Research Papers:

Metastases risk in thin cutaneous melanoma: prognostic value of clinical-pathologic characteristics and mutation profile

Antonio G. Richetta, Virginia Valentini, Federica Marraffa, Giovanni Paolino, Piera Rizzolo, Valentina Silvestri, Veronica Zelli, Anna Carbone, Cinzia Di Mattia, Stefano Calvieri, Pasquale Frascione, Pietro Donati and Laura Ottini _

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Oncotarget. 2018; 9:32173-32181. https://doi.org/10.18632/oncotarget.25864

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Antonio G. Richetta1, Virginia Valentini2, Federica Marraffa1, Giovanni Paolino1,3, Piera Rizzolo2, Valentina Silvestri2, Veronica Zelli2, Anna Carbone4, Cinzia Di Mattia5, Stefano Calvieri1, Pasquale Frascione4, Pietro Donati5 and Laura Ottini2

1Department of Internal Medicine and Medical Specialties, Unit of Dermatology, “Sapienza” University of Rome, Rome, Italy

2Department of Molecular Medicine, “Sapienza” University of Rome, Rome, Italy

3Unit of Dermatology and Cosmetology, IRCCS, University Vita-Salute San Raffaele, Milan, Italy

4Department of Oncological and Preventative Dermatological, San Gallicano Dermatological Institute, IRCCS, Rome, Italy

5Laboratory of Cutaneous Histopathology, San Gallicano Dermatologic Institute, Rome, Italy

Correspondence to:

Laura Ottini, email: [email protected]

Keywords: thin melanoma; metastases; prognostic factors; Breslow thickness; mutation profile

Received: May 22, 2018     Accepted: July 13, 2018     Published: August 14, 2018


Background: A high percentage of patients with thin melanoma (TM), defined as lesions with Breslow thickness ≤1 mm, presents excellent long-term survival, however, some patients develop metastases. Existing prognostic factors cannot reliably differentiate TM patients at risk for metastases.

Objective: We aimed at characterizing the clinical-pathologic and mutation profile of metastatic and not-metastatic TM in order to distinguish lesions at risk of metastases.

Methods: Clinical-pathologic characteristics were recorded for the TM cases analyzed. We used a Next Generation Sequencing (NGS) multi-gene panel to characterize TM for multiple somatic mutations.

Results: A statistically significant association emerged between the presence of metastases and Breslow thickness ≥0.6 mm (p=0.003). None of TM with lymph-node involvement had Breslow thickness <0.6 mm. Somatic mutations were identified in 19 of 21 TM analyzed (90.5%). No mutations were observed in two not-metastatic cases with the lowest Breslow thickness (≤0.4 mm), whereas mutations in more than one gene were detected in one metastatic case with the highest Breslow thickness (1.00 mm).

Conclusion: Our study indicates Breslow thickness ≥0.6 mm as a valid prognostic factor to distinguish TM at risk for metastases.

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