title: Clinicopathological and prognostic relevance of Rap1-GAP expression in melanocytic tumors.
abstract: Rap1-GAP protein has been identified as an inactivator of Rap1 activity, a putative endogenous antagonist of Ras proteins. The Rap1-GA1 locus maps to 1p36.1-35, the region which may harbor a gene for familial melanoma. In the present immunohistochemical study we analyzed the clinicopathological and prognostic relevance of Rap1-GAP expression in 60 benign and 103 malignant melanocytic tumors. Cytoplasmic immunoreactivity was detected in the cells of 27/60 nevi (45%) and 59/103 melanomas (57%). In the latter group the frequency of Rap1-GAP expression increased (P < 0.05) with the thickness of primary tumors and was highest in metastatic lesions. Rap1-GAP protein was detected in 15/19 subsequently recurring primary melanomas (79%) but only in 32/67 tumors (47%) of patients who remained free of disease (P < 0.05) for at least 6 years. Five out of six recurring thin melanomas (< 2 mm) were found to be immunoreactive. Although being no indicator for malignant transformation of melanocytic lesions, Rap1-GAP overexpression may represent a useful marker for identifying thin high-risk melanomas. Cytoplasmic expression of Rap1-GAP has also been observed in the cells of skin appendages and in keratinocytes, particularly in suprabasal layers of the epidermis. Therefore, Rap1-GAP is likely to be associated with cellular growth and/or differentiation. However, the present study did not provide evidence that this gene, despite its chromosomal localization, represents an early melanoma gene.
authors.affiliation: Department of Dermatology, Hannover Medical School, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Weiss
authors.forename: B
authors.initials: B
authors.lastname: Biwer
authors.forename: M
authors.initials: M
authors.lastname: Schliz
authors.forename: E G
authors.initials: EG
authors.lastname: Jung
mesh_terms: D014408:Biomarkers, Tumor; D019204:GTP-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009506:Nevus / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000032:analysis*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D020668:rap GTP-Binding Proteins
chemical_list: D014408:Biomarkers, Tumor; D020690:GTPase-Activating Proteins; D011506:Proteins; C484658:RAP1GAP protein, human; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins