Expression of p53, p21/waf, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas

This study investigated the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas and correlated expression patterns with tumour stage and grade. Paraffin sections from 98 cases of colorectal adenocarcinomas were stained by immunohistochemistry for p53, p21, bcl-2, bax, Rb and MIB-1 (Ki67) proteins. In addition, 12 cases of colorectal adenomas and normal colorectal mucosa were studied in parallel. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in at least 5% of tumour cells in 63/98, 72/98, 52/98, 96/98 and 98/98 adenocarcinomas, respectively. Comparative study of the normal-adenoma-carcinoma tissues revealed abrogation of the normal immunotopography in adenomas and adenocarcinomas, and considerable modifications, increase or reduction, of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in adenocarcinomas when compared with normal mucosa and adenomas. Statistically significant correlations were found between low bax expression and Dukes C stage of carcinomas, Ki67 expression and carcinoma grade, and Ki67 and Rb expression. P53, p21, bcl-2 and Rb immunoexpression did not correlate with tumour stage or grade. Our findings show that low bax immunoexpression is frequently related to colorectal adenocarcinomas with lymph node metastases suggesting that low levels of bax expression play a role in late stage colorectal cancer. The correlation between Ki67 and Rb expression, in view of previous data that the hyperphosphorylated inactive Rb protein is frequently increased in colorectal adenocarcinomas, suggests that Rb protein is somewhat ineffective in inhibiting the cell-cycle progression in these malignancies. Furthermore, our findings provide immunohistochemical evidence that the abrogation of the normal immunotopography and the modifications of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins reflect important events in colorectal oncogenesis.     

Expression of p16, p27, p53, p73 and Nup88 proteins in matched primary and metastatic melanoma cells

Cutaneous melanoma is a tumor with high metastatic potential, but the mechanisms leading to progression are still not fully understood. In this study, we examined whether p16, p27, p53, p73 and Nup88 proteins were involved in the progression from primary to metastatic melanomas by immunocytochemistry and Western blotting in eleven melanoma cell lines from five matched primary and metastatic melanomas. We demonstrated that the primary and metastatic melanomas expressed differently p16, p27, p73 and Nup88 proteins. When expressed in the primary melanoma cells p16 and p27 were lost or reduced in almost all the metastatic melanoma cell lines. In contrast, p73 and Nup88 were expressed in most of the tested melanoma cell lines and were increased in the metastatic melanomas. p53 was expressed at the same level in both the primary and metastatic melanoma cells. These data suggest that a reduced expression of p16 and p27 and an enhanced expression of p73 and Nup88 might play an important role in the progression of melanoma from primary tumor to metastasis.     

Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma

BACKGROUND AND OBJECTIVES: To investigate the immunohistochemical expression of three apoptosis-related genes (bax, bcl-2, and p53) and apoptosis (TUNEL) in patients with primary osteosarcoma, and examine potential correlations between gene expression and clinicopathological characteristics in these patients. MATERIALS AND METHODS: Thirty-five primary osteosarcoma specimens and 18 tissue specimens deriving from non-malignant osseous lesions were immunohistochemically stained for bax, bcl-2, and p53 proteins, while apoptosis was investigated by the TUNEL method. The results were statistically analyzed. RESULTS: P53, bax, and bcl-2 protein expression was observed in 22 (62.9%), 29 (82.9%), and 18 (51.4%) osteosarcoma patients, respectively. Non-specific positive TUNEL staining (+/-) was observed in two primary osteosarcoma cases (5.7%). None of the benign controls expressed any of the genes studied. None of the apoptosis-related genes studied was able to predict overall or disease-free survival in our group of patients. Nevertheless, increased bax/bcl-2 protein expression ratio was associated with a decreased 4-year survival and disease free survival (P = 0.0229 and P = 0.0370, respectively). Furthermore, all the patients who were bax(+)/bcl-2(-)/p53(+) relapsed within the 4-year follow-up period (P = 0.0385). CONCLUSIONS: The increased apoptotic rate as determined by an elevated bax/bcl-2 protein expression ratio or by the bax(+)/bcl-2(-)/p53(+) protein expression pattern, appears to identify groups of osteosarcoma patients with unfavorable prognosis.     

p53mRNA、bcl-2、bax蛋白在肺癌中的表达

目的 :探讨原发性肺癌中 bcl- 2、bax和 p5 3m RNA表达水平及其与临床病理特征的关系。方法 :用免疫组织化学 Dako Envision TM二步法、反转录聚合酶链反应 (RT- PCR)方法分别检测5 2例肺癌组织中 bcl- 2、bax、p5 3m RNA表达情况。结果 :5 2例肺癌组织中 bcl- 2、bax蛋白表达阳性率分别为 4 2 .3%、5 9.6 1%。肺癌中 bcl- 2蛋白过表达在低分化癌、 期肺癌中高于高分化癌以及 期肺癌差异有显著性意义 (P<0 .0 1)。 p5 3m RNA、bax蛋白的阳性表达与 bcl- 2蛋白呈负相关。结论 :bcl- 2蛋白在晚期肺癌中过表达 ,p5 3m RNA、bax蛋白在早期肺癌中起着重要作用 ,它们共同参与细胞内死亡和存活信息的平衡状态的调节。     

Expression of apoptosis-related proteins (p53, p21WAF1, bcl-2, and bax) and sensitivity to chemotherapy in squamous cell carcinoma of the esophagus

Background. Chemotherapy is an important component of the multimodal approach to the treatment of advanced esophageal squamous cell carcinoma. Methods. We investigated the associations between p53, p21 (Waf1), bcl-2, and bax expression and response to chemotherapy (cisplatin + 5-fluorouracil + leucovorin) in 43 patients with advanced esophageal squamous cell carcinoma. The expression of p53, p21 (Waf1), bcl-2, and bax proteins was analyzed immunohistologically in pretreatment biopsy and post-treatment resected specimens. Results. The 23 patients who had objective evidence of either a complete response (CR) or a partial response (PR) to chemotherapy survived for significantly longer than the 20 patients who had no response (NR). The expression of p53, p21 (Waf1), bcl-2, and bax was detected in 26 (61%), 12 (28%), 6 (14%), and 19 (44%) of the pretreatment biopsy specimens, respectively. The response to chemotherapy was not independently associated with the expression of any of these proteins. However, in the 26 patients with p53-expressing tumors, the response rate was 80% in patients whose tumor also expressed p21, whereas it was 19% in those whose tumor did not coexpress p21. No change in p53 expression was observed before and after chemotherapy, except in 1 patient; however, p21 expression appeared to be induced by chemotherapy in 5 patients. Patient survival was also not independently associated with the expression of any of these proteins. However, patients with p53-negative or p21-positive tumors had a better response to chemotherapy and survived for longer than those with p53-positive and p21-negative tumors. Conclusion. p53 and p21 expression in biopsy specimens obtained before chemotherapy could be useful predictors of response and survival in patients with advanced esophageal squamous cell carcinoma. Received: April 14, 1999 / Accepted: November 8, 1999     

Expression of pro-apoptotic (p53, p21, bax, bak and fas) and anti-apoptotic (bcl-2 and bcl-x) proteins in serous versus mucinous borderline ovarian tumours

BACKGROUND: We examined the expression of apoptosis-related proteins in serous versus mucinous borderline ovarian tumours, in comparison with benign and malignant ovarian tumours. MATERIALS AND METHODS: Immunohistochemical expression of pro-apoptotic (p53, p21, bax, bak, fas) and anti-apoptotic proteins (bcl-2, bcl-x) was determined in 34 borderline (19 mucinous, 15 serous), 20 benign (10 mucinous, 10 serous) and 28 malignant ovarian tumours (9 mucinous, 19 serous). RESULTS: A difference in semi-quantitative p53 expression was found between benign and borderline tumours (P = 0.01), but not between borderline and malignant tumours. Increased p21 expression was found in borderline versus benign tumours (P = 0.004). Bcl-2 expression was lower in borderline than in benign (P = 0.01) and malignant tumours (P = 0.02). No difference in bax, bak, fas or bcl-x expression was observed among the three tumour types. Higher percentage of p21 positive cells was found in serous than in mucinous borderline tumours (P < 0.001). Bcl-2 expression was higher in serous than in mucinous forms of benign (P < 0.001), borderline (P < 0.001), and malignant tumours (P < 0.003). No difference in p53, bax, bak, fas or bcl-x expression was observed between serous and mucinous borderline ovarian tumours. CONCLUSION: Although p53 overexpression was a common feature of both mucinous and serous borderline tumours, p21 and bcl-2 overexpression appeared specific to serous tumours.     

Ki-67, Bcl-2 and p53 expression in primary and metastatic melanoma

The aim of this study was to clarify the roles of the tumour proliferation marker Ki-67, the anti-apoptotic protein Bcl-2 and the cell cycle regulator p53 in primary cutaneous and metastatic melanoma. One hundred and seventeen primary melanomas and 18 metastatic tissue samples were analysed for immunohistochemical expression of Ki-67, Bcl-2 and p53. The staining results were correlated with disease progression and clinical outcome. The patient population comprised patients diagnosed with melanoma between 1988 and 1991. The clinical follow-up period for disease recurrence was 4.6 years (median; range, 0.2-7.5 years) and the follow-up period for overall survival was 10.0 years (median; range, 8.6-15.6 years). Ki-67 expression was not a prognostic factor in primary melanoma. High Bcl-2 expression was associated with such adverse prognostic factors as male gender, old age of the patient and tumour ulceration. High Bcl-2 expression was also associated with an adverse prognosis in intermediate-thickness (1.01-4.0 mm) melanomas (n=52) for disease-free (P=0.09) and overall (P=0.08) survival. In multivariate analysis, tumour thickness was the strongest prognostic factor for disease-free survival (P<0.01). High p53 expression indicated a poorer prognosis (P=0.05). In metastatic melanoma, the expression levels of Bcl-2 and p53 were lower than those in their primary counterparts (P=0.08 for each). Ki-67 expression showed no remarkable changes. It can be concluded that high p53 expression in tumour cells is associated with a poorer prognosis in primary melanoma, and high Bcl-2 expression in tumour cells is an adverse prognostic marker in intermediate-thickness primary melanoma.     

Expression profiles of Id1 and p16 proteins in all-trans-retinoic acid-induced apoptosis and cell cycle re-distribution in melanoma

All-trans-retinoic acid (atRA) exerts its effects via apoptosis and cell cycle re-distribution. However, the mechanisms behind the effects have not been fully understood. In this study, we used a model system of matched primary and metastatic melanoma cells to investigate whether expression of Id1 and p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution. Melanoma cells were exposed to 0.1 or 10 microM atRA for 1-96 h. Apoptosis and cell cycle were measured by flow cytometry. Expression of Id1 and p16 proteins was examined by Western blotting and immunocytochemistry. After exposure to atRA we found a marked increase in apoptosis and cell cycle re-distribution in both primary and metastatic melanoma cells. Expression level of Id1 protein was decreased and the p16 was increased in a dose- and time-dependent (P<0.05) manner after treatment with atRA. Alterations of these proteins were more pronounced in the primary melanoma cells than the matched metastases (P<0.05). These data suggested that the alterations of Id1 and/or p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution in melanoma. These expression profiles of Id1 and p16 proteins may provide molecular evidence for better chemotherapy primarily for early stages of melanoma.     

消化道多原发癌组织中凋亡相关蛋白p53和bcl-2的表达

目的研究消化道多原发癌组织中的p53和bcl-2蛋白表达状况，探讨p53和bcl-2基因在多原发癌的发生发展中的意义。方法应用免疫组织化学方法检测17例消化道双原发癌组织中的p53和bcl-2蛋白表达。结果17例患者34个独立癌灶中p53阳性者21个(21／34)，bcl-2阳性者14个(14／34)。3例患者第一癌和第二癌的p53和bcl-2表达均为阴性，其它14例患者第一癌和第二癌则有p53或／和bcl-2表达；5例患者p53和bcl-2在第一癌和第二癌中的结果一致，其它12例患者则有不同程度的区别。结论p53和bcl-2基因在消化道多原发癌的发生发展中可能起重要作用，对这些发现的意义值得进一步研究。     

p53 mRNA及bcl-2、bax蛋白在直肠癌组织中的表达及意义

目的研究p53mRNA及bcl-2、bax蛋白在直肠癌组织中的表达及其意义。方法应用组织芯片技术制作正常直肠、腺瘤组织标本各16例及80例直肠癌石蜡标本的组织芯片,采用原位分子杂交检测p53 mRNA,免疫组织化学SP法检测bcl-2、bax蛋白,脱氧核糖核苷酸末端转移酶介导的缺口末端标记技术(TUNEL)检测直肠癌细胞的凋亡指数。结果正常直肠组织平均p53mRNA阳性细胞率为15.26%±3.24%,腺瘤组织平均阳性细胞率为27.32%±5.54%,直肠癌组织平均阳性细胞率为75.38%±9.61%,三者比较,差异有统计学意义(P<0.01),直肠癌患者不同年龄、性别、肿瘤部位、大小、血清CEA水平、组织学类型的p53表达程度差异无统计学意义(P>0.05);不同分化程度、病理分期、淋巴转移、5年生存率的p53表达程度差异有统计学意义(P<0.05);直肠癌组织bcl-2蛋白表达水平明显高于正常直肠组织和腺瘤(P<0.01),bax蛋白表达水平低于正常直肠组织和腺瘤(P<0.01),直肠癌组织p53mRNA阳性细胞率与bcl-2蛋白表达呈正相关(P<0.01),与bax蛋白表达呈负相关(P<0.01);直肠癌p53mRNA表达程度不同的直肠癌细胞凋亡指数(AI)差异有统计学意义(F=49.85,P<0.01)。结论直肠癌中p53及bcl-2、bax的异常表达共同参与了肿瘤的发生发展和浸润转移,联合检测上述标志物有一定的临床意义。     

Expression of bcl-2, bax,and bcl-XL proteins in azoxymethane-induced rat colonic adenocarcinomas

Using western blotting and immunochemical analysis, we investigated alterations in the expression of the apoptosis-related proteins bcl-2, bax, and bcl-X in colonic adenocarcinomas induced by subcutaneous injection of azoxymethane (AOM) (15 mg/kg body weight weekly for 2 wk) into male Sprague-Dawley rats. Expression of the apoptosis-repressor bcl-2 in the colonic tumors was significantly weaker (0.6-fold) than that in adjacent non-neoplastic mucosa. The expression of bax protein, an apoptosis accelerator, was significantly stronger (7.33-fold) in all the tumors than in the non-tumoral mucosa. bcl-X_L protein, which functions as a repressor of apoptosis, was significantly upregulated (3.23-fold) in all the tumors when compared with the non-neoplastic mucosa. There was no significant difference between the expression of these proteins in the non-neoplastic mucosa of the AOM-treated rats and in the normal mucosa of saline-treated control rats. As determined by immunohistochemical analysis, the tumor cells had more bax and bcl-X protein. These findings indicate that the regulation of the apoptosis-related proteins bcl-2, bax, and bcl-X_L was altered in the AOM-induced colonic neoplastic tissue. In terms of resistance to apoptosis, elevated levels bcl-X_L protein may have considerable meaning in this experimental model as well as in human colorectal cancer. Mol. Carcinog. 19:25–30, 1997. © 1997 Wiley-Liss, Inc.     

脑膜瘤细胞凋亡及凋亡相关基因bcl—2、p53蛋白的表达

目的 探讨脑膜瘤自发性细胞凋亡相关基因bcl-2、p53蛋白在脑膜瘤中的表达及其意义。方法 采用TUNEL法和免疫组化S－P法检测40例脑膜瘤中细胞凋亡及凋亡相关基因bcl-2,p53蛋白的表达。结果 恶性和非典型脑膜瘤中的细胞凋亡指数（AI）明显高于良性脑膜瘤（P＜0．05）,良性脑膜瘤不同亚型之间bcl-2,p53表达无显著性差异（P＞0．05）;p53蛋白表达随脑膜瘤恶性程度增高而增强,具有显著性差异（P＜0．05）,p53阳性与阴性的脑膜瘤中的细胞凋亡指数无显著性差异;bcl-2蛋白表达与脑膜瘤细胞凋亡呈负相关。结论 恶性及非典型脑膜瘤中自发性细胞凋亡增多;凋亡是脑膜瘤恶性或不典型的1个重要的生物学行为;p53基因在脑膜瘤的恶变过程中发生重要作用,与脑膜瘤的恶性进展密切相关;bcl-2基因在脑膜瘤中可抑制细胞凋亡。     

bcl-2、bax和p53在鼻咽鳞癌中的表达及其与瘤细胞凋亡的关系

目的探讨bcl-2、bax和p53在鼻咽鳞癌中的表达及其与瘤细胞凋亡指数的关系。方法用免疫组织化学SP法检测48例鼻咽鳞癌中bcl-2、bax和p53的表达,用TUNEL法检测鼻咽鳞癌细胞的凋亡指数。结果48例鼻咽鳞癌中bcl-2、bax和p53阳性率分别为85.00%(41/48)、68.00%(33/48)和77.00%(37/48)。48例鼻咽鳞癌细胞的平均凋亡指数为25.62±25.78/HPF,凋亡指数与bcl-2、bax和p53的表达无相关性。结论鼻咽鳞癌中bcl-2和bax均呈高表达且已达到相对平衡,推测它们可能并不起到介导瘤细胞凋亡的主导作用。鼻咽鳞癌中p53的过表达可能已经失去了对bcl-2和bax表达的调节进而影响细胞凋亡的功能。     

bc1-2、p53和c-erb-B_2基因在卵巢癌中的表达

目的：探讨癌基因在卵巢癌发生发展过程中的意义。方法：应用免疫组化S－P（过氧化物酶-链霉卵白素）法对50例卵巢癌组织中bcl－2,p53和C－erb－B2的表达产物进行检测。结果：bcl－2、p53和C－erb－B2的表达率分别为42％、50％和46％，c－erb-B2表达与肿瘤的分级、分期和组织类型有关，bcl－2表达与分级、分期有关，p53表达与分期有关。66％的肿瘤癌基因表达异常，26％的肿瘤同时有多个癌基因的表达异常，多个癌基因表达异常与分级和分期有关。bcl-2的表达与p53的表达呈负相关（r＝－0．47，P＜0．01）。结论：上述癌基因参与了卵巢癌的发生发展过程。肿瘤多个癌基因分析比单个分析更有价值。     

bcl-2、bax、P53在肺神经内分泌癌中表达的意义

背景与目的bcl-2和bax是调控细胞凋亡的主要因素,两者均为野生型p53的下游基因。本研究旨在分析肿瘤相关基因蛋白bcl-2、bax、P53、C-erbB-2和nm23-H1在肺神经内分泌癌中的表达与肿瘤生物学特点及患者生存时间的关系。方法采用HE染色及免疫组化SP法,对59例肺神经内分泌癌患者的预后和免疫表型进行分析,采用χ2检验、Kaplan-Meier生存分析和Cox风险模型分析。结果bcl-2、bax、P53、C-erbB-2、nm23-H1蛋白的阳性率分别为46%、56%、27%、14%、90%。bcl-2表达与肺神经内分泌癌类型、TNM分期及淋巴结有无转移有关(P值分别为0.037、0.011及0.020),但与肿瘤大小无明显相关性;bax表达则与肿瘤大小、种类、分期及淋巴结转移情况均无密切关系。单因素生存分析显示bcl-2、P53均与生存时间呈负相关(P值分别为0.0338和0.0375),nm23-H1与生存时间呈正相关(P值为0.0021)。Cox多因素生存分析发现,只有bcl-2与生存时间密切相关(P值为0.011)。结论bcl-2是肺神经内分泌癌独立的预后因子。     

肝细胞肝癌中VEGF、p53、mdm2蛋白表达及其相互关系

目的　研究肝细胞肝癌 (HCC) VEGF、p5 3、m dm2蛋白表达及其相互关系。方法　用免疫组化 S- P法或SAP法检测 HCC组织 VEGF、mdm2和 p5 3蛋白表达 ,计数微血管密度 (MVD) ,并与临床病理指标比较分析。结果　 72例 HCC中 VEGF、p5 3、mdm2蛋白阳性表达分别为 6 2 .5 %、4 1.6 %和 33.3% ;VEGF和 p5 3,VEGF和 m dm2 ,mdm2和 p5 3蛋白表达有相关性 (P<0 .0 5 )。 2 5例癌旁组织中 VEGF蛋白阳性表达为 2 0 .0 % ,m dm2蛋白阳性表达为 8.0 % ,p5 3蛋白阳性表达为 8.0 %。肝癌组织和癌旁组织 VEGF、m dm2和 p5 3蛋白表达差异有显著性 (P<0 .0 5 )。 10例正常肝组织无 VEGF、mdm2和 p5 3蛋白表达。 HCC组织中 VEGF、p5 3、mdm2蛋白阳性表达以及高MVD与血管侵犯和转移倾向明显相关 (P<0 .0 5 )。结论　 HCC组织中 VEGF、p5 3、mdm2蛋白过表达。p5 3突变和mdm2蛋白过表达 ,是 VEGF表达上调的原因之一 ,并与 HCC组织中血管侵犯和转移倾向有关     

视网膜母细胞瘤p53、bcl-2、bax及增殖细胞核抗原的表达意义

目的　了解视网膜母细胞瘤 (retinoblastoma ,Rb)p5 3、bcl 2、bax和增殖细胞核抗原表达与Rb及其分化程度的关系。方法　用免疫组化检测 2 1例Rb和 6例正常视网膜常规石蜡标本进行 p5 3、bcl 2、bax和PCNA表达。 结果　bcl 2、bax和PCNA在Rb中的表达较高 ,与正常视网膜相比有显著性差异 ,分化性Rb组织bcl 2阳性表达率较高 ,与未分化型Rb组织相比有显著性差异。p5 3、bcl 2、bax在Rb中的表达与PCNA的表达有显著相关性。 结论　Rb的发生与多个细胞凋亡调控基因异常有关 ,测定和分析Rb的bcl 2、PCNA、bax和表达 ,对于Rb的诊断和分化程度有重要意义。     

Expression of bcl-2, c-erbB-2, p53, and p21 (waf1-cip1) protein in thyroid carcinomas

The study was carried out on 53 patients who had thyroid cancer with various degree of differentiation. We studied the expression of bcl-2, a-erbB-2, p53, and p21 ras protein. The protein encoded by bCL-2 proto-oncogene is implicated in the prolongation of cell survival by blocking programmed cell death, i.e. apoptosis. The role of p53 and bcl-2 genes in the regulation of apoptosis has important implications in oncogenesis. Wild-type p53 is thought to promote apoptosis, whilst mutant p53 has a similar effect on apoptosis as bcl-2 that is inhibition of programmed cell kinase activity. C-erb-2 protein overexpression is currently being evaluated as a potential risk factor in breast cancer patients? The ras gene family codes for a 21 kD protein (p21), which binds guanine nucleotides and possesses GTPase activity. Through this mechanism, the ras p21 protein participates in the control of cell proliferation, possibly as a signal transducer from cell surface receptors to the nucleus. Activation of ras genes has been implicated in neoplastic transformation of cells. The aim of our study is to evaluate the expression of these markers in thyroid carcinomas. All immunohistochemical study was performed in paraffin-embedded tissues pathology specimen. Any well differentiated tumor in our study was positive for bcl-2 protein. C-erb-2 immunostaining was present in tumor samples in 60% of cases. In most cases, specific membrane staining as well as a weak cytoplasmic positivity of tumor cells were seen. Immunoreactivity for p53 was positive only in 10% of cases. By immunostaining, p21 protein was expressed in 55% of the 53 tumors tested, with different degree of expression. Only some poorly differentiated tumours were positive for bcl-2, furthermore all markers tested were strongly positive in these tumours. In conclusion, our results indicate that bcl-2, c-erbB-2, p53, and p21 ras protein are differently expressed in thyroid carcinomas in relation to the degree of aggressiveness and differentiation.     

脑星形细胞瘤组织中p16 bcl-2、bax蛋白的表达及其意义

目的：探讨p16,bcl-2,bax蛋白在脑星形细胞瘤中的表达及其意义。方法：采用S－P免疫组织化学法，检测P16，bcl-2,bax蛋白在60例不同病理分级脑星形细胞瘤组织中的表达情况。结果：60例脑星形细胞瘤组织中，p16,bcl-2,bax蛋白表达阳性率分别为50．0％（30／60），58．3％（35／60），66．7％（40／60），其中P16蛋白阳性表达与病理分级有显著性相关（P＜0．05），bcl-2,bax蛋白表达与病理分级无相关性（P＞0．05），60例脑星形细胞瘤组织中，p16,bcl-2,bax蛋白共同表达率，I级为47．8％（11／23），Ⅲ-Ⅳ级为0（0／16），在bcl-2,bax蛋白表达的基础上，不同病理分组织中p16蛋白的缺失率：I级为4．3％（1／23），Ⅲ-Ⅳ级为50．0％（8／16），有非常显著性差异（P＜0．01），结论：P16蛋白表达与脑星形细胞瘤的发生发展密切相关，在脑星形细胞瘤的发展过程中，bcl-2,bax,p16蛋白可能有某种协调作用。     

p21、p27、bcl-2和bax在肺癌组织中表达的意义及相关性研究

目的:探讨p21、p27、bcl-2、bax蛋白在肺癌中的表达及其临床意义.方法:采用免疫组化S-P法,检测85例肺癌患者及21例良性肺疾病患者术后组织标本中p21、p27、bcl-2、bax的表达.结果:p21、p27、bcl-2、bax蛋白总阳性表达率分别为72.94%、37.65%、61.18%、41.18%.各种蛋白的阳性表达率在肺癌组织与对照组间均存在差异性(P＜0.05).仅bcl-2蛋白表达与肺癌的不同病理类型有关,其中在小细胞肺癌中表达率最高、鳞癌次之、腺癌最低.p27、bcl-2、bax三者的阳性表达随病理分化程度的降低而降低(P＜0.05).p21与bcl-2蛋白的阳性表达与肺癌临床TNM分期有关(P＜0.05).bax蛋白的表达与有无淋巴结转移有关.p27、bcl-2、bax三者之间存在相关性.结论:p21、p27、bcl-2、bax蛋白与肺癌的发生、发展有密切关系.联合检测p21、p27、bcl-2、bax对于临床诊断肺癌及判断病情、预后有重要意义.