Expression of Amphiregulin, Epidermal Growth Factor Receptor (EGFR) and Phosphorylated EGFR in Ampullary Carcinoma
Kaidi Mikhitarian, Nipun Merchant, Frank Revetta, Chanjuan Shi. Vanderbilt University Medical Center, Nashville
Background: Most ampullary carcinomas have either pancreaticobiliary or intestinal type morphology. Activation of the EGFR signaling pathway has been implicated in both pancreatic and intestinal carcinogenesis. In addition, amphiregulin (AR) is thought to be an important ligand for EGFR activation in colorectal cancer. The contribution of the EGFR signaling pathway in the development of ampullary carcinoma has not been established.
Design: Fifty two surgically resected ampullary carcinomas were immunohistochemically labeled for AR, EGFR, and phosphorylated EGFR (pEGFR). The results were correlated with pathologic type and tumor stage. Fisher's exact test was used to determine significant association.
Results: The pathologic types included pancreaticobiliary type (14/52, 27%), intestinal type (33/52. 63%), and rare variants (5/52, 10%). The rare variants were 1 signet ring cell carcinoma, 3 mucinous carcinomas and 1 adenosquamous carcinoma. Five of 14 pancreaticobiliary type tumors showed a very prominent papillary architecture. Overall, moderate to strong AR expression was observed in 33 of 52 (64%) cases. This expression was more common in the intestinal type (75%) than in the pancreaticobiliary type without prominent papillae (33%, p<0.05). However, 4 of 5 pancreatobiliary type carcinomas with prominent papillae showed strong AR expression. EGFR and pEGFR were labeled in 14 (26.9%) and 11 (21.2%) of 52 ampullary carcinomas, respectively. While no difference in EGFR expression was observed between two major pathologic types (43% versus 19%, p>0.05), more pancreaticobiliary type (43%) had activated EGFR than the intestinal type (9%, p<0.05). Interestingly, three mucinous adenocarcinomas showed no expression of AR, EGFR or pEGFR. The expression of AR was not correlated to that of pEGFR, whereas EGFR labeling was significantly associated with activation of EGFR (p<0.05). Neither AR labeling nor EGFR activation was correlated with tumor stage (p>0.05).
Conclusions: Activation of EGFR may play a role in carcinogenesis in a subset of ampullary carcinomas. While AR is commonly expressed in the intestinal type carcinomas, it does not appear to be a key ligand for activation of EGFR in ampullary carcinomas.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 256, Wednesday Morning