Loss of sequences on the short arm of chromosome 17 is a late event in squamous carcinoma of the cervix

C S Herrington¹, M Worsham², S A Southern¹, P Mackowiak² and S R Wolman³

¹ Department of Pathology, University of Liverpool, Royal Liverpool University Hospital, Liverpool L69 3GA, UK
² Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD20814, USA
³ Department of Pathology, Henry Ford Hospital, 2799 W Grand Boulevard, Detroit, MI 48202, USA

Correspondence to:
Professor Herringtonc.s.herrington{at}liv.ac.uk

Aims—To determine by fluorescence in situ hybridisation (FISH) whether deletion of D17S34, a subtelomeric probe for 17p, occurs in invasive squamous carcinoma of the cervix, and to determine the extent of such loss by analysis of the p53 and HER2/NEU genes.

Methods—Fourteen invasive squamous cell carcinomas of the cervix were investigated by FISH for D17S34, p53, and HER2/NEU. Dual hybridisation of each probe with the chromosome 17 satellite (D17Z1) probe was performed on paraffin wax embedded sections, and the fluorescence ratios of the paired signals were determined. Broad spectrum human papillomavirus (HPV) typing by ISH and GP5+/6+ polymerase chain reaction was also performed.

Results—Twelve tumours were HPV positive, nine with HPV-16, and one each with types 18, 31, and 39. Loss of D17S34 was identified in four tumours, one of which was HPV negative. In one tumour, D17S34 loss was accompanied by loss of p53 only, suggesting that deletion was limited to the p arm. A second tumour showed simultaneous losses of all probes, indicative of whole chromosome 17 loss during tumour growth. The two remaining specimens showed loss of D17S34 only, diffuse in one, and localised within the tumour in the other. Aberrations of p53 or HER2/NEU were not seen independently of D17S34 loss, and loss did not correlate with HPV presence or type.

Conclusions—These data show that D17S34 loss is prevalent, marking 28% of the invasive squamous carcinomas in this study. The observed intratumoral heterogeneity indicates that, at least in some cases, this loss occurs after invasion and is therefore a late event in the path of cervical carcinogenesis.

Key Words: cervix • fluorescence in situ hybridisation • chromosome 17 • papillomavirus

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