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Expression of an Inhibitor of Apoptosis, Survivin, in Oral Carcinogenesis

¹ First Department of Oral and Maxillo-Facial Surgery, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan;
² Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
³ Division of Oral Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;

View larger version (72K): [in this window] [in a new window]   Figure 1. Immunohistochemical staining of survivin in normal, pre-malignant (leukoplakia), and malignant (squamous cell carcinoma) tissue. (A) Normal oral tissue exhibited negative survivin protein expression. Original magnification, X50. (B) Moderately differentiated primary OSCC. Note the strong cytoplasmic immunoreaction for survivin. Original magnification, X100. (C) Survivin-positive case of leukoplakia. Note that strong positive immunoreaction for survivin was detected on the epithelial cell cytoplasm. Original magnification, X25. (D) The border between normal epithelium (right side) and the dysplastic lesion (left side) is indicated. Note that while no survivin expression was detected in normal epithelial cellular cytoplasm, strong survivin protein expression was evident in the lesion. Original magnification, X50. Bar = 100 µm.

View larger version (22K): [in this window] [in a new window]   Figure 2. State of survivin protein expression in normal tissues (n = 71), leukoplakias (n = 38), and primary OSCCs (n = 71). The survivin-IHC scores were calculated as follows: survivin-IHC score = (the percentage of positive tumor cells) X the staining intensity. Survivin protein expressions in leukoplakias and OSCCs were significantly higher than in normal oral tissues (p < 0.0001, Student’s t test), whereas no statistical difference in the protein expression was observed between leukoplakias and OSCCs (p = 0.3364, Student’s t test). The results represent the mean ± SD.

View larger version (52K): [in this window] [in a new window]   Figure 3. Representative results of RT-PCR and methylation assay in tissue samples obtained from normal mucosa and tumor, and in OSCC-derived cell lines. Each lower panel reveals GAPDH mRNA expression as an internal control for RT-PCR analysis. N, normal tissue; T, primary OSCC; M, molecular marker (X174-HaeIII). (A) RT-PCR analysis with the use of specific primers for survivin gene showed that survivin was expressed in tumors but not in corresponding normal tissues, except for case No. 8. Methylation assay revealed survivin-methylation in normal tissues of cases 17, 21, 9, and 13, respectively, which showed no survivin gene mRNA expression. (B) Survivin mRNA expression was detected in OSCC-derived cell lines (HSC-3, OK-92, Ca9-22, and SAS). All cell lines, with the exception of Ca9-22 cell line, showed survivin-methylation.

Journal of Dental Research, Vol. 82, No. 8, 607-611 (2003)
DOI: 10.1177/154405910308200807


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