[1855] Immunophenotypic and Molecular Alterations in the Carcinogenetic Progression of Mucinous Cystic Neoplasm of the Pancreas

Kee-Taek Jang, Yoon La Choi, Charles Hill, Edward Stelow, Dustin Walters, Olca Basturk, Pelin Bagci, Giuseppe Zamboni, David S Klimstra, Ralph H Hruban, Volkan Adsay. Emory U, Atlanta; SMC, Seoul, Korea; UVA, Charlottesville; MSKCC, New York; U of Verona, Verona, Italy; JHU, Baltimore

Background: Mucinous cystic neoplasm (MCN) is one of the precursors of invasive pancreatic carcinoma. The molecular alterations that take place during the progression of MCNs, however, have not been fully elucidated, with most of the literature focusing on the non-invasive examples.
Design: Immunolabeling of MUC1, MUC2, MUC5AC, MUC6, CDX2, and p53 were examined in 40 MCNs, consisting of 9 low-grade, 8 high-grade and 23 with an associated invasive carcinoma. Mutational analysis for BRAF and KRAS was performed in 15 (4; low-grade, 6; high-grade, 5; invasive).
Results: Among low-grade MCNs, 4 of 9 (44%) expressed MUC5AC and MUC6, but MUC1/MUC2/CDX2 were negative in all. MUC1 was expressed in 50% (4/8) of high-grade and 92% (20/23) of invasive carcinoma. However, MUC2/5AC/6 and CDX2 expression was rarely identified in either high-grade or invasive cases. p53 was expressed in 25% (2/8) high-grade and 39% (9/23) invasive carcinoma, but not in low-grade MCNs. Immunophenotypic changes are summarized in Table 1. No BRAF mutations were identified, but KRAS was mutated in 5 of 6 high-grade and 5 of 5 invasive carcinoma (Table 2).

Immunophenotypic changes of MCN

	MUC1	MUC2	CDX2	MUC5AC	MUC6	P53
Low-grade (n=9)	0	0	0	4/9 (44%)	4/9 (44%)	0
High-grade (n=8)	4/8 (50%)	1/8 (13%)	1/8 (13%)	0	2/8 (25%)	2/8 (25%)
Invasive carcinoma (n=23)	20/23 (92%)	0	0	2/23 (9%)	1/23 (4%)	9/23 (39%)

Mutational study of BRAF and KRAS in MCN

	Low-grade (n=4)	High-grade (n=6)	Invasive carcinoma (n=4)
BRAF	0	0	0
KRAS	0	5/6	5/5

Conclusions: At immunohistochemical and molecular levels, MCN pathway of carcinogenesis in the pancreas shows various parallels with that of PanIN pathway and is dissimilar to intraductal papillary mucinous neoplasms: While gastric-lineage markers (MUC5AC/6) are expressed in low-grade lesions, these are replaced by MUC1 as the disease progresses, and p53 and KRAS also play a role in the carcinomatous transformation. By contrast BRAF mutation is not involved in MCN carcinogenesis.
Category: Pancreas

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 264, Tuesday Morning