FGFR3 Transcript and Protein Down-Regulation Is a Negative Prognostic Factor and Correlates with Promoter Methylation in Pancreatic Islet Cell Tumors.
Mehdi Nassiri, Sharon Ramos, Merce Jorda. Indiana University School of Medicine, Indianapolis; Univerisity of Miami, FL
Background: Prognostic factors for pancreatic islet cell tumors are few. Recently fibroblast growth factor receptor pathway role in endocrine neoplasm has been investigated and new drugs that affect this pathway have been introduced. We studied the expression of fibroblast growth factor receptor-3 (FGFR-3) and its correlation with clinical behavior of pancreatic islet cell tumors.
Design: Thirty-five cases of islet cell tumors were evaluated for hormone expression (gastrin, insulin, glucagon, ACTH, somatostatin, pancreatic polypeptide, calcitonin, serotonin and vasoactive intestinal polypeptide) and proliferation index (PCNA). FGFR-3 was studied by immunohistochemistry and quantitative real-time PCR. FGFR3 promoter region methylation was studied by MSP-PCR.
Results: Cytoplasmic expression of FGFR-3 was associated with lower proliferation index; 94% of cases with low PCNA score were positive for FGFR-3 vs. 35% of cases with high score (p<0.001). Less differentiated tumors (as evidenced by lack of hormone's expression) showed low or no expression FGFR-3 (p= 0.02), and loss of FGFR-3 expression was associated with metastasis (p= 0.02). FGFR3 transcript level correlated with its protein expression and promoter methylation status, as lower transcript levels were associated with promoter methylation and lower protein expression.
Conclusions: Decreased cytoplasmic expression of FGFR-3 is associated with less differentiated tumors; higher proliferation index and poor outcome in islet cell tumors and correlates well with decreased FGFR3 transcript level and promoter methylation.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 55, Tuesday Afternoon