title: Apoptosis in CD30-positive lymphoproliferative disorders of the skin.
abstract: The spectrum of CD30-positive cutaneous lymphoproliferative disorders (CD30+ CLPD) includes lymphomatoid papulosis (LyP), primary cutaneous CD30+ large T-cell lymphoma (LTCL) and rare borderline patients. Despite their malignant histopathology, CD30+ CLPD exhibit a low-grade malignant course with an excellent prognosis and a characteristic tendency for spontaneous regression. Apoptosis of tumour cells is considered a principal mechanism of tumour regression. We examined the proliferation and apoptosis rates as well as the expression of apoptosis-related proteins in various clinical entities, tumour cell lines and evolutional (evolving and regressing) stages of CD30+ CLPD. Skin biopsies of LyP (n = 20) and LTCL (n = 19) and five CD30+ lymphoma cell lines were analysed by means of immunohistochemistry and Western blotting in order to evaluate the proliferation (Ki67), apoptosis (FragEl) and expression of Bax, Bcl-x, C-kit and Mcl-1. A significantly higher apoptotic index (AI) was found in LyP (AI = 12.5%) than in LTCL (AI = 3.1%, P < 0.005). Bax was expressed by the majority of tumour cells in all forms of CD30+ CLPD and CD30+ cell lines. However, no Bax expression was found in tumour cell lines derived from systemic CD30+ lymphomas, which lack spontaneous regression and display an aggressive clinical course. No significant correlation was found between the expression of apoptosis-related proteins and the tumour type and evolutional stage of CD30+ CLPD. We conclude that the higher AI in LyP may contribute to the regression of LyP lesions and the excellent prognosis of the disease. Pro-apoptotic protein Bax is expressed at high levels in CD30+ CLPD and may play a crucial role in mediating apoptosis of tumour cells.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Greisser
authors.forename: Udo
authors.initials: U
authors.lastname: Doebbeling
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Roos
authors.forename: Beatrix
authors.initials: B
authors.lastname: Mueller
authors.forename: Mirka
authors.initials: M
authors.lastname: Schmid
authors.forename: Günter
authors.initials: G
authors.lastname: Burg
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Kadin
authors.forename: Werner
authors.initials: W
authors.lastname: Kempf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000378:metabolism*; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D017730:Ki-1 Antigen