Clinic and prognostic significance of Phosphatase and tensin homolog (PTEN), Phosphoinositide 3 kinase (PI3K), mammalian target of rapamycin (MTOR), KRAS expression in differentiated thyroid cancer

Background and Aims: Thyroid cancer is the most common type of endocrine malignancy. The vast majority of differentiated thyroid tumors orginate from thyroid follicular cells and encompass well differentiated papillary and follicular carcinoma. As in many other human cancers, genetic alterations are the driving force for the tumorigenesis and pathogenesis of thyroid cancer, particularly those that occur in genes encoding for key players of major signaling pathways. In this study we investigated clinic and prognostic role of the key players of this pathway PTEN, PI3K-p85, mTOR expressions and K-Ras mutational status in differentiated thyroid cancer.Methods: Patients with pathologically proven thyroid cancer between 2005-2011 were enrolled to this study. Tissue samples were obtained from parafine blocks and evaluated for PTEN, PI3K-p85, mTOR expression with immunohistochemical method. K-Ras mutational status was assessed by the PCR. Data was compared with clinicopathologic characteristics of patients. Khi2 test was used for categoric measurements between groups. Progression free survival was analyzed using Kaplan-Meier plots and log rank test.Results: In this study 101 differential thyroid cancer were studied. The mean of the patients ages were 46,3±12,1. 78,2% of patients were female and the others were male. PTEN, mTOR, PI3K expressions were found in different levels on tumor tissue samples. PTEN, mTOR, PI3K-p85, K-ras expressions were compared with gender, histological subtype, lenfovascular invasion, capsular invasion, multifocality, tumor size, disease progression. Statistically significant was found between p85 and lenfovascular invasion and PTEN and multifocality (respectively p=0,048, p=0,04). Limited significant difference was found between p85 and capsular invasion by stastically. (p=0,056) K-ras mutation was found in the rate of %17,4. K-ras mutation was observed mostly in female groups though there was no mutation in male groups statistically significant difference was found between groups .(p=0,047). Progression free survival was found lower (37,1 months ) in the group of moderate expression with p85. (%95 CI 32,8-41.5) p=0,043. Survival data could not be given that all of the patients are stil alive.Conclusion: The relation was found between expression of PTEN, mTOR and P13K-p85 and some pathologic features of tumor. In terms of K-ras the significant difference was found between gender. It was suggested that the determination of these expressions in the tissues may be both predictive and prognostic markers for the further improvable targeted treatments and management of disease. Over all survival data would be more useful to indicate the significance of these markers if the patients will be studied for the longer periods.