Manuel Sobrinho Simões

Dimeric sialyl-Lex expression in gastric carcinoma correlates with venous invasion and poor outcome

BACKGROUND & AIMSnHigh expression of sialyl-Le(x) in tumors of different organs correlates with hematogenous metastasis and adverse outcome. Dimeric sialyl-Le(x) expression in gastric carcinoma was evaluated, and its prognostic significance within this setting was determined.nnnMETHODSnDimeric sialyl-Le(x) immunohistochemical expression in 97 gastric carcinomas was analyzed using the FH6 monoclonal antibody. Scoring was based on the percentage of immunoreactive cells: negative, low expression (< or = 25%), and high expression (> 25%).nnnRESULTSnImmunoreactivity was observed in 45 cases (46.4%), encompassing 27 and 18 cases with low and high expression, respectively. Significant relationships were found between dimeric sialyl-Le(x) expression and venous invasion (P = 0.0025) and histological classification (P = 0.05). No correlation was observed with other clinicopathologic features. Patients with tumors showing high expression of dimeric sialyl-Le(x) had a significantly shorter survival time than those with low or no expression (P = 0.03). By multivariate analysis, pathological TNM (pTNM) staging and venous invasion emerged as independent prognostic factors in the whole series. Within the group of patients with tumors in pTNM stages II and III, dimeric sialyl-Le(x) was the only independent prognostic factor.nnnCONCLUSIONSnHigh expression of dimeric sialyl-Le(x) correlates with venous invasion and poor outcome in gastric carcinoma.

mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression

The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathological features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex. To approach this question, we performed immunohistochemistry for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression. We evaluated the impact of each mTOR complex on SLC5A5 mRNA expression by treating cell lines with RAD001 (mTORC1 blocker) and Torin2 (mTORC1 and mTORC2 blocker). Phospho-AKT Ser473 expression was positively correlated with phospho-mTOR expression. Nuclear expression of phospho-AKT Ser473 was significantly associated with the presence of distant metastases. Treatment of cell lines with RAD001 did not increase SLC5A5 mRNA levels, whereas Torin2 caused a ~6 fold increase in SLC5A5 mRNA expression in the TPC1 cell line. In PTC, phospho-mTOR activation may lead to the activation of the mTORC2 complex. Its downstream effector, phospho-AKT Ser473, may be implicated in distant metastization, therapy resistance, and downregulation of SLC5A5 mRNA expression.