title: Stromal thrombospondin-1 expression is a prognostic indicator and a new marker of invasiveness in intraductal papillary-mucinous neoplasm of the pancreas.
abstract: The invasion of intraductal papillary-mucinous neoplasm (IPMN) is sometimes difficult to diagnose using only ordinary hematoxylin-eosin sections. The aim of this study was to evaluate the invasion of IPMN more precisely using thrombospondin-1 (TSP1) immunohistochemistry as a useful adjunct to morphological examination. Eighty patients that underwent primary resection for pancreatic IPMNs were retrospectively analyzed. The 80 IPMNs were studied for the expression of TSP1, MUC1-CORE, MUC2, and MUC5AC. The cases were evaluated for dysplasia, the presence of invasion, hisological subtypes, and survival. The 80 IPMNs were classified into 29 intraductal papillary-mucinous adenomas (IPMAs), 10 borderline IPMNs, 18 noninvasive intraductal papillary-mucinous carcinomas (IPMCs), and 23 invasive IPMCs according to the WHO classification. Invasive IPMCs were further divided into 12 minimally invasive IPMCs (MI-IPMCs) and 11 invasive carcinomas originating from IPMCs (IC-IPMCs) according to the Japan Pancreatic Society classification. The rate of strongly positive cases with more than 30% of the cancer stroma area expressing TSP1 was significantly higher in MI-IPMC and IC-IPMC than in noninvasive IPMC (P = 0.035, 0.005). Furthermore, patients in the strongly positive group had a significantly poorer prognosis compared to patients in the negative-weakly positive group (P = 0.008, log-rank test). Of the 80 tumors, 22 were classified into gastric-, 45 into intestinal-, 7 into pancreatobiliary-, and 6 into oncocytic-type IPMNs according to criteria described previously. The cases with a strongly positive expression of TSP1 were frequently detected in the pancreatobiliary and oncocytic types (P = 0.001). In conclusion, stromal TSP1 expression is a prognostic indicator and a new marker of invasiveness in IPMN.
authors.affiliation: Department of Surgery, Tokai University School of Medicine, Isehara, Kanagawa, Japan. okada@is.icc.u-tokai.ac.jp
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Okada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Naoki
authors.initials: N
authors.lastname: Yazawa
authors.forename: Shoichi
authors.initials: S
authors.lastname: Dowaki
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tobita
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohtani
authors.forename: Makiko
authors.initials: M
authors.lastname: Tanaka
authors.forename: Sadaki
authors.initials: S
authors.lastname: Inokuchi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Makuuchi
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000145:classification / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000145:classification / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D015996:Survival Rate; D019700:Thrombospondin 1 / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D019700:Thrombospondin 1