Epidermal Growth Factor Receptor (EGFR), HER2 and Insulin Growth Factor Receptor-1 (IGFR-1) Status in Ovarian Adult Granulosa Cell Tumours

abstract

Aims

Adult granulosa cell tumours (AGCTs) are uncommon ovarian sex cord-stromal tumours which recur following surgical removal in up to 50% of patients. Treatment options for recurrent and advanced stage AGCTs are limited with poor response to chemotherapy and radiotherapy. We aimed to assess the Epidermal Growth Factor Receptor (EGFR) (HER1), HER2 and Insulin Growth Factor Receptor-1 (IGFR-1) status in AGCTs with a view to investigating whether these receptors might be potential therapeutic targets in these neoplasms.

Methods And Results

Immunohistochemical staining for EGFR, HER2 and IGFR-1 was undertaken in 31 AGCTs. Tumour DNA was also analysed for mutations in the tyrosine kinase domain of EGFR (exons 18-21) by Cobas mutation RT-PCR. 23/31 (74%) AGCTs showed some degree of EGFR expression, generally with cytoplasmic or mixed membranous and cytoplasmic staining of variable intensity. 11/27 (41%) cases exhibited strong membranous and cytoplasmic expression of IGFR-1. HER2 expression was not seen. No mutations were found in exons 18-21 of the EGFR gene in hotspots of therapeutic relevance.

Conclusions

This study raises the possibility that anti-EGFR and/or anti-IGFR-1 therapies may be potential agents in ovarian AGCTs and this requires further study. Lack of known mutations within the tyrosine kinase domain of EGFR suggests that EGFR-related tyrosine kinase inhibitors may not be useful therapeutically.