Proliferation measurement in breast cancer by two different methods.
BACKGROUND
Different studies show that proliferation measurement in breast cancer may have an independent prognostic value. In the present study, tumor proliferation in breast cancer was analyzed by two radically different methods according to the technique used (immunohistochemistry and flow cytometry), associated costs and necessary equipment. The aim was to evaluate which method discriminates better between tumors with high and low proliferation in relation to all other available clinical and biological parameters.


METHODS
Two hundred and eighty breast cancers (231 ductal infiltrating, 30 lobular, 19 or less frequent varieties) were studied. The post-surgical staging was as follows: 164 pT1, 87 pT2, 7 pT3, the remaining 22 were multifocal, diffuse tumors. Axillary nodal invasion was found in 99 cases (35.4%). Proliferation was studied by means of flow cytometry (DNA index and S-phase) in fresh tumor tissue and immunohistochemistry (Ki67) in paraffin-embedded tissue. Furthermore, hormone receptor (estrogen receptor, ER; progesterone receptor, PR), c-erb-B2 and p53 expressions were studied using the same method. Finally, histological and nuclear grade, tumor size and axillary nodal invasion were also included as variables of the study.


RESULTS
A DNA index >1 (aneuploidy) correlated significantly with histological grade 3 (p = 0.01), nuclear grade 3 (p < 0.0001), nodal invasion (p = 0.007), absence of ER (p = 0.006) and of PR (p = 0.002), c-erb-B2 expression (p = 0.008), p53 expression (p = 0.007) and tumor size (p = 0.01). An expression of Ki67 in 20% or more of tumor cell nuclei, on the other hand, correlated significantly with histological grade 3 (p < 0.0001), nuclear grade 3 (p < 0.0001), absence of ER (p < 0.0001) and of PR (p < 0.0001), c-erb-B2 expression (p < 0.0001), p53 expression (p < 0.0001) and tumor size (p = 0.0005), but not with nodal invasion.


CONCLUSIONS
Although flow cytometry provides additional data (association with nodal invasion), the study of Ki67 expression emerges from this study as a simple, inexpensive and reliable method to study the proliferation rate of breast cancer.
Martínez-Arribas
Fernando
F
Fundación Tejerina-Centro de Patología de la Mama, Madrid.
Martín-Garabato
Elena
E
Lafuente
Pilar
P
Tejerina
Armando
A
Lucas
Raúl
R
Sánchez
Jaime
J
Schneider
José
J
D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D003584:Cytological Techniques / Q000379:methods*; D004171:Diploidy; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D016196:S Phase / Q000502:physiology
D019394:Ki-67 Antigen