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Immunohistochemical detection of p53 in melanomas with rare p53 gene mutations is associated with mdm-2
C Poremba1, D W Yandell, D Metze
1Gerhard-Domagk-Institute of Pathology, University of Münster, Germany.
Abstract:
Expression of mutant p53 detected by immunohistochemistry has been described in human malignant melanoma, but there are few reports of molecular analyses. To investigate the genetic basis for p53 expression in malignant melanoma, we examined 58 primary tumors and 5 cutaneous metastases. The entire coding sequence of the p53 gene was screened by single-strand conformation polymorphism analysis and direct genomic sequencing of polymerase chain reaction products. p53 and mdm-2 expression were studied by immunohistochemistry. Two p53 gene mutations could be found in 1/63 samples examined, both having occurred in the same specimen from a patient with a nodular melanoma. p53 and mdm-2 expression were found immunohistochemically to increase with tumor progression both in frequency and in the mean proportion of positive cells, with the same cases staining positively for both antibodies. Our results suggest that a) p53 gene mutations are a rare event in human melanoma; b) accumulation and thus immunohistochemically detectable expression of p53 may result from posttranslational mechanisms affecting the p53 gene product; and c) p53 and mdm-2 are more important in late events in melanoma carcinogenesis.
Insights
p53 gene mutations are rare in melanoma. Instead, p53 and mdm-2 expression increases with tumor progression, suggesting post-translational regulation and late-stage involvement in melanoma development.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Immunohistochemistry detects mutant p53 in human malignant melanoma.
- Limited molecular analyses exist for p53 expression in melanoma.
Purpose of the Study:
- Investigate the genetic basis of p53 expression in malignant melanoma.
- Examine p53 gene mutations and expression patterns in melanoma tumors.
Main Methods:
- Screened the entire p53 coding sequence using single-strand conformation polymorphism and direct genomic sequencing.
- Analyzed p53 and mdm-2 expression via immunohistochemistry in 58 primary tumors and 5 cutaneous metastases.
Main Results:
- Identified only two p53 gene mutations in 63 samples, both in a single nodular melanoma specimen.
- Observed increased p53 and mdm-2 expression with melanoma tumor progression in frequency and positive cell proportion.
- Noted concurrent positive staining for both p53 and mdm-2 antibodies in the same cases.
Conclusions:
- p53 gene mutations are infrequent in human melanoma.
- Accumulation and detectable expression of p53 may stem from post-translational modifications.
- p53 and mdm-2 play significant roles in later stages of melanoma carcinogenesis.