Histologic features of melanoma associated with CDKN2A genotype - 15/02/15
, Peter A. Kanetsky, PhD, MPH b, Julia Newton-Bishop, MD, FMedSci c, Nicholas K. Hayward, PhD d, Graham J. Mann, MBBS, PhD e, Nelleke A. Gruis, PhD f, Margaret A. Tucker, MD g, Alisa M. Goldstein, PhD g, Giovanna Bianchi-Scarra, PhD h, Susana Puig, MD i, j, David E. Elder, MB, ChB, FRCPA kAbstract |
Background |
Inherited susceptibility genes have been associated with histopathologic characteristics of tumors.
Objective |
We sought to identify associations between histology of melanomas and CDKN2A genotype.
Methods |
This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations.
Results |
Compared with CDKN2A− cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation (Ptrend = .02) and increased pagetoid scatter (Ptrend = .07) after adjusting for age at diagnosis, sex, and American Joint Committee on Cancer thickness category. Similar associations were observed when comparing mutation carriers with a combined group of CDKN2A− (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the 15 cases with this phenotype, none were observed to harbor a CDKN2A mutation.
Limitations |
Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype.
Conclusion |
Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase.
Le texte complet de cet article est disponible en PDF.Key words : CDKN2A, classification and regression tree analysis, familial melanoma, genetic testing, histology, pagetoid scatter, pigmentation, sporadic melanoma
Abbreviations used : AJCC, CART, MITF, RGP, SSM, TIL, VGP
Plan
| Research at each of the participating institutions is funded by the National Cancer Institute of the US National Institutes of Health (R01 CA83115). The research at the Melanoma Unit in Barcelona is partially funded by Spanish Fondo de Investigaciones Sanitarias (grants 09/01393 and 12/00840); Centro de Investigaciones Biomédicas en Red (CIBER) de Enfermedades Raras of the Instituto de Salud Carlos III, Spain; Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) 2009 Sociedades de Garantia Recíproca (SGR) 1337 of the Catalan Government, Spain; European Commission under the 6th Framework Program, Contract No. LSHC-CT-2006-018702 (Melanoma Genetics Consortium, GenoMEL). The Leeds research group is partially funded by Cancer Research UK (C588/A4994 and C588/A10589). Research at QIMR Berghofer Medical Research Institute is partially funded by the National Health and Medical Research Council of Australia (NHMRC). Work in Sydney was also funded by program grants of NHMRC (402761, 633004) and Cancer Institute New South Wales (05/TPG/1-01, 10/TPG/1-02). |
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| Disclosure: Dr Mann was a speaker for Roche and received honoraria. Drs Sargen, Kanetsky, Newton-Bishop, Hayward, Gruis, Tucker, Goldstein, Bianchi-Scarra, Puig, and Elder have no conflicts of interest to declare. |
Vol 72 - N° 3
P. 496 - mars 2015 Retour au numéro
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