Department of Dermatology, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 255, 3 andar, 05403-900, São Paulo SP, Brazil
Division of Clinical Immunology and Allergy, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 255, 8 andar, 05403-900, São Paulo SP, Brazil
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 15 Shattuck Street, Boston MA, 02115, USA
Mihm Cutaneous Pathology Consultative Service, Emmanuel College, 41 Louis Pasteur Street, Room 360, Boston MA, 02115, USA
Dermatopathology Unit, Pathology Service, Massachusetts General Hospital, Harvard Medical School, Warren Building 825, 55 Fruit Street, Boston MA 02114, USA
Background: In previous studies, patients with Stage III melanomas expressing PD-L1 in more than 5% of their neoplastic cells had improved recurrence-free survival with anti-PD1 adjuvant therapy. Objectives: We examined PD-L1 expression as a possible biomarker of primary cutaneous melanomas in the vertical growth phase. Materials and Methods: This was a retrospective study including 66 patients with invasive primary cutaneous melanomas. We assessed patient clinical and histopathological data and performed immunohistochemical assays with melanoma specimens from the patients to evaluate PD-L1, PD-1, CD3, CD8 and FoxP3 expression. Results: We observed PD-L1 expression in 21% (14/66) of our samples, and this expression correlated with increased melanoma thickness (p = 0.002) and nodular-type melanoma (p = 0.001). After adjusting for tumor thickness using a logistic regression test, the association of PD-L1 with nodular-type melanoma persisted. Nodular-type melanoma was 6.48 times more likely to be positive for PD-L1 than other histological types (p = 0.014; 95% CI: 1.46-28.82). As expected, PD-L1 expression correlated with the number of PD-1-expressing cells in the tumor-infiltrating lymphocyte population (p = 0.04). No correlation with PD-L1 was observed for age, sex, tumor site, skin phototype, ulceration status, sentinel lymph node status, metastasis development or survival. Regarding the immune profile of the tumor-infiltrating lymphocytes of PD-L1-positive and -negative groups, no significant differences were observed in the numbers of CD3 + , CD8 + FoxP3-, CD8-FoxP3+ and CD8 + FoxP3+ cells by immunohistochemistry. Conclusion: Nodular-type melanoma is associated with PD-L1 expression and may be a suitable candidate for adjuvant therapy of primary melanomas treated with immunotherapy.