Immunohistochemical study of PTEN and phosphorylated mTOR proteins in familial and sporadic invasive breast carcinomas Panagiotis Bakarakos, Irene Theohari, Alexandros Nomikos, Eleni Mylona, Christos Papadimitriou, 1 Athanasios-Meletios Dimopoulos 1 & Lydia Nakopoulou 1st Department of Pathology, and 1 Department of Clinical Therapeutics, Medical School, University of Athens, Athens, Greece Date of submission 27 May 2009 Accepted for publication 1 September 2009 Bakarakos P, Theohari I, Nomikos A, Mylona E, Papadimitriou C, Dimopoulos A-M & Nakopoulou L (2010) Histopathology 56, 876–882 Immunohistochemical study of PTEN and phosphorylated mTOR proteins in familial and sporadic invasive breast carcinomas Aims: Loss of phosphatase and tensin homologue (PTEN) leads to activation of several kinases, including mammalian target of rapamycin (mTOR), which pro- motes 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 evalua- tion 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. Keywords: breast cancer, familial, mTOR, PTEN, sporadic Abbreviations: DFS, disease-free survival; ER, oestrogen receptor; mTOR, mammalian target of rapamycin; OS, overall survival; p-mTOR, phosphorylated mammalian target of rapamycin; PI3K, phosphatidylinositol-3 kinase; PTEN, phosphatase and tensin homologue; TBS, Tris-buffered saline Introduction The tumour suppressor protein phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid protein phosphatase playing a central role in the regulation of cells’ normal cellular function. Its basic targets are 3, 4, 5-trisphosphoinositides, which PTEN dephosphorylates. This dephosphorylation results in the inhibition of the phosphatidylinositol-3 kinase (PI3K) pathway. 1 Loss of function or total lack of PTEN protein from cancer cells causes hyperactivation of the PI3K pathway, leading to uncontrolled function of several kinases, including the serine ⁄ threonine kinase mammalian target of rapamycin (mTOR). 2 mTOR protein controls cell cycle progression, cell proliferation and tumour growth, and plays a pivotal role in the translation of specific mRNAs, such as those Address for correspondence: L Nakopoulou, Professor of Pathology, 1st Department of Pathology, Medical School, University of Athens, Mikras Asias St. 75, Goudi, 11527 Athens, Greece. e-mail: lnako@med.uoa.gr Ó 2010 Blackwell Publishing Limited. Histopathology 2010, 56, 876–882. DOI: 10.1111/j.1365-2559.2010.03570.x