title: Role and prognostic significance of the Ki-67 index in non-Hodgkin's lymphoma.
abstract: Expression of Ki-67, a nuclear antigen protein present in all cycling cells, is used to determine the growth fraction of tumors. The aim of this study was to evaluate the role and prognostic significance of the Ki-67 proliferation index (PI) in non-Hodgkin's lymphoma. Ki-67 was assayed immunohistochemically in tissue samples of 319 patients with newly-diagnosed non-Hodgkin's lymphoma. In 268 patients, the Ki-67 PI was correlated with clinical course and outcome. The mean Ki-67 PI ranged from 26.6% in indolent lymphomas to 97.6% in very aggressive lymphomas (P < 0.001). The index was <45% in 82.8% of indolent lymphomas and >45% in 85% of aggressive lymphomas (AUC = 0.877, P < 0.001). In patients with diffuse large B-cell lymphoma (n = 141), a Ki-67 PI of 70% was found to significantly discriminate patients with good or bad prognosis (AUC = 0.65, P = 0.004). Three-year survival was 75% +/- 5.6% in patients with a low Ki-67 index compared with 55.9% +/- 6% in patients with a high index (P = 0.015). In patients with a low IPI (<or=2), 3-year survival was 94% +/- 4% in those with a Ki-67 index <or=70% and 64% +/- 8.1% in those with a higher index (P = 0.002); in patients with bulky disease (>10 cm), the corresponding 3-year survival by Ki-67 index was 100% and 25% +/- 12% (P = 0.012). Our results suggest that the mean Ki-67 PI differs by type of lymphoma. A cut-off value of 45% can help differentiate indolent from aggressive disease. In diffuse large B-cell lymphoma, a cut-off value of 70% can distinguish patients with a good and bad prognosis when combined with other prognostic factors of low IPI score and bulky disease.
authors.affiliation: Institute of Hematology, Rabin Medical Center, Beilinson Hospital, Petah Tiqwa, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Broyde
authors.forename: Olga
authors.initials: O
authors.lastname: Boycov
authors.forename: Yulia
authors.initials: Y
authors.lastname: Strenov
authors.forename: Elimelech
authors.initials: E
authors.lastname: Okon
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Osnat
authors.initials: O
authors.lastname: Bairey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen