title: Cyclin A expression in superficial spreading malignant melanomas correlates with clinical outcome.
abstract: The present study analysed by immunohistochemistry the protein level of cyclin A and Ki-67 in a panel of paraffin-embedded tissue obtained from 172 primary (110 superficial and 62 nodular) and 73 metastatic melanomas, and ten benign naevi. Since cyclin A exists in the same quaternary complex in the S-phase of the cell cycle as the cdk inhibitor p21WAF1/CIP1, the levels of the two proteins were compared. Cyclin A and Ki-67 were heterogeneously expressed in the malignant tumours, whereas in benign naevi, only rare positive cells were detected. In superficial spreading melanomas, the cyclin A level was related to tumour thickness, with less expression in thinner lesions (p<0.00001), and to Ki-67 (p<0.00001) and p21WAF1/CIP1 (p=0.01) scores. Multivariate analysis showed that in addition to the depth of the primary tumour, the protein level of cyclin A was an independent indicator of relapse-free period (thickness, p<0.00001; cyclin A, p=0.0003). In contrast, in nodular melanoma, the cyclin A level was associated with Ki-67 expression, but neither cyclin A nor Ki-67 was related to tumour thickness (cyclin A, p=0.06; Ki-67, p=0.61) and neither had any impact on relapse-free (cyclin A, p=0.64; Ki-67, p=0.32) or overall (cyclinA, p=0.94; Ki-67, p=0.45) survival. In conclusion, the results indicate that cyclin A is a strong prognostic factor for patients with superficial spreading melanomas. In nodular melanomas, the proliferation rate seems to have little impact on disease progression.
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, 0310, Oslo, Norway. v.a.florenes@labmed.uio.no
authors.forename: V A
authors.initials: VA
authors.lastname: Flørenes
authors.forename: G M
authors.initials: GM
authors.lastname: Maelandsmo
authors.forename: R
authors.initials: R
authors.lastname: Faye
authors.forename: J M
authors.initials: JM
authors.lastname: Nesland
authors.forename: R
authors.initials: R
authors.lastname: Holm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism*; D018572:Disease-Free Survival; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019925:Cyclin A; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins