{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T12:44:35Z","timestamp":1749127475396},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,11,3]],"date-time":"2005-11-03T00:00:00Z","timestamp":1130976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Research"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Malignant melanoma is notoriously refractive to therapy and resistant to apoptosis. This may reflect the downregulation of Apaf\u20101, an important mediator of mitochondrial\u2010dependent apoptosis, observed in vitro in melanoma cell lines and by immunohistochemistry for Apaf\u20101 protein in histological samples of primary and metastatic melanomas. Although it has been suggested that loss of Apaf\u20101 expression may be an indicator of malignant transformation in melanoma, previous studies on Apaf\u20101 expression in benign pigmented nevi were performed without reference to their histologic type. Here we have evaluated the expression of Apaf\u20101 mRNA by fluorescence in situ hybridization and of Apaf\u20101 protein by immunohistochemistry in a large panel of human melanomas and in eight types of pigmented nevi, considered potential precursors for cutaneous melanoma. We observe a strong negative correlation between melanoma progression assessed according to Clark classification and the expression of Apaf\u20101. A significant decrease in Apaf\u20101 expression was observed between Clark II and Clark III lesions, the stages usually associated with a transition from horizontal to vertical growth phase of melanoma. There was also statistically significant difference in Apaf\u20101 mRNA expression between melanomas of Breslow thickness &lt;1\u2003mm and &gt;4\u2003mm. No Apaf\u20101 expression could be detected in lymph node melanoma metastases. These results suggest that Apaf\u20101 expression may become a prognostic marker for progress of human cutaneous melanoma and further support the notion that loss of Apaf\u20101 may be an important contributory factor in the development of the disease.<\/jats:p>","DOI":"10.1111\/j.1600-0749.2005.00280.x","type":"journal-article","created":{"date-parts":[[2005,11,3]],"date-time":"2005-11-03T09:57:42Z","timestamp":1131011862000},"page":"43-50","source":"Crossref","is-referenced-by-count":17,"title":["Apaf\u20101 expression in human cutaneous melanoma progression and in pigmented nevi"],"prefix":"10.1111","volume":"19","author":[{"given":"Katarzyna","family":"Niedojad\u0142o","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"\u0141ab\u0119dzka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewelina","family":"\u0141ada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Milewska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara W.","family":"Chwirot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,3]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"Pitfalls in Histopathologic Diagnosis of Malignant Melanoma","author":"Ackerman 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