Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-12-09T12:24:56Z
No. of bitstreams: 1
TES_ANDRE_POISL_FAY_COMPLETO.pdf: 12654104 bytes, checksum: ad2a22881e2edf0bfef5f136f9a5e457 (MD5) / Made available in DSpace on 2016-12-09T12:24:56Z (GMT). No. of bitstreams: 1
TES_ANDRE_POISL_FAY_COMPLETO.pdf: 12654104 bytes, checksum: ad2a22881e2edf0bfef5f136f9a5e457 (MD5)
Previous issue date: 2016-02-22 / 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. / Objetivo: este estudo visa caracterizar a express?o de PD-L1 em amostras tumorais de pacientes com neoplasias genito-urin?rias de baixa incid?ncia e correlacionar seus n?veis de express?o com caracter?sticas e desfechos cl?nicos. M?todos: blocos de parafina foram obtidos de pacientes com carcinoma de c?lulas renais (CCR) de c?lulas n?o claras e carcinoma do c?rtex da adrenal. A express?o de PD-L1 foi avaliada por imuno-histoqu?mica na membrana das c?lulas tumorais e nas c?lulas mononucleares infiltradas no tumor (CMIT). Compara??es entre a express?o de PD-L1 e caracter?sticas cl?nico-patol?gicas foram analisadas utilizando teste t n?o pareado e teste exato de Fisher. Metodologia de Kaplan-Meier e teste de log-rank foram utilizados para avaliar a associa??o entre a express?o de PD-L1 e desfechos de sobrevida nas duas histologias. Resultados: Entre 101 pacientes com CCR de c?lulas n?o claras, 11 (10.9%) foram considerados PD-L1 positivo (+) na membrana das c?lulas tumorais: em 2/36 (5.6%) dos tumores de c?lulas crom?fobas, 5/50 (10%) de tumores papilares, 3/10 (30%) dos tumores com transloca??o Xp11.2 e em 1/5 (20%) dos tumores do ducto coletor. Por outro lado, positividade de PD-L1 em CMIT foram observadas em 57 (56.4%) dos pacientes: em 13/36 (36.1%) dos tumores de c?lulas crom?fobas, 30/50 (60%) de tumores papilares, 9/10 (90%) dos tumores com transloca??o de Xp11.2 e em 5/5 (100%) dos tumores do ducto coletor. PD-L1+ em ambos, membrana da c?lulas tumorais e CMIT, foram associados com um tempo mais curto at? recorr?ncia de doen?a em pacientes com CCR de c?lulas n?o claras (p=0.02 e p=0.03, respectivamente). Entre os 28 pacientes com tumores do c?rtex da gl?ndula adrenal, 3 (10.7%) foram considerados positivos na membrana das c?lulas tumorais. Por outro lado, a express?o de PD-L1 em CMIT foram realizadas em 27 pacientes e PD-L1+ foi observado em 19 (70.4%) pacientes. Positividade para PD-L1 em ambos, membrana da c?lulas tumorais e CMIT, n?o foi associado com maior est?gio cl?nico ao diagn?stico, alto grau tumoral, produ??o excessiva de horm?nios ou sobrevida. Conclus?o: Em suma, CCR de c?lulas n?o claras e carcinoma do c?rtex da adrenal expressam PD-L1 na membrana da c?lula tumoral e em infiltrados inflamat?rios e isto pode representar um poss?vel alvo para interven??es terap?uticas.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/7085 |
| Date | 22 February 2016 |
| Creators | Fay, Andr? Poisl |
| Contributors | Figueiredo, Carlos Eduardo Poli de, Choueiri, Toni K. |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de, PUCRS, Brasil, Faculdade de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7620745074616285884, 600, 600, 600, -8624664729441623247, -969369452308786627 |
Page generated in 0.0024 seconds