Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 L1 gene of human papillomavirus (HPV) did not detect the virus that could inactivate p53 and retinoblastoma tumour-suppressor 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.
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PMID:Tumour cells of extramammary Paget's disease do not show either p53 mutation or allelic loss at several selected loci implicated in other cancers. 932 50

Extramammary Paget's disease (EMPD) is an uncommon neoplasm of the skin that shows differentiation to an apocrine sweat gland. Although we previously showed that erbB-2 overexpression may play a part in the progression of EMPD, molecular genetic defects underlying the development of EMPD are poorly understood. In the study described here, we examined androgen receptor expression and gene alterations in 30 cases of EMPD without internal malignancy. Immunohistochemistry revealed that 24 of 30 (80%) cases of EMPD variably expressed nuclear androgen receptor. Semi-quantitation of receptor content by scoring immunostained sections showed no difference between in situ (n = 17) and invasive (n = 13) EMPD tumors. Androgen receptor expression was also observed in four of six lymph node metastases. In these lymph nodes, expression of androgen receptor mRNA was confirmed by reverse transcriptase-polymerase chain reaction. Direct sequencing of exon 2 through exon 8, which encodes DNA- and hormone-binding domains of the androgen receptor gene, revealed no mutation in any of the 10 advanced stage tumors. Neither amplification nor deletion of the androgen receptor gene locus was detected by dual color fluorescence in situ hybridization analysis in 14 tumors. The present findings showing frequent expression of structurally unaltered androgen receptor in an advanced stage of EMPD may provide a rational basis for hormone therapy, which is widely used in the treatment of metastatic prostate cancer and androgen receptor-positive breast cancer recurrence.
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PMID:Expression of structurally unaltered androgen receptor in extramammary Paget's disease. 1100 14

Extramammary Paget's disease (EMPD) is a rare condition whose importance is amplified by its association with either cutaneous or internal malignancy. Recently it has been shown that EMPD is not a single disease but can be divided into cutaneous and endodermal subtypes. The authors studied 12 new cases of immunohistochemically well-characterized EMPD, including HER-2/neu and CDX-2 immunophenotyping. The latter represents a novel application of this nuclear transcription factor, considered to be a relatively specific IHC marker for gastrointestinal-type epithelium. Cutaneous EMPD, accounting for 10 of the 12 (83%) cases, was CDX2-/HER2+; endodermal EMPD, accounting for 2 of the 12 (17%) cases, was CDX2+/HER2-. Four of the 12 cases (33%) were associated with a malignancy (two cutaneous adenocarcinomas, two colorectal carcinomas). The two cases of cutaneous adenocarcinoma occurred in the cutaneous group (2/10 [20%]), while the two cases of rectal carcinoma (one invasive, one in situ) occurred in the endodermal group (2/2 [100%]). Since EMPD subtypes have specific implications with regard to cancer risk, immunophenotyping should be performed in all cases. CDX-2 immunoreactivity may be useful in the subtyping of EMPD.
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PMID:Potential diagnostic utility of CDX-2 immunophenotyping in extramammary Paget's disease. 1628 Jun 63

Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma. The common sites of EMPD involvement are the vulva, perineal, perianal, scrotal and penile skin. Several studies have shown that HER-2/neu, also known as c-erbB-2, is amplified and overexpressed in many cancers. In this study, we investigated the expression and clinical significance of HER-2 in Japanese patients with EMPD. Keratinocytes in epidermis were slightly positive for HER-2. As for EMPD, 19 of 31 EMPD were positive for HER-2 (61%). There is significant correlation between the presence of invasion and strong positivity (3+) for HER-2 (p < 0.02). Furthermore, there is significant correlation between the presence of lymph node metastasis and strong positivity (3+) for HER-2 (p < 0.02). These results suggest that patients with EMPD strongly positive for HER-2 may have high risk for lymph node metastasis and should be followed up carefully. The observed overexpression of HER-2 in EMPD presents a potential therapeutic target for adjuvant treatment of this disease. Treatment with trastuzumab is well established in breast cancer with HER-2 overexpression and is recommended by several consensus statements. The results of the present study indicate that targeting therapies for HER-2, such as trastuzumab, may be used for EMPD particularly in patients with invasive and/or metastatic EMPD.
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PMID:The expression of HER-2 in extramammary Paget's disease. 2191 49