TY - JOUR TI - Immunohistochemical study of PTEN and phosphorylated mTOR proteins in familial and sporadic invasive breast carcinomas AU - Bakarakos, P. AU - Theohari, I. AU - Nomikos, A. AU - Mylona, E. AU - Papadimitriou, C. AU - Dimopoulos, A.-M. AU - Nakopoulou, L. JO - Diagnostic Histopathology PY - 2010 VL - 56 TODO - 7 SP - 876-882 PB - SN - 1756-2317 TODO - 10.1111/j.1365-2559.2010.03570.x TODO - mammalian target of rapamycin; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; Wnt1 protein; MTOR protein, human; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein serine threonine kinase; signal peptide; target of rapamycin kinase, adult; article; breast carcinoma; cancer staging; cancer survival; controlled study; cytoplasm; female; human; human tissue; image analysis; immunohistochemistry; lymph node; major clinical study; overall survival; phenotype; priority journal; protein depletion; protein determination; protein expression; protein phosphorylation; aged; breast tumor; carcinoma; cell nucleus; immunohistochemistry; metabolism; middle aged; pathology; phosphorylation; proportional hazards model; very elderly, Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Cell Nucleus; Cytoplasm; Female; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Middle Aged; Phosphorylation; Proportional Hazards Models; Protein-Serine-Threonine Kinases; PTEN Phosphohydrolase, Mammalia, Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Cell Nucleus; Cytoplasm; Female; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Middle Aged; Phosphorylation; Proportional Hazards Models; Protein-Serine-Threonine Kinases; PTEN Phosphohydrolase; TOR Serine-Threonine Kinases TODO - Aims: Loss of phosphatase and tensin homologue (PTEN) leads to activation of several kinases, including mammalian target of rapamycin (mTOR), which promotes cell cycle progression. The aim was to study the expression of PTEN and phosphorylated (p)-mTOR in familial and sporadic invasive breast carcinomas and their relation to clinicopathological features, molecular indices (Wnt1) and patients' survival. Methods and results: PTEN and p-mTOR were detected immunohistochemically in 215 sections of invasive breast carcinomas (112 with a familial history of breast cancer). Image analysis was used and univariate and multivariate analyses employed for statistical evaluation of results. PTEN was detecte5d in the nucleus (73.5%) and p-mTOR in the cytoplasm (44.2%) of cancer cells. Loss of PTEN protein was more frequently detected in women with a familial history of breast cancer (72%) (P < 0.0001), while its expression was negatively correlated with Wnt1, in total (P = 0.049). p-mTOR showed a positive association with lymph node status (P = 0.010) and was found to have a negative impact on patients' overall survival (P = 0.016). Conclusions: Loss of PTEN protein expression appears to occur more frequently in women with a family history of breast cancer, whereas activation of mTOR protein seems to be related to a more aggressive phenotype. © 2010 Blackwell Publishing Limited. ER -