DNA ploidy, proliferation, and neu-oncogene protein overexpression in breast carcinoma.

TitleDNA ploidy, proliferation, and neu-oncogene protein overexpression in breast carcinoma.
Publication TypeJournal Article
Year of Publication1992
AuthorsLee AK, Wiley B, Loda M, Bosari S, Dugan JM, Hamilton W, Heatley GJ, Cook L, Silverman ML
JournalMod Pathol
Date Published1992 Jan
KeywordsAntibodies, Monoclonal, Breast Neoplasms, Cell Division, Cell Transformation, Neoplastic, DNA, Neoplasm, Female, Flow Cytometry, Gene Expression Regulation, Neoplastic, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Ki-67 Antigen, Nuclear Proteins, Ploidies, Prognosis, Proto-Oncogene Proteins, Receptor, ErbB-2, S Phase

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)

Alternate JournalMod Pathol
PubMed ID1347424
Related Faculty: 
Massimo Loda, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700