Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff value.
BACKGROUND
Cell proliferation is a major determinant of the biologic behavior of breast carcinoma. MIB-1 monoclonal antibody is a promising tool for determining cell proliferation on routine histologic material. The objectives of this study were to compare MIB-1 evaluation to other methods of measuring cell proliferation, with a view to refining the cutoff used to classify tumors with low and high proliferation rates in therapeutic trials.


METHODS
One hundred eighty-five invasive breast carcinomas were evaluated for cell proliferation by determining monoclonal antibody MIB-1 staining, histologic parameters (Scarff-Bloom-Richardson grade and mitotic index) on paraffin sections, S-phase fraction (SPF) by flow cytometry, and thymidine-kinase (TK) content of frozen samples.


RESULTS
There was a high correlation (P = 0.0001) between the percentage of MIB-1 positive tumor cells and SPF, TK, histologic grade, and the mitotic index. Multivariate analyses including MIB-1 at 5 different cutoffs (10%, 15%, 17% [median], 20%, 25%) and the other proliferative markers showed that the optimal MIB-1 cutoff was 25% and that the mitotic index was the proliferative variable that best discriminated between low and high MIB-1 samples. A MIB-1 cutoff of 25% adequately identified highly proliferative tumors. Conversely, with a MIB-1 cutoff of 10%, few tumors with low proliferation were misclassified.


CONCLUSIONS
The choice of MIB-1 cutoff depends on the following clinical objective: if MIB-1 is used to exclude patients with slowly proliferating tumors from chemotherapeutic protocols, a cutoff of 10% will help to avoid overtreatment. In contrast, if MIB-1 is used to identify patients sensitive to chemotherapy protocols, it is preferable to set the cutoff at 25%. The MIB-1 index should be combined with some other routinely used proliferative markers, such as the mitotic index.
Spyratos
Frédérique
F
Laboratoire d'Oncobiologie, Centre René Huguenin, Saint-Cloud, France. f.spyratos@stcloud-huguenin.org
Ferrero-Poüs
Magali
M
Trassard
Martine
M
Hacène
Kamel
K
Phillips
Edelmira
E
Tubiana-Hulin
Michèle
M
Le Doussal
Viviane
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen; D008875:Middle Aged; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism
D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013937:Thymidine Kinase