[1667] Molecular Characteristics and Biological Behavior of Intraductal Papillary-Mucinous Neoplasm, Oncocytic Type (IPMN-O)

HD Xiao, H Yamaguchi, D Dias-Santagata, Y Kuboki, S Akhavanfard, T Hatori, M Yamamoto, K Shiratori, M Kobayashi, M Shimizu, M Mino-Kenudson, T Furukawa. Massachusetts General Hospital, Boston; Saitama Medical University, Saitama, Japan; International Research and Educational Institute for Integrated Medical Sciences, Tokyo, Japan; Tokyo Women's Medical University, Tokyo, Japan

Background: Both IPMN-O and the pancreatobiliary type of IPMN (IPMN-PB) are usually diagnosed to have high-grade dysplasia with or without invasive components. However, since KRAS mutation has been reported to be absent in IPMN-O, some consider that IPMN-O is distinct form other types of IPMN. The aim of this study was to compare molecular alterations and biologic behavior between IPMN-O and IPMN-PB.
Design: Our cohort consisted of 12 IPMN-PBs and 18 IPMN-Os that were diagnosed and classified based on histologic and immunohistochemical evaluation. Point mutations of KRAS, BRAF and PIK3CA were studied using either multiplex PCR or by direct sequencing. Nuclear expression of p53 and ß-catenin, and loss of SMAD4 nuclear staining were assessed by immunohistochemistry. (Table 1) The results of molecular profile and clinical outcome were compared between the 2 types.
Results: KRAS mutation was identified in 17% of IPMN-Os and in 58% of IPMN-PBs. BRAF mutation was identified only in one IPMN-O. Loss of SMAD4, overexpression of p53 and nuclear ß-catenin expression were also found in a fraction of both types (IPMN-PB > IPMN-O) (Table 1).

Table 1

	IPMN-PB	IPMN-O
KRAS	7(58%)*	3(17%)*
BRAF	0	1(6%)
PIK3CA	0	0
SMAD4a	4(33%)	2(12%)
TP53b	7(58%)**	1(6%)**
β-cateninc	2(17%)	3(17%)

a: any loss of nuclear expression, b: presence of expression in > 30% of tumor cells, c: any nuclear expression, *: p<0.05, **: p<0.01.

92% of IPMN-PB and 50% of IPMN-O contained invasive adenocarcinoma. At the end of follow-up (1 to 165 months after resection), 4 patients with IPMN-PB and 2 with IPMN-O died of the disease. All showed invasive carcinoma. Although the overall survival was better in IPMN-O than in IPMN-PB (Kaplan-Meier survival analysis, p < 0.05), there was no difference in survival of cases with invasive components between the 2 types (p = 0.16).
Conclusions: The results of our study indicate that molecular alterations as well as biological behavior are not significantly different between IPMN-O and IPMN-PB, especially in those with invasive components. In addition, it is the first report demonstrating KRAS mutation in IPMN-O, thus supporting the notion that IPMN-O is not distinct from the other types of IPMN.
Category: Liver & Pancreas

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 218, Monday Morning