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Melanoma-prone families: new evidence of distinctive clinical and histological features of melanomas in CDKN2A mutation carriers

  • Laura Cristina Gironi
  • Enrico Colombo
  • Barbara Pasini
  • Roberto Giorgione
  • Pamela Farinelli
  • Francesca Zottarelli
  • Elia Esposto
  • Elisa Zavattaro
  • Elias Allara
  • Paola Ogliara
  • Marta Betti
  • Irma Dianzani
  • Paola Savoia
Original Paper
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Abstract

Germline mutations on the CDKN2A gene, the most important known genetic factors associated with cutaneous melanomas (CMs), predispose carriers to multiple primary CMs (MPMs) with higher frequency and younger onset compared to non-carriers. Most of the largest published studies concerning clinical and histological characteristics of CMs with CDKN2A mutation carriers did not specify if the described CMs are first or subsequent to the first, and they used sporadic CMs from non-genotyped patients as controls. We conducted a single-centre observational study to compare clinical and histological CM features of 32 unrelated carriers (MUT) of 5 germline CDKN2A mutations (one of which was never previously described) compared to 100 genotyped wild-type (WT) patients. We stratified the data based on time of diagnosis, anatomical site and histological subtype of CMs, demonstrating several significant unreported differences between the two groups. MUT developed a higher number of dysplastic nevi and MPMs. We proved for the first time that anatomical distribution of CMs in MUT was independent of gender, unlike WTs. MUTs developed in situ and superficial spreading melanomas (SSMs) more frequently, with significantly higher number of SSMs on the head/neck. In MUTs, Breslow thickness was significantly lower for all invasive CMs. When CMs were stratified on the basis of the time of occurrence, statistical significance was maintained only for SSMs subsequent to the first. In WTs, Clark level was significantly higher, and ulceration was more prevalent than in MUTs. Significant differences in ulceration were observed only in SSMs. In nodular CMs, we did not find differences in terms of Breslow thickness or ulceration between WTs and MUTs. In situ CMs developed 10 years earlier in MUTs with respect to WTs, whereas no significant differences were observed in invasive CMs. In contrast to those reported previously by other authors, we did not find a difference in skin phototype.

Keywords

CDKN2A Familial melanoma Cutaneous melanoma Melanoma-susceptibility genes Risk factor for cutaneous melanoma 

Abbreviations

CM

Cutaneous melanoma

PC

Pancreatic cancer

MUT

Carrier of CDKN2A germline mutation

WT

Wild type

UM

Uveal melanoma

FCS

Familial cancer syndrome

N_CM1

First CM

N_CM1.5

CM diagnosed within 3 months after the first (metachronous CM)

MPMs

Multiple primary melanomas

SLNB

Sentinel node biopsy

y

Years

SNM

Sentinel node metastases.

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Notes

Funding

None.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval(Research involving Human Participants)

This study obtained approval from the Ethics Committee of our Institution (Comitato Etico Interaziendale, Azienda Ospedaliero Universitaria Maggiore della Carità di Novara, Italy).

Informed consent

Written informed consent for genetic analysis was obtained from all patients.

Supplementary material

403_2018_1866_MOESM1_ESM.doc (22 kb)
Supplementary material 1 (DOC 22 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Laura Cristina Gironi
    • 1
  • Enrico Colombo
    • 2
  • Barbara Pasini
    • 3
  • Roberto Giorgione
    • 1
  • Pamela Farinelli
    • 1
  • Francesca Zottarelli
    • 1
  • Elia Esposto
    • 1
  • Elisa Zavattaro
    • 1
  • Elias Allara
    • 4
  • Paola Ogliara
    • 3
  • Marta Betti
    • 1
  • Irma Dianzani
    • 1
  • Paola Savoia
    • 1
  1. 1.Department of Health SciencesA. Avogadro University of Eastern PiedmontNovaraItaly
  2. 2.Department of Translational MedicineA. Avogadro University of Eastern PiedmontNovaraItaly
  3. 3.Department of Medical SciencesUniversity of TurinTurinItaly
  4. 4.NIHR Blood and Transplant Research Unit, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK

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