TROP-2 expression in vulval carcinoma – as a possible target for the treatment approach with antibody drug conjugates (ADC)
Bibliographic record
Abstract
Question/Background The Trophoblast Cell Surface Antigen 2 (TROP-2) is associated with invasiveness and tumor progression in several malignancies. Strong TROP-2-expression is associated with poor prognosis in cervical carcinoma. Recently, TROP-2 was identified as a target protein for treatment of solid tumors using antibody-drug conjugates (ADC). There are no details about the expression profiles of TROP-2 in vulval cancer (VCX). Methods 55 cases of squamous cell carcinomas oft he vulva were immunohistochemically analysed for TROP-2 expression using a H-score. The staining intensity (SI) was score das negative (0), weak (1), moderate (2) and strong (3). The percentage of positive stained tumor cells was calculated as 0 (complete negative staining of tumor cells), 1 (1-10% positive stained tumor cells), 2 (11-50%) and 3 (51-100%). Overall staining results were calculated by SI x percentage staining score as follows: negative (core 0), + (scores 1;2;3), ++ (scores 4-6) and +++ (score 7-9) as previously described. Overall staining scores were compared to the molecular subtypes of vulval carcinoma, defining p16+ve/p53wt, p16-ve/p53mut and p16-ve/p53wt VCX. Staining evaluation of TROP-2 was blinded to the molecular subtype. Results All 55 cases were immunohistochemically positive for TROP2. 7 cases (13%) showed weak reactivity (+), 31 cases (56%) represented moderate reactivity (++) and 17 cases (31%) strong positivity (+++). There were no significant differences within the median h-score values when the different molecular subtypes of vulvar cancer were compared (9 in p16+ve/p53wt versus 6 in p16-ve/p53mut versus 4 in p16-ve/p53wt ; p=0.079). Conclusion It has been shown that the antibody drug conjugate (ADC) topoisomerase-1-inhibitor irinotecan, coupled via a linker to a humanised IgG-1ntibody hRS7 binding to TROP-2 (i.e. sacitumzumab) represents an effective treatment approach to several carcinoma types. Virtually all examined VCX showed at least weak staining for TROP-2 within the tumor cells. So, TROP-2 may represent a potential target for ADC in vulval cancer. There are no differences of TROP-2 expression within the different molecular subtypes of VCX. Publication History Article published online: 21 June 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".