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

作者：Carmen Mir Maria; Trilla Enrique; Maria de Torres Ines; Panizo Angel; Zlotta Alexander R; Van Rhijn Bas; Morote Juan

来源：BJU International, 2011, 108(2B): E71-E76.

DOI：10.1111/j.1464-410X.2010.09818.x

• renal carcinoma
• translocation carcinoma
• immunohistochemistry
• cromosome Xp 11.2

OBJECTIVES
To evaluate the clinical and pathologic features and the prognostic relevance of unclassified RCC with - TFE3 overexpression 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 overexpression.
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.

• 出版日期2011-7