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Annals of Oncology 14:214-219, 2003
© 2003 European Society for Medical Oncology


Original Paper

Chemosensitivity and p53–Bax pathway-mediated apoptosis in patients with uterine cervical cancer

H. Sultana1, J. Kigawa1,+, Y. Kanamori1, H. Itamochi1, T. Oishi1, S. Sato1, S. Kamazawa1, M. Ohwada2, M. Suzuki2 and N. Terakawa1

1 Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago; 2 Department of Obstetrics and Gynecology, Jichi Medical School Hospital, Ustunomiya, Japan

Received 21 May 2002; revised 26 July 2002; accepted 17 October 2002

Objectives:

To determine whether and how apoptosis through the p53–Bax pathway affects sensitivity to chemotherapy in cervical cancer.

Materials and 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.

Key words: apoptosis, Bax, cervical carcinoma, chemotherapy, p53, uterus


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