Altered transcription factor E3 expression in unclassified adult renal cell carcinoma indicates adverse pathological features and poor outcome

Abstract

What's known on the subject? and What does the study add? This is a short series of unclassified RCC with positivity for TFE3 staining an association with poor outcome on those patients' follow-up. The paper supports the idea of TFE3 positivity as a marker for poor outcome in RCC patients. It has already been stated in some manuscripts; however, not in this number of patients. Objective:S To evaluate the clinical and pathologic features and the prognostic relevance of unclassified RCC with - TFE3 over-expression in our adult series. Recent studies suggest that renal cell carcinomas (RCCs) associated with the newly recognized Xp11.2 translocation (transcription factor E3 [TFE3] gene fusions) can be found among adults with RCC showing a very aggressive disease-course. Material and methods: We evaluated tumour specimens from 25 patients with unclassified RCC morphology out of 298 RCCs in the last 12 years in a tertiary academic centre. Immunohistochemistry was performed using monoclonal antibody for TFE3 C-terminal section, taking nuclear label into consideration. RT-PCR technique was performed for ASPL-TFE3 gene fusion on two tumours with available frozen tissue. Results: Of the 25 cases analyzed, 8 (32%) showed positivity for TFE3 and 17 were negative for TFE3 staining. Two tumors with ASPL-TFE3 gene fusion also showed TFE3 over-expression. Fifty percent of the positive patients had lymph node metastatic disease, whereas only one TFE3-negative patient (5.8%) showed evidence of lymph node spread and cava thrombus at diagnosis. Of the TFE3-positive patients, three had a vena cava thrombus (37.5%). Seven of the eight positive cases (87.5%) were diagnosed with a high Fuhrman grade (III/IV). In comparison, five of 17 (29.4%) TFE3-negative patients had a high Fuhrman grade. Five of eight TFE3-positive patients relapsed rapidly at 3 month follow-up; conversely none of the negative cases relapsed. At 36-month mean follow-up, 5-year cancer-specific survival was 15.6% for TFE3-positive patients and 87.5% for TFE3-negative patients (P < 0.001). Conclusion: Patients with unclassified RCC and TFE3 positivity have a grim prognosis due to their advanced stage at presentation and aggressive biologic features compared with the TFE3-negative unclassified RCC cases. © 2010 BJU International.