Associação dos níveis de expressão de PD-L1 com desfechos clínicos e características clinico-patológicas em pacientes com neoplasias genito-urinárias de baixa incidência

• Ano de defesa: 2016
• Autor(a) principal: Fay, André Poisl
• Orientador(a): Figueiredo, Carlos Eduardo Poli de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
• Programa de Pós-Graduação: Programa de Pós-Graduação em Medicina e Ciências da Saúde
• Departamento: Faculdade de Medicina
• País: Brasil
• Palavras-chave em Português: NEOPLASIAS RENAIS; CARCINOMA; IMUNOTERAPIA; MEDICINA
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/7085

Objective: This study aims to characterize PD-L1 expression in tumor tissue from low incidence genitourinary malignancies and to correlate levels of PD-L1 expression with clinico-pathological features as well as survival outcomes. Methods: Formalin-fixed paraffin-embedded specimens were obtained from patients with non-clear cell renal cell carcinoma (non-ccRCC) and adrenocortical carcinoma (ACC). PD-L1 expression was evaluated by immunohistochemistry (IHC) in both tumor cell membrane and tumor infiltrating mononuclear cells (TIMC). Comparisons between PD-L1 expression and clinico-pathological features were evaluated using unpaired t-test and Fisher’s exact test. Kaplan-Meier method and log-rank test were used to assess association between PD-L1 expression and survival outcome in both histologies. Results: Among 101 patients with non-ccRCC, 11 (10.9%) were considered PD-L1+ in tumor cells: 2/36 (5.6%) of chromophobe RCC, 5/50 (10%) of papillary RCC, 3/10 (30%) of Xp11.2 translocation RCC and 1/5 (20%) of collecting duct carcinoma. On the other hand, PD-L1 positivity by TIMC was observed in 57 (56.4%) patients: 13/36 (36.1%) of chromophobe RCC, 30/50 (60%) of papillary RCC, 9/10 (90%) of Xp11.2 translocation RCC and 5/5 (100%) of collecting duct carcinoma). PD-L1+ in both tumor cell membrane and TIMC cells were associated with shorter time to recurrence (p=0.02 and p=0.03, respectively). Among 28 patients with surgically treated ACC, 3 (10.7%) were considered PD-L1 positive on tumor cell membrane. On the other hand, PD-L1 expression in TIMC was performed in 27 specimens and PD-L1 positive staining was observed in 19 (70.4%) patients. PD-L1 positivity in either tumor cell membrane or TIMC was not significantly associated with higher stage at diagnosis, higher tumor grade, excessive hormone secretion, or survival. Conclusion: In summary, Non-ccRCC and ACC can express PD-L1 on both tumor cell membrane and immune cells and it may represent a potential target for therapeutic interventions.