Mucin 5AC expression is common but unrelated to tumor progression in pancreatic adenocarcinoma

Abstract

Introduction: Mucin 5AC (MUC5AC) belongs to the family of secreted gel-forming mucins. It is physiologically expressed in some normal mucin producing epithelial cells but also in pancreatic, ovarian, and colon cancer cells. The role of MUC5AC expression in cancer is not fully understood. This study was designed to explore the role of MUC5AC for pancreatic cancer progression, its association to microsatellite instability, and its diagnostic utility. Methods: Mucin 5AC expression was studied immunohistochemically in a tissue microarray (TMA) from 532 pancreatic cancers, 61 cancers of the ampulla Vateri, six acinar cell carcinomas and 12 large sections of pancreatitis. Results: Mucin 5AC staining was interpretable in 476 of 599 (79%) arrayed cancers. Staining was completely absent in normal pancreas and pancreatitis, but frequent in pancreatic cancer. Membranous and cytoplasmic MUC5AC expression was most common in pancreatic adenocarcinomas (71% of 423), followed by carcinomas of the ampulla Vateri (43% of 47), and absent in six acinar cell carcinomas. Mucin 5AC expression was unrelated to tumor phenotype (tumor stage, tumor grade, lymph node, and distant metastasis), and microsatellite instability in ductal adenocarcinomas and carcinomas of the ampulla Vateri. Conclusion: Our study indicates that MUC5AC is an excellent biomarker for pancreatic cancer diagnosis, especially to support the sometimes-difficult diagnosis on small biopsies. Mucin 5AC expression is unrelated to pancreatic cancer aggressiveness.

Differential Expression and Diagnostic Value of MUC5AC Glycoforms in Pancreatic Ductal Adenocarcinoma

“…Our study shows MUC5AC (combination of IM and MM) has low SN (59%) and high SP (96%) to diagnose PDA from non-PDA tissues (NET + non-NpD). MUC5AC was not expressed in normal and pancreatitis tissues, and it was detected in PDA which is consistent with prior studies [11,13,15]. Inflammatory responses do not seem to trigger MUC5AC production.…”

“…The heterogeneity of MUC5AC expression in tumors (MM > IM) as seen in our study is confirmed by other studies, and it is interesting to note that more than half of patients positive for MM could have been missed if just one core was used for examination [17]. This raises a question of whether this could be the reason for inconclusive results noted in previous TMA-based studies with just one core [11,13,16].…”

“…Among the PTs, IM detection (66%) was similar to other studies in the literature, but MM expression was low (47%) [10,11,17,18]. A study published two decades ago that used different MM clones, 21-M1 and Nd-2, showed a prevalence of 92% and 68%, respectively [17].…”

“…We assessed the diagnostic value of MM and IM, individually and in combination, to distinguish NpD from non-NpD and PDA from non-PDA. This study is in line with prior TMA based studies that studied IM expression in various pancreatic disease groups, but for the first time the focus was on the differential expression (MM vs. IM) of the glycoforms for diagnosis and prognosis in PDA [11,13].…”

“…The IM expression-based studies could distinguish abnormal pancreatic tissues, including PDA, mucinous cystic neoplasms, intraductal papillary mucinous neoplasm (IPMN), and metaplastic pancreatic duct epithelium from normal pancreatic tissues but did not give conclusive results on its predictive and prognostic value [6,10]. As we argued in our recent reviews, the impact of MUC5AC expression on PDA outcomes is unclear as the published studies did not explore the clinical significance of MM as a potential diagnostic, prognostic (survival or aggressive clinicopathological characteristics), or predictive biomarker (treatment response) [6,11]. There is strong preclinical evidence suggesting MM offers gemcitabine resistance to PDA; it was first reported by Krishn et al but escaped attention as none of the prior studies were designed to examine it [12].…”