|
|
- 2016
ADM及β-catenin在人骨肉瘤中的表达及其临床意义
|
Abstract:
摘要：目的 探讨肾上腺髓质素(ADM)及β-catenin在人不同分化程度骨肉瘤组织中的表达及其临床意义。方法 采用免疫组化方法检测33例不同病理分级人骨肉瘤组织(高分化14例，低分化19例)及10例骨软骨瘤组织石蜡切片中的ADM、总β-catenin(T-β-catenin)及磷酸化β-catenin蛋白(P-β-catenin)的表达。结果 ADM在骨肉瘤细胞质内表达，在高、低分化骨肉瘤表达阳性率分别为57.1%(8/14)和100%(19/19)，差异有统计学意义(P=0.003<0.05)。在高分化骨肉瘤中，T-β-catenin在胞质胞核中均有表达，阳性表达率为85.7%(12/14)；而在低分化骨肉瘤中，T-β-catenin仅在胞膜上胞质内有表达，阳性表达率为94.7%(18/19)；T-β-catenin在不同恶性程度骨肉瘤中阳性表达率的差异无统计学意义(P=0.561>0.05)。P-β-catenin在骨肉瘤细胞质内表达，在高、低分化骨肉瘤中表达阳性率分别为35.7%(5/14)和78.9%(15/19)，差异有统计学意义(P=0.029<0.05)。ADM与P-β-catenin(r=0.424，P=0.025<0.05)之间有相关性，ADM与T-β-catenin(P=0.078>0.05)、T-β-catenin与P-β-catenin(P=0.052>0.05)之间均无显著相关性。结论 ADM、P-β-catenin蛋白表达量的高低以及总β-catenin在细胞核、细胞质内的表达差异可作为判断骨肉瘤组织恶性程度的重要指标。其为进一步研究ADM与β-catenin在骨肉瘤的关系及对骨肉瘤细胞分化的作用提供了理论依据。
ABSTRACT: Objective To study the expressions of adrenomedullin (ADM) and β-catenin in human osteosarcoma of different differentiation grading and their clinical significance. Methods We chose 33 cases of human osteosarcoma with different pathological grading (14 cases of high differentiation grading and 19 cases of low grading) and 10 cases of human osteochondroma to detect the expressions of ADM protein, total (T) β-catenin and phosphorylated (P) β-catenin using immunohistochemical method. Results The expression of ADM was detected in the cytoplasm. In osteosarcomas of higher and lower differentiation grading, the positive rate of ADM was 57.1% (8/14) and 100% (19/19), respectively, with significant differences (P=0.003<0.05). The expression of T-β-catenin was observed in both the cytoplasm and the nucleus in higher differentiation grading and in only cytoplasm in lower grading. In osteosarcomas of higher and lower differentiation grading, the positive rate of T-β-catenin was 85.7% (12/14) and 94.7% (18/19), with no significant difference (P=0.561>0.05). The expression of P-β-catenin was detected in the cytoplasm. In osteosarcomas of higher and lower differentiation grading, the positive rate of P-β-catenin was 35.7% (5/14) and 78.9% (15/19), with a significant difference (P=0.029<0.05). There was a significant correlation between ADM and P-β-catenin (r=0.424, P=0.025<0.05), but no significant correlation between ADM and T-β-catenin (P=0.078>0.05) or between T-β-catenin and P-β-catenin (P=0.052>0.05). Conclusion The expressions of ADM and P-β-catenin proteins and the different distributions of expression of T-β-catenin protein in cytoplasm and/or nucleus are important indicators for judging the pathological grading of osteosarcoma
| [1] | MIRABELLO L, TROISI RJ, SAVAGE SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons[J]. Int J Cancer, 2009, 125(1):229-234. |
| [2] | LUETKE A, MEYERS PA, LEWIS I, et al. Osteosarcoma treatment--where do we stand? A state of the art review[J]. Cancer Treat Rev, 2014, 40(4):523-532. |
| [3] | MCQUEEN P, GHAFFAR S, GUO Y, et al. The Wnt signaling pathway: implications for therapy in osteosarcoma[J]. Expert Rev Anticancer Ther, 2011, 11(8): 1223-1232. |
| [4] | WU XY, HAO CP, LING M, et al. Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells[J]. Oncol Rep, 2015, 34:787-794. |
| [5] | DAI X, MA W, HE XJ, et al. Elevated expression of adrenomedullin is correlated with prognosis and disease severity in osteosarcoma[J]. Med Oncol, 2013, 30(1):347-356. |
| [6] | LAUSSON S, CRESSENT M. Signal transduction pathways mediating the effect of adrenomedullin on osteoblast survival[J]. J Cell Biochem, 2011, 112(12):3807-3815. |
| [7] | KELEG S, KAYED H, JIANG X, et al. Adrenomedullin is induced by hypoxia and enhances pancreatic cancer cell invasion[J]. Int J Cancer, 2007, 121(1):21-32. |
| [8] | HAYDON RC, LUU HH, HE TC. Osteosarcoma and osteoblastic differentiation: a new perspective on oncogenesis[J]. Clin Orthop Relat Res, 2007, 454:237-246. |
| [9] | TANG N, SONG WX, LUO J, et al. Osteosarcoma development and stem cell differentiation[J]. Clin Orthop Relat Res, 2008, 466(9):2114-2130. |
| [10] | DAI X, MA W, JHA RK, et al. Adrenomedullin and its expression in cancers and bone. A literature review[J]. Front Biosci (Elite Ed), 2010, 2:1073-1080. |
| [11] | JAWAD MU, SCULLY SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system[J]. Clin Orthop Relat Res, 2010, 468(7):2000-2002. |
| [12] | WANG L, GALA M, YAMAMOTO M, et al. Adrenomedullin is a therapeutic target in colorectal cancer[J]. Int J Cancer, 2014, 134(9):2041-2050. |
| [13] | ZUDAIRE E, MARTINEZ A, CUTTITTA F. Adrenomedullin and cancer[J]. Regul Pept, 2003, 112(1-3):175-183. |
| [14] | LIN CH, JI T, CHEN CF, et al. Wnt signaling in osteosarcoma[J]. Adv Exp Med Biol, 2014, 804:33-45. |
| [15] | HAYDON RC, DEYRUP A, ISHIKAWA A, et al. Cytoplasmic and/or nuclear accumulation of the beta-catenin protein is a frequent event in human osteosarcoma[J]. Int J Cancer, 2002, 102(4):338-342. |
| [16] | DAINO K, UGOLIN N, ALTMEYER-MOREL S, et al. Gene expression profiling of alpha-radiation-induced rat osteosarcomas: identification of dysregulated genes involved in radiation-induced tumorigenesis of bone[J]. Int J Cancer, 2009, 125(3):612-620. |
| [17] | CAI Y, MOHSENY AB, KARPERIEN M, et al. Inactive Wnt/beta-catenin pathway in conventional high-grade osteosarcoma[J]. J Pathol, 2010, 220(1):24-33. |
