Chemosensitivity and p53-Bax pathway-mediated apoptosis in patients with uterine cervical cancer.
OBJECTIVE
To determine whether and how apoptosis through the p53-Bax pathway affects sensitivity to chemotherapy in cervical cancer.


METHODS
Thirty patients with cervical squamous cell carcinoma, who had human papilloma virus (HPV) and underwent neoadjuvant chemotherapy, were entered in the present study. Tumor specimens were obtained before and after chemotherapy. HPV was detected by polymerase chain reaction. The expression of Ki-67, p53, Bax and Bcl-2 proteins was determined by immunohistochemical staining. Apoptotic cells were identified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling method.


RESULTS
Of 30 patients, 18 responded to chemotherapy and 12 did not. The apoptotic index in tumors of responders was significantly higher than in non-responders after chemotherapy. The Ki-67 labeling index (LI) in responders was significantly higher than in non-responders before chemotherapy. Patients with tumors >33% of the LI, which was determined by a receiver operating characteristic curve, had a better survival rate. The incidence of p53 protein expression did not differ between responders and non-responders. After chemotherapy, the expression of Bax protein in responders was more frequent and Bcl-2 protein expression was less frequent than in non-responders.


CONCLUSIONS
Chemosensitivity in cervical cancer may be associated with apoptosis via the p53-Bax pathway.
Sultana
H
H
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.
Kigawa
J
J
Kanamori
Y
Y
Itamochi
H
H
Oishi
T
T
Sato
S
S
Kamazawa
S
S
Ohwada
M
M
Suzuki
M
M
Terakawa
N
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis; D014412:Tumor Virus Infections / Q000150:complications; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein