Targeting the molecules useful for the diagnosis and treatment of endometrial cancers

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Endometrial cancer is the second most common gynecological malignancy and its incidence has increased dramatically over the last decade in Japan. Although the surgical and chemotherapeutic treatments for endometrial cancers are well-established, the need for molecular-target therapy has increased, especially for recurrent and/or radio- or chemo-resistant diseases. Thus there is a need for a better understanding of the molecular pathway of endometrial carcinogens.The most frequent genetic abnormalities are mutations in PTEN and ERAS. A PTEN mutation and ERAS mutation activates the PI3K pathway and ERK - MAP pathway, respectively. In the present study using the clinical samples, there is no significant association between KRAS or BRAF and p-ERK1/2 expression. Patients with low expression have a favorable prognosis. Thus, the activation of ERK1/2 occurs in a ERAS and BRAF I dependent manner in endometrial cancer. A High level of p-AKT expression was observed in approximately 60% of endometrial cancers. It occurs independently of both PTEN mutations and PIK3CA mutations. Furthermore, p-AKT expression did not correlated with expression of potential downstream targets such as p-mTOR and/or p TORO 1/3a. The high-expression of p-AKT was strongly associated with ERK. The present study revealed the presence of complex signaling pathways other than the conventional carcinogenic pathway. The molecular targeting for the diagnosis and treatment of endometrial cancers is a long way for the success.