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Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic ductal adenocarcinomas are frequently of gastric subtype.
Ann Surg 2013; 258(1):141-51AnnS

Abstract

OBJECTIVE

To identify a high-risk group of patients with pancreatic ductal adenocarcinoma (PDAC), independently arising in the pancreas with intraductal papillary mucinous neoplasm (IPMN), using histopathologic subtypes.

BACKGROUND

Pathologic features of IPMN with distinct PDAC, including histopathologic subtypes of IPMN and PDAC phenotypes, have not been well characterized. Mucin expression patterns and the mutational status of GNAS and KRAS are useful to explore the relationship between these 2 lesion types.

METHODS

Clinicopathologic data of 179 resected IPMNs and 180 resected PDACs without IPMNs as a control group were reviewed. IPMNs were classified into 4 grades (low-grade, intermediate-grade, high-grade dysplasia, and an associated invasive carcinoma) and 4 subtypes (gastric, intestinal, pancreatobiliary, and oncocytic). The expression of MUC1, MUC2, MUC5AC, MUC6, and CDX2 was investigated by immunohistochemistry in IPMNs and PDACs with and without IPMNs. The mutational status of GNAS and KRAS was evaluated by cycle sequencing in PDACs and pre-/coexisting IPMNs.

RESULTS

Twenty-six synchronous or metachronous PDACs were identified in 20 patients (11.2%) with IPMNs. Occurrence of concomitant PDACs was more frequently observed in gastric-type IPMNs (18/110, 16.4%) compared with intestinal (1/49, 2.0%), pancreatobiliary (1/17, 5.9%), or oncocytic-type (0/3, 0%) (P = 0.047). Both PDACs with and without IPMNs were frequently positive for MUC1, MUC5AC, and MUC6 expression, as assessed by immunohistochemistry, but were negative for MUC2 and CDX2. The mucin-staining patterns were similar to those of invasive tubular adenocarcinoma arising from gastric-type IPMNs. Mutation of GNAS within codon 201 was not detected in PDACs and gastric-type IPMNs, whereas most of these exhibited KRAS mutations. However, the R201H GNAS mutation was detected in 1 intestinal-type IPMN with distinct PDAC.

CONCLUSIONS

Mucin expression patterns demonstrate that PDAC without GNAS mutations of an aggressive phenotype frequently arise in the pancreas with benign gastric-type IPMN in the absence of GNAS mutations.

Authors+Show Affiliations

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23532108

Citation

Ideno, Noboru, et al. "Intraductal Papillary Mucinous Neoplasms of the Pancreas With Distinct Pancreatic Ductal Adenocarcinomas Are Frequently of Gastric Subtype." Annals of Surgery, vol. 258, no. 1, 2013, pp. 141-51.
Ideno N, Ohtsuka T, Kono H, et al. Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic ductal adenocarcinomas are frequently of gastric subtype. Ann Surg. 2013;258(1):141-51.
Ideno, N., Ohtsuka, T., Kono, H., Fujiwara, K., Oda, Y., Aishima, S., ... Tanaka, M. (2013). Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic ductal adenocarcinomas are frequently of gastric subtype. Annals of Surgery, 258(1), pp. 141-51. doi:10.1097/SLA.0b013e31828cd008.
Ideno N, et al. Intraductal Papillary Mucinous Neoplasms of the Pancreas With Distinct Pancreatic Ductal Adenocarcinomas Are Frequently of Gastric Subtype. Ann Surg. 2013;258(1):141-51. PubMed PMID: 23532108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic ductal adenocarcinomas are frequently of gastric subtype. AU - Ideno,Noboru, AU - Ohtsuka,Takao, AU - Kono,Hiroshi, AU - Fujiwara,Kenji, AU - Oda,Yasunori, AU - Aishima,Shinichi, AU - Ito,Tetsuhide, AU - Ishigami,Kousei, AU - Tokunaga,Shoji, AU - Ohuchida,Kenoki, AU - Takahata,Shunichi, AU - Nakamura,Masafumi, AU - Mizumoto,Kazuhiro, AU - Tanaka,Masao, PY - 2013/3/28/entrez PY - 2013/3/28/pubmed PY - 2013/8/28/medline SP - 141 EP - 51 JF - Annals of surgery JO - Ann. Surg. VL - 258 IS - 1 N2 - OBJECTIVE: To identify a high-risk group of patients with pancreatic ductal adenocarcinoma (PDAC), independently arising in the pancreas with intraductal papillary mucinous neoplasm (IPMN), using histopathologic subtypes. BACKGROUND: Pathologic features of IPMN with distinct PDAC, including histopathologic subtypes of IPMN and PDAC phenotypes, have not been well characterized. Mucin expression patterns and the mutational status of GNAS and KRAS are useful to explore the relationship between these 2 lesion types. METHODS: Clinicopathologic data of 179 resected IPMNs and 180 resected PDACs without IPMNs as a control group were reviewed. IPMNs were classified into 4 grades (low-grade, intermediate-grade, high-grade dysplasia, and an associated invasive carcinoma) and 4 subtypes (gastric, intestinal, pancreatobiliary, and oncocytic). The expression of MUC1, MUC2, MUC5AC, MUC6, and CDX2 was investigated by immunohistochemistry in IPMNs and PDACs with and without IPMNs. The mutational status of GNAS and KRAS was evaluated by cycle sequencing in PDACs and pre-/coexisting IPMNs. RESULTS: Twenty-six synchronous or metachronous PDACs were identified in 20 patients (11.2%) with IPMNs. Occurrence of concomitant PDACs was more frequently observed in gastric-type IPMNs (18/110, 16.4%) compared with intestinal (1/49, 2.0%), pancreatobiliary (1/17, 5.9%), or oncocytic-type (0/3, 0%) (P = 0.047). Both PDACs with and without IPMNs were frequently positive for MUC1, MUC5AC, and MUC6 expression, as assessed by immunohistochemistry, but were negative for MUC2 and CDX2. The mucin-staining patterns were similar to those of invasive tubular adenocarcinoma arising from gastric-type IPMNs. Mutation of GNAS within codon 201 was not detected in PDACs and gastric-type IPMNs, whereas most of these exhibited KRAS mutations. However, the R201H GNAS mutation was detected in 1 intestinal-type IPMN with distinct PDAC. CONCLUSIONS: Mucin expression patterns demonstrate that PDAC without GNAS mutations of an aggressive phenotype frequently arise in the pancreas with benign gastric-type IPMN in the absence of GNAS mutations. SN - 1528-1140 UR - https://www.unboundmedicine.com/medline/citation/23532108/Intraductal_papillary_mucinous_neoplasms_of_the_pancreas_with_distinct_pancreatic_ductal_adenocarcinomas_are_frequently_of_gastric_subtype_ L2 - http://Insights.ovid.com/pubmed?pmid=23532108 DB - PRIME DP - Unbound Medicine ER -