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

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.