膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义(英文)

目的探讨膀胱癌中 bcl-2、p53、PCNA 表达与细胞增殖、凋亡和临床病理学参数之间的关系。方法 SABC 免疫组化分折62例(T1G1-G339例,T2-T4aG3 NOM023例)甲醛固定和石蜡包埋的膀胱癌标本 bcl-2、p53和 PCNA 蛋白的免疫反应性。平均随访37个月,24例复发。增殖指数(PI)表示肿瘤细胞中 PCNA 阳性细胞百分比。TUNEL 法检测细胞凋亡,凋亡指数(AI)表示肿瘤细胞中凋亡细胞的百分比。结果 62例膀胱癌中,50例(80.0%)发生 p53突变,与 G1(72.7%)和 G2(78.5%)相比较 G3(91.3%)更多见(P<0.05);pT2期(95.7%)p53突变率较 pTa-1期(74.3%)高(P<0.01)。14例(22.5%)发现有 bcl-2表达,bcl-2表达阳性率 G3明显高于 G1和 G2(P<0.05),与分期无关(P>0.05)。Bcl-2表达与 p53突变无关。在膀胱癌中,PI 为17.2%～41.8%(平均为22.4%),AI 为1.9%～3.5%(平均为2.9%)。统计分析显示 PI 与肿瘤分级、分期关系密切,AI 与肿瘤的分级有明显关系。结论结果表明,p53突变与浸润性行为呈正相关。在膀胱癌中 p53和 PCNA 过表达可能能提供有价值的预后信息。随着肿瘤的进展,肿瘤细胞过度增殖可能伴有频繁的凋亡,但增殖指数的增加明显强于凋亡指数的增加。     

膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义

目的　　探讨膀胱癌中bcl-2、p53、PCNA表达与细胞增殖、凋亡和临床病理学参数之间的关系。方法　　SABC 免疫组化分折62例(T1GI —G339 例,T2-T4aG3　NOM023例)甲醛固定和石蜡包埋的膀胱癌标本bcl-2、p53 和PCNA蛋白的免疫反应性。平均随访37个月,24例复发。增殖指数(PI)表示肿瘤细胞中PCNA阳性细胞百分比。TUNEL法检测细胞凋亡,凋亡指数(AI)表示肿瘤细胞中凋亡细胞的百分比。结果　　62例膀胱癌中,50例(80.0%)发生p53突变,与G1(72.7%)和G2(78.5%)相比较G3(91.3%)更多见(P<0.05);pT2期(95.7%)p53突变率较pTa-1期(74.3%)高(P<0.叭)。14例(22.5%)发现有bel-2表达,bcl-2表达阳性率G3明显高于G1和G2(P<0.05),与分期无关(P>0.05)。Bcl-2表达与p53突变无关。在膀胱癌中,PI 为17.2%～41.8%(平均为22.4%),AI为1.9%-3.5%(平均为2.9%)。统计分析显示PI与肿瘤分级、分期关系密切,AI与肿瘤的分级有明显关系。结论　　结果表明,p53突变与浸润性行为呈正相关。在膀胱癌中p53和PCNA过表达可能能提供有价值的预后信息。随着肿瘤的进展,肿瘤细胞过度增殖可能伴有频繁的凋亡,但增殖指数的增加明显强于凋亡指数的增加。     

Apoptosis in transitional cell carcinoma of bladder and its relation to proliferation and expression of P53 and Bcl-2

Transitional cell carcinoma of bladder (TCC) is a relatively common cancer among men. Tumor progression is associated with expression or modulation of several gene products that control apoptosis and proliferation. Apoptosis is a negative growth regulatory mechanism in tumors. The aim of this study is to examine apoptosis and related regulatory molecular markers in a group of patients with TCC. Paraffinembedded tissues from 49 patients with TCC were examined for the expression of bcl-2, p53 and Ki-67 by immunohistochemistry. Apoptosis was detected by TUNEL method. Correlation between apoptotic index (AI), proliferation index (PI) and bcl-2 and p53 expression with each other and with pathological grade was determined. Apoptosis was observed in 28.1% of TCC cases. The mean AI of all cases was 13.7+/-24. No correlation was found between apoptosis and differentiation status of carcinoma. Bcl-2 expression was weakly detected in only one sample. P53 expression was detected in 26 of cases with mean staining index of 102+/-96. A significant correlation between p53 and Ki-67 staining indices was observed (r=0.521, p=0.001). Both p53 and Ki-67 expression showed a good association with the pathological grade (p=0.0001 and p=0.004, respectively). None of the markers showed significant correlation with AI and no correlation was found between the ratio of AI to PI and other parameters either. In conclusion, the frequency of apoptosis in TCC of bladder appears not to be associated with tumor grade, and with bcl-2, p53 and Ki-67 expression.     

PCNA及bcl-2基因在膀胱移行细胞癌组织中的表达及其意义

目的 :探讨PCNA和bcl 2基因在膀胱癌组织中的表达及其预后意义 ,了解肿瘤增殖与凋亡的特点 ,揭示细胞凋亡和增殖在膀胱癌发生发展中的作用。方法 :采用免疫组织化学LSAB法 ,对 78例膀胱移行细胞癌组织进行PCNA和bcl 2表达的检测。结果 :在膀胱癌中 ,PCNA主要呈胞核表达 ,bcl 2呈胞质表达 ,PCNA和bcl 2染色阳性率分别为 35 9%和 5 6 4 % ;PCNA表达与膀胱移行细胞癌组织分级、预后呈正相关 (P =0 0 1,P =0 0 386 ) ,bcl 2亦与肿瘤分级、预后呈高度正相关 (P =0 0 0 0 2 ,P =0 0 116 ) ;PCNA和bcl 2表达无明显相关 (P =0 2 32 7)。结论 :PCNA和bcl 2参与膀胱癌的恶性转化、侵袭及进展的过程 ;检测PCNA和bcl 2有助于判断膀胱肿瘤恶性分化程度 ,并且二者可以作为预后的评价指标     

Chemosensitivity and p53-dependent apoptosis in epithelial ovarian carcinoma.

BACKGROUND: Although p53 gene mutation frequently is observed in ovarian carcinoma, the function of the p53 gene in chemosensitivity has not been defined conclusively. The objective of the current study was to elucidate the relation between chemotherapy-induced apoptosis through the p53 pathway and chemosensitivity to ovarian carcinoma. METHODS: Tumor samples were obtained from 24 patients with epithelial ovarian carcinoma before and after chemotherapy with cisplatin, doxorubicin, and cyclophosphamide. Mutations in the p53 gene were screened by polymerase chain reaction-single-strand conformation polymorphism analysis and determined by cycle sequencing. Expression of the p53, Bax, and bcl-2 proteins and proliferating cell nuclear antigen (PCNA) were determined by immunohistochemical staining. Apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling method. RESULTS: Of the 24 patients, 12 responded to chemotherapy and 12 did not. p53 gene mutation was observed in ten nonresponders and two responders. The incidence of p53 protein expression in tumors with the gene mutation was 58% (7 of 12) and was 17% (2 of 12) in tumors without the gene mutation. A significant reverse correlation between apoptotic index (AI) and labeling index (LI), determined by the percentage of PCNA positive cells, was observed in tumors after chemotherapy. AI was found to increase significantly after chemotherapy in tumors with the wild-type p53 gene (3.84 +/- 1.64 vs. 7.13 +/- 5.23) but LI did not change in either tumor type. The expression of Bax protein was significantly greater in tumors with the wild-type p53 gene after chemotherapy. bcl-2 protein expression did not relate to p53 gene status before or after chemotherapy. CONCLUSIONS: The current study suggests that p53-dependent apoptosis in tumors is strongly related to the chemosensitivity in epithelial ovarian carcinoma.     

膀胱癌癌旁组织的病理学及p53蛋白、bcl-2表达意义

 目的　探讨膀胱癌癌旁组织的病理学改变和p5 3、bcl 2基因的表达意义。方法　采用免疫组化SP法 ,对 5 8例行手术治疗的膀胱癌标本 ,分别进行 p5 3、bcl 2基因的检测。 结果　p5 3阳性表达在膀胱癌的不同病理分期及分级中具有显著性差异 (P <0 .0 1) ;bcl 2基因阳性表达在浅表性膀胱癌与浸润性膀胱癌具有差异 (P <0 .0 5 ) ,bcl 2基因阳性表达在不同病理分级中具有显著性差异 (P <0 .0 1)。结论　p5 3阳性表达、bcl 2阴性表达的膀胱癌具有恶性程度高、易复发的特点 ;癌旁组织恶变发生率 ,浸润性膀胱癌 5 6 .4 % ,浅表性膀胱癌 2 1.1% ,提示手术时尽可能保证足够的切除范围。     

Spontaneous apoptosis in ovarian carcinomas: a positive association with p53 gene mutation is dependent on growth fraction

Changes in cell survival contribute to tumour development, influence tumour biology and its response to chemotherapy. p53 gene alterations should negatively affect apoptosis by impaired p53-dependent apoptotic response. We looked for associations between spontaneous apoptosis, p53 gene mutation, p53 protein accumulation, growth fraction, bcl-2 expression and histological parameters in 64 ovarian, four tubal and three peritoneal carcinomas. Apoptotic cells were detected with the TUNEL method. p53 gene variants were detected by the single-strand conformation polymorphism and were sequenced directly. P53, Ki-67 and bcl-2 protein expressions were detected immunohistochemically. A weighed multiple logistic regression model was applied. Apoptotic index (AI) ranged 0.02-0.18 (mean 0.11); proliferation index (PI) ranged 3-90% (mean 54%). p53 gene mutations were present in 51, p53 protein accumulation in 46, and diffuse bcl-2 expression in 29 of 71 tumours. The AI was positively associated with the presence of p53 gene mutation (P = 0.011). However, the PI included into the analysis did positively influence the AI (P = 0.02) and diminished the association with p53 gene mutation (P = 0.082). The AI was negatively associated with good histological differentiation (P = 0.0006), the serous tumour type (P = 0.002), and diffuse bcl-2 expression (P = 0.025). Strong bcl-2 expression was associated with endometrioid tumour type (P = 0.002). FIGO stage and p53 protein accumulation were the only parameters that influenced overall survival time. Thus, our results suggest that histological tumour type and grade are major determinants of spontaneous apoptosis in ovarian carcinomas; p53 alterations do not adversely but rather positively affect spontaneous apoptosis by increasing growth fraction. This, in turn, suggests p53-independency of spontaneous apoptosis in ovarian carcinomas.     

Growth characteristics of rectal carcinoid tumors

PURPOSE: Tissue growth depends on both cell proliferation and cell death. This study was designed to examine the growth characteristics of rectal carcinoid tumors. METHODS: Fifty rectal carcinoid tumors were studied clinicopathologically and experimentally. Expression of Ki-67, TGF-alpha, p53, and bcl-2 was examined immunohistochemically, and apoptotic cells were identified by the in situ DNA nick end labeling method. EGF receptor expression was examined by a colorimetric in situ mRNA hybridization technique. RESULTS: The median Ki-67 labeling index (LI) in all lesions was 0.62 +/- 0.59%. Ki-67 LI was significantly (p < 0.01) higher in lesions larger than 5 mm than in lesions smaller than 5 mm. TGF-alpha was expressed more frequently (p < 0.01) in lesions larger than 5 mm (100%) than in lesions smaller than 5 mm (65.2%). Ki-67 LI was significantly (p < 0. 05) higher in lesions with TGF-alpha expression than in lesions without TGF-alpha expression. The in situ hybridization revealed EGF receptor expression in all 46 lesions with intact mRNA (100%), and coexpression of TGF-alpha and EGF receptor was found in 39 of the 46 (84.8%) lesions. The median apoptotic index (AI) in all lesions was 0.15 +/- 0.12%. AI has increased with tumor size and was significantly (p < 0.05) higher in lesions with a higher Ki-67 LI than in lesions with a lower Ki-67 LI. p53 protein was detected in only 1 patient who had liver metastases, and the gene mutation was confirmed by polymerase chain reaction and single-strand conformation polymorphism analysis. bcl-2 expression was absent in all lesions. CONCLUSIONS: The Ki-67 LI indicated a low cellular proliferative activity in rectal carcinoid tumors. AI was very low, and was significantly correlated with proliferative rate. Inhibition of apoptosis by mutated p53 or bcl-2 may not have occurred in most of these tumors. TGF-alpha/EGF receptor autocrine mechanisms may play a possible role in tumor growth, and the cellular proliferative activity may increase as tumors grow larger.     

Apoptosis and its correlation with proliferative activity in rectal cancer

BACKGROUND AND OBJECTIVES: Alterations in the normal control of apoptosis and cell proliferation are important factors in multistep colorectal carcinogenesis. The aim of this study was to determine the frequency of apoptosis and cell proliferation in rectal cancers and to examine their relationship to clinicopathological variables and expression of bcl-2 and p53. METHODS: Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and immunohistochemical staining for Ki-67, bcl-2, and p53 were performed on paraffin-embedded tissue samples of 57 rectal cancers. RESULTS: There was a positive linear correlation between apoptotic index (AI) and proliferative index (PI) (gamma = 0.276, P = 0.038). Both apoptosis and cell proliferation were more frequently found in rectal cancers with lymph node metastasis (P = 0.045 and 0.010, respectively). However, the ratio of AI and PI was not different by nodal status. There was no association between Dukes stage and AI or PI. The frequency of apoptosis was inversely related to the expression of bcl-2, but was not related to the p53 status of rectal cancer. There were no association between cell proliferation and the expression of bcl-2 or p53. CONCLUSIONS: Our results suggest that the susceptibility to apoptosis in rectal cancer is clearly related to the proliferative activity and high turnover rate of tumor cells may contribute to lymph node metastasis.     

Biological features of sporadic colorectal carcinoma with high-frequency microsatellite instability: special reference to tumor proliferation and apoptosis

Background We evaluated the relationship between biological behavior and microsatellite instability (MSI) status, with or without p53 status, in sporadic colorectal carcinoma.Methods MSI was analyzed with regard to biological features such as cellular proliferation and apoptotic cell death, in addition to clinicopathological features, in 87 patients with sporadic colorectal carcinoma.Results Fourteen (16.1%) of 87 tumors showed instability at two or more of the five loci examined (high-frequency MSI [MSI-H]). Four demonstrated instability at one locus (low-frequency MSI [MSI-L]), and 69 showed no instability (microsatellite-stable [MSS]). The MSI-H tumors tended to be located in the proximal colon and more often were mucinous carcinoma. The MSI-H tumors also tended to be in patients with multiple colorectal carcinomas and to demonstrate, rarely, an infiltrating growth pattern or venous invasion. The incidence of p53 protein overexpression in the MSI-H tumors was significantly lower than that in the MSI-L/MSS tumors (21% vs 54%). There was no significant difference in the proliferating-cell nuclear antigen (PCNA) labeling index (PI) or apoptotic index (AI) between the MSI-H and MSI-L/MSS tumors. The AI in the MSI-H tumors with p53 overexpression was significantly lower than that in the MSI-H tumors without p53 overexpression, and was also significantly lower than that in the MSI-L/MSS tumors with p53 overexpression. In the MSI-H tumors with p53 overexpression, no expression of BAX protein was found, and there was high expression of bcl-2 protein, resulting in a low BAX/bcl-2 ratio.Conclusion In sporadic colorectal carcinoma, an MSI-H tumor with p53 protein overexpression may display aggressive biological features.