DNA ploidy, proliferation, and neu-oncogene protein overexpression in breast carcinoma.
DNA content, proliferative activity (Ki-67 immuno-staining and S-phase fraction by flow cytometry), and neu-oncogene overexpression were studied in 135 patients with invasive breast carcinoma. Image analysis and flow cytometry of fresh tumors showed good correlation between the two methods and yielded 39% diploid tumors and 61% aneuploid tumors. Aneuploidy, including tetraploidy, was significantly related to the loss of estrogen (p = 0.0002) and progesterone (p = 0.03) receptors, high histologic (p = 0.014) and nuclear (p less than 0.0001) grades, and mitotic rate (p = 0.0001). Immunohistochemical evaluation of proliferation by staining with Ki-67 monoclonal antibody and of neu-oncogene protein overexpression was performed in fresh frozen tissue from 83 tumors. The Ki-67 score, quantitated by the CAS-200 image analyzer, correlated only moderately with S-phase fraction obtained by flow cytometry by linear regression analysis (r = 0.39, p less than 0.001). However, both of these proliferation markers correlated strongly with the mitotic rate (p less than 0.0001). Aneuploid and tetraploid tumors demonstrated higher Ki-67 scores and S-phase fractions than diploid tumors. Neu-oncogene protein overexpression was seen in 24 tumors (29%) overall and was much higher in aneuploid tumors (38%) and tetraploid tumors (50%) than in diploid tumors (7%). However, the concentration of neu-oncogene protein positive tumors in the tetraploid region reported by others was not observed. Neu-oncogene protein overexpression was also associated with higher Ki-67 scores (p = 0.016) and S-phase fractions (p = 0.037).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anatomic Pathology, Lahey Clinic Medical Center, Burlington, Massachusetts.
A K
AK
Lee
B
B
Wiley
M
M
Loda
S
S
Bosari
J M
JM
Dugan
W
W
Hamilton
G J
GJ
Heatley
L
L
Cook
M L
ML
Silverman
D000911:Antibodies, Monoclonal / Q000276:immunology; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics*; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen; D009687:Nuclear Proteins / Q000276:immunology; D011003:Ploidies; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases; D016196:S Phase / Q000502:physiology
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases