Tamoxifen modulates the expression of Ki67, apoptosis, and microvessel density in cervical cancer

Citation
G. Ferrandina et al., Tamoxifen modulates the expression of Ki67, apoptosis, and microvessel density in cervical cancer, CLIN CANC R, 7(9), 2001, pp. 2656-2661
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
9
Year of publication
2001
Pages
2656 - 2661
Database
ISI
SICI code
1078-0432(200109)7:9<2656:TMTEOK>2.0.ZU;2-L
Abstract
Purpose: The aim of the study was to investigate if a short-term administra tion of high-dose Tamoxifen (Tam) could affect the expression of biological ly relevant biochemical parameters in cervical cancer tissue. Experimental Design: The study was conducted in 24 patients with histologic ally confirmed cervical tumors. Biopsies were obtained by colposcopy on day 0 in all patients, who then received either 80 mg/die or 160 mg/die for 5 consecutive days until the second biopsy was obtained. Immunohistochemistry was performed with antiestrogen receptor (ER), anti-Ki67, anticaspase clea vage product of keratin 18 (M30), and anti-CD31 monoclonal antibodies. Results: Eleven (45.8%) of 24 cervical tumors were ER positive. The percent age of Ki67-positive tumor cells in pre-Tam biopsies was significantly high er than the percentage in the corresponding posttreatment biopsies (z = 4.2 9, P = 0.0001). No difference in the pretreatment percentage of Ki67-positi ve cells according to ER status was found. The percentage of M30 positivity was higher in post-Tam than in pre-Tam biopsies. Microvessel density value s in pre-Tam biopsies were significantly higher than corresponding values i n posttreatment tissues (z = -3.72, P = 0.0002). The reduction in the perce ntage of Ki67-positive tumors was significantly (z = 3.58, P = 0.0003) high er in ER-positive than in ER-negative tumors, whereas no difference in Tam- induced reduction of microvessel density values according to ER status (z = -0.18, P = 0.85) was found. Tam treatment did not induce any change of M30 positivity in ER-positive tumors, whereas in ER-negative tumors, it produc ed a significant (P = 0.015) increase in the percentage of M30-positive cel ls in post-Tam versus pre-Tam biopsies. Conclusions: A short-term treatment with Tam at doses 4-8-fold higher than those in conventional schemes is associated with modifications of biologica l parameters associated with tumor cell proliferation, apoptosis, and neoan giogenesis in cervical cancer.