Expression, activation and clinical relevance of CHK1 and CHK2 in metastatic high-grade serous carcinoma.
Gynecol Oncol
; 150(1): 136-142, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29804637
ABSTRACT
OBJECTIVE:
To analyze the expression and clinical role of CHK1 and CHK2 in metastatic high-grade serous carcinoma (HGSC).METHODS:
HGSC effusions (nâ¯=â¯335; 280 peritoneal, 55 pleural) were analyzed for protein expression of total CHK1 and its phosphorylated forms p-ser317 and p-ser296, as well as total CHK2 and its phosphorylated form p-thr68 using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including chemotherapy response, and survival.RESULTS:
Carcinoma cells stained positive, predominantly at the nuclei, in the majority of cases (range 83-100% for the five antibodies), while expression in reactive mesothelial cells and tumor-associated macrophages was more variable. Total CHK1 (pâ¯=â¯0.037), p-CHK1ser317 (pâ¯=â¯0.001), p-CHK1ser296 (pâ¯=â¯0.002) and p-CHK2thr68 (pâ¯<â¯0.001) expression was significantly higher in post-chemotherapy disease recurrence compared to pre-chemotherapy effusions obtained at diagnosis. CHK1, p-CHK1ser296, p-CHK2thr68 and p-CHK1ser317 nuclear expression was positively related to expression of the checkpoint regulator WEE1, previously studied in this cohort (pâ¯=â¯0.003, pâ¯=â¯0.013, pâ¯=â¯0.001 and pâ¯=â¯0.01, respectively). Higher total CHK1 (pâ¯=â¯0.007), p-CHK1ser317 (pâ¯=â¯0.004), CHK2 (pâ¯=â¯0.01) and p-CHK2thr68 (pâ¯=â¯0.048) expression was significantly related to shorter overall survival in univariate analysis, and CHK1ser317 was an independent prognostic marker in multivariate analysis (pâ¯=â¯0.025). Higher p-CHK1ser317 (pâ¯=â¯0.03) and CHK2 (pâ¯=â¯0.034) expression was additionally associated with poor progression-free survival.CONCLUSIONS:
CHK1 and CHK2 and their activated forms are frequently expressed in HGSC effusions, with higher expression following exposure to chemotherapy, and their expression is related to survival.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cistadenocarcinoma Seroso
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Quinase do Ponto de Checagem 2
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Quinase 1 do Ponto de Checagem
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article