{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T15:53:41Z","timestamp":1765727621605},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,4,17]],"date-time":"2002-04-17T00:00:00Z","timestamp":1019001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Little is known about genomic alterations during development of the radial growth phase (RGP) of cutaneous malignant melanomas (CMMs). In this investigation polymerase chain reaction\u2013based microsatellite assays were applied to analyze 13 RGP\u2010CMMs with 18 microsatellite markers at six chromosomal regions: 1p, 3p, 4q, 6q, 9p, and 10q. Loss of heterozygosity (LOH) was found in eight cases (62%), at 9p22, 1p36, and 10q11, suggesting the presence of tumor\u2010suppressor genes at these regions. LOH was encountered frequently at the interferon\u2010\u03b1 (31%) and <jats:italic>D10S249<\/jats:italic> loci (15%). Low\u2010level microsatellite instability (MSI) (11\u201316% of investigated loci unstable) was noted in three cases (23%). Two MSI banding patterns were seen: band shift and the presence of additional bands. To investigate the underlying mechanisms of the low\u2010level MSI pattern, we analyzed the lesions for expression of mismatch repair (MMR) proteins with immunoperoxidase methods and mouse monoclonal antibodies. The average percentages of positively stained cells for human MutL homolog 1 (hMLH1), human MutS homolog 2 (hMSH2), and human MutS homolog 6 (hMSH6) in RGP\u2010CMM (75.6\u2009\u00b1\u20093.4%, 67.20\u2009\u00b1\u20097.71%, and 76.6\u2009\u00b1\u20092.1%, respectively) were reduced compared with benign nevi. No statistically significant differences in MMR protein expression were found between microsatellite\u2010stable and low\u2010level MSI lesions (<jats:italic>P<\/jats:italic>\u2009=\u20090.173, <jats:italic>P<\/jats:italic>\u2009=\u20090.458, and <jats:italic>P<\/jats:italic>\u2009=\u20090.385 for hMLH1, hMSH2, and hMSH6, respectively). There was a direct correlation between values for percentages of positively stained cells for hMSH2 and hMSH6 (<jats:italic>r<\/jats:italic>\u2009=\u2009+0.9, <jats:italic>P<\/jats:italic>\u2009=\u20090.03), suggesting that common mechanisms regulate their expression. In conclusion, LOH, MSI, and reduced MMR protein expression appear to be present in at least some RGP\u2010CMMs and may play a role in their pathogenesis. Further studies are necessary to support these finding and to determine their diagnostic and prognostic significance. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.10047","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:24:15Z","timestamp":1030317855000},"page":"35-44","source":"Crossref","is-referenced-by-count":34,"title":["Loss of heterozygosity, microsatellite instability, and mismatch repair protein alterations in the radial growth phase of cutaneous malignant melanomas"],"prefix":"10.1002","volume":"34","author":[{"given":"Mahmoud R.","family":"Hussein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Roggero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eulalia 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