title: Relationship of family cancer history to the expression of p53, p21WAF-1, HER-2/neu, and K-ras mutation in pancreatic adenocarcinoma.
abstract: CONCLUSIONS
  In our series of 81 cases, a history of family cancer was present in 52% of patients (42/81) with pancreatic cancer. Nine percent (7/81)had a family history of pancreatic cancer. Our studies suggest a possible relationship of family cancer history to the expression of 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 lower incidence of p53 expression observed in patients with a family history of cancer suggests normal p53 protein is present in a majority of patients who develop pancreatic tumors related to other--as yet unidentified-inherited or familial risk factors. There was no significant difference in survival of pancreas cancer patients with and without a family history of cancer. However, survival in pancreas cancer patients may be influenced (improved) by p21WAF-1 expression.
  
  
  BACKGROUND
  Pancreas cancer is the fifth leading cause of cancer deaths (27,800 deaths/yr) in the United States. Various risk factors, including cigarette smoking, high-fat diet, DDT exposure, chronic pancreatitis, and diabetes mellitus, have been associated with pancreatic carcinoma. A few studies have suggested a genetic predisposition or increased risk for pancreatic cancer within families, but the exact etiology is largely unknown. In a series of 81 patients with pancreatic carcinoma, we analyzed the status of K-ras gene mutations and the expression of P21WAF-1, p53, and HER-2/neu protein to identify possible molecular associations in pancreas cancer cases of these molecular markers to family histories of cancer and pancreas cancer.
  
  
  METHODS
  Paraffin-embedded tissue sections from 81 cases of pancreatic adenocarcinoma were used for DNA extraction and immunohistochemical staining. K-ras mutation was studied by single-stranded conformation polymorphism (SSCP) and slot-blot allele-specific oligonucleotide (ASO) hybridization of PCR-amplified DNA product. Overexpression (aberrant expression) of p53, p21WAF-1, and HER-2/neu was documented by scoring nuclear localized p53, p21WAF-1 protein and cell membrane expression of HER-2/neu after immunostaining with gene product-specific monoclonal antibodies (MAbs).
  
  
  RESULTS
  Forty-two (42) of 81 patients studied in this series had a history of cancer in their families (52%). Seven of those 42 had a history of pancreatic carcinoma (17% or 9% of total cases). The incidence of K-ras mutation and the expression of p21WAF-1 and HER-2/neu in patient groups with and without a family history of cancer was not statistically different (83 vs 74%, p = 0.416; 57 vs 41%, p = 0.184; and 83 vs 81%, p = 1.000, respectively). However, the incidence of p53 expression was significantly 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-ras mutation, p53 expression, p21, or HER-2/neu expression. However, patients lacking a family history of cancer showed improved survival trends in relation to p21 expression (median survival of 16 vs 8 mo, p = 0.029).
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Dergham
authors.forename: M C
authors.initials: MC
authors.lastname: Dugan
authors.forename: P
authors.initials: P
authors.lastname: Arlauskas
authors.forename: W
authors.initials: W
authors.lastname: Du
authors.forename: V K
authors.initials: VK
authors.lastname: Vaitkevicius
authors.forename: J D
authors.initials: JD
authors.lastname: Crissman
authors.forename: F H
authors.initials: FH
authors.lastname: Sarkar
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D005260:Female; D018734:Genes, erbB-2; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D017354:Point Mutation