{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T04:22:01Z","timestamp":1767846121476,"version":"3.49.0"},"reference-count":38,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2010,8,3]]},"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p>\n                  <jats:italic>EGFR<\/jats:italic> copy number increases have been frequently reported in cancer including vulvar carcinomas. Co-amplification of cancer genes plays an important role in the development of many tumour types. To better understand the effect of <jats:italic>EGFR<\/jats:italic> aberrations on vulvar cancer phenotype and patient prognosis, the authors analysed <jats:italic>EGFR<\/jats:italic> copy number changes using fluorescence in situ hybridisation and EGFR expression by immunohistochemistry in a tissue microarray containing 183 squamous cell carcinomas of vulva. Furthermore, the authors analysed the co-amplification frequency of <jats:italic>EGFR<\/jats:italic> with <jats:italic>HER2<\/jats:italic>, <jats:italic>CCND1<\/jats:italic>, <jats:italic>MYC<\/jats:italic> and <jats:italic>PIK3CA<\/jats:italic>, respectively. <jats:italic>EGFR<\/jats:italic> copy number increase was found in 39.3% of the tumours. Seventeen per cent of vulvar carcinomas showed <jats:italic>EGFR<\/jats:italic> high polysomy including 9% with amplification of the <jats:italic>EGFR<\/jats:italic> gene. Copy number gain of the <jats:italic>EGFR<\/jats:italic> locus was associated with non-basaloid phenotype (p=0.03), high-tumour stage (p&lt;0.001), human papillomaviruse negativity of tumours (p=0.04) and the number of lymph node metastases (p=0.02). EGFR protein expression was statistically correlated to <jats:italic>EGFR<\/jats:italic> copy number increase (p&lt;0.05). The observed co-amplification rate of <jats:italic>EGFR<\/jats:italic> with all four additionally examined oncogenes was much higher than statistically expected. There was a highly significant association between <jats:italic>EGFR<\/jats:italic> copy number increase and <jats:italic>CCND1<\/jats:italic> amplifications (p&lt;0.001) as well as the total number of gene amplifications (p=0.04). <jats:italic>EGFR<\/jats:italic> copy number gains were significantly related to unfavourable patient outcome in univariate analysis and multivariate Cox regression analysis. In conclusion, <jats:italic>EGFR<\/jats:italic> copy number increases are detectable in a substantial proportion of vulvar carcinomas with relationships to advanced tumour stages and the development of lymph node metastases. <jats:italic>EGFR<\/jats:italic> copy number aberrations are connected to other gene amplifications and probably define an human papillomaviruses-independent pathway in the development of vulvar carcinomas. These data support the potential utility of <jats:italic>EGFR<\/jats:italic> inhibitors as a therapeutic alternative in a subset of vulvar carcinomas.<\/jats:p>","DOI":"10.1136\/jcp-2010-079806","type":"journal-article","created":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T08:38:19Z","timestamp":1322728699000},"page":"133-139","source":"Crossref","is-referenced-by-count":30,"title":["<i>EGFR<\/i> gene copy number increase in vulvar carcinomas is linked with poor clinical 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