Expression of mitotic-arrest deficiency 2 predicts the efficacy of neoadjuvant chemotherapy for locally advanced uterine cervical cancer

有丝分裂停滞缺陷 2 的表达可预测局部晚期宫颈癌新辅助化疗的疗效

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作者:Masanari Morishita, Toshiyuki Sumi, Yusuke Nakano, Masatomo Teramae, Takeshi Fukuda, Hiroyuki Nobeyama, Hiroyuki Yoshida, Yoshinari Matsumoto, Tomoyo Yasui, Osamu Ishiko

Abstract

We previously reported satisfactory therapeutic results when using cisplatin-based cyclic balloon-occluded arterial infusion chemotherapy as neoadjuvant chemotherapy (NAC), which enabled hysterectomy to be performed for patients with locally advanced cervical cancer. Mitotic arrest deficiency 2 (MAD2) is a key component of the mitotic spindle checkpoint pathway. The expression of MAD2 is associated with tumor progression and resistance to chemotherapy. Therefore, the aim of the present study was to examine whether the expression of MAD2 is related to the efficacy of NAC for locally advanced uterine cervical cancer. We reviewed 53 cases of locally advanced uterine cervical cancer (stage IIIa-IIIb; based on the International Federation of Gynecology and Obstetrics criteria). These patients were initially treated at Osaka City University Medical School Hospital, Japan, from 1995 to 2008 and were under 70 years old. Tumor samples were obtained by biopsy prior to NAC. Cases were divided into two groups: one group in which NAC was effective, surgery was possible and radiotherapy was performed (NAC+OP+R group; n=33), and another group in which NAC was ineffective and radiation therapy was performed (NAC+R group; n=20). MAD2 expression was examined in paraffin-embedded sections using the avidin-biotin peroxidase complex method. The results showed that MAD2 expression was significantly higher in the NAC+R group compared to the NAC+OP+R group (P<0.001). There was no significant difference in overall survival between the two groups, although the prognosis for the NAC+OP+R group tended to be slightly better (P=0.064). Taken together, these results suggest that the expression of MAD2 may predict the efficacy of NAC as a treatment for locally advanced uterine cervical cancer.

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