Altered transcriptional and translational levels of Nm23H1 in north Indian breast cancer females and it’s prognostic relevance

Background: Breast cancer is the commonest female cancer worldwide and metastasis deteriorates it’s therapeutic outcome. Several clinicopathological parameters have been associated with metastatic suppressor gene (MSG) expression levels that decipher it’s prognostic/predictive significance. The role of MSG Nm23H1 in breast cancer is inconclusive. Our goal was to investigate the possible clinical significance and correlation of Nm23H1 with metastatic breast cancer. Materials & methods: The study was conducted on 178 histologically proven cases of breast cancer and similar number of matched controls. Semi quantitative reverse transcriptase polymerase chain reaction (RT PCR) and immunohistochemistry (IHC) were used to investigate KiSS1 at gene and protein level, respectively. The Nm23H1 levels were correlated with several patient characteristics including age, family history, hormonal receptor status, stage, tumor size, nodal involvement and metastatic manifestation. Statistical analysis was done to evaluate correlation between expression of Nm23H1 and clinicopathological parameters. Results: Our study revealed (i) Diminished Nm23H1 levels in normal vs breast cancer (p < 0.05). (ii) Likewise, a statistically significant down-regulation of NM23H1 was observed in metastatic cases vs non metastatic in breast cancer (P = 0.04). (iii) NM23H1 levels strongly correlated with T,N,M category, histological grade and advanced stage (p<0.001) and not associated with any other studied parameter. Conclusion: Conclusively, reduced Nm23H1 expression is a negative prognostic factor for OS, advancing tumor stage, axillary lymph node status, metastatic propensity and advancing grade of the breast cancer patient. Patients with negative Nm23H1 expression may require a more intensive therapeutic strategy.