The role of Her-2 in EOC is still unclear. Several studies support a potential role upon EOC survival  while others consider it as not being related to prognosis . This can be mainly attributed to the fact that up to-date there is no consensus about the evaluation protocol applied for Her-2 overexpression in EOC. The situation became even more complex due to the fact that different antibodies are used. It can thus be concluded that regarding Her-2 in EOC there is a far more imperative need at least for a consensus in the way Her-2 overexpression will be evaluated.
The existing reports upon efficacy of anti-Her-2 treatment in ovarian cancer patients are few and not encouraging, mainly because the response rate was rather low [4, 5]. Such finding though can be explained possibly by the hypothesis that other molecular pathways interfere with the EGFR/Her-2 signalling [6, 10], potentially minimizing Her-2 impact on ovarian cancer cell proliferation and ultimately to the Her-2 effect on disease progression and prognosis.
Herein we hypothesized that such interference could involve the FSHR and its downstream signalling. Although FSHR-expressing EOC patients have been shown to be of worse prognosis compared to FSHR non-expressing EOC patients , an effective selective anti-FSHR intervention has not been published so far. Several clinical trials using anti-gonadotropin receptor (GnR) agents have failed to demonstrate a significant improvement in EOC patient survival [11, 12], most possibly due to the fact that such treatments target simultaneously the luteinizing hormone receptor (LHR) as well, a receptor being a positive prognosticator for EOC survival. Thus, anti-GnR failure can be attributed to the combined cancelling of a negative and a positive prognosticator.
Despite the failure of anti-GnR treatment, the idea of using FSHR - a negative prognosticator for EOC - as a stratifying factor in order to evaluate Her-2 impact on EOC survival, is still appealing. Most possibly FSHR signalling by interfering with Her-2 could abrogate Her-2 signalling and thus its effect on survival. The results presented herein verify this hypothesis. Only in FSHR negative EOC cases does the Her-2 expression present a significant negative impact on patient survival. Of course it could be argued that the sample size of Her-2 positive cases presented herein is rather small. We would agree on such comment, highlighting at the same time though the fact that Her-2 expression in EOC is also restricted. Additionally, by dissecting the Her-2 expressing cases into FSHR positive and negative, we provide an explanation for the restricted impact of anti-Her-2 treatment in EOC. It can be hypothesized that it is likely for EOC patients with the specific phenotype (FSHR negative/Her-2 positive) to benefit from anti-Her-2 treatment. Since, though such patients consist a very small proportion of EOC patients (in our series 3 out of 153), a multicentre clinical study would be necessary to obtain an adequate sample to prove in a statistically significant way whether our current findings and hypothesis are of clinical importance.