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Relationship of family cancer history to the expression of P53, P21WAF-1, HER-2/neu, and K-ras mutation in pancreatic adenocarcinoma

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Summary

Conclusion

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 p21 WAF in pancreatic tumors, but show no relationship to the expression of HER-2/neuor 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 cigaret 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 and 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).

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Authors and Affiliations

  1. Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI

    Pat Arlauskas & Vainutis K. Vaitkevicius

  2. Division of Biostatistics, Wayne State University School of Medicine, Detroit, MI

    Wei Du

  3. Harper Hospital, Detroit, MI

    Sanaa T. Dergham, Michael C. Dugan, Pat Arlauskas, Wei Du, Vainutis K. Vaitkevicius, John D. Crissman & Hazlul H. Sarkar

  4. Detroit Medical Center, Detroit, MI

    Sanaa T. Dergham, Michael C. Dugan, Pat Arlauskas, Wei Du, Vainutis K. Vaitkevicius, John D. Crissman & Hazlul H. Sarkar

  5. Karmanos Cancer Institute, Detroit, MI

    Sanaa T. Dergham, Michael C. Dugan, Pat Arlauskas, Wei Du, Vainutis K. Vaitkevicius, John D. Crissman & Hazlul H. Sarkar

  6. Department of Pathology, Wayne State University School of Medicine, 9374 Scott Hall, 540 E. Canfield Avenue, 48201, Detroit, MI

    Sanaa T. Dergham, Michael C. Dugan, John D. Crissman & Hazlul H. Sarkar

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  1. Sanaa T. Dergham
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Dergham, S.T., Dugan, M.C., Arlauskas, P. et al. Relationship of family cancer history to the expression of P53, P21WAF-1, HER-2/neu, and K-ras mutation in pancreatic adenocarcinoma. Int J Gastrointest Canc 21, 225–234 (1997). https://doi.org/10.1007/BF02821608

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  • DOI: https://doi.org/10.1007/BF02821608

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