Different expression of BRAFV600E, ALK and PD-L1 in melanoma in children and adolescents: a nationwide retrospective study in Finland in 1990–2014

Abstract

Background

Pediatric melanoma may have a different biological background and more favorable prognosis compared with melanoma in adults. The aim of this study was to investigate melanoma in children and adolescents in the Finnish population in terms of incidence, clinical course, treatment, prognosis and BRAFV600E-, ALK- and PD-L1-positivity of the primary tumors.

Materials and Methods

Primary tumor samples and clinical records of all patients aged 0-19 years diagnosed with cutaneous melanoma in Finland in 1990–2014 were collected using the Finnish Cancer Registry database, Finnish hospitals and private pathology laboratories. BRAFV600E, ALK and PD-L1 were analyzed from 54 primary tumors and BRAFV600E from six metastasis samples.

Results

A total of 122 patients diagnosed with cutaneous melanoma were retrieved from the Cancer Registry database. The primary tumor samples of 73 patients were obtained for the review, and 56 cases were included in the study. The incidence of pediatric melanoma increased from 0.02 to 0.1/100 000 during the period 1990–2014. Spitzoid melanoma was the most common subtype (66%). The 10-year cancer-specific survival (CSS) was 88.7% in all patients. The 10-year-CSS did not differ in SLNB-positive or -negative groups. BRAFV600E was positive in 48%, ALK in 9% and PD-L1 in 2% of the tumors. BRAFV600E mutation was associated with 83% of melanoma deaths.

Conclusions

Young melanoma patients had more favorable prognosis and a different staining profile for BRAFV600E, ALK, and PD-L1 in primary tumor than reported in adults. SLNB status was not an indicator for survival. BRAFV600E-positive patients have worse prognosis and could benefit from surveillance and treatment similarly to adults.

Acknowledgements

The authors thank Laboratory Manager Sinikka Collanus and Medical Cell Biologist Minnamaija Lintunen for preparing the immunohistochemical stainings, colleagues and staff in Finnish hospitals and pathology laboratories for their contributions for collecting the data, Dr. Harry Kujari for his assistance with digital pathology and sample collection, and Dr. Tero Valhberg for his assistance with statistical analyses.

Disclosure statement

Micaela Hernberg: BMS, MSD, Novartis, Roche, Sanofi, Pierre Fabre and Varian (consultations, lectures). PiaVihinen: Pierre-Fabre, BMS, Amgen, Sanofi and Roche (congress fees, travel expenses). Others declare no conflicts of interests.

Author contributions

Micaela Hernberg: BMS, MSD, Novartis, Roche, Sanofi, Pierre Fabre and Varian (consultations, lectures). Pia Vihinen: Pierre-Fabre, BMS, Amgen, Sanofi and Roche (congress fees, travel expenses). Others declare no conflicts of interests.

ER, IK and VMK planned the study. ER collected and analyzed the data, performed statistical analyses and was responsible for writing the manuscript. SJ and LT analyzed the histopathological samples. MH and PV collected and analyzed the oncological data. IK and VMK supervised the study. All authors participated in writing and critical reviewing the manuscript.

Additional information

Funding

This work was supported by the Doctoral Program in Clinical Research, University of Turku, Cancer Society of Southwest Finland, Finnish Dermatological Society (ER) and by Finnish Cancer Research Foundation, Sigrid Jusélius Foundation (VMK), and Turku University Hospital VTR grant (projects 13336 (VMK) and 11006 (ER)).