HER2/NEU PROTEIN OVEREXPRESSION BY IMMUNOHISTOCHEMICAL ANALYSIS AND PROGNOSIS IN COLORECTAL CANCER CASES

Abstract

Background: HER2/neu is a member of the human epidermal growth factor receptors which includes HER1, HER3, and HER4, all of them are involved in the complex regulation of cell growth, proliferation and survival. HER2 is also known as proto-oncogene Neu. HER2 activation initiates signal cascades including the MAPK and P13K/AKT {3-kinase} pathways that are essential for cell proliferation and differentiation. In cancer cells dysregulation of these pathways and increased expression of HER2/neu promotes tumour cell growth and as a factor of poor prognosis. AIM: To determine overexpression of HER2/NEU protein by immunohistochemistry analysis in colorectal carcinoma cases.

Methods: A prospective study of 47 cases was carried out in the department of pathology in collaboration with department of surgery after consent of all cases. Clinical data like patient age, sex and other relevant details were noted from the pathological records. All cases of clinically diagnosed colorectal cancers prior to therapy were included. Cases diagnosed or suspected to be benign by clinically or colonoscopy were excluded.

Observations: Her2n/neu expression was correlated with age, gender, tumour location, lymph node status, Age more than 50 years shows 15 cases of her2 positive and three cases shows her2 negative. The correlation with age was statistically significant with p-value0.03.  Seven cases were her2/neu positive and twenty-one (21) cases were her2/neu negative in females. Two (2) cases were her2/neu positive and 17 cases were her2/neu negative in males. Histopathological types of colorectal cancers were compared between the two groups and found insignificant with p-value 0.992. All the grades of the tumour significantly related to Her-2/neu expression of tumour. Death rate due to colorectal cancers were compared between Her2 positive and Her2negative groups were found insignificant with p-value0.07 whereas two year disease free survival rate when compared found significantly related with p-value0.01. Grade-3 tumour was significantly associated with HER2/neu expression of the malignancy excluding others as confounding factors as proved by multivariate logistic regression with odds ratio1.34 and 95%CI (0.75-9.34) P-value0.007. Colorectal cancer with grade -3 growth was the only independent prognostic factor of the malignancy with irrespective of Her2/neu status. Thus Grade-3 of CRC had proved for the poor prognosis with HR 2.0, 95% CI (0.95-4.23), P=0.03.

Conclusion: HER2/neu overexpression indicates higher tumour grade, stage and prognosis of the patient while the patients undergone neoadjuvant chemo-radiotherapy were more risk in the Her2 negative groups than Her2/neu positive cases. A monoclonal antibody, Trastuzumab (marketed as Herceptin) directed against HER-2/neu has increased survival in many tumours. Two-year disease-free survival rate more in the her2/neu positive cases when compared to her2 neg patients. Hence targeted Therapy could be helpful in patients with high grade and lymph node or distant metastases. Grade-3 of CRC had proved for the poor prognosis. Because of many pitfalls in immunohistochemistry, further studies such as gene amplification studies involving large no of patients are needed to assess HER-2/neu expression in colorectal carcinomas and to develop new targeted therapy.