Altered transcription factor E3 expression in unclassified adult renal cell carcinoma indicates adverse pathological features and poor outcome
Bibliographic record
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. OBJECTIVES • 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".