Loss of retinoblastoma protein expression is frequent in small cell neuroendocrine carcinoma of the cervix and is unrelated to HPV type

We have previously identified an inverse relationship between p53 and retin oblastoma protein (pRb) immunoreactivity in non-small cell carcinoma of the cervix. Because pRb is infrequently expressed in small cell carcinoma of t he lung, we analyzed 25 small cell neuroendocrine carcinomas of the cenix t o test the hypotheses that 1) lack of pRb expression is associated with the neuroendocrine phenotype in human papillomavirus (HPV)-associated cervical carcinoma and 2) the inverse relationship between p53 and pRb immunoreacti vity also occurs in these tumors. HPV type was analyzed by PCR, HPV distrib ution by in situ hybridization and expression of p53 and pRb by immunohisto chemistry. All of the tumors contained HPV sequences, with 13 tumors HPV 16 positive, 11 HPV 18 positive, and 1 HPV 45 positive. Zn situ hybridization showed large intranuclear dot-like signals in all positive tumors, suggest ing viral integration. No multiple infections were identified. Expression o f retinoblastoma protein was not detectable in 23 tumors (92%), the remaini ng two showing only weak, focal expression. Expression of p53 protein was v ariable in distribution and intensity. It did not correlate with HPV type, and there was no relationship with pRb immunoreactivity. These data indicat e that, although there is no reciprocal relationship between p53 and pRb im munoreactivity in these tumors, retinoblastoma protein is infrequently expr essed in HPV-containing small cell neuroendocrine carcinoma of the cervix, irrespective of infecting HPV type. This is consistent with the reported fi ndings in small cell carcinoma of the lung and suggests that the small cell neuroendocrine phenotype may be related to the abrogation of retinoblastom a protein function. (C) 1999 by W.B. Saunders Company .