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Impact of HER2 and PTEN simultaneous deregulation in non-small cell lung carcinoma: correlation with biological
Ioannis Panagiotou1, Stavros N Georgiannos, Evangelos Tsiambas
1Department of Thoracic Surgery, 401 General Military Hospital, Athens, Greece. panagiotouioannis@yahoo.gr
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 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs.
Materials And Method:
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 PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03) . Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the 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 developing metastases (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 event that leads to a more aggressive phenotype of NSCLC.
Insights
Simultaneous HER2 and PTEN protein deregulation in non-small cell lung carcinoma (NSCLC) is linked to increased metastasis and a more aggressive disease. This genetic event highlights potential therapeutic targets for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- HER2/neu overexpression is crucial in breast cancer therapy sensitivity.
- The role of HER2 in non-small cell lung carcinoma (NSCLC) is under investigation.
- PTEN tumor suppressor gene regulates the HER2/PI3K/Akt pathway.
Purpose of the Study:
- To assess the impact of simultaneous HER2 and PTEN protein alterations on NSCLC behavior.
- To investigate the relationship between HER2 and PTEN expression and NSCLC aggressiveness.
Main Methods:
- Immunohistochemistry for HER2 and PTEN protein expression in 61 NSCLC cases.
- CISH for HER2 gene amplification and chromosome 17 aneuploidy detection.
- Patient follow-up for 34-41 months post-surgery.
Main Results:
- HER2 overexpression in 27.9%, PTEN loss/low expression in 39.3% of NSCLC cases.
- Simultaneous HER2 overexpression and PTEN low/loss expression correlated with metastasis (71.4% vs 36.2%, p=0.03).
- HER2 overexpression increased metastasis risk (OR: 4.3), while PTEN overexpression decreased it (OR: 0.1).
Conclusions:
- Simultaneous HER2/PTEN deregulation signifies a more aggressive NSCLC phenotype.
- This genetic event is a significant factor in NSCLC progression.
- Targeting HER2/PTEN pathways may offer therapeutic strategies for NSCLC.
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