EGFR Expression in Pancreatic Adenocarcinoma. Relationship to Tumor Biology and Cell Adhesion Proteins
Adriana Handra-Luca, Pascal Hammel, Philippe Ruszniewski, Anne Couvelard. APHP Hôpital Avicenne, Université Paris Nord Sorbonne Cite, Bobigny, Ile de France, France; APHP Hôpital Bichat, Université Paris Nord Sorbonne Cite, Paris, Ile de France, France; APHP Hôpital Beaujon, Université Paris Nord Sorbonne Cite, Clichy, Ile de France, France
Background: In pancreatic ductal adenocarcinoma (PDAC), EGFR tumor expression has been reported to relate to an adverse outcome although with less relevance than VEGF, bcl2 bax or p16. The underlying mechanism is incompletely understood, possibly intricated since EGFR in PDAC relates to advanced tumor stage and metastases, to histological dedifferentiation and to cell proliferation proteins such as PCNA and cyclin D1.
Design: We aimed to study EGFR expression in surgically resected pancreatic ductal adenocarcinomas by immunohistochemistry and the relationship to clinicopathological features, cell proliferation and cell adhesion protein expression. A total of 99 PDAC were analysed on tissue microarrays for EGFR, E-cadherin, beta-catenin expression patterns in tumour cells. The percentage of cells expressing the three proteins (membrane, cytoplasmic, or nuclear pattern) and of Ki67 positive tumor cells was assessed. Tumour protein expression was studied with regard to clinicomorphological features, Ki67 index and for postsurgical survival.
Results: Membrane tumor EGFR correlated to histological dedifferentiation (poor differentiation), increased number of mitoses and severe tumor cell pleiomorphism (Fisher p<0.01, p=0.05, and p=0.03 respectively) as well as to aberrant adhesion protein expression such as nuclear beta catenin and cytoplasmic E-cadherin (Kendall p<0.01 tau 0.230 and p<0.01 tau 0.216). Cytoplasmic tumor E-cadherin correlated to a high Ki67 positive tumor cell component (Kendall p<0.01 tau 0.263) while nuclear E-cadherin to a shorter postsurgical overall survival (logrank p<0.01) as well as tumor necrosis and presence of an abundant clear cell component (logrank p<0.01 and p=0.03).
Conclusions: The results of our study suggest a complex role for EGFR in PDAC carcinogenesis, tumor expression of this protein being associated to tumor dedifferentiation, mitotic activity or pleiomorphism, as well as to aberrant tumor cell adhesion protein expression.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 164, Tuesday Afternoon