Tamoxifen modulates the expression of Ki67, apoptosis, and microvessel density in cervical cancer.
OBJECTIVE
The aim of the study was to investigate if a short-term administration of high-dose Tamoxifen (Tam) could affect the expression of biologically relevant biochemical parameters in cervical cancer tissue.


METHODS
The study was conducted in 24 patients with histologically 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 cleavage product of keratin 18 (M30), and anti-CD31 monoclonal antibodies.


RESULTS
Eleven (45.8%) of 24 cervical tumors were ER positive. The percentage of Ki67-positive tumor cells in pre-Tam biopsies was significantly higher than the percentage in the corresponding posttreatment biopsies (z = 4.29, P = 0.0001). No difference in the pretreatment percentage of Ki67-positive cells according to ER status was found. The percentage of M30 positivity was higher in post-Tam than in pre-Tam biopsies. Microvessel density values in pre-Tam biopsies were significantly higher than corresponding values in posttreatment tissues (z = -3.72, P = 0.0002). The reduction in the percentage of Ki67-positive tumors was significantly (z = 3.58, P = 0.0003) higher 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 produced a significant (P = 0.015) increase in the percentage of M30-positive cells 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 biological parameters associated with tumor cell proliferation, apoptosis, and neoangiogenesis in cervical cancer.
Ferrandina
G
G
Department of Gynecology/Obstetrics, Catholic University of Rome, Italy.
Ranelletti
F O
FO
Larocca
L M
LM
Maggiano
N
N
Fruscella
E
E
Legge
F
F
Santeusanio
G
G
Bombonati
A
A
Mancuso
S
S
Scambia
G
G
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001808:Blood Vessels / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology
D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011960:Receptors, Estrogen; D013629:Tamoxifen; D007633:Keratins