Impact of HER2 and PTEN Simultaneous Deregulation in Non-small Cell Lung Carcinoma: Correlation with Biological Behavior

Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer,modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expressionin non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTENnegatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate therole of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour ofNSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one(n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy.Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases,low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTENlow/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship betweenthe number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04).Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developingmetastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR:0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic eventthat leads to a more aggressive phenotype of NSCLC.