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ABSTRACT: Mucinous ovarian carcinomas (MC) typically do not respond to current conventional therapy. We have previously demonstrated amplification of HER2 in 6 of 33 (18.2%) mucinous ovarian carcinomas (MC) and presented anecdotal evidence of response with HER2 targeted treatment in a small series of women with recurrent HER2 amplified (HER2+) MC. Here, we explore HER2 amplification and KRAS mutation status in an independent cohort of 189 MCs and 199 mucinous borderline ovarian tumours (MBOT) and their association to clinicopathologic features. HER2 status was assessed by immunohistochemistry (IHC), FISH and CISH and interpreted per ASCO/CAP guidelines, with intratumoral heterogeneity assessment on full sections, where available. KRAS mutation testing was performed with Sanger sequencing. Stage and grade were associated with recurrence on both univariate and multivariate analysis (p< 0.001). Assessment of HER2 status revealed overexpression/amplification of HER2 in 29/154 (18.8%) MC and 11/176 (6.2%) MBOT. There was excellent agreement between IHC, FISH and CISH assessment of HER2 status (perfect concordance of HER2 0 or 1+ IHC with non-amplified status, and 3+ IHC with amplified status). KRAS mutations were seen in 31/71 (43.6%) MC and 26/33 (78.8%) MBOT, and were near mutually exclusive of HER2 amplification. In the 189 MC cases a total of 54 recurrences and 59 deaths (53 of progressive disease) were observed. Within MC either HER2 amplification/overexpression or KRAS mutation was associated with decreased likelihood of disease recurrence (p=0.019) or death (p=0.0041) when compared to cases with neither feature. Intra-tumoral heterogeneity was noted in 26% of HER2 overexpressing cases. These data support the stratification of MC for the testing of new treatments, with HER2 targeted therapy as a viable option for HER2+ advanced or recurrent disease. Further research is required to delineate the molecular and clinical features of the 34% of MC cases with neither HER2 amplification nor KRAS mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology 08/2012; · 7.59 Impact Factor