RELATIONSHIP OF FAMILY CANCER HISTORY TO THE EXPRESSION OF P53, P21(WAF-1), HER-2 NEU, AND K-RAS MUTATION IN PANCREATIC ADENOCARCINOMA/

Conclusion. In our series of 81 cases, a history of family cancer was present in 52% of patients (42/81) with pancreatic cancer, Nine percen t (7/81) had a family history of pancreatic cancer, Our studies sugges t a possible relationship of family cancer history to the expression o f p53 and p21WAF in pancreatic tumors, but show no relationship to the expression of HER-2/neu or to the prevalence of K-ras mutations, A lo wer incidence of p53 expression observed in patients with a family his tory of cancer suggests normal p53 protein is present in a majority of patients who develop pancreatic tumors related to other-as yet uniden tified-inherited or familial risk factors, There was no significant di fference in survival of pancreas cancer patients with and without a fa mily history of cancer, However, survival in pancreas cancer patients may be influenced (improved) by p21(WAF-1) expression, Background. Pan creas cancer is the fifth leading cause of cancer deaths (27,800 death s/yr) in the United States. Various risk factors, including cigaret sm oking, high-fat diet, DDT exposure, chronic pancreatitis, and diabetes mellitus, have been associated with pancreatic carcinoma. A few studi es have suggested a genetic predisposition or increased risk for pancr eatic cancer within families, but the exact etiology is largely unknow n. In a series of 81 patients with pancreatic carcinoma, we analyzed t he status of K-ras gene mutations and the expression of p21(WAF-1), p5 3, and HER-2/neu protein to identify possible molecular associations i n pancreas cancer cases of these molecular markers to family histories of cancer and pancreas cancer. Methods. Paraffin-embedded tissue sect ions from 81 cases of pancreatic adenocarcinoma were used for DNA extr action and immunohistochemical staining. K-ms mutation was studied by single-stranded conformation polymorphism (SSCP) and slot-blot allele- specific oligonucleotide (ASO) hybridization of PCR-amplified DNA prod uct. Overexpression (aberrant expression) of p53, p21(WAF-1) and HER-2 /neu was documented by scoring nuclear localized p53 and p21(WAF-1) pr otein and cell membrane expression of HER-2/neu after immunostaining w ith gene product-specific monoclonal antibodies (MAbs). Results. Forty -two (42) of 81 patients studied in this series had a history of cance r in their families (52%). Seven of those 42 had a history of pancreat ic carcinoma (17%, or 9% of total cases). The incidence of K-ras mutat ion and the expression of p21(WAF-1) and HER-2/neu in patient groups w ith and without a family history of cancer was not statistically diffe rent (83 vs 74%,p = 0.416; 57 vs 41%, p = 0.184; and 83 vs 81%,p = 1.0 00, respectively). However, the incidence of p53 expression was signif icantly lower in patients with a family history of cancer (40 vs 72%,p = 0.007). There was no statistical difference in survival of patients with a family history of cancer in relation to either K-rns mutation, p53 expression, p21, or HER-2/neu expression. However, patients lacki ng a family history of cancer sl-rowed improved survival trends in rel ation to p21 expression (median survival of 16 vs 8 mo, p = 0.029).