Adenosquamous Carcinoma of the Pancreas Harbors KRAS2, DPC4 and TP53 Molecular Alterations Similar to Pancreatic Ductal Adenocarcinoma
AK Witkiewicz, JB Brody, CL Costantino, CJ Yeo, PM McCue, RH Hruban. Thomas Jefferson University, Philadelphia, Philadelphia, PA; The Johns Hopkins University, Baltimore, MD
Background: Adenosquamous carcinoma of the pancreas is one of the most malignant forms of pancreatic cancer.There is a lack of comprehensive molecular information about this rare tumor. We analyzed the pathologic and molecular features of eight cases of pancreatic adenosquamous carcinomas.
Design: For KRAS2 and p16/CDKN2a mutational analysis, squamous and adenocarcinoma components of adenosquamous carcinomas were isolated by Laser Capture Microdissection . DNA sequencing was done by capillary gel electrophoresis. Immunohistochemistry was performed using the Envision Plus system (DAKO) with antibodies to DPC4 (Santa Cruz, 1:500), p53 (DAKO,1:100), E-cadherin (DAKO, 1:100), EGFR (Santa Cruz, 1: 100) and p16 (Novocastra, 1:100).
Results: We detected KRAS2 gene mutations in all cases, all at codon 12, in both the squamous and adenocarcinomatous portions. All cases also showed loss of p16 protein; in three of these it was due to p16/CDKN2a gene exon 2 homozygous deletion. The majority of cases had loss of Dpc4 protein and nuclear p53 staining similar to the molecular signature found in pancreatic ductal adenocarcinoma. E-cadherin was either lost or reduced in almost all cases and all cases were EGFR positive. The squamous component stained with p63 antibody and this antibody was helpful in identifying squamous differentiation in adenosquamous carcinomas with an acantholytic growth pattern.
Immunohistochemical profile of adenosquamous carcinoma defined as nuclear staining in >75% of tumor cells. <10% of the neoplastic cells labeled, labeling in 10-50%
Conclusions: In summary, although pancreatic adenosquamous and ductal adenocarcinoma have overlapping molecular characteristics, frequent loss of E-cadherin and higher percentage of EGFR expression could account for the more aggressive nature of this tumor and thus could be potential therapeutic targets.
Category: Liver & Pancreas
Tuesday, March 10, 2009 1:45 PM
Platform Session: Section E, Tuesday Afternoon