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

Aims-To determine by fluorescence in situ hybridisation (FISH) whether dele tion of D17S34, a subtelomeric probe for 17p, occurs in invasive squamous c arcinoma of the cervix, and to determine the extent of such loss by analysi s of the p53 and HER2/NEU genes. Methods-Fourteen invasive squamous cell carcinomas of the cervix were inves tigated by FISH for D17S34, p53, and HER2/NEU. Dual hybridisation of each p robe with the chromosome 17 alpha satellite (D17Z1) probe was performed on paraffin wax embedded sections, and the fluorescence ratios of the paired s ignals were determined. Broad spectrum human papillomavirus (HPV) typing by ISH-I and GP5+/6+ polymerase chain reaction was also performed. Results-Twelve tumours were HPV positive, nine with HPV-16, and one each wi th 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 l oss of p53 only, suggesting that deletion was limited to the p arm. A secon d tumour showed simultaneous losses of all probes, indicative of whole chro mosome 17 loss during tumour growth. The two remaining specimens showed los s of D17S34 only, diffuse in one, and localised within the tumour in the ot her. Aberrations of p53 or HER2/NEU were not seen independently of D17S33 l oss, and loss did not correlate with HPV presence or type. Conclusions-These data show that D17S34 loss is prevalent, marking 28% of t he invasive squamous carcinomas in this study. The observed intratumoral he terogeneity indicates that, at least in some cases, this loss occurs after invasion and is therefore a late event in the path of cervical carcinogenes is.