Fas and Fas Ligand Expression in Pancreatic Adenocarcinoma
Nat Pernick, Fazlul H. Sarkar, Pam Tabaczka, Glenn Kotcher, John Frank, Volkan Adsay
Abstract
Nat Pernick, Fazlul H. Sarkar, Pam Tabaczka, Glenn Kotcher, John Frank, Volkan Adsay
Abstract
INTRODUCTION: Fas and Fas ligand (FasL) mediate apoptosis of tumor cells in immune surveillance, and expression of FasL by tumors may mediate their counterattack on cytotoxic lymphocytes. Both proteins are expressed in most if not all pancreatic carcinoma cell lines, but their study in primary human tumors has been limited. AIM: We performed Fas and FasL immunohistochemical staining on 81 primary pancreaticobiliary or ampullary ductal adenocarcinomas of patients in our institutional database to determine the extent and strength of staining. METHODOLOGY: The expression of Fas and FasL was compared with regard to clinicopathologic variables, K- mutations, and immunoexpression of HER2, p21, p27, and p53. RESULTS AND CONCLUSION: Fas was expressed in 19% of patients with strong or intermediate intensity but with variable percentages of tumor cell staining. FasL was expressed in 49% of patients, usually with diffuse expression but variable intensity. Fas expression was more common in women than men, as women had 93% of Fas-positive tumors but only 55% of Fas-negative tumors ( = 0.007), and was associated with strong HER2 expression (67% of Fas-positive versus 18% of Fas-negative patients; = 0.04). Fas expression tended to be less common in blacks (4% had Fas-positive tumors) than whites (22% had Fas-positive tumors; = 0.052). FasL expression tended to be associated with stage 4 disease at diagnosis (24% versus 0%; = 0.07). Neither Fas expression nor FasL expression was associated with survival, a circumstance suggesting that their role, if any, in contributing to the aggressiveness of these tumors is complex.
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INTRODUCTION: Fas and Fas ligand (FasL) mediate apoptosis of tumor cells in immune surveillance, and expression of FasL by tumors may mediate their counterattack on cytotoxic lymphocytes. Both proteins are expressed in most if not all pancreatic carcinoma cell lines, but their study in primary human tumors has been limited. AIM: We performed Fas and FasL immunohistochemical staining on 81 primary pancreaticobiliary or ampullary ductal adenocarcinomas of patients in our institutional database to determine the extent and strength of staining. METHODOLOGY: The expression of Fas and FasL was compared with regard to clinicopathologic variables, K- mutations, and immunoexpression of HER2, p21, p27, and p53. RESULTS AND CONCLUSION: Fas was expressed in 19% of patients with strong or intermediate intensity but with variable percentages of tumor cell staining. FasL was expressed in 49% of patients, usually with diffuse expression but variable intensity. Fas expression was more common in women than men, as women had 93% of Fas-positive tumors but only 55% of Fas-negative tumors ( = 0.007), and was associated with strong HER2 expression (67% of Fas-positive versus 18% of Fas-negative patients; = 0.04). Fas expression tended to be less common in blacks (4% had Fas-positive tumors) than whites (22% had Fas-positive tumors; = 0.052). FasL expression tended to be associated with stage 4 disease at diagnosis (24% versus 0%; = 0.07). Neither Fas expression nor FasL expression was associated with survival, a circumstance suggesting that their role, if any, in contributing to the aggressiveness of these tumors is complex.
Key concepts: Fas ligand, Apoptosis, Immunohistochemistry, Pathology, Fas receptor, Cancer research, Immune system, Medicine