title: Bcl-2 expression in rituximab refractory cutaneous B-cell lymphoma.
abstract: Rituximab has been established as an effective and safe therapy for cutaneous B-cell lymphoma (CBCL). Different survival pathways, that is the Raf/MEK/Erk- or the p38MAPK cascade, have been suggested as downstream mediators of rituximab and may be involved in treatment failure. Biopsies from four patients, suffering from different subtypes of CBCL, which were obtained at various time points of relapse during or after therapy with 375 mg rituximab per m2 of body surface area, were analysed for the expression of CD20, CD3, Ki-67, Raf-kinase inhibitory protein (RKIP) and bcl-2 by immunohistochemistry. No CD20-loss variants, that is the suggested main tumour escape mechanism to rituximab therapy, were observed in any specimen of relapsing CBCL. Notably, the expression of proapoptotic RKIP remained increased in these tumour samples. This was concomitated by a constant to slightly reduced proliferation status as demonstrated by Ki-67 staining. However, relapsing CBCL exhibited a strong upregulation of the antiapoptotic molecule bcl-2 in comparison to pretherapeutic levels. The immunohistochemical analyses of this case series of rituximab refractory CBCL suggest that upregulation of bcl-2 may play a major role in therapy resistance.
authors.affiliation: Department of Dermatology, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080 Wuerzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wobser
authors.forename: H
authors.initials: H
authors.lastname: Voigt
authors.forename: A O
authors.initials: AO
authors.lastname: Eggert
authors.forename: R
authors.initials: R
authors.lastname: Houben
authors.forename: C S
authors.initials: CS
authors.lastname: Kauczok
authors.forename: E B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: J C
authors.initials: JC
authors.lastname: Becker
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics; D000069283:Rituximab; D017211:Treatment Failure
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D000069283:Rituximab