Abstract C008: MUC16 expression in pancreatic ductal adenocarcinoma patient samples after neoadjuvant chemotherapy

Abstract

Abstract Purpose Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with low five-year survival rates. Currently, surgical resection is the only potentially curative treatment available to patients. However, few patients are eligible for surgery without receiving prior therapy due to disease progression. Of those that receive upfront surgery, up to 60% develop recurrent disease within 5 years. Therefore, there is a need to increase the rate of complete surgical resections and the number of eligible patients for surgery. In the last decade, neoadjuvant therapy or treatment prior to surgery has increased for patients diagnosed with borderline resectable and locally advanced PDAC. Often, this therapy consists of chemotherapy alone or chemoradiotherapy treatment intended to downstage the tumor and reduce micrometastatic disease. Fluorescence-guided surgery (FGS) is a potential tool to increase the rate of complete surgical resections by specifically targeting a protein biomarker upregulated in the tumor with a fluorescent dye conjugated probe. Previous in vitro and in vivo research from our lab has indicated that the transmembrane mucin, MUC16, is a promising target for FGS in PDAC. However, protein expression has the potential to deviate after chemotherapy treatment. Therefore, this research aimed to determine the effect of neoadjuvant chemotherapy treatment (NCT) on the FGS-targetable biomarker, MUC16, in PDAC patient specimens. Experimental Procedures Deidentified PDAC and matched adjacent patient specimens receiving the NCT regimen or surgery-first treatment were obtained from UNMC Pathology and the UNMC Paraffin Tissue Bank. Deidentified normal pancreas specimens were received from the Normal Organ Recovery program, UNMC. MUC16 expression was investigated in each specimen. The presence of PDAC tumor and MUC16 stain expression patterns were confirmed by a specimen-blinded, board-certified pathologist. The expression of MUC16 between the NCT, surgery-first, and normal pancreas specimens was compared via statistical analysis. Results MUC16 was expressed in both the NCT and surgery-first specimens. There was a significant difference in MUC16 expression between the NCT specimens and both the normal pancreas (P = 0.0450) and surgery-first (P = 0.0494) specimens. In matched adjacent tissue, MUC16 expression was found to be higher in the NCT (P = 0.0003) and surgery-first (P = 0.1446) tumor specimens allowing for distinct tumor margins; however, this difference was not significant in the surgery-first specimens. Conclusions MUC16 expression retention in NCT PDAC specimens may indicate that MUC16 is a stable biomarker after chemotherapy treatment. Distinct MUC16 expression between tumor and matched adjacent specimens indicates the ability to achieve distinguishable tumor margins allowing for complete tumor resection. Therefore, MUC16 remains targetable for FGS in chemotherapy-treated patients. This has the potential to broaden the benefiting patient population and increase the number of patients that may undergo a complete surgical resection. Citation Format: Kathryn M. Muilenburg, Evie G. Ehrhorn, Madeline T. Olson, Carly C. Isder, Kelsey A. Klute, Geoffrey A. Talmon, Mark A. Carlson, Quan P. Ly, Aaron M. Mohs. MUC16 expression in pancreatic ductal adenocarcinoma patient samples after neoadjuvant chemotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C008.