Prevalence and Clinical Outcomes of Human Epidermal Growth Factor Receptor 2 Expression in Patients With Advanced Urothelial Carcinoma
Bibliographic record
Abstract
Background: The prognosis for urothelial carcinoma remains poor, with limited therapeutic options, emphasizing the need for further research into targeted therapies. The prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) expression in urothelial carcinoma remains unclear, with previous studies reporting conflicting results. Methods: We conducted a retrospective analysis of advanced urothelial carcinoma cases diagnosed between January 2017 and December 2022. HER2 status was prospectively determined using the Leica CB11 antibody on available biopsy specimens. Patient data, tumor characteristics, and survival outcomes were retrieved from hospital records for analysis. Results: Of the 84 patients initially identified with muscle-invasive disease, HER2 immunohistochemistry (IHC) was performed on 50 samples. Among these, 54% exhibited HER2 scores ≥ 1+, with 22% classified as HER2-positive (3+ score by IHC), 10% as equivocal (2+ score by IHC), and 22% as HER2-low (1+ score by IHC). The distribution of HER2 score ≥ 1+ tumors included 25.7% in the bladder, 20.0% in the renal pelvis, and none in the ureter. HER2-positive (3+ score by IHC) tumors were all histological grade 3. Among these patients, 13.4% presented with localized disease, 20% with locally advanced disease, and 50% with metastatic disease at the time of diagnosis. Notably, 42.8% of recurrent tumors originating from the renal pelvis and 62.5% of those from the bladder exhibited HER2 scores ≥ 1+. Among patients diagnosed with non-metastatic disease, 100% with renal pelvis tumors and 75% with bladder tumors experienced metastatic recurrence if they were HER2-positive (3+ score by IHC). The overall survival for HER2-negative patients was 31.0 months (95% confidence interval (CI): 15.29 - 66.70) compared to 13.0 months (95% CI: 7.32 - 18.68) in the HER2 score ≥ 1+ population (P = 0.0029). Conclusions: In this cohort of Mexican patients with urothelial carcinoma, HER2 expression was observed in 54.4% of cases. HER2-positive (+3 by IHC) tumors were associated with higher histological grade and worse prognostic outcomes, including increased recurrence, progression, and mortality.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| 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".