Abstract A015: Tissue MUC5AC expression predicts recurrence patterns following resection in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDA) has consistently poor outcomes, even for early-stage tumors that undergo resection (>70%), despite completion of prescribed perioperative systemic therapy. Mucin 5AC (MUC5AC), a heavy glycoprotein, exists in two major glycoforms: heavily glycosylated mature (MM) and less glycosylated immature (IM) forms. MM is located in the apical region and extracellular space, whereas IM is in the perinuclear region. Our previous work demonstrated the association between MM and treatment response and outcomes in resected PDA after neoadjuvant therapy (NAT). In this study, we investigate the impact of MUC5AC tissue expression in resected PDA samples on recurrence site characteristics (local (LR) vs. distant metastasis (mets) vs. both LR and mets). Resected PDA formalin-fixed paraffin-embedded tissue blocks from January 2010 to June 2021 were obtained from the Ohio State University biorepository. Immunohistochemistry was performed to study the expression for MM and IM using monoclonal antibodies 45M1 and CLH2, respectively, and H-scores (0-300) were calculated. Logistic regression was used to study this association of interest. We had 100 R-PDA (43 received NAT, and 57 had upfront surgery (UpS)) available for testing. The median age of diagnosis was 65 years, and 50% were males. Most of the patients in the NAT group received FOLFIRINOX (n=36) and received gemcitabine/nab-paclitaxel (n=5) or FOLFOX (n=2). The median number of doses received is 6 (range 2-9). The results in these groups can be summarized as follows: a) 35/43 had recurrence (LR=7, mets=21, and LR+mets=7), with the liver being the most common site of metastasis (13/28) followed by lung (5/28) and peritoneum (5/28), b) Higher IM expression (mean H-score) was significantly (p=0.0275) higher in LR+mets (H-score 196) than in LR (H-score 69) or mets (H-score 115) groups, c) Higher MM expression (mean H-score) was also significantly different among these groups (LR vs. mets vs. LR+mets = 81 vs. 120 vs. 206, p= 0.0358), e) similar trend of mean H-scores was noted in FOLFIRINOX sub-group (LR vs. mets vs. LR+mets = 205 vs. 109 vs. 60, p=0.0185 for IM and 65 vs. 116 vs. 205, p=0.0329 for MM). No significant association between recurrence patterns and tissue MUC5AC expression in the UpS group. These findings concur with our prior observations, underscoring the clinical significance of MUC5AC in resected PDA post-NAT and suggesting its potential role in facilitating pancreatic tumor cell metastasis. Although larger prospective studies are needed to confirm these results, our study highlights MUC5AC as a potential therapeutic target to prevent metastasis in early-stage PDA, potentially improving overall outcomes. Citation Format: Ashish Manne, Lianbo Yu, Ashwini Esnakula. Tissue MUC5AC expression predicts recurrence patterns following resection in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A015.