Detection of Survivin and COX-2 in Thyroid Carcinoma: Anaplastic Carcinoma Shows Overexpression of Nuclear Survivin and Low COX-2 Expression
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Background: Overexpression of survivin, a member of the inhibitors of apoptosis protein, has been reported in various carcinomas, and its interaction with cyclooxygenase 2 (COX-2) results in accelerated tumor progression. The purpose of this study is to investigate the immunohistochemical expression of survivin and COX-2 in benign and malignant thyroid tissues and to define its association with pathologic and clinical features. Methods: We examined expression of survivin and COX-2 by immunohistochemistry in 334 benign and malignant thyroid tissues and evaluated their clinical significance. Results: Expression of survivin showed an increase along the spectrum of thyroid carcinoma progression; rarely positive in adenomatous goiter, moderately positive in papillary carcinoma, and strongly positive in anaplastic carcinoma (AC). Papillary microcarcinoma revealed the highest COX-2 positivity and AC demonstrated the lowest positivity among thyroid cancers. Node negative carcinomas showed higher COX-2 expression than node positive tumors. Survivin expression did not correlate with COX-2. Conclusions: Our findings suggest that survivin overexpression may be related to the pathogenesis of AC and can be a predictor of disease progression. COX-2 may be involved in the early phase of thyroid carcinoma.
Abstract
Background: Overexpression of survivin, a member of the inhibitors of apoptosis protein, has been reported in various carcinomas, and its interaction with cyclooxygenase 2 (COX-2) results in accelerated tumor progression. The purpose of this study is to investigate the immunohistochemical expression of survivin and COX-2 in benign and malignant thyroid tissues and to define its association with pathologic and clinical features. Methods: We examined expression of survivin and COX-2 by immunohistochemistry in 334 benign and malignant thyroid tissues and evaluated their clinical significance. Results: Expression of survivin showed an increase along the spectrum of thyroid carcinoma progression; rarely positive in adenomatous goiter, moderately positive in papillary carcinoma, and strongly positive in anaplastic carcinoma (AC). Papillary microcarcinoma revealed the highest COX-2 positivity and AC demonstrated the lowest positivity among thyroid cancers. Node negative carcinomas showed higher COX-2 expression than node positive tumors. Survivin expression did not correlate with COX-2. Conclusions: Our findings suggest that survivin overexpression may be related to the pathogenesis of AC and can be a predictor of disease progression. COX-2 may be involved in the early phase of thyroid carcinoma.
참고문헌 (25)
- Segev DL, "Molecular pathogenesis of thyroid cancer", Surg Oncol, 12, pp.69~90 (2003)
- Ambrosini G, "Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting", J Biol Chem, 273, pp.11177~11182 (1998)
- Tracey L, "Expression of the NF-kappaB targets BCL2 and BIRC5", Survivin characterizes small B-cell and aggressive B-cell lymphomas, respectively, 2005, pp.206, 123~134
- Adida C, "Prognostic significance of survivin expression in diffuse large B-cell lymphomas", Blood, 96, pp.1921~1925 (2000)
- Kawasaki H, "Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis", Cancer, 91, pp.2026~2032 (2001)
- Herschman HR, "TIS10, a mitogen-inducible glucocorticoid-inhibited gene that encodes a second prostaglandin synthase", cyclooxygenase enzyme, 1993, pp.6, 89~99
- Liu CH, "Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice", J Biol Chem, 276, pp.18563~18569 (2001)
- Krysan K, "Cyclooxygenase 2-dependent expression of survivin is critical for apoptosis resistance in non-small cell lung cancer", Cancer Res, 64, pp.6359~6362 (2004)
- Erkanli S, "COX-2 and survivin are overexpressed and positively correlated in endometrial carcinoma", Gynecol Oncol, 104, pp.320~325 (2007)
- Costa P, "Expression of prolactin receptor and prolactin in normal and malignant thyroid: a tissue microarray study", Endocr Pathol, 17, pp.377~386 (2006)
- Barnes N, "Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence", Br J Cancer, 94, pp.253~258 (2006)
- Ito Y, "Survivin expression is significantly linked to the dedifferentiation of thyroid carcinoma", Oncol Rep, 10, pp.1337~1340 (2003)
- Kleinschmidt-DeMasters BK, "Survivin in glioblastomas: protein and messenger RNA expression and comparison with telomerase levels", Arch Pathol Lab Med, 127, pp.826~833 (2003)
- Nagaiah G, "Anaplastic thyroid cancer: a review of epidemiology, pathogenesis, and treatment", J Oncol, 2011, pp.542358~ (2011)
- Tirrò E, "Altered expression of c-IAP1, survivin, and Smac contributes to chemotherapy resistance in thyroid cancer cells", Cancer Res, 66, pp.4263~4272 (2006)
- Namba H, "Nuclear factor-kB in thyroid carcinogenesis and progression: a novel therapeutic target for advanced thyroid cancer", Arq Bras Endocrinol Metabol, 51, pp.843~851 (2007)
- Ambrosini G, "A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma", Nat Med, 3, pp.917~921 (1997)
- Antonaci A, "Survivin and cyclin D1 are jointly expressed in thyroid papillary carcinoma and microcarcinoma", Oncol Rep, 20, pp.63~67 (2008)
- Martinez A, "Nuclear survivin expression in mantle cell lymphoma is associated with cell proliferation and survival", Am J Pathol, 164, pp.501~510 (2004)
- Li F, "Control of apoptosis and mitotic spindle checkpoint by survivin", Nature, 396, pp.580~584 (1998)
- Sun Y, "Cyclooxygenase-2 overexpression reduces apoptotic susceptibility by inhibiting the cytochrome c-dependent apoptotic pathway in human colon cancer cells", Cancer Res, 62, pp.6323~6328 (2002)
- García-González M, "Cyclooxygenase-2 in normal, hyperplastic and neoplastic follicular cells of the human thyroid gland", Virchows Arch, 447, pp.12~17 (2005)
- Ito Y, "Cyclooxygenase-2 expression in thyroid neoplasms", Histopathology, 42, pp.492~497 (2003)
- Lee KJ, "Cyclooxygenase-2 expression in human thyroid disease", J Endocrinol Invest, 31, pp.111~118 (2008)
- Lo CY, "High prevalence of cyclooxygenase 2 expression in papillary thyroid carcinoma", Eur J Endocrinol, 152, pp.545~550 (2005)