This first decision impact study in a Middle Eastern country showed the significant effect of Oncotype DX testing on clinical practice, further demonstrating the consistent impact of such testing worldwide.

BackgroundBreast carcinoma is the commonest cancer among UAE population and the most common cancer among females. Examination of the 5′ promoter regions of trefoil factor 3 (TFF3) gene has identified putative estrogen and progesterone receptor–DNA binding domains as direct response elements to estrogen and progesterone that are linked to breast functions or steroid regulation. The study was designed to determine the role of TFF3 in breast cancer chemoresistance with the aim of establishing TFF3 expression as a biomarker for drug resistance.MethodsIn total, 133 cases of breast carcinoma treated with neo-adjuvant therapy were collected. Tissue samples from pre-neoadjuvant therapy as well as tissues from post-neo-adjuvant therapy of those cases were collected and stained with immunohistochemistry for TFF3, Bcl2, BAX, cleaved caspase-3, AKT-1, NF kappa B and Ki-67.ResultsThere was increased expression of TFF3 in residual invasive carcinoma cells. There was a significant correlation between the expression of TFF3 in breast carcinoma cells and response to neoadjuvant chemotherapy (p = 0.0165). There was significant co-expression of TFF3 with AKT1 (p = 0.0365), BCl2 (p = 0.0152), and NF Kappa-B (p = 0.0243) in breast carcinoma cases with residual carcinoma following neoadjuvant therapy which support the role of TFF3 in chemoresistance.ConclusionThe expression of TFF3 is significantly associated with residual breast carcinoma following neoadjuvant chemotherapy suggesting its expression is associated with increased resistance to chemotherapy. This is supported by its co-expression with antiapoptotic proteins; BCl2, AKT1 and NF Kappa-B in residual breast carcinoma cells and very low proliferating index and apoptotic bodies in residual tumors.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5316-y) contains supplementary material, which is available to authorized users.

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BackgroundUp-regulation of the PI3K/mTOR (phosphatidylinositol-3′ kinase/mammalian target of rapamycin) signaling is common in carcinoma. Consistently, targeting these molecules has been shown to halt the growth of many tumors. The main purpose of this study was to develop surrogate biomarkers of the antitumor activity of PI3K/mTOR inhibitors.MethodsFragments from eight tumors were collected immediately after resection in ice-cold RPMI gassed with 95% O2 :5% CO2. Viability was determined by measuring tumor cellular respiration (mitochondrial O2 consumption). The specimens were incubated at 37°C with and without 50 nM GSK2126458 (a highly potent and selective inhibitor of PI3K/mTOR) for 90 min. The tissue was then processed for histology, measurement of intracellular caspase-3 activity (using the caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin), and immunohistochemical detection of the apoptotic biomarkers caspase-3, cytochrome C, and annexin A2.ResultsGSK2126458 induced morphologic changes in four tumors (two invasive ductal carcinomas, one invasive lobular carcinoma, and one ovarian dysgerminoma), intracellular caspase-3 activity in three tumors (two invasive ductal carcinomas and one poorly differentiated signet ring adenocarcinoma of gastric origin), and immunohistochemical evidence of apoptosis in at least four tumors (three invasive ductal carcinomas and one adenocarcinoma of gastric origin). Two tumors (ovarian serous carcinoma and moderately differentiated adenocarcinoma of colorectal origin) demonstrated no treatment effect.ConclusionThese preliminary results demonstrate the feasibility of using in vitro biomarkers for detecting antitumor activities of the rapidly emerging PI3K/mTOR inhibitors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-014-0090-z) contains supplementary material, which is available to authorized users.