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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Prognostic implications of phosphatidylinositol 3-kinase/AKT signaling pathway activation in gastric carcinomas

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Autor(es):
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Ola Chiappini, Paula Blandina [1] ; Dantas de Medeiros, Ivan Ucella [1] ; Cenaglia Lima, Luiz Guilherme [1] ; Fregnani, Jose Humberto [2] ; Nonogaki, Suely [1] ; da Costa, Jr., Wilson Luiz [1] ; Coimbra, Felipe Jose Fernandez [1] ; de Barros e Silva, Milton Jose [1] ; Lopes de Mello, Celso Abdon [1] ; Lopes Pinto, Clovis Antonio [1] ; Begnami, Maria Dirlei [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] AC Camargo Canc Ctr, Rua Antonio Prudente 211, BR-01509010 Sao Paulo - Brazil
[2] Hosp Canc Barretos, Barretos - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Archives of Medical Science; v. 13, n. 6, p. 1262-1268, 2017.
Citações Web of Science: 2
Resumo

Introduction: Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway plays a critical role in carcinogenesis and resistance to anticancer drugs. In this study, gastric carcinomas (GC) were investigated and statistical analyses were performed concerning the correlation between the clinicopathological features and activation of the PI3K/AKT pathway. Material and methods: Immunohistochemistry for p-AKT, p-mTOR and PTEN was performed in 239 GC and 200 non-neoplastic gastric tissues. The clinicopathological parameters were recorded from the medical charts. Statistical significance was defined by a p-value < 0.05. Results: High p-AKT expression was observed in 10% of the normal gastric tissue and in 90% of GC, and it was significantly associated with tumor size (p < 0.001), T3/T4 tumors (p < 0.001), and presence of metastases (p = 0.02). Similarly, p-mTOR positivity was found in GC cells, but not in the normal gastric mucosa, and was correlated with perineural invasion (p = 0.02) and T3/T4 tumors (p = 0.03). On the other hand, PTEN expression was weak and focal in the tumor cells, while in the normal gastric tissue this staining was strong and diffuse. Importantly, the expression of p-mTOR and PTEN was associated with overall survival. Conclusions: The results of the present study, characterized by the loss of PTEN expression and higher expression of p-AKT and p-mTOR in the majority of tumor cells, apparently are implicated in the carcinogenesis and progression of GC. The identification of p-mTOR and PTEN expression as prognostic factors corroborates the identification and use of potential target drugs that could be more efficient for the treatment of these patients. (AU)

Processo FAPESP: 10/16262-6 - Análise da participação dos genes mTOR e PTEN na carcinogênese gástrica, através de imunoistoquímica e hibridação in situ fluorescente (FISH)
Beneficiário:Maria Dirlei Ferreira de Souza Begnami
Linha de fomento: Auxílio à Pesquisa - Regular