Prognostic impact of mitotic index of proliferating cell populations in cervical cancer patients treated with carbon ion beam

BACKGROUND: The authors previously reported that the mitotic index of a proliferating cell population (pMI) was a potent prognostic factor in cervical cancer patients treated with photon beam therapy. In this study, they investigated whether the pMI accurately predicted prognosis in cervical cancer patients treated with carbon ion beam. METHODS: Tissue sections were obtained from 27 consecutively treated patients with stage IIIB bulky (19 patients) and stage IVA (8 patients) squamous cell carcinomas of the cervix treated with carbon ion beam at the National Institute of Radiological Sciences, Japan, as a phase I/II study with dose escalation methodology (52.8-72 grays equivalent radiation dose/24 fractions). The mitotic index (MI) and Ki-67 labeling index (Ki-67-LI) were determined by hematoxylin and eosin staining and immunohistochemical staining, respectively. The pMI was calculated using the following formula: pMI ¼ MI/Ki-67-LI. RESULTS: The pMI ranged from 0.6 to 8.9 (mean, 3.9 � 2.6; median, 3.2). Twelve of the 27 specimens had a pMI >3.5. The local control rate in tumors with a pMI >3.5 was 17%, significantly lower than the 73% in the tumors with a pMI <3.5 (P ¼ .005). Multivariate analysis indicated that the pMI had the strongest impact on local control (standard regression coefficient ¼ 0.48, P ¼ .002) among the variables, including clinical stage, irradiated dose, age, and tumor volume. CONCLUSIONS: These results suggest that a high pMI is an indication of a poorer prognosis, and is a powerful prognostic factor in patients with squamous cell carcinomas of the cervix treated with carbon ion beam therapy. Cancer 2009;115:1875–82. V C 2009 American Cancer Society.