Breast cancer cell kinetics: Immunocytochemical determination of growth fractions by monoclonal antibody Ki-67 and correlation with flow cytometric S-Phase and with some features of tumor aggressiveness

G. Gasparini, F. Pozza, S. Meli, M. Reitano, G. Santini, P. Bevilacqua

Research output: Contribution to journalArticle

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Abstract

In operable breast cancer, cell kinetics can be utilized in the prediction of the clinical outcome of patients. The discovery of monoclonal antibodies recognizing antigens related to cell proliferation has permitted the assessment of cell kinetics by rapid and practical immunocytochemical methods. It is claimed that the Ki-67 mouse monoclonal antibody recognizes an antigen expressed in proliferating cells but not present in quiescent (G0) cells. To study the relationship between Ki-67 score and DNA flow cytometric S-Phase Fraction (SPF), the latter being one of the most widely used methods to assess cell kinetics, we compared these two techniques of measurement in 122 breast carcinomas using both for each specimen. In this series 90% of tumors were Ki-67 positive, with a median value of 7.5% (range 1% to 70%). DNA flow cytometric analysis revealed that 69 tumors (57%) were aneuploid, whereas 53 were diploid. The median SPF value was 8% for diploid and 15% for aneuploid tumors (range 2% to 32%). Ki-67 scores were significantly higher in the DNA aneuploid compared to the diploid carcinomas (p=0.015). Overall, a good correlation was found between Ki-67 and SPF values both in diploid (r=0.60) and in aneuploid (r=0.38) tumors. High Ki-67scores were associated with the presence of axillary lymph node metastases (p=0.0023) and poor histologic differentiation (p=0.0028). Menopausal status, tumor size and peritumoral vessel invasion were unrelated to the Ki-67 score. Over-expression of the Epidermal Growth Factor receptor (EGF-r) and the c-erbB-2 oncogene were not correlated with Ki-67 staining. In conclusion, in this study Ki-67 immunostaining correlated with other indices of cell proliferation (SPF and Grade) and with some features of tumor aggressiveness (DNA aneuploidy and lymph node metastases) but seemed to be independent of some biological markers (EGR-r and c-erbB-2). Since the major objective for assessing proliferative status in Stage I-II breast carcinoma is to determine prognosis, it will have to be evaluated whether the determination of the Growth Fraction has comparable or even greater prognostic value than other cell kinetics markers.

Original languageEnglish
Pages (from-to)2015-2021
Number of pages7
JournalAnticancer Research
Volume11
Issue number6
Publication statusPublished - 1991

Fingerprint

S Phase
Aneuploidy
Monoclonal Antibodies
Breast Neoplasms
Diploidy
Growth
Neoplasms
DNA
Lymph Nodes
Cell Proliferation
Neoplasm Metastasis
Antigens
Oncogenes
Epidermal Growth Factor Receptor
Biomarkers
Staining and Labeling
Carcinoma

Keywords

  • Breast cancer
  • Cell kinetics
  • Flow cytometric
  • Ki-67 antibody
  • S-phase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Breast cancer cell kinetics : Immunocytochemical determination of growth fractions by monoclonal antibody Ki-67 and correlation with flow cytometric S-Phase and with some features of tumor aggressiveness. / Gasparini, G.; Pozza, F.; Meli, S.; Reitano, M.; Santini, G.; Bevilacqua, P.

In: Anticancer Research, Vol. 11, No. 6, 1991, p. 2015-2021.

Research output: Contribution to journalArticle

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abstract = "In operable breast cancer, cell kinetics can be utilized in the prediction of the clinical outcome of patients. The discovery of monoclonal antibodies recognizing antigens related to cell proliferation has permitted the assessment of cell kinetics by rapid and practical immunocytochemical methods. It is claimed that the Ki-67 mouse monoclonal antibody recognizes an antigen expressed in proliferating cells but not present in quiescent (G0) cells. To study the relationship between Ki-67 score and DNA flow cytometric S-Phase Fraction (SPF), the latter being one of the most widely used methods to assess cell kinetics, we compared these two techniques of measurement in 122 breast carcinomas using both for each specimen. In this series 90{\%} of tumors were Ki-67 positive, with a median value of 7.5{\%} (range 1{\%} to 70{\%}). DNA flow cytometric analysis revealed that 69 tumors (57{\%}) were aneuploid, whereas 53 were diploid. The median SPF value was 8{\%} for diploid and 15{\%} for aneuploid tumors (range 2{\%} to 32{\%}). Ki-67 scores were significantly higher in the DNA aneuploid compared to the diploid carcinomas (p=0.015). Overall, a good correlation was found between Ki-67 and SPF values both in diploid (r=0.60) and in aneuploid (r=0.38) tumors. High Ki-67scores were associated with the presence of axillary lymph node metastases (p=0.0023) and poor histologic differentiation (p=0.0028). Menopausal status, tumor size and peritumoral vessel invasion were unrelated to the Ki-67 score. Over-expression of the Epidermal Growth Factor receptor (EGF-r) and the c-erbB-2 oncogene were not correlated with Ki-67 staining. In conclusion, in this study Ki-67 immunostaining correlated with other indices of cell proliferation (SPF and Grade) and with some features of tumor aggressiveness (DNA aneuploidy and lymph node metastases) but seemed to be independent of some biological markers (EGR-r and c-erbB-2). Since the major objective for assessing proliferative status in Stage I-II breast carcinoma is to determine prognosis, it will have to be evaluated whether the determination of the Growth Fraction has comparable or even greater prognostic value than other cell kinetics markers.",
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AU - Santini, G.

AU - Bevilacqua, P.

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