Re-Classification of Carcinoma of Breast According To Molecular Classification and Its Correlation with Histologic Features

Background: Breast cancer shows marked heterogeneity which is proven by the fact that tumors with similar morphologic and immuno histo-chemical features show distinct clinical behavior and different response to therapy. This led to microarray-based global gene expression profiling (GEP) and new avenues for classifying breast cancer into molecular subtypes. Among all molecular subtypes, the worst prognosis group has been identified as triple negative phenotype (TN). Further within this group, basal like breast cancer (BLBC) was identified using a 5 marker surrogate panel including ER-PR-HER2–negative and basal markers i.e. epidermal growth factor receptor (EGFR) or Cytokeratin 5/6 (CK5/6) positive. CK 5/6 is easily available and specific IHC surrogate basal markers and can be readily included in a five marker panel in prognostication of breast cancers. BME is not limited to triple negative subtypes but is also seen in other molecular subtypes. Methods: 61 cases of invasive breast carcinoma in which detailed clinical and histological prognostic factors could be determined were classified into molecular phenotype using IHC surrogate classification. Tumors expressing basal markers CK5/6 were classified as basal marker expressing (BME) tumors and were also compared with ER, PR, Her-2/neu expressing and also triple negative tumors. These tumors were compared with various prognostic and predictive markers of invasive breast carcinoma. Results: BME was seen in 50/106 cases. Also BME showed a significant association with tumor necrosis, lymph node metastasis and high histological grade. Conclusion: BME in breast carcinomas is an independent prognostic marker and its expression is not limited to triple negative cases. An expanded surrogate panel of ER, PR, Her-2 neu, and CK 5/6 provides more prognostic value than three panel marker.

Anti-depressant-like activity of a novel serotonin type-3 (5-HT3) receptor antagonist in rodent models of depression.

N-Cyclohexyl-3-methoxyquinoxalin-2-carboxamide (QCM-13), a novel 5-HT3 antagonist identified from a series of compounds with higher pA2 (7.6) and good log P (2.91) value was screened in rodent models of depression such as forced swim test (FST), tail suspension test (TST), interaction studies with standard anti-depressants and confirmatory studies such as reversal of parthenolide induced depression and reserpine induced hypothermia. In FST (2 and 4 mg/kg) and TST (2 and 4 mg/kg), QCM-13 significantly reduced the duration of immobility in mice without affecting the base line locomotion. QCM-13 (2 and 4 mg/kg) was also found to have significant interaction with standard anti-depressants (fluoxetine and bupropion in FST and TST respectively). Further, reversal of parthenolide induced depression in mice and reserpine induced hypothermia in rat models indicate the serotonergic influence of QCM-13 for anti-depressant potential.