HER2/neu over Expression: A Prognostic Marker and a Possible Therapeutic Target in Ovarian Carcinoma- An Outlook for the Future

Abstract

Background: Ovarian cancer is the 2^nd most common cancer of gynaecological origin. Its prognosis is poor due to its presentation in the advanced stages and the 5-year survival rate is <50% with the available therapies. So, there is a constant need for new biological markers. The association between HER2/neu overexpression and ovarian cancer has been studied, but the results are still controversial. Therefore, this study was aimed at evaluating the association of HER2/neu with the clinicopathological features of epithelial ovarian cancers (EOC).

Objective(s):

1. To evaluate HER2/neu over expression as a prognostic marker for epithelial ovarian cancer.
2. To find out the association of HER-2/neu overexpression with chemotherapy response in epithelial ovarian cancer.

Methodology: It was a prospective study with a quantitative correlational study design of 90 epithelial ovarian cancer (EOC) cases presenting to Fauji Foundation Hospital, Rawalpindi between Nov 2018 to Oct 2019. Immunohistochemistry (IHC) was applied for HER2/neu expression and IHC 3+ patients were considered HER2 positive. The association of HER2/neu with clinicopathological factors of ovarian cancer e.g. stage, grade, pretreatment CA-125 levels and with chemotherapy response were assessed.

Results: Mean age of diagnosis was 53 ± 8.022 years. Mean pre-treatment CA-125 level was 1262 ± 1683 and 81.1% (n=73) had raised pre-treatment CA-125 levels.

Most of the patients presented with advanced stage i.e. stage III (56.7%, n=51) and high grade i.e. grade III (54.4%, n=49). Most common histological type seen was high grade serous carcinoma (51.1%). It was seen that 24.4% (n= 22) of the tumors over expressed HER2/neu, 65.6% (n=59) were HER2/neu negative, whereas 10% (n=9) were equivocal for HER2/neu expression. Overall, 72.2% patients had platinum sensitive disease. According to HER2/neu status, 20% HER2/neu positive patients had platinum sensitive disease & 3.3% had resistant disease whereas 47.8% HER2/neu negative patients had platinum sensitive disease & 10% were platinum resistant.

There was a statistically significant association of HER2/neu expression with grade (p 0.040) and pre-treatment CA-125 levels (p 0.032) whereas our study failed to show significant association between stage (p 0.383) and chemotherapy response (p 0.055).

Conclusion: Our study demonstrated that, like other tumors, HER2/neu was positive in 24.4% patients and its association with grade & pre-treatment CA-125 level was statistically significant, but we could not establish its association with chemotherapy response. However, this result needs to be validated in a larger study population and patients need to be followed up for longer duration to conduct survival analyses so as to establish HER2/neu as a prognostic marker for epithelial ovarian cancer.