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.