title: Epidermal growth factor receptor (EGFR), HER2 and insulin-like growth factor-1 receptor (IGF-1R) status in ovarian adult granulosa cell tumours.
abstract: OBJECTIVE
  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 epidermal growth factor receptor (EGFR), HER2 and insulin-like growth factor-1 receptor (IGF-1R) status in AGCTs with a view to investigating whether or not these receptors might be potential therapeutic targets in these neoplasms.
  
  
  RESULTS
  Immunohistochemical staining for EGFR, HER2 and IGF-1R 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. Twenty-three of 31 (74%) AGCTs showed some degree of EGFR expression, generally with cytoplasmic or mixed membranous and cytoplasmic staining of variable intensity. Eleven of 27 (41%) cases exhibited strong membranous and cytoplasmic expression of IGF-1R. HER2 expression was not seen. No mutations were found in exons 18-21 of the EGFR gene in hot-spots of therapeutic relevance.
  
  
  CONCLUSIONS
  This study raises the possibility that anti-EGFR and/or anti-IGF-1R therapies may be of potential benefit 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.
authors.affiliation: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast Health and Social Care Trust, Belfast, UK; Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Higgins
authors.forename: Aidan
authors.initials: A
authors.lastname: Brady
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Dobbs
authors.forename: Manuel
authors.initials: M
authors.lastname: Salto-Tellez
authors.forename: Perry
authors.initials: P
authors.lastname: Maxwell
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D005260:Female; D006106:Granulosa Cell Tumor / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: adult granulosa cell tumour; epidermal growth factor receptor; immunohistochemistry; mutation analysis; ovary; tyrosine kinase; tyrosine kinase inhibitors