갑상선유두암에서 p53과 Cyclin D1의 발현이 가지는 예후인자로서의 의미
Prognostic Value of p53 and Cyclin D1 in Papillary Thyroid Carcinoma
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: P53 and cyclin D1 have been evaluated as a prognostic marker in papillary thyroid carcinoma (PTC). However, the relationship between p53/cyclin D1 and PTC prognosis has not yet been confirmed. Therefore, we investigated the relationship between p53/cyclin D1 and PTC prognostic factors.Methods: 919 patients with PTC were enrolled. Immunohistochemistry slides were reviewed for p53 and cyclin D1 immunoreactivity. Patients were classified into two groups according to the p53 and cyclin D1 grade: negative for ≤5% and positive for >5%. Medical records were reviewed to evaluate the prognostic factors, lymph node metastatic ratio (LNMR), and MACIS score. We analyzed patients based on p53/cyclin D1(−/−), p53/cyclin D1(−/+), p53/cyclin D1(+/−), p53/cyclin D1(+/+) separately for evaluation of independent effect of p53 and cyclin D1.Results: Mean age of the patients was 49.73 years (range 15∼87), and tumor size was 1.19 cm (range 0.1∼5.0). P53 was positive in 809 (88.0%) and cyclin D1 was positive in 748 (81.4%). Positivity of p53 and cyclin D1 were correlated (r=0.448). There was no statistical significance in MACIS score. Positivity of p53 and cyclin D1 were related with larger tumor size, older age, early T stage, more tumor capsulation, and female. LNMR was higher in p53/cyclin D1(+/−) than p53/cyclin D1(−/−) (P=0.036), p53/cyclin D1(−/+) than p53/cyclin D1(−/−) (P=0.034), and p53/cyclin D1(+/+) than p53/cyclin D1(−/−) (P=0.007). Conclusion: There was no consistent relationship between p53/cyclin D1 and worse prognostic factors of PTC. However, LNMR was higher in p53(+) and cyclin D1(+) cases independently, much more in p53/cyclin D1(+/+) than p53/cyclin D1(−/−).
Abstract
Purpose: P53 and cyclin D1 have been evaluated as a prognostic marker in papillary thyroid carcinoma (PTC). However, the relationship between p53/cyclin D1 and PTC prognosis has not yet been confirmed. Therefore, we investigated the relationship between p53/cyclin D1 and PTC prognostic factors.Methods: 919 patients with PTC were enrolled. Immunohistochemistry slides were reviewed for p53 and cyclin D1 immunoreactivity. Patients were classified into two groups according to the p53 and cyclin D1 grade: negative for ≤5% and positive for >5%. Medical records were reviewed to evaluate the prognostic factors, lymph node metastatic ratio (LNMR), and MACIS score. We analyzed patients based on p53/cyclin D1(−/−), p53/cyclin D1(−/+), p53/cyclin D1(+/−), p53/cyclin D1(+/+) separately for evaluation of independent effect of p53 and cyclin D1.Results: Mean age of the patients was 49.73 years (range 15∼87), and tumor size was 1.19 cm (range 0.1∼5.0). P53 was positive in 809 (88.0%) and cyclin D1 was positive in 748 (81.4%). Positivity of p53 and cyclin D1 were correlated (r=0.448). There was no statistical significance in MACIS score. Positivity of p53 and cyclin D1 were related with larger tumor size, older age, early T stage, more tumor capsulation, and female. LNMR was higher in p53/cyclin D1(+/−) than p53/cyclin D1(−/−) (P=0.036), p53/cyclin D1(−/+) than p53/cyclin D1(−/−) (P=0.034), and p53/cyclin D1(+/+) than p53/cyclin D1(−/−) (P=0.007). Conclusion: There was no consistent relationship between p53/cyclin D1 and worse prognostic factors of PTC. However, LNMR was higher in p53(+) and cyclin D1(+) cases independently, much more in p53/cyclin D1(+/+) than p53/cyclin D1(−/−).
참고문헌 (30)
- Omur O, "An update on molecular biology of thyroid cancers", Crit Rev Oncol Hematol, 90, pp.233~252 (2014)
- Zafon C, "Clinical significance of RET", PTC and p53 protein expression in sporadic papillary thyroid carcinoma, 2007, pp.50, 225~231
- Karlidag T, "Expression of Bax, p53, and p27", kip in patients with papillary thyroid carcinoma with or without cervical nodal metastasis, 2007, pp.28, 31~36
- Morita N, "Clinical significance of p53 protein expression in papillary thyroid carcinoma", World J Surg, 32, pp.2617~2622 (2008)
- Balta AZ, "Prognostic value of oncoprotein expressions in thyroid papillary carcinoma", Med Oncol, 29, pp.734~741 (2012)
- 김병섭, "갑상선유두암에서 Galectin-3, p53, Ki-67 단백질의 발현과 임상학적 의미", 대한외과학회지, 77(1), pp.29~36 (2009), 대한외과학회
- Ji WB, "The significance of bcl-2 and p53 expressions in the papillary thyroid cancer", Korean J Endocr Surg, 7, pp.231~236 (2007)
- Lee SH, "The expressions of CK7, CK20, vimentin, p53 and ki-67 in papillary thyroid carcinoma", Korean J Endocr Surg, 9, pp.7~13 (2009)
- Lee YM, "Prognostic value of epidermal growth factor receptor, p53 and galectin-3 expression in papillary thyroid carcinoma", J Int Med Res, 41, pp.825~834 (2013)
- Shin MK, "Clinicopathologic and diagnostic significance of p53 protein expression in papillary thyroid carcinoma", Asian Pac J Cancer Prev, 15, pp.2341~2344 (2014)
- Basolo F, "Cyclin D1 overexpression in thyroid carcinomas: relation with clinico-pathological parameters, retinoblastoma gene product, and Ki67 labeling index", Thyroid, 10, pp.741~746 (2000)
- Temmim L, "Cyclin D1 protein expression in human thyroid gland and thyroid cancer", Anat Histol Embryol, 35, pp.125~129 (2006)
- Lee SH, "Expression of cell-cycle regulators (cyclin D1, cyclin E, p27kip1, p57kip2) in papillary thyroid carcinoma", Otolaryngol Head Neck Surg, 142, pp.332~337 (2010)
- 김호진, "유두상 갑상선 암에서 Cyclin D1, Cytokeratin 7, Cytokeratin 20, Vimentin의 발현 및 예후 인자와의 연관성에 대한 분석", 대한내분비외과학회지, 12(2), pp.92~97 (2012), 대한갑상선-내분비외과학회[DOI]
- Melck A, "Cell cycle regulators show diagnostic and prognostic utility for differentiated thyroid cancer", Ann Surg Oncol, 14, pp.3403~3411 (2007)
- Rocha S, "p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-kappaB subunit with histone deacetylase 1", Mol Cell Biol, 23, pp.4713~4727 (2003)
- Ullmannová V, "Relationship between cyclin D1 and p21(Waf1", Cip1) during differentiation of human myeloid leukemia cell lines, 2003, pp.27, 1115~1123
- Pines J, "Four-dimensional control of the cell cycle", Nat Cell Biol, 1, pp.E73~E79 (1999)
- Hay ID, "Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779patients surgically treated at one institution during 1940through 1989", Surgery, 114, pp.1050~1057 (1993)
- Marcello MA, "P53 protein profile by IHC may be helpful to define patient prognosis", Med Oncol, 29, pp.2309~2310 (2012)
- Londero SC, "Papillary microcarcinoma of the thyroid gland: is the immunohistochemical expression of cyclin D1 or galectin-3 in primary tumour an indicator of metastatic disease?", Acta Oncol, 47, pp.451~457 (2008)
- Lantsov D, "Cyclin D1 overexpression in thyroid papillary microcarcinoma: its association with tumour size and aberrant beta-catenin expression", Histopathology, 47, pp.248~256 (2005)
- Khoo ML, "Overexpression of cyclin D1 and underexpression of p27 predict lymph node metastases in papillary thyroid carcinoma", J Clin Endocrinol Metab, 87, pp.1814~1818 (2002)
- Pesutić-Pisac V, "Cyclin D1 and p27 expression as prognostic factor in papillary carcinoma of thyroid: association with clinicopathological parameters", Croat Med J, 49, pp.643~649 (2008)
- Ioachim E, "Expression patterns of cyclins D1, E and cyclin-dependent kinase inhibitors p21waf1", cip1, p27kip1 in colorectal carcinoma: correlation with other cell cycle regulators (pRb, p53 and Ki-67 and PCNA) and clinicopathological features, 2008, pp.62, 1736~1743
- Oh YL, "Expression of p21Waf1, p27Kip1 and cyclin D1 proteins in breast ductal carcinoma in situ: Relation with clinicopathologic characteristics and with p53 expression and estrogen receptor status", Pathol Int, 51, pp.94~99 (2001)
- Raju B, "Expression of p53, cyclin D1 and Ki-67 in pre-malignant and malignant oral lesions: association with clinicopathological parameters", Anticancer Res, 25, pp.4699~4706 (2005)
- Ryu IS, "Lymph node ratio of the central compartment is a significant predictor for locoregional recurrence after prophylactic central neck dissection in patients with thyroid papillary carcinoma", Ann Surg Oncol, 21, pp.277~283 (2014)
- Jeon MJ, "The prognostic value of the metastatic lymph node ratio and maximal metastatic tumor size in pathological N1a papillary thyroid carcinoma", Eur J Endocrinol, 168, pp.219~225 (2013)
- Lang BH, "Significance of metastatic lymph node ratio on stimulated thyroglobulin levels in papillary thyroid carcinoma after prophylactic unilateral central neck dissection", Ann Surg Oncol, 19, pp.1257~1263 (2012)
