Abstract 4603: Monoclonal P40 antibody BC28 identifies neoplastic cells with basal-like differentiation in a subset of pancreatic ductal adenocarcinoma

Abstract Background: Transcriptomic analysis of pancreatic ductal adenocarcinoma (PDAC) has identified classical and basal-like subtypes of PDAC as discrete entities with distinct outcomes that require transcriptomic analysis for accurate diagnosis. Adenosquamous carcinoma of the pancreas (ASPC) is a histologic variant of pancreatic cancer with a basal-like transcriptomic phenotype and a distinctly poor prognosis. Current guidelines for diagnosing ASPC require the presence of at least 30% squamous component. We hypothesized that classical and basal-like PDAC may exist along a spectrum with ASCP at one end. DeltaNp63 (P40) immunohistochemistry (IHC) is an excellent marker for diagnosing primary lung squamous cell carcinoma. The use of P40 IHC in pancreatic carcinoma is less well established. This study was performed to determine the percentage P40 positive cells in ASCP and PDAC. Method: Archived tissue slides and blocks from patients with PDAC (N = 58) and ASPC (N = 3) were retrieved from the files of Hoag Hospital using Hoag tumor registry data. Tissue sections of selected blocks from each case were stained by IHC using monoclonal anti-P40 antibody clone BC28 (Abcam, Waltham, Mass). IHC staining was performed with the BOND III automated immunostainer (Leica Biosystems, Nusslock, Germany). Any neoplastic cells with strong nuclear P40 staining were considered P40+. For tumors with P40+ neoplastic cells, the percentage of tumor surface area that contained P40+ neoplastic cells was estimated and the percentage of P40+ cells within the P40 positive component was estimated. IRB approval was obtained to conduct the study with exemption for patient consent. Results: Greater than 90% of the surface area and >90% of the tumor cells in each ASCP tumor studied were P40 positive. Within the 58 PDAC, 12 cases (21%) contained P40 positive tumor cells. The median percentage of P40 positive cells within the P40+ PDAC components was 3.5%. P40 positive cells were distributed focally in 10 cases and diffusely in 2 cases. In PDAC cases with focal P40 staining, the P40+ components represented between 5% and 50% of the total surface area of the tumor. Most P40+ neoplastic cells in PDAC were cytologically indistinguishable from P40 negative tumor cells, but a subset had a flattened shape and peripheral distribution within the neoplastic glands reminiscent of basal cells. The median length of follow-up/survival in the study cohort was 18 months. Thirty-one of the PDAC patients were alive and 24 were dead. The survival status of 3 patients was not recorded in the registry data. 42% of PDAC patients with P40+ cells were alive at the time of study whereas 60% of patients with P40 negative PDAC were alive, but this difference did not reach statistical significance. Conclusions: These findings support the hypothesis that a subset of PDAC contains a minor population of neoplastic cells with basal-like differentiation. Citation Format: Sourat Darabi, Derek Cridebring, Daniel Von Hoff, Haiyong Han, Michael J. Demeure, F. Scott Heinemann. Monoclonal P40 antibody BC28 identifies neoplastic cells with basal-like differentiation in a subset of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4603.