Effectiveness of screening in families with a foundermutation in CDKN2A

J. van der Rhee1, H. Vasen2, W. Mooi3, F. de Snoo4, H. Putter5, N. Gruis1, N. Kukutsch1, W. Bergman1
Departments of Dermatology1, Clinical Genetics4, Medical Statistics5, Leiden University Medical Center; Netherlands Foundation for the Detection of Hereditary Tumours, Leiden2; Department of Pathology, VU Medical Center, Amsterdam3

Because there is no effective treatment for most metastasized melanomas, early detection is a promising strategy to reduce mortality and morbidity. Familial melanoma families have been under surveillance in the LUMC for over 25 years. Many families where proven to have a founder mutation (p16-Leiden) in CDKN2A. We evaluated the effectiveness of screening in these high risk families.

Method. In a retrospective case-control study melanomas categorized on an intention to screen basis as screening or non-screening were compared. Melanomas diagnosed between 1968 and 2006 in patients from p16-Leiden families that were under surveillance in the Leiden University Medical Center were included. All melanomas in situ and melanomas with missing data were histologically revised. Screening and non-screening melanomas were compared with regard to Breslow thickness and the odds of developing thick melanomas (Breslow thickness > 1.00 mm) by means of a linear and a logistic regression analysis.

Results. 53 non-screening and 226 screening melanomas were included. Non-screening melanomas were 1.5 times as thick as screening melanomas (CI 1.2-1.9, p=0.000), with a mean corrected Breslow thickness of 0.89 mm and 0.57 mm respectively. The odds ratio for being diagnosed with a Breslow thickness > 1.00 mm was 2.5 for non-screening compared to screening melanomas (CI:1.1-6.3, p=0.037).

Conclusion. During surveillance invasive melanomas are diagnosed with a significantly lower Breslow thickness and the chance of diagnosing melanomas in a prognostic unfavorable tumor stage is significantly lower.