TY - JOUR
T1 - How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss working group of breast- and gynecopathologists
AU - Varga, Zsuzsanna
AU - Diebold, Joachim
AU - Dommann-Scherrer, Corina
AU - Frick, Harald
AU - Kaup, Daniela
AU - Noske, Aurelia
AU - Obermann, Ellen
AU - Ohlschlegel, Christian
AU - Padberg, Barbara
AU - Rakozy, Christiane
AU - Oliver, Sara Sancho
AU - Schobinger-Clement, Sylviane
AU - Schreiber-Facklam, Heide
AU - Singer, Gad
AU - Tapia, Coya
AU - Wagner, Urs
AU - Mastropasqua, Mauro G.
AU - Viale, Giuseppe
AU - Lehr, Hans Anton
PY - 2012/5/25
Y1 - 2012/5/25
N2 - Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. Methods: Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. Results: The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56-0.72). However, we found very high inter-observer variabilities (Kappa 0.04-0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01-0.04) and intra-observer agreement was likewise poor (Kappa 0.00-0.35). Conclusion: Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas.
AB - Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. Methods: Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. Results: The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56-0.72). However, we found very high inter-observer variabilities (Kappa 0.04-0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01-0.04) and intra-observer agreement was likewise poor (Kappa 0.00-0.35). Conclusion: Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas.
UR - http://www.scopus.com/inward/record.url?scp=84861478152&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0037379
DO - 10.1371/journal.pone.0037379
M3 - Article
C2 - 22662150
AN - SCOPUS:84861478152
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e37379
ER -