Margulis Vitaly, Shariat Shahrokh F, Ashfaq Raheela, Thompson Melissa, Sagalowsky Arthur I, Hsieh Jer-Tsong, Lotan Yair
Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9110, USA.
J Urol. 2007 Mar;177(3):1163-8. doi: 10.1016/j.juro.2006.10.033.
We compared the differential expression of cyclooxygenase-2 in normal bladder tissue, primary bladder transitional cell carcinoma and transitional cell carcinoma metastases to lymph nodes, and determined whether cyclooxygenase-2 expression is associated with molecular alterations commonly found in bladder transitional cell carcinoma and clinical outcomes after radical cystectomy.
Immunohistochemical staining for cyclooxygenase-2, survivin (Novus Biologicals, Littleton, Colorado), p21, p27, pRB, p53, MIB-1, Bax, Bcl-2, cyclin D(1) (Dakotrade mark), cyclin E (Oncogene, Cambridge, Massachusetts) and caspase-3 (Cell Signaling, Beverley, Massachusetts) was performed on archival bladder specimens from 9 subjects who underwent cystectomy for benign causes, 21 patients who underwent transurethral resection and 157 consecutive patients after radical cystectomy, and on 41 positive lymph nodes.
Cyclooxygenase-2 was expressed in none of the 9 normal bladder specimens (0%), 52% of transurethral resection specimens, 62% of cystectomy specimens and 80% of lymph nodes involved with transitional cell carcinoma. Cyclooxygenase-2 expression was associated with higher pathological stage, lymphovascular invasion and metastases to lymph nodes (p=0.001, 0.045 and 0.002, respectively). Cyclooxygenase-2 expression was associated with altered expression of p53 (p=0.039), pRB (p=0.025), cyclin D1 (p=0.034) and caspase-3 (p=0.014). On univariate analysis cyclooxygenase-2 expression was associated with an increased risk of disease recurrence and bladder cancer specific mortality (p=0.0189 and 0.0472, respectively). However, on multivariate analysis only pathological stage and metastases to lymph nodes were associated with disease recurrence (p<0.001 and <0.001) and survival (p<0.001 and 0.015, respectively).
Cyclooxygenase-2 is not expressed in normal bladder urothelium. Cyclooxygenase-2 over expression is associated with pathological and molecular features of biologically aggressive disease, suggesting a role for cyclooxygenase-2 in bladder cancer development and invasion.
我们比较了环氧化酶-2在正常膀胱组织、原发性膀胱移行细胞癌及移行细胞癌淋巴结转移灶中的差异表达，并确定环氧化酶-2表达是否与膀胱移行细胞癌中常见的分子改变以及根治性膀胱切除术后的临床结局相关。
对9例因良性原因接受膀胱切除术的患者、21例行经尿道切除术的患者以及157例根治性膀胱切除术后的连续患者的存档膀胱标本，以及41个阳性淋巴结进行环氧化酶-2、生存素（Novus Biologicals公司，科罗拉多州利特尔顿）、p21、p27、pRB、p53、MIB-1、Bax、Bcl-2、细胞周期蛋白D1（Dakotrade商标）、细胞周期蛋白E（Oncogene公司，马萨诸塞州剑桥）和半胱天冬酶-3（Cell Signaling公司，马萨诸塞州贝弗利）的免疫组织化学染色。
9例正常膀胱标本中均未检测到环氧化酶-2表达（0%），经尿道切除术标本中52%有表达，膀胱切除术标本中62%有表达，移行细胞癌累及的淋巴结中80%有表达。环氧化酶-2表达与更高的病理分期、淋巴管浸润及淋巴结转移相关（分别为p = 0.001、0.045和0.002）。环氧化酶-2表达与p53（p = 0.039）、pRB（p = 0.025）、细胞周期蛋白D1（p = 0.034）和半胱天冬酶-3（p = 0.014）的表达改变相关。单因素分析显示，环氧化酶-2表达与疾病复发风险增加及膀胱癌特异性死亡率增加相关（分别为p = 0.0189和0.0472）。然而，多因素分析显示，仅病理分期和淋巴结转移与疾病复发（p < 0.001和< 0.001）及生存（分别为p < 0.001和0.015）相关。
正常膀胱尿路上皮中不表达环氧化酶-2。环氧化酶-2的过表达与具有生物学侵袭性疾病的病理及分子特征相关，提示环氧化酶-2在膀胱癌发生和侵袭中起作用。
