factors. RESULTS: The ERG-positive rate was 24.4% (74/303) and significantly higher ERG expression was observed in the subgroup with a lower Gleason score (p=0.004). Analysis of the histologic pattern of prostate adenocarcinomas revealed that tumors with discrete glandular units (Gleason pattern 3) displayed higher frequency of ERG expression (p=0.016). The ERG-positive rate was lower than that found (approximately 50%) in studies involving western populations. Other factors including age, tumor volume, initial protein-specific antigen level, a pathological stage and margin status were not significantly related with the ERG expression. CONCLUSIONS: ERG immunohistochemical staining is significantly higher in tumors with well-formed glands and is associated with a lower Gleason score.