Tumour cells of extramammary Paget's disease do not show either p53 mutation or allelic loss at several selected loci implicated in other cancers

Abstract

Summary Extramammary Paget's disease is a particular form of skin cancer of unknown histogenesis. To look for the genetic defects underlying the pathogenesis of this tumour, we have examined loss of heterozygosity (LOH), p53 and human papillomavirus (HPV) status, and the expression of c-erbB-2 and bcl-2 proteins in 14 cases. Unexpectedly, no LOH was detected at several loci commonly lost in other human cancers (namely 3p, 9p, 9q, 13q, 16q, 17p, and 17q) in 12 tumours examined. Altered p53 protein expression was entirely or mostly negative in all 14 cases. Direct sequencing of exons 5-8 of the p53 gene in eight cases revealed no mutation. Polymerase chain reaction amplification of the Ll gene of human papillomavirus (HPV) did not detect the virus that could inactivate p53 and retinoblastoma tumoursuppressor gene products. As expected, c-erbB-2 proto-oncogene protein was overexpressed in six cases. The expression of bcl-2 was negative in all cases. The results presented in this study suggest that molecular events underlying extramammary Paget's disease differ from those of other common epithelial malignancies and that tumour-suppressor genes located in chromosome regions not examined in this study may be important.

BD ProEx™C immunostaining in extramammary Paget's disease and perineal melanoma

“…8,9,[12][13][14] PCR studies for HPV have also been reported as negative in all mammary and extramammary Paget's disease (20/20 and 14/14 cases, respectively). 15,16 Although most of our cases of anal Paget's disease were positive for ProExtC, HPV type 16 was detected by PCR in one case where 75% of Paget cells stained positive. This case did not show histologic changes diagnostic of HPV nor was HPV DNA detected by in situ hybridization.…”

Vulvar Paget Disease: One Century After First Reported

“…No study has evidenced human papillomavirus (HPV) antigen or HPV DNA in the cells of vulvar Paget disease specimens [42,[86][87][88][89], so that the participation of HPV infection in the pathogenesis of the disease is unlikely. On the other hand neither p53 gene mutations nor loss of heterozygosity at selected loci were detected in Paget cells [89]. Immunohistochemical analyses for c-erb-B2 antigen [22,30,90], bcl2, and p53 protein expression [59,84,91,92] have revealed conflicting and inconclusive results.…”

Expression of Structurally Unaltered Androgen Receptor in Extramammary Paget's Disease

“…Tumor tissue was isolated from 5 to 10 consecutive 6 m frozen tissue sections by microdissection, and genomic DNA was isolated according to standard methods by proteinase K digestion and phenol-chloroform extraction (Takata et al, 1997). Exons 2 to 8 of the androgen receptor gene were amplified using primers and PCR conditions as described previously (Tilley et al, 1996).…”

“…We previously showed that erbB-2 overexpression by either gene amplification or transcriptional activation may play a part in the progression of EMPD (Takata et al, 1999). However, other molecular genetic defects, including p53 mutations, allelic loss of several selected chromosome arms as well as abnormal activation of the ␤-catenin gene, which are commonly seen in other epithelial malignancies, were not detected in EMPD (Takata et al, 1999;Takata et al, 1997). To explore further the molecular pathogenesis of EMPD, we aimed at examining androgen receptor expression in Paget's cells of EMPD for several reasons.…”