HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy.

Jessica N Mcalpine,Dianne M Miller,Kimberly C Wiegand,Martin Köbel,David G Huntsman,Brigitte M Ronnett,Steve E Kalloger,Anna Adamiak,Kenneth D Swenerton,Russell Vang,C Blake Gilks

doi:10.1186/1471-2407-9-433

Jessica N Mcalpine, Dianne M Miller + Show 9 more

Open Access

https://doi.org/10.1186/1471-2407-9-433

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Abstract

BackgroundThe response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer.MethodsHER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy.ResultsAmplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy.ConclusionHER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.

Highlights

The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies
This cohort has been described previously [36] and the 34 mucinous carcinomas are part of a tissue microarray consisting of 541 cases of ovarian cancer, 2) three mucinous carcinomas and seven mucinous borderline ovarian tumor (BOT) collected as part of our Ovarian Tumor Bank in BC, since 2000, 3) three archival cases from a previously published series on mucinous ovarian carcinomas from our institution [37], and 4) 15 mucinous BOT cases, gastrointestinal type, from the pathology archives of Johns Hopkins University School of Medicine collected from their institution (n = 12) or as consults from other institutions (n = 3) during the period between 1994-2005
Immunostaining and FISH data were available for 33 cases of mucinous carcinoma and 16 cases of mucinous BOT (Figure 1)

Summary

Introduction

The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. In a series of 41 patients with HER2 overexpressing EOC, identified from a series of 837 EOC tested for HER2 expression, there was only one complete responder and two partial responders for an overall response rate of 7.3% and a median progression-free interval of two months [19]. In this series, HER2 expression was determined by immunohistochemistry (IHC) only, and none of the patients in this series had carcinomas of mucinous subtype

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