Reappraisal of the Immunophenotype of Pancreatic Intraductal Papillary Mucinous Neoplasms (IPMNs)—Gastric Pyloric and Small Intestinal Immunophenotype Expression in Gastric and Intestinal Type IPMNs—

Abstract

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are mucin-producing neoplasms of the main and/or branch pancreatic ducts. To assess differences between various IPMN subtypes, immunohistochemical markers of gastric surface mucous cells (MUC5AC), gastric gland mucous cells (MUC6 and GlcNAcα1→4Galβ→R), gastric pyloric and duodenal epithelial cells (PDX1), intestinal cells (MUC2 and CDX2), small intestinal cells (CPS1) and large intestinal cells (SATB2) were evaluated in 33 surgically treated IPMNs. MUC2 expression classified IPMNs into gastric (n=17), intestinal (n=8) and mixed gastric and intestinal type (collision=7, composite=1). No differences in age or sex were observed among these types. MUC5AC and PDX1 were expressed in all IPMNs. MUC6 expression was higher in gastric and mixed types than in intestinal type. GlcNAcα1→4Galβ→R was detected in gastric and mixed type, but not in intestinal type. MUC2 and CDX2 expression were higher in intestinal type than gastric and mixed type. CPS1 expression was higher in intestinal type than gastric type. SATB2 was not observed in any IPMNs. Frequent abrupt transition between the two IPMN types in mixed-type IPMNs was observed. Gastric pyloric and small intestinal differentiation are characteristic of gastric and intestinal type IPMN, respectively, and these two IPMN types may have distinct pathogenesis.

A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas

“…Pancreatic cysts have a tendency to take on altered morphologies that reflect other tissue types [40], so the presence of αGlcNAc could indicate transdifferentiation of some sort. A previous study demonstrated positive staining for αGlcNAc in IPMNs mainly of the gastric type, suggesting its use as a marker of gastric differentiation [41], but we also observed it in IPMNs with intestinal differentiation. Future studies should further examine the origin and functions of the αGlcNAc epitope.…”

Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles

“…Our findings correlated with previous studies where MUC2 and CDX2 were seen in nonintestinal subtypes and most but not all intestinal subtypes had immunoreactivity with CDX2. 3,4 When CDX2 was classified as positive (defined as ≥ 10% immunoreactivity) in the intestinal subtypes though, all cases showed that ≥ 50% of the lesional cells were positive. In addition, a lack of staining may also be seen in areas with high-grade dysplasia.…”

“…The cases with o 80% interobserver agreement were categorized into IPMN subtypes using previously published immunohistochemical data on IPMN classification, when possible. 2,4 Immunohistochemical Studies All 50 cases of IPMN had immunohistochemical staining performed on 5-μm tissue sections from the same formalin-fixed, paraffin-embedded tissue block, which was selected for initial hematoxylin and eosin stained slide examination. MUC1 (MA695; NovoCastra, UK; 1:400), MUC2 (CCP58; NovoCastra; 1:25), MUC5AC (CLH2; NovoCastra; 1:25), MUC6 (CLH5; NovoCastra; 1:25), and CDX2 (CDX2-88; Biogenex, Fremont, CA, USA; 1:100) immunohistochemical staining was performed on all cases.…”

“…Additional studies observed MUC6 and CDX2 as useful gastric and intestinal markers in IPMNs, respectively. 3,4 Following categorization into histologic subtypes, multiple clinicopathological correlation studies were performed. Gastric subtype is commonly seen in branch duct IPMNs whereas intestinal and pancreatobiliary subtypes usually involve the main pancreatic duct.…”

Gastric gland mucin‐specific O‐glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer

“…In normal human pancreas, MUC6 and αGlcNAc are co‐expressed in periductal mucous gland cells of the main pancreatic duct . In addition, we and others reported that αGlcNAc is expressed in PanIN . However, the relationship between αGlcNAc expression and pancreatic tumor progression remains unknown.…”