NEOADJUVANT INTRAARTERIAL INFUSION CHEMOTHERAPY INDUCES APOPTOTIC CELL-DEATH IN LOCALLY ADVANCED UTERINE CERVICAL CARCINOMAS - A PRELIMINARY-REPORT

The purpose of this study was to evaluate the mechanism which leads to cell death in locally advanced uterine cervical carcinoma treated by neoadjuvant intra-arterial infusion chemotherapy (IAC). Cancer tissues surgically obtained from 11 patients (stages Ib-IIIb) receiving preop erative IAC of two courses of mitomycin-C (10 mg/m(2)), therarubicin ( 10 mg/m(2)) and cisplatin (100 mg/body), were examined. Biopsy specime ns from the 11 patients before IAC were also used. Terminal deoxynucle otidyl transferase-mediated digoxigenin-dUTP nick end-labeling (TUNEL) and immunohistochemical staining with anti-P53 and bcl-2 antibodies w ere performed for cancer tissues from these 11 patients before and aft er IAC. The evaluation of the clinical response to IAC revealed comple te response (CR) in two patients, partial response (PR) in five, and s table disease (SD) in four. Careful observation of routine H. & E. sec tions showed some tumor cells with apoptosis, especially in patients w ith CR and PR. Intense TUNEL signals were observed both in ordinary, n on-pyknotic nuclei of tumor cells and in nuclear fragments correspondi ng to apoptotic bodies. Apoptotic indices (AI) of the seven patients w ith CR or PR after IAC were significantly higher than those before IAC . There was no obvious correlation between apoptosis and P53 expressio n, but bcl-2 immunoreactivity was markedly decreased after IAC. These results suggest that the antitumor effects of neoadjuvant IAC are clos ely associated with apoptotic cell death in locally advanced cervical carcinomas.