ABSTRACT
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.
ABSTRACT
In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.
Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.
Subject(s)
Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Brazil , Combined Modality Therapy , Embolization, Therapeutic , HumansABSTRACT
ABSTRACT In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.
RESUMO Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.
