Prognostic implications of p53 overexpression in cutaneous melanoma from sun-exposed and nonexposed sites.
BACKGROUND
There is increasing evidence that mutations in the p53 tumor suppressor gene are among the most common genetic alterations in human malignancies. Because ultraviolet light can induce specific p53 mutations and is linked to the development of skin cancers, this study was done to determine the significance of p53 protein (p53p) overexpression in melanomas originating at different cutaneous sites varying in frequency of sunlight exposure.


METHODS
Sixty-three paraffin embedded primary and metastatic melanoma biopsy specimens from 61 patients were deparaffinized and stained with the mouse monoclonal antibody DO-1 to wild-type and mutant p53p. Twenty-eight specimens were from primary tumors and 35 specimens were from lymph node, subcutaneous, or visceral metastases. The chi-square test was used to assess the significance of p53p overexpression, and the Cox proportional hazards model was used to estimate the impact of p53p overexpression on survival.


RESULTS
Of the 61 patients studied, 37 had primary cutaneous melanomas arising on chronically sun-exposed head and neck sites, 12 patients on intermittently exposed extremity sites, and 12 patients on rarely exposed trunk sites. Thirteen of the 63 primary or metastatic specimens (21%) overexpressed p53p. Overexpression of p53p was not related to patient gender or age, anatomic site of the primary tumor, Clark level, or Breslow thickness. However, those patients with p53p positive primary tumors or metastases had significantly better survival than those determined to be negative for p53p overexpression (P = 0.045). The median survival was 152.4 months for p53p positive patients versus 55.7 months for p53p negative patients. The risk ratio of dying from melanoma was 0.32 for patients with tumor specimens overexpressing p53p.


CONCLUSIONS
In this study, p53p overexpression was infrequent in paraffin embedded melanoma specimens and independent of the primary melanoma's anatomic site. Although p53p overexpression was not related to other prognostic features of primary or metastatic lesions, it was associated with a significantly improved survival in this group of melanoma patients.
Essner
R
R
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
Kuo
C T
CT
Wang
H
H
Wen
D R
DR
Turner
R R
RR
Nguyen
T
T
Hoon
D S
DS
D000328:Adult; D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal; D001706:Biopsy; D016009:Chi-Square Distribution; D004396:Coloring Agents; D004781:Environmental Exposure; D005121:Extremities; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016017:Odds Ratio; D016612:Paraffin Embedding; D011379:Prognosis; D016016:Proportional Hazards Models; D012737:Sex Factors; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects*; D015996:Survival Rate; D013909:Thorax; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D004396:Coloring Agents; D016159:Tumor Suppressor Protein p53