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Manganese Superoxide Dismutase Expression Correlates with p53 Status and Local Recurrence of Cervical Carcinoma Treated with Radiation Therapy

Division of Radiation Medicine, National Institute of Radiological Sciences, 9-1, Anagawa-4-chome, Inage-ku, Chiba-shi 263 [T. N., K. O.], and Department of Biochemistry, Osaka University Medical School, Osaka [N. T.], Japan

Managanese superoxide dismutase (Mn-SOD) inactivates the radiation effect by removal of radiation-induced toxic superoxide radicals. The purpose of this study was to assess the correlation among Mn-SOD, radiation sensitivity, and prognosis following radiation therapy.

The Mn-SOD, p53 oncoprotein, and c-erbB-2 oncoprotein expressions in 52 specimens from patients with cervical cancer treated with radiation therapy were investigated immunohistochemically. The frozen sections were stained using antihuman Mn-SOD, anti-p53 monoclonal antibodies, and anti-c-erbB-2 oncoprotein polyclonal antibody followed by the avidinbiotin peroxidase complex method. Correlations among Mn-SOD expression, prognosis, and failure patterns were analyzed. Additionally, correlations between p53 and c-erbB-2 oncoproteins and Mn-SOD expression were investigated.

Positive expression of Mn-SOD in cervical carcinoma was 48.1%. No significant difference in positivity of Mn-SOD expression was noted according to stage and histological subtypes. The 5-year survival rate of Mn-SOD-positive patients was 42.5%, significantly poorer than the 77.0% of Mn-SOD-negative patients (P < 0.05). Analysis of the failure patterns revealed that patients with Mn-SOD expression showed a significantly higher incidence of local recurrence than those without. However, there was no difference in distant metastasis between them. Although both p53 and c-erbB-2 oncoprotein expressions were significantly associated with the prognosis of the same patients, Mn-SOD expression was associated with p53 oncoprotein expression but not with that of c-erbB-2 oncoprotein.

Our results demonstrate that the Mn-SOD level of cancer cells is correlated with local control and is an important prognostic factor in radiation therapy for cervical cancer. The Mn-SOD level may help explain the intrinsic radiosensitivity of cervical cancer cells.

¹ To whom requests for reprints should be addressed. Phone: 043(251)2111, ext. 512; Fax: 043(256)8301.

Received 11/16/95. Accepted 4/16/96.

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