Immunohistochemical Analysis of the Progression of Flat Versus Tumoral Intraepithelial Neoplasia (Intracholecysitc Papillary-Tubular Neoplasm) in Gallbladder Carcinogenesis.
Kee-Taek Jang, Nevra Dursun, Olca Basturk, Juan Carlos Roa, Oscar Tapia, Paul Terry, NVolkan Adsay. Samsung MC, Seoul, Korea; Emory, GA; MSKCC, NY; UFRO, Temuco, Chile
Background: It is becoming clear that the dichotomy of “flat” versus “tumoral” intraepithelial neoplasia in early carcinogenesis, which has been well established in pancreatobiliary tract (pancreas;PanIN vs IPMN, and bile duct; BilIN vs IPNB) may also exist in the gallbladder in forms of conventional flat dysplasia/CIS versus intracholecystic papillary-tubular neoplasms (ICPN).
Design: We investigated IHC expression of MUC1 (biliary), MUC5AC (foveolar), MUC6 (pyloric), MUC2/CDX2 (intestinal) and p53 in the progression of these two pathways in 142 resected gallbladders (55 flat IN and 87 ICPNs, as well as 46 and 36 invasive carcinomas associated with these, respectively).
Results: The incidence of invasive carcinoma was significantly higher in flat IN than ICPN (p=0.001). MUC1 expression was also significantly higher in invasive carcinoma arising from flat IN (p=0.001) than in that of ICPN. Conversely, MUC6 expression was higher in ICPN (p=0.001) than flat IN, and there was no invasive carcinoma in flat IN with MUC6 expression. Intestinal differentiation markers of CDX2 or MUC2 were uncommon in both pathways, but if present, they occurred predominantly in the ICPN. There were no significant differences in MUC5AC and p53 expression between both groups. Separately, non-conventional types of invasive carcinoma occurred in 11.4% of ICPN (signet ring cell, 3; mucinous, 1; neuroendocrine carcinoma, 1) but those were uncommon in flat IN.
|ICPN||87||57 (66%)||11 (13%)||47 (54%)||35 (40%)*||25 (29%)|
|Flat IN||55||43 (78%)||3 (7%)||23 (42%)||2 (4%)||16 (29%)|
|Inv C-ICPN||35 (40%)||18 (51%)||4 (11%)||14 (40%)||7 (20%)||14 (40%)|
|Inv C-Flat IN||46 (84%)*||45 (98%)*||2 (4%)||25 (54%)||0||18 (38%)|