Prognostic Significance of p53 Protein Accumulation in Stage pT1 Transitional Cell Carcinoma of the Bladder

Objective: Mutations in the tumour suppressor gene p53 results in the production of a mutant type, dysfunctional p53 protein which can readily be detected in the cell nucleus by immunohistochemical staining. This study aims to investigate the association of nuclear p53 protein accumulation with the clinical outcome of stage pT1 transitional cell carcinoma of the bladder which is renowned for high rates of recurrence and progression. Methods: TUR samples of the tumours from fifty-two patients with primary stage T1 bladder cancer were analyzed immunohistochemically using the standard avidin-biotin peroxidase method for nuclear p53 accumulation. Status of p53 immunostaining was correlated with tumour recurrence, disease progression and three-year survival of each patient. Results: The rate of tumour recurrence in pT1 bladder cancer was 36% in patients with tumours stained negatively for p53 protein and 78% in patients with tumours stained positively for p53 protein. Disease progression was seen in 15% of p53 (-) patients and in 56% of p53 (+) patients. Conclusions: In stage pT1 bladder tumours p53 nuclear accumulation indicates higher rates of tumour recurrence and disease progression. Accordingly, in patients who have pT1 bladder tumours with nuclear p53 accumulation, institution of more aggressive therapy should be considered and early radical therapeutic modalities should be offered to these patients.     

人丝氨酸蛋白酶抑制因子HAI-1在膀胱移行细胞癌中的表达及意义

目的 检测HAI-1基因在膀胱移行细胞癌(BTCC)中的表达,探讨与BTCC临床病理参数间的关系及其临床意义.方法 应用免疫组化SP法检测HAI-1在BTCC及正常膀胱黏膜中的表达,并结合临床病理资料分析.结果 HAl-1在BTCC及正常膀胱组织中均有表达;在BTCC中的表达阳性率明显低于正常膀胱组织,差异有统计学意义(P＜0.001);HAI-1表达随肿瘤病理分级、临床分期的升高、肿瘤转移的发生而显著性降低(P＜0.001).结论 HAI-1异常表达在BTCC的发生发展过程中可能具有重要作用,HAI-1蛋白可作为判断BTCC恶性程度及预后的新型生物学标记.     

Bulky Transitional Cell Carcinoma of Bladder with Inverted Proliferation

Two women, aged 51 and 62 years, had unusual transitional cell carcinomas of the urinary bladder which were > 5 cm and had a structural resemblance to inverted papilloma or Brunn's nest. They were treated by bladder-preserving surgery with no evidence of recurrence after 30 and 1 03 months follow-up, respectively. Our cases show some hitherto unrecognized aspects of transitional cell carcinoma with inverted proliferation because the tumors are usually found in males and tend to be aggressive.     

Cyclooxygenase-2 Expression Increases with the Stage and Grade in Transitional Cell Carcinoma of the Urinary Bladder

Objectives: Experimental models of carcinogenesis show that non-steroidal anti-inflammatory drugs (NSAIDs) increase apoptosis, inhibit angiogenesis and reduce metastases. A linkage between the activity of prostaglandin synthase enzyme cyclooxygenase-2 (COX-2), a known mediator of inflammation, and cancer angiogenesis is implicated. We investigated the expression of COX-2 in bladder cancer tissue specimens using immunohistochemistry. Methods: The immunohistochemical expression of COX-2 in bladder cancer was evaluated by scoring the intensity of immunoreactivity from 0 to 3. Further, the degree of COX-2 expression was correlated with the tumor grade and depth of invasion (T stage). Result: Fifty eight percent patients (n=22) had superficial bladder tumors, while 42% (n=16) were invasive bladder cancers. Overall, COX-2 immuno-positivity was seen in 84.2% (32/38) patients. COX-2 expression was positive in 76.4% (13/17) cases with pTa tumors, 100% (5/5) of pT1 tumors, 86.6% (13/15) of pT2 tumors and in 100% (1/1) of pT3 tumor. The higher stage tumors stained more intensely; this correlation wassignificant(p=0.01987; χ2=19.6977). With reference to the grade of tumors, a positive expression was seen in 81.25% (13/16) of the low-grade tumors and 89% (17/19) of the high-grade tumors. The differential COX-2 expression relative to the grade of tumor was found to be statistically significant (p=0.05; χ2=15.8612). Conclusion: The degree of COX-2 expression is significantly increased with advancing grade and T stage of disease (p < 0.05).     

Case report: Microcystic Transitional Cell Carcinoma of the Urinary Bladder

We report a rare case of microcystic transitional cell carcinoma involving the urinary bladder, in a 38-year-old man, and we add our experience in the treatment of this neoplasm. The tumor was muscle invasive, and a radical cystectomy was performed. The patient received no postoperative chemotherapy or radiotherapy, and he has not signs of local recurrence or distal metastasis after 3 years of intense follow up. Even though the number of cases documented so far, is insufficient to draw safe conclusions regarding the optimal treatment of the microcystic variant of transitional cell carcinoma. Our case indicates that even in cases of microcystic transitional cell carcinoma with infiltrative nature, aggressive therapy is associated with good control of the disease locally and distally.     

CyclinD1蛋白在T2-3N0M0期食管癌中的表达及其与预后的关系

目的探讨CyclinDl蛋白在T2-3N0M0期食管鳞状细胞癌（食管鳞癌）组织中的表达及其与预后的关系。方法用免疫组织化学染色方法检测227例T2-3N0M0期食管癌组织中CyclinD1蛋白的表达,应用受试者工作（receiveroperatingcharacteristic,ROC）曲线确定CyclinD1免疫组织化学高表达和低表达的分界点,分析CyclinD1表达与食管癌临床病理因素和预后之间的关系。结果CyclinD1在食管癌组织中低表达90例（39．6％）,高表达137例（60．4％）。CyclinDl蛋白的表达与性别（P=-0．298）、年龄（P=O．525）、肿瘤位置（P=0．570）、肿瘤长度（P=-0．056）、分化程度（P=0．713）和浸润深度（P=0．557）无明显相关性,但CyclinD1低表达组与cyclinD1高表达组的预后差异有统计学意义（3年生存率：51．1％VS．43．8％;5年生存率：43．3％VS．30．7％;P=-0．047）。Cox风险比例模型分析显示CyclinD1不是T2-3N0M0期食管癌独立预后因素（艘值=1．378,95％CI：0．990—1．919,P=-0．057）。结论CyclinD1过表达可能是影响T2-3N0M0期食管癌不良预后的因素。     

Treatment of modified Stage II (T1 N1 M0, T2 N1 M0) non-small cell bronchogenic carcinoma. A combined modality approach

Twenty patients with postsurgical, modified Stage II (T2 N1 M0, T1 N1 M0) non-small cell bronchogenic carcinoma were seen between 1974 and 1981 and were evaluated in a retrospective manner. Fifteen patients had T2 N1 M0 lesions, while 5 patients had T1 N1 M0 disease. Eight patients were treated with surgical resection alone, of whom seven had died, with a median survival of 12.0 months. Four patients received surgical resection and postoperative radiation therapy, of whom two have died, with a median survival not reached at 37 months. Eight patients were treated with surgical resection, radiation therapy, and adjuvant chemotherapy including cyclophosphamide (C), doxorubicin (A), methotrexate (M), and procarbazine (P). Six patients are alive and free of disease, with a median survival not yet reached at 72 months. There is a significant survival advantage for the 12 patients treated with combined modality therapy (surgical resection + radiation therapy; surgical resection + radiation therapy + chemotherapy) compared to the eight patients treated with SR alone (p less than 0.01), and for the eight patients receiving chemotherapy versus the 12 patients who did not (p less than 0.01). In spite of thorough clinical and surgical staging, patients with T1 and T2 primary tumors with N1 disease have a high relapse rate, predominantly in metastatic sites. Adjuvant radiation therapy and chemotherapy appear to benefit these patients with modified Stage II non-small cell bronchogenic carcinoma.     

Treatment of stage I lung cancer (T1N0M0, T2N0M0)

Patients with stage I lung cancer can be offered surgical treatment with an excellent prognosis for recovery and long-term cure. The recent revision of the staging definition has rearranged the prognostic categories, further improving the prognosis in Stage I disease by eliminating patients with a higher risk of recurrence. The most vexing issues remaining are the infrequency of diagnosis of lung cancer at this stage and the increasing incidence of lung cancer of all stages, even among nonsmokers. Economical screening, abolition of cigarette smoking, control of airborne environmental carcinogens, and the continued search for effective systemic treatment remain challenges for the future.     

BRMS1mRNA在膀胱移行细胞癌组织中的表达及临床意义

目的：探讨膀胱移行细胞癌组织中乳腺癌转移抑制基因（breast cancer metastasis suppressor1,BRMSl）mRNA表达水平与膀胱移行细胞癌的发生和转移的关系。方法：以β-actin为内参照,用荧光RT—PCR方法分别检测正常膀胱、未转移膀胱癌、转移膀胱癌三组标本组织中BRMSlmRNA的表达。结果：未转移膀胱癌和转移性膀胱癌BRMslmRNA表达水平显著低于正常膀胱组织（P〈0．01）,转移膀胱细胞癌BRMSlmRNA水表达平显著低于未转移膀胱细胞癌（P〈0．01）。结论：BRMSlmRNA在膀胱癌组织中的表达水平与膀胱癌的发生和淋巴结转移呈负相关;BRMSlmRNA表达的下降可能促进了膀胱癌的转移。     

膀胱癌错配修复基因hMSH2表达的研究

目的 探讨错配修复基因hMSH2在膀胱移行细胞癌中的表达情况及其与肿瘤细胞增殖、凋亡的关系.方法 采用免疫组化法检测101例膀胱移行细胞癌错配修复基因hMSH2以及细胞增殖抗原Ki-67的表达情况,原位末端标记(TUNEL)法检测肿瘤细胞凋亡情况.结果 hMSH2表达于非膀胱肿瘤尿路上皮及部分膀胱移行细胞癌的细胞核,膀胱移行细胞癌组低表达率较非膀胱肿瘤膀胱组织组高(P=0.004,＜0.05);膀胱移行细胞癌pT2-pT4组中hMSH2的低表达率比pTis-pT1组的低表达率高(P=0.016,＜0.05);G1、G2、G3三组间低表达率的总体差别有统计学意义(P=0.033,＜0.05),G1+G2组与G3组之间差别有统计学意义(P=0.036＜0.05);有无淋巴结转移组差别无统计学意义(P=0.317).hMSH2弱表达组与强表达组间凋亡指数(AI)均值差异非常显著(P＜0.01),Ki-67标记指数(Ki-67 LI)均值差异不显著(P＞0.05),AI/KI值差异经统计学分析具有统计学意义(P＜0.05).结论 hMSH2基因突变或功能缺失与膀胱移行细胞癌的发生有关,可能系肿瘤发生过程中的重要事件,并可能与肿瘤细胞凋亡有关,而与增殖活性无关.     

趋化因子受体CXCR4在膀胱移行细胞癌中的表达

目的：研究趋化因子受体CXCR4在膀胱移行细胞癌（BTCC）组织中的表达及其临床意义。方法：运用免疫组化技术，检测42例膀胱移行细胞癌组织、5例腺性膀胱炎组织、5例移行细胞乳头状瘤及10例正常膀胱黏膜上皮CXCR4的表达，染色结果采用免疫反应积分（IRS）和积分光密度值（IOD）分别进行评分。结果：42例BTcc组织中，4｜D例cxcR4表达阳性（95.2％）。随着肿瘤细胞病理分级、临床分期的增加，CXCR4的表达强度升高（P〈0.05）。正常膀胱组织和各阳性对照组中CXCR4的表达呈阴性。结论：CXCR4的表达与BTCC的分级分期有相关性；CXCR4的异常表达与BTCC的复发、转移有关，并有可能成为一种新的预后判断指标。