Abstract 5150: An immunohistochemical survey of predictive biomarkers for immunotherapy in ampullary carcinoma identifies strata with unique prognostic signatures
Bibliographic record
Abstract
Abstract Introduction: Carcinomas located in the ampulla of Vater are a low incidence malignancy. Therapeutic options for early stage disease largely consist of pancreaticoduodenectomy followed by adjuvant chemotherapy with or without radiation. We explored the localization of CD8 and CD3 positive cells in addition to PDL-1 staining and mismatch repair deficiency markers to gain insight into the potential applicability of immunotherapy for patients with this disease. Methods: Excess material from clinically diagnosed cases collected between 1997 - 2013 were used to construct a duplicate 0.6mm core tissue microarray (TMA). All cases were derived from the Vancouver Coastal Health Region. Immunohistochemical staining was performed with the following markers: CD8, CD3, PD-L1, and the mismatch repair (MMR) markers: MSH2, MSH6, MLH1 and PMS2. CD3 and CD8 were quantified using localization within the tissue. PD-L1 was considered positive with >1% of cells stating positive. MMR markers were confirmed using full section and cases with convincing loss of any MMR marker were considered MMR deficient. Univariable disease specific survival analysis was performed to identify unique prognostic signatures and contingency analysis was performed to identify co-expression of the aforementioned biomarkers. Results: Ninety-eight cases were evaluable for all markers. The median age of the cohort was 69 [41 - 84] years. Forty-two percent were female. Adjuvant chemotherapy was provided to 15% of patients with the remainder undergoing post-surgical observation. Almost 90% were pT3 or pT4 and 48% had regional lymph node metastasis. CD3+ T-cells were either localized in the tumor stroma only (59%) or in both the stroma and epithelial compartments (41%). CD8+ T-cells were principally located in the stroma (66%) and both the epithelial and stroma (24%). Ten percent of cases had no CD8+ T-cells. PD-L1 staining was found in 10% of cases. MMR deficiency was found in 5% of cases. Improved prognostic signatures were found for cases with CD3+ and CD8+ T-cells in both the epithelial and stromal compartments (p <= 0.02). A trend towards a negative prognostic signature was observed for MMR deficient cases and for PD-L1 positive cases. The only significant positive association between biomarkers was found for CD3+ and CD8+ in both the epithelial and stromal compartments. Conclusions: The results of this analysis suggest that enhancement of an immune response yielding an increase CD3+ and CD8+ T-cells in the epithelial compartment may have a beneficial effect on prognosis. The relative scarcity of MMR deficiency in this disease is within the expected prevalence supported by other studies. Further exploration of the potential role of immunotherapy in immune enhanced subgroups of ampullary cancers is warranted. Citation Format: Steve E. Kalloger, Joanna Karasinska, James Topham, Daniel J. Renouf, David F. Schaeffer. An immunohistochemical survey of predictive biomarkers for immunotherapy in ampullary carcinoma identifies strata with unique prognostic signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5150.
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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 | 0.001 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".