TP53 mutation and tumoral PD-L1 expression are associated with depth of invasion in desmoplastic melanomas

Llucia Alos; Carla Fuster; Paola Castillo; Pedro Jares; Adriana Garcia-Herrera; Marta Marginet; Fernando Agreda; Ana Arance; Elena Gonzalvo; Mireia Garcia; Susana Puig; Cristina Teixido

doi:10.21037/atm-20-1846

TP53 mutation and tumoral PD-L1 expression are associated with depth of invasion in desmoplastic melanomas

Ann Transl Med. 2020 Oct;8(19):1218. doi: 10.21037/atm-20-1846.

Authors

Llucia Alos^{1

2}, Carla Fuster¹, Paola Castillo¹, Pedro Jares^{1

2}, Adriana Garcia-Herrera^{1

2}, Marta Marginet¹, Fernando Agreda³, Ana Arance⁴, Elena Gonzalvo¹, Mireia Garcia¹, Susana Puig^{2

5}, Cristina Teixido^{1

2}

Affiliations

¹ Department of Pathology, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain.
² August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
³ Department of Urological Surgery, Hospital Trias I Pujol, Carretera de Canyet, Badalona, Spain.
⁴ Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain.
⁵ Department of Dermatology, Hospital Clínic of Barcelona, Barcelona, Spain.

Abstract

Background: Desmoplastic melanoma (DM) is a rare subtype of spindle cell malignant melanoma characterized by frequent local recurrences and hematogenous spread, but without molecular classification. The aim of the study was to investigate in a DM series the incidence of relevant gene alterations in cancer, the programmed death-ligand 1 (PD-L1) expression status and the association with clinicopathological features and melanoma progression.

Methods: A total of 38 patients were included. Clinical follow-up and the histopathological features of all cases were retrospectively collected. PD-L1 expression by immunohistochemistry (IHC) and BRAF genomic alterations by real-time PCR were determined in 34 samples. Additionally, a molecular analysis by next-generation sequencing was performed in 25 DMs.

Results: Tumors occurred predominantly in men (76%) and in the head and neck region (50%). Most tumors were pure DMs (66%), containing less than 10% of conventional melanoma. Overall, 48% of our cohort harbored TP53 mutations, most of them showing a molecular signature associated with ultraviolet (UV)-oncogenesis, and 29%, BRAF mutations. A positive correlation between TP53 with depth of invasion (P=0.005) and presence of elastosis (P=0.002) was found. High-expression of PD-L1 in tumor cells was observed in 38% of cases and correlated with depth of tumoral infiltration (P=0.003), TP53 (P=0.016), PD-1 (P<0.001) and tumor-infiltrating lymphocytes (TILS) (P<0.001). PD-L1 expression in immune cells correlated with PD-1 (P=0.006), tumoral PD-L1 expression (P=0.029) and TP53 mutation (P=0.002). Survival correlated with depth of invasion (P=0.003), stage of tumors (P=0.015), positive sentinel lymph node (P=0.004), lymph node metastasis (P=0.024) and distant metastasis (P<0.001).

Conclusions: Our results suggest that progressed DMs with deep tumoral infiltration frequently harbor TP53 mutations, PD-L1 expression and present a high inflammatory response, probably related to adaptive immune resistance in this tumor-type.

Keywords: Desmoplastic melanoma (DM); Oncomine; TP53; next-generation sequencing (NGS); programmed death-ligand 1 (PD-L1).