title: Different methods of pretreatment Ki-67 labeling index evaluation in core biopsies of breast cancer patients treated with neoadjuvant chemotherapy and their relation to response to therapy.
abstract: Increased proliferation activity of breast cancer cells evaluated by Ki-67 immunohistochemistry, i.e. a high Ki-67 labeling index (Ki-67 LI), may predict better tumor regression in case of neoadjuvant chemotherapy. Despite recommendations for the evaluation of Ki-67 LI, there are variations in methodology. We assessed the effect of different evaluation methods on the Ki-67 LI in patients with different response to neoadjuvant chemotherapy. Thirty pretreatment core-biopsy samples of patients receiving neoadjuvant docetaxel-epirubicin chemotherapy with or without capecitabine were evaluated for their Ki-67 LI. Pathologic regression was categorized as no regression, partial regression and complete regression, with 10 cases in each category. Three antibodies (MIB1, B56, SP6), 4 observers and 4 methods (counting or estimating on glass slides and counting or estimating on representative digital images) were compared. The Kruskal-Wallis test and analyses of variance were performed to investigate the differences in Ki-67 LIs between different clinical outcomes (tumor regression categories). Breast carcinomas with pathological complete regression had a higher mean Ki-67 LI than tumors not achieving complete regression with any methods, observers and antibodies investigated, although there was a variation between different evaluations in what may represent high proliferation. Estimating the Ki-67 LI on digital images representing the highest proliferation in the core biopsy seemed the best in separating complete responders from non-responders. High Ki-67 LI values were more likely associated with pathological complete regression independently of the method of evaluation used, although the definition of high proliferation is problematic. Estimating the Ki-67 LI may be an adequate method of evaluation.
authors.affiliation: Department of Pathology, University of Szeged, Allomás u 2, 6725, Szeged, Hungary, andrasvoros@libero.it.
authors.forename: András
authors.initials: A
authors.lastname: Vörös
authors.forename: Erika
authors.initials: E
authors.lastname: Csörgő
authors.forename: Bence
authors.initials: B
authors.lastname: Kővári
authors.forename: Péter
authors.initials: P
authors.lastname: Lázár
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Kelemen
authors.forename: Orsolya
authors.initials: O
authors.lastname: Rusz
authors.forename: Tibor
authors.initials: T
authors.lastname: Nyári
authors.forename: Gábor
authors.initials: G
authors.lastname: Cserni
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy / Q000379:methods; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D000069287:Capecitabine; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D020360:Neoadjuvant Therapy / Q000379:methods; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D019394:Ki-67 Antigen; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D000069287:Capecitabine; D005472:Fluorouracil