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).
|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%)|
|Low-grade (n=4)||High-grade (n=6)||Invasive carcinoma (n=4)|