Etiologic factors associated with nevus involvement and p53 abnormality in cutaneous malignant melanoma.
Published: 2004
Language: eng
Number of pages: 204
Description: Tumour characteristics found to be associated with nevus involvement included thin Breslow thickness and superficial spreading histologic subtype. Subjects with many nevi were significantly more likely to have a melanoma with nevus involvement. Two indicators of high cumulative exposure to sunlight (melanoma location on the head and neck, solar elastosis adjacent to the melanoma) were less prevalent among melanomas with no nevus involvement. Factors found to be positively associated with the presence of strong p53 staining (>10% of cells positively stained, vs. tumours with no staining) included thicker Breslow thickness, male sex, having few nevi on the back, no evidence of nevus involvement, and having ever received a blistering sunburn. Melanomas exhibiting strong p53 staining were also positively associated with some indicators of high cumulative sun exposure (lentigo maligna melanoma subtype, melanoma location on the head or neck, evidence of solar elastosis, previous diagnosis of non-melanoma skin cancer).Recent studies have reported different risk factor distributions between subgroups of cutaneous malignant melanoma (CMM) characterized by the presence or absence of tumour markers (nevus involvement, p53 protein abnormality). These findings have led to hypotheses positing the existence of etiologically distinct disease pathways in melanoma tumourigenesis. In order to address the hypothesis of etiologic heterogeneity in melanoma, a case-only analysis was performed to identify etiologic factors associated with evidence of nevus involvement and p53 protein abnormality in CMM. The analysis employed data from Canadian (Ontario, British Columbia) and Australian (New South Wales) subjects with a first primary CMM participating in the International Study of Genes, Environment and Melanoma. Evidence of nevus involvement was assessed for 932 subjects as part of a histopathologic review of diagnostic slides by study pathologists. Immunohistochemical staining using the monoclonal antibody DO-7 was conducted on tumour sections from 523 subjects to assess the presence of p53 protein abnormality. Measures of skin pigmentation phenotype, sun sensitivity and past sun exposure were measured using a self-administered questionnaire and telephone interview.The findings from this analysis offer limited evidence in support of a multiple-pathway model of melanoma pathogenesis; additional research investigating the existence of etiologic heterogeneity in melanoma is warranted.
Notes: Adviser: Loraine Marrett.

Thesis (Ph.D.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Dissertation Abstracts International, Volume: 65-05, Section: B, page: 2374.