TY - JOUR
T1 - Preferential expression of MUC6 in oncocytic and pancreatobiliary types of intraductal papillary neoplasms highlights a pyloropancreatic pathway, distinct from the intestinal pathway, in pancreatic carcinogenesis
AU - Basturk, Olca
AU - Khayyata, Said
AU - Klimstra, David S.
AU - Hruban, Ralph H.
AU - Zamboni, Giuseppe
AU - Coban, Ipek
AU - Adsay, Nazmi Volkan
PY - 2010/3
Y1 - 2010/3
N2 - The expression of different MUC glycoproteins has helped define cellular lineage in variety of pancreatic neoplasms, and has helped identify distinct carcinogenic pathways such as the intestinal pathway characterized by diffuse/strong MUC2/CDX2 expression in intestinal-type intraductal papillary mucinous neoplasms (IPMNs) and their associated colloid carcinomas (CCs). In this study, the expression profile of MUC6, a pyloric-type mucin, was investigated in both preinvasive and invasive pancreatic neoplasia. Florid papillary ("in-situ") components of 9 intraductal oncocytic papillary neoplasms (IOPNs), 24 IPMNs, and 7 mucinous cystic neoplasms (MCNs), were analyzed immunohistochemically for MUC6 expression, as were 15 PanINs, 112 usual invasive ductal adenocarcinomas (DAs), and 14CCs. In PanINs, MUC6 expression was limited to the very early areas of PanIN-1A that typically have pyloric features. Expression was lost in later stages. Similarly, in IOPNs or IPMNs or MCNs, MUC6 expression was detectable in the cystic or flat areas that have pyloric-like histology. However, in the more advanced (papillary) components of these neoplasms, MUC6 expression was mostly limited to the "cuboidal- cell" but was not seen in the "columnar-cell" phenotype: there was diffuse or strong expression in 8/9 IOPN and, relatively weaker but consistent expression in all 6/6 pancreatobiliary-type IPMNs; whereas virtually no expression in villous or intestinal-type IPMNs. The 7/8 gastric or foveolar-type IPMNs were also negative; in the single case with positivity, the labeling was limited to high-grade dysplastic areas. Interestingly, the papillae in MCNs were also mostly negative. Among invasive carcinomas, 39/112 DAs and only 1/14CC expressed MUC6. In DA, the expression did not correlate with survival (P=0.94), or any of the markers of aggressiveness: more than 2-cm tumor size (P=0.76), positive surgical margins (P=0.27), lymph node metastasis (P=0.82), or high grade (P=0.08). In conclusion: (1) The expression of MUC6 in oncocytic and pancreatobiliary-type neoplasms but not in villous or intestinal-type neoplasms supports the presence of a pyloropancreatic pathway distinct from the MUC2/CDX2 expressing intestinal pathway in intraductal papillary neoplasia. (2) MUC6 expression is present in the earliest (nonpapillary) form of any type of preinvasive neoplasia regardless of whether it is PanIN or IOPN or IPMN or MCN suggesting that these entities may share some characteristics early on, but evolve along divergent pathways as they progress.
AB - The expression of different MUC glycoproteins has helped define cellular lineage in variety of pancreatic neoplasms, and has helped identify distinct carcinogenic pathways such as the intestinal pathway characterized by diffuse/strong MUC2/CDX2 expression in intestinal-type intraductal papillary mucinous neoplasms (IPMNs) and their associated colloid carcinomas (CCs). In this study, the expression profile of MUC6, a pyloric-type mucin, was investigated in both preinvasive and invasive pancreatic neoplasia. Florid papillary ("in-situ") components of 9 intraductal oncocytic papillary neoplasms (IOPNs), 24 IPMNs, and 7 mucinous cystic neoplasms (MCNs), were analyzed immunohistochemically for MUC6 expression, as were 15 PanINs, 112 usual invasive ductal adenocarcinomas (DAs), and 14CCs. In PanINs, MUC6 expression was limited to the very early areas of PanIN-1A that typically have pyloric features. Expression was lost in later stages. Similarly, in IOPNs or IPMNs or MCNs, MUC6 expression was detectable in the cystic or flat areas that have pyloric-like histology. However, in the more advanced (papillary) components of these neoplasms, MUC6 expression was mostly limited to the "cuboidal- cell" but was not seen in the "columnar-cell" phenotype: there was diffuse or strong expression in 8/9 IOPN and, relatively weaker but consistent expression in all 6/6 pancreatobiliary-type IPMNs; whereas virtually no expression in villous or intestinal-type IPMNs. The 7/8 gastric or foveolar-type IPMNs were also negative; in the single case with positivity, the labeling was limited to high-grade dysplastic areas. Interestingly, the papillae in MCNs were also mostly negative. Among invasive carcinomas, 39/112 DAs and only 1/14CC expressed MUC6. In DA, the expression did not correlate with survival (P=0.94), or any of the markers of aggressiveness: more than 2-cm tumor size (P=0.76), positive surgical margins (P=0.27), lymph node metastasis (P=0.82), or high grade (P=0.08). In conclusion: (1) The expression of MUC6 in oncocytic and pancreatobiliary-type neoplasms but not in villous or intestinal-type neoplasms supports the presence of a pyloropancreatic pathway distinct from the MUC2/CDX2 expressing intestinal pathway in intraductal papillary neoplasia. (2) MUC6 expression is present in the earliest (nonpapillary) form of any type of preinvasive neoplasia regardless of whether it is PanIN or IOPN or IPMN or MCN suggesting that these entities may share some characteristics early on, but evolve along divergent pathways as they progress.
KW - Intestinal
KW - Intraductal
KW - Intraductal papillary mucinous neoplasm
KW - MUC6
KW - Mucinous cystic neoplasm
KW - Pancreas
KW - Papilla
KW - Pyloric
UR - http://www.scopus.com/inward/record.url?scp=77649197079&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649197079&partnerID=8YFLogxK
U2 - 10.1097/PAS.0b013e3181cf8bb6
DO - 10.1097/PAS.0b013e3181cf8bb6
M3 - Article
C2 - 20139757
AN - SCOPUS:77649197079
SN - 0147-5185
VL - 34
SP - 364
EP - 370
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 3
ER -