Presentation of underglycosylated mucin 1 in pancreatic adenocarcinoma (PDAC) at early stages.

Underglycosylated mucin 1 antigen (uMUC1) is a proven biomarker of cancer progression relevant to many malignancies including pancreatic ductal adenocarcinoma (PDAC). However, while ample evidence exists of the expression of total MUC1, little is known about the abundance of the underglycolsylated form of the antigen and its significance in disease progression. Such knowledge is important because the underglycosylated form of MUC1 is intimately linked to metastatic potential. Here, we investigated the expression uMUC1 at various stages of PDAC including pancreatic intraepithelial neoplasia (PanIN). Immunohistochemical analysis was performed on human tissue microarrays (TMAs) containing PDAC and PanIN using monoclonal antibody specific to uMUC1. uMUC1 expression was analyzed by a traditional pathological scoring system and using automatic imaging analysis software. Our results demonstrated low uMUC1 abundance in PanIN lesions and a transient increase in antigen availability in stage I PDAC, followed by decreased expression in later stages of the disease. An additional finding was that there was intermediate expression of uMUC1 in adjacent normal tissues from PDAC irrespective of the stage. These studies suggest the intriguing possibility that a pro-metastatic uMUC1 expression signature may appear at early stages of PDAC, providing an additional clue about the aggressive nature of pancreatic cancer.