P21WAF1/CIP1在卵巢上皮性肿瘤中的表达与临床意义的研究

目的 :探讨P2 1WAF1/CIP1在恶性卵巢上皮性肿瘤中的表达与临床意义。方法 :应用免疫组化S P检测P2 1WAF1/CIP1在 2 0例良性、10例交界性、5 5例恶性卵巢上皮性肿瘤中的表达 ,并分析P2 1WAF1/CIP1与恶性卵巢上皮性肿瘤临床病理指标的关系。结果 :P2 1WAF1/CIP1在良性、交界性与恶性卵巢上皮性肿瘤中的表达总阳性率及强阳性率均有显著性差异 (P =0 0 0 7,P强 =0 0 0 1) ,并随良性、交界性、恶性而降低表达 (P <0 0 1,P强 <0 0 0 1) ;与恶性卵巢上皮性肿瘤的临床分期、组织分化、淋巴转移、腹水及预后均有关 (P =0 0 11,0 0 0 0 ,0 0 14 ,0 0 11;P强 =0 0 37,0 0 0 3,0 0 16 ,0 0 0 2 ,P <0 0 5 )。结论 :P2 1WAF1/CIP1在恶性卵巢上皮性肿瘤的形成和发展中发挥重要作用 ,检测P2 1WAF1/CIP1蛋白表达情况对卵巢肿瘤的良恶性鉴别 ,判断预后 ,探索卵巢癌的发生过程 ,从而指导卵巢癌的基因治疗均有积极的意义。     

Clinical significance of p21(WAF1/CIP1) and p53 expression in serous cystadenocarcinoma of the ovary

There have been many reports indicating that the down-regulation of p21(WAF1/CIP1) is related to carcinogenesis and the development of various tumors; nevertheless, its association with epithelial ovarian cancer (EOC) remains controversial. In this study, we focused on serous ovarian cancer, which is the most prevalent histological type, and performed immunohistochemical analysis to examine the expression of p21(WAF1/CIP1) and p53 in 43 cases of serous-type EOC sourced from a single University Hospital: 14 stage I, 4 stage II, 21 stage III, and 4 stage IV. Positive p21(WAF1/CIP1) was found in 24 of 43 cases (56%), and positive p53 was detected in 21 of 43 cases (49%). Among stage III/IV cases, positive p21(WAF1/CIP1) staining was found in 11 of 25 cases (44%), and positive p53 staining was detected in 13 of 25 cases (52%). Univariate survival analysis for the entire cohort revealed that positive p21(WAF1/CIP1) was associated with a survival benefit. The 10-year survival rates of p21(WAF1/CIP1)-positive staining and p21(WAF1/CIP1)-negative staining were 82.4 and 39.5%, respectively, and there was a significant difference between the two groups (p<0.01). Overall survival for p21(WAF1/CIP1)-positive with p53-negative staining [p21(+)/p53(-)] was significantly different from p21(WAF1/CIP1)-positive with p53-positive [p21(+)/p53(+)], p21(WAF1/CIP1)-negative with p53-positive staining [p21(-)/p53(+)], and p21(WAF1/CIP1)-negative with p53-negative staining [p21(-)/p53(-)] (p<0.05). When only III/IV cases were evaluated, overall survival for [p21(+)/p53(-)] was significantly different from [p21(+)/p53(+)], [p21(-)/p53(+)], and [p21(-)/p53(-)] (p<0.05). These results suggested that the overexpression of p21(WAF1/CIP1) in conjunction with the loss of p53 expression was a stronger predictor of survival benefit than either molecule alone in Japanese serous-type advanced ovarian cancers with more than 10-year follow-up.     

P53、P21^WAF1和CDK1在卵巢上皮性癌组织中的表达及意义

背景与目的：P53、P21^WAF1,和CDK1是细胞周期中G2／M期DNA损伤检验点“P53通路”的关键因子,本研究拟探讨P53、P21^WAF1和CDKl在卵巢上皮性癌组织中的表达及意义。方法：应用免疫组织化学技术检测20例正常卵巢组织、20例卵巢良性上皮性肿瘤组织、76例卵巢上皮性癌组织中P53、P21^WAF1、CDK1蛋白的表达,并分析卵巢上皮性癌组织中P53、P21^WAF1、CDK1蛋白表达与其临床病理特征的关系以及各蛋白表达之间的相关性。结果：P53、P21^WAF1和CDK1蛋白在卵巢上皮性癌中的阳性率与正常卵巢组织和良性卵巢肿瘤相比其差异均有统计学意义（P〈0．05）,而在正常卵巢组织与良性卵巢肿瘤之间其阳性率差异均无统计学意义（P〉0．05）。在卵巢上皮性癌中,临床分期越晚、组织分化越差,P53蛋白表达越高;随着临床分期的增加,P21^WAF1蛋白表达逐渐降低;CDK1蛋白的表达与各临床病理特征无相关性。卵巢上皮性癌中P53蛋白和P21^WAF1蛋白的表达与CDK1蛋白的表达呈负相关（r=0．388,P=0．001;r=-0．282,P=0．014）,P53蛋白与CDK1蛋白表达呈正相关（r=0．263,P=0．022）。结论：1〉53蛋白与卵巢上皮性癌的恶性程度相关,P53和P21^WAF1蛋白可能与卵巢上皮性癌的恶性进展有关。检测CDK1可能有助于卵巢癌的早期诊断。     

The abnormalities in the p53/p21WAF1 pathway have a significant role in the pathogenesis and progression of gastrointestinal stromal tumors

To elucidate the prognostic role and relationship of the p53/p21/PCNA pathway in gastrointestinal stromal tumors (GISTs), a total of 167 resected gastric and small intestinal CD117-positive stromal tumor specimens were collected from January 1987 to December 2000. Immunohistochemical studies were performed on the paraffin sections with antibodies of p53, p21/WAF1, proliferating cell nuclear antigen (PCNA) and Ki-67. The immunoreactivity of four markers was recorded by labeling index (LI, %) for clinicopathologic and survival correlation. The labeling index was 0-83% for p53, 0-81% for p21/WAF1, 0-33% for Ki-67 and 12-92% for PCNA. Completely negative immunostaining (LI<1%) was found in 54.5% of p53, 25.8% of p21/WAF1 and 44.3% of Ki-67. The LI of four markers strongly correlate with each other (p<0.05). Furthermore, the LI of all four markers positively correlate to microscopic tumor mitotic counts (p<0.05). Only the LI of p53 and PCNA positively correlate to tumor sizes. Tumors with non-spindle cell type (versus spindle cell) and high cellular pleomorphism (versus low) exhibited a higher p53, p21/WAF1 and PCNA LI (p<0.05). Increased NIH risk significantly correlates to increased p53, PCNA and Ki-67 (p<0.05) LI. Survival analysis indicated that a large tumor size (> or =5 cm, p=0.003), increased tumor mitosis (> or =5/50 HPF, p<0.001), high NIH risk (p<0.001), non-spindle cell type (p=0.024), high p53 LI (p<0.001), high p21/WAF1 LI (p=0.007), high Ki-67 LI (p<0.001) and high PCNA LI (p<0.001) were prognostic factors for poor disease-free survival. Independent factors are tumor size, NIH risk, p53 and p21/WAF1 LI. We demonstrated the first evidence of the linear relationship and prognostic role of the p53/p21/PCNA pathway in gastrointestinal stromal tumors. Abnormalities of the p53/p21WAF1 pathway lead to increased proliferating states, thereby triggering the progression of GISTs.     

Reduced p21(WAF1/CIP1) protein expression is predominantly related to altered p53 in hepatocellular carcinomas

To investigate the relationship between the expression of p21(WAF1/CIP1) protein and p53 status and the possible role of the two proteins in hepatocellular carcinomas (HCCs), we examined the expression of p21(WAF1/CIP1) and p53 immunohistochemically in 81 tumours from 65 patients with hepatocellular carcinoma. p21(WAF1/CIP1) protein was absent from 59 of 81 tumours (72.8%), and altered p53 expression was found in 43 (53.1%). p21(WAF1/CIP1) expression was significantly associated with p53 status (P = 0.0008); 38 of 59 tumours lacking p21(WAF1/CIP1) protein were accompanied by altered p53 expression. Further analyses showed that p21(WAF1/CIP1) expression was inversely correlated with p53 expression in hepatitis C virus (HCV)-related HCCs, but not in HBV-related hepatocellular carcinomas and hepatocellular carcinomas without viral infection. All 11 tumours with intrahepatic metastasis showed altered p21(WAF1/CIP1) or p53 expression. In contrast, no intrahepatic metastasis was found in any of the 17 tumours without abnormal expression of either of the two proteins. These results suggest that: (1) different modes of p21(WAF1/CIP1) regulation are involved in HCCs differing in their hepatitis viral infection status, and p21(WAF1/CIP1) expression appears to be predominantly related to altered p53 in HCV-related HCCs; (2) disruption of the p53-p21(WAF1/CIP1) cell-cycle-regulating pathway may contribute to malignant progression of HCC.     

Prognostic significance of p27KIP1 protein and ki-67 growth fraction in non-small cell lung cancers.

We immunohistochemically examined specimens of 215 surgically resected non-small cell lung cancers (NSCLCs) for p27KIP1 protein (p27) expression and the growth fraction determined by the Ki-67 labeling index (LI). The NSCLCs analyzed showed considerable heterogeneity in both p27 and Ki-67 LIs; 25 of 207 (13%) lacked p27 expression (p27 LI < 5%), and 116 of 215 (54%) showed a high Ki-67 LI (>30%). The p27 LI was not significantly associated with the Ki-67 LI. A chi2 test showed that loss of p27 expression was inversely correlated with smoking (P = 0.01) and that a high Ki-67 LI was significantly associated with male gender, squamous cell carcinoma histology, and smoking (P < 0.0001 each). Prognostic values of p27 and Ki-67 expression were evaluated in 109 tumors of postsurgical pathological stages I and II. Patients with tumors lacking p27 expression survived for a significantly shorter time than patients with tumors expressing p27 (5-year survival rates, 38% and 68%, respectively; P = 0.02). Patients with tumors having a high Ki-67 LI survived for a significantly shorter time than patients with tumors having a low Ki-67 LI (5-year survival rates, 48% and 78%, respectively; P = 0.005). Multivariate analysis showed that loss of p27 expression tended to be an unfavorable prognostic factor (P = 0.054), whereas a high Ki-67 LI was a significant and independent unfavorable prognostic factor (P = 0.004). When analyzed by cell types, loss of p27 expression was a significant and independent unfavorable prognostic factor in squamous cell carcinomas (P = 0.01), whereas a high Ki-67 LI was a significant and independent unfavorable prognostic factor in nonsquamous cell carcinomas (P = 0.007). We further evaluated the importance of p27 expression in clinical outcome in combination with the Ki-67 LI and ras p21 protein (ras) expression, which we previously reported as an important prognostic factor in NSCLCs. Patients with tumors lacking p27 expression and having a high Ki-67 LI survived for a significantly shorter time than those with tumors expressing p27 and having a high Ki-67 LI (5-year survival rates, 17% and 52%, respectively; P = 0.003). Patients with p27-negative and ras-positive tumors survived for a significantly shorter time than those with both p27- and ras-positive tumors (5-year survival rates, 0% and 38%, respectively; P < 0.0001). These results indicate the pivotal roles of p27 and Ki-67 expression in the clinical outcome of NSCLCs.     

结直肠癌中survivin 、caspase-3 、p21WAF1的蛋白表达及其意义

 目的 探讨结直肠癌中survivin、caspase-3和p21^WAF1的蛋白表达与临床病理参数的联系以及survivin与caspase-3和p21^WAF1蛋白表达之间的关系。方法 采用免疫组织化学SP方法检测15例正常结直肠粘膜和62例结直肠腺癌标本中survivin、caspase-3和p21^WAF1的蛋白表达。结果 结直肠腺癌与正常结直肠粘膜比较,survivin、caspase-3和p21^WAF1的蛋白表达差异均有显著性（P〈0.05）。survivin和caspase-3的蛋白表达与淋巴结转移无明显相关（P〉0.05）;而与分化程度均显著相关（P〈0.05）。survivin蛋白与Dukes分期相关（P〈0.05）;但caspase-3的蛋白表达与Dukes分期无关（P〉0.05）。p21^WAF1蛋白表达与分化程度、淋巴结转移和Dukes分期均显著相关（P〈0.05）。survivin蛋白分别与caspase-3、p21^WAF1蛋白表达之间均呈显著负相关（P〈0.01）。结论 survivin、caspase-3和p21^WAF1蛋白在结直肠癌的发生和进展中都起着重要的作用。p21^WAF1基因与结直肠癌的恶性进展显著相关,此结论鲜见报道。     

High frequency of allelic loss at the BRCA1 locus in ovarian cancers: clinicopathologic and molecular associations

BRCA1 dysfunction may occur by different mechanisms that are rarely evaluated concomitantly. We aimed to analyze BRCA1 germline mutations, loss of heterozygosity (LOH) and promoter methylation in unselected ovarian carcinomas in the context of their clinicopathologic characteristics and other molecular changes. BRCA1 mutations were analyzed in 257 carcinomas using single-strand conformation polymorphism (SSCP), heteroduplex, and sequencing methods. LOH at the BRCA1 locus was screened for in 180 cancers. Methylation analysis was performed for 241 tumors using quantitative methylation specific PCR?(qMSP). BRCA1 alterations, comprising germline mutations, allelic loss, and/or aberrant promoter methylation, were found in 77.6% (125/161) of ovarian carcinomas. Patients with germline mutations were younger than non-carriers (P < 0.0001). Germline mutations and LOH were associated with advanced stages (P=0.009, P < 0.0001), high tumor grade (P=0.005, P?相似文献   

Overriding of cyclin-dependent kinase inhibitors by high and low risk human papillomavirus types: evidence for an in vivo role in cervical lesions.

High risk types of human papillomavirus (HPV) are agents in the aetiology of cervical carcinoma. The products of two early genes, E6 and E7, appear to be the principal transforming proteins. Studies of various monolayer cell culture systems have shown that the E7 oncoprotein of human papillomavirus type 16 is able to neutralize or bypass the inhibitory effect of the cell cycle-dependent kinase (CDK) inhibitors (CKIs) p21WAF1/CIP1 and p27KIP1. To understand whether the p21WAF1/CIP1 or p27KIP1 neutralization also plays a role in vivo, we performed studies on clinical specimens. Forty-five cervical biopsies, including HPV-negative mucosa, HPV 16-positive preinvasive (low and high grade lesions) and invasive neoplasia as well as HPV 6-positive condyloma acuminatum were analysed by single and double immunohistology. We examined the positive cell cycle regulator cyclin A and the universal cell cycle marker Ki67 as well as the negative cell cycle regulators p21WAF1/CIP1 and p27KIP1. Here, we show that in a significant fraction of cells the G1 block can be overcome despite high levels of CKIs in HPV lesions. This phenomenon, which was more evident for p21WAF1/CIP1 than for p27KIP1 was most marked in low grade lesions and in condylomata acuminata, in which a high viral productivity is expected. These results indicate that the overriding of CKI inactivation by viral oncoproteins appears to be a conserved property between low and high risk HPV types. We conclude that the CKI neutralization by HPVs is likely to be required for viral DNA replication rather than for malignant transformation of the host cell.     

AEG-1与Ki-67在上皮性卵巢组织中的表达及其临床病理相关性的研究

目的 探讨AEG-1和Ki-67在上皮性卵巢组织中的表达与临床病理因素的关系,同时为研究卵巢癌的发病机制提供一定的理论基础。方法 通过免疫组化的方法检测在21例正常卵巢组织,32例卵巢交界性肿瘤,157例性恶性肿瘤中AEG-1和Ki-67的蛋白表达水平,并运用统计学方法分析AEG-1与Ki-67之间的相关性,同时观察其表达与上皮性卵巢肿瘤的临床病理因素之间的相关性。结果 AEG-1和Ki-67在正常卵巢组织中均未见表达,在癌组织中的表达水平显著高于交界性肿瘤中的表达水平,并且发现两者之间的表达存在显著的相关性。AEG-1的高表达水平与上皮性卵巢癌患者组织学分化程度,残留肿物大小及临床分期之间有显著统计学意义(P＜0.01),但与患者年龄,血清CA125值,腹水量及病理学类型之间均无统计学意义(P＞0.05)。结论 AEG-1和Ki-67可能在上皮性卵巢癌的发生与发展中扮演重要的作用。同时其高表达水平可能作为判断卵巢癌恶性程度、病情进展的重要指标,联合检测其表达情况有助于卵巢癌患者的早期发现与治疗。     

Minichromosome maintenance protein 7 in colorectal cancer: implication of prognostic significance

Minichromosome maintenance (MCM) proteins are essential components for DNA replication, and also prognostic markers for various human tumors. MCM-positive but Ki67-negative cells (e.g. primary oocytes) are thought to be licensed non-proliferating populations, and are significantly correlated with the clinicopathological profiles of some human tumors. In the present study, we evaluated the expression levels of MCM7, MCM2 and Ki67 in colorectal cancer to clarify their pathobiological significance. We carried out Western blot analyses of 5 human colorectal cancer cell lines and performed immunohistochemistry on 202 surgically removed colorectal cancers of Dukes' B and C stages. Double-labeling immunofluorescence was also carried out on the cancer specimens to identify MCM-positive but Ki67-negative tumor cells. MCM proteins were detected in all the 5 cell lines examined. MCM7 and MCM2 were coexpressed in almost the same populations of tumor cells, whereas MCM7-negative but Ki67-positive tumor cells were absent in the double-labeled specimens, except for mitotic cells. The mean positive tumor labeling indexes (LIs) for MCM7, MCM2 and Ki67 were 58.1, 57.1 and 40.6%, respectively. The mean LI for MCM7-positive but Ki67-negative tumor cells was 17.6%, and significantly correlated with the N status (P=0.01), distant metastasis (P=0.01) and UICC stage (P=0.02). The high LI of >58.1% for MCM7 were independent prognostic factors in multivariate Cox regression analysis (relative risk = 2.12; P=0.02). Our results indicate that MCM7 expression is an independent prognostic factor for human colorectal cancer, and MCM7-positive but Ki67-negative tumor cells are correlated with tumor metastases.     

Expression of cell-cycle regulators, cyclin E and p21WAF1/CIP1, potential prognostic markers for gastric cancer.

AIMS: The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human cancers. METHODS: In this study, we analysed the expression of cyclin D1, cyclin E, p21WAF1/CIP1 and p27KIP1 in 84 surgically resected gastric cancers by immunohistochemistry with long-term follow-up (median 38 months). We also evaluated the relation between each cell cycle regulator and various clinicopathological findings, including age, sex, histological grade, tumour location, tumour type and stage and lymph-node metastasis. RESULTS: Overexpression of cyclin D1 and E was detected in 21/84 (25%) and 34/84 (40.5%) patients, respectively. Normal gastric epithelium showed consistently positive immunostain for p21WAF1/CIP1 and p27KIP1 in more than 50% of nuclei. Loss of p21WAF1/CIP1 and p27KIP1 expression was noted in 45/84 (53.6%) and 44/84 (52.4%) patients, respectively. Among the various clinicopathological findings, overexpression of cyclin E was associated with lymph-node metastasis (P=0.003) and recurrence (P=0.043). Loss of p21WAF1/CIP1 expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.002). Overexpression of cyclin E and loss of p21WAF1/CIP1 expression were significantly correlated with decreased disease-free (P=0.037; P= 0.001) and overall (P=0.031; P=0.001) survival. CONCLUSIONS: These results suggest that immunohistochemical analysis for cell cycle regulators, especially cyclin E and p21WAF1/CIP1, might be a useful prognostic indicator in gastric cancer.     

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatin-based chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P=0.005) or the only (in FIGO IIIC, P=0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(-) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P=0.047) and by BCL2 expression in the TP53(-) group (P=0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P=0.049); its loss was found with advancing FIGO stage (P=0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.     

p21-激活激酶1基因在卵巢上皮性肿瘤中的过度表达及其机制和意义

目的探讨p21-激活激酶1（PAK1）基因在卵巢上皮性肿瘤中的过度表达及其机制和意义。方法运用免疫组化、荧光原位杂交和末端脱氧核苷酸转移酶介导缺口末端标记方法,结合组织芯片技术,检测PAK1基因在30例卵巢腺瘤、20例卵巢交界性肿瘤和80例卵巢癌中的表达、扩增及其细胞凋亡情况。结果在免疫组化有效检测的病例中,7例（25．9％）卵巢良性腺瘤、7例（36．8％）交界性肿瘤和53例（68．8％）卵巢癌出现PAK1蛋白的过度表达,而且PAK1蛋白过表达与卵巢肿瘤的细胞凋亡指数呈负相关（P=0．002）。此外,87．1％（27／31）的低分化卵巢癌（Silverberg G3级）出现PAK1蛋白的过度表达,其过表达率显著高于G1～G2级的卵巢癌（26／46,56．5％;P=0．01）。荧光原位杂交结果显示,只有2例（4．7％）卵巢癌出现PAK1基因扩增,卵巢交界性肿瘤和良性腺瘤均未观察到PAK1基因的扩增。结论PAK1蛋白过度表达可能在卵巢上皮性肿瘤的发生发展中起重要作用,而且与卵巢癌的恶性组织学表型密切相关;在卵巢肿瘤PAK1蛋白的表达调控中,基因扩增以外的其他调节机制可能起更为关键的作用。     

The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients

BACKGROUND: The variability of prognosis within a pathological stage of gastric cancer (GC) at presentation, underscores the need for specific biological markers to identify subgroups of patients with aggressive course for intensive treatment. To our knowledge, this is the first study from an Arab population reporting on the relationship of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 expression, and clinicopathological features and their prognostic significance. METHODS: Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67. The results were correlated with clinicopathological features and survival. RESULTS: M:F = 80:41; median age = 60 years; stage III and IV = 71%; and median follow-up = 34.4 months. Positive expression rates of p53, p27 kip1, p21 waf1, Ki67, and HER-2/neu were 54%, 40%, 8.3%, 70%, and 12% respectively. p53 expression correlated with age <60 years (P = 0.03), tumor size >5 cm (P = 0.01), p27 kip1 and Ki67 expression (P = 0.0001), and HER-2/neu (P = 0.04). p21 waf1 correlated inversely with T-stage (P = 0.008) and Her-2/neu expression correlated with histological grade (P = 0.04) and T-stage (P = 0.008). Univariate analysis showed that p53 overexpression (P = 0.01), fungating and infiltrative macroscopic appearance (P = 0.02), size >5 cm (P = 0.0001), lymph node metastasis (P = 0.0001), p T3 and T4 disease (P = 0.01), and overall stage III and IV (P = 0.0001) disease were adverse prognostic factors. Patients with tumor profiles p53 (-)/p27 (+) had better survival than those with p53 (+)/p27 kip1 (-)(P = 0.02). On multivariate analysis by Cox regression model, the expression of p53 (P = 0.03) and lymph node involvement (P = 0.01) were significant adverse prognostic factors for overall survival. CONCLUSIONS: The expression of p53 in Arab patients with GC correlates with aggressive tumor characteristics and is an independent prognostic factor. The combined analysis of p53 and p27 kip1 is of added prognostic value.     

P53表达对晚期上皮性卵巢癌一线化疗方案选择的意义

背景与目的:目前,上皮性卵巢癌的术后一线化疗方案主要包括铂类联合紫杉醇(TC)和铂类联合环磷酰胺(PC)。本研究拟观察分子标记物P53表达与上述两种化疗方案疗效的关系,分析P53表达在化疗疗效预测上的价值,探讨检测P53表达在选择化疗方案上的意义。方法:回顾性分析53例以TC或PC作为术后一线化疗方案的Ⅲc期上皮性卵巢癌,用免疫组化方法检测标本的P53表达,比较P53阳性组和P53阴性组中各化疗方案的完全缓解(completeresponse,CR)率和无进展生存时间(progression-freesurvival,PFS),并行多因素分析影响PFS的预后因素。结果:53例患者中22例P53阳性,其中13例采用TC方案,CR10例(76.9%),中位PFS102周;9例采用PC方案,CR3例(33.3%),中位PFS43周。TC组CR率稍高于PC组(P=0.05),TC组患者PFS长于PC组(P=0.04)。对31例P53阴性患者采用不同化疗方案治疗的CR率和PFS无显著性差异(P>0.05)。多因素分析提示残留病灶大小是独立预后因素。结论:检测P53表达在选择化疗方案上可能有意义。对于P53阳性患者首选TC方案,对于P53阴性患者可以选择PC或TC方案。确切结论尚需进一步在大样本前瞻性研究中验证。     

p53 、p21 WAF1及p16 在胃癌前病变和胃癌中的表达

 目的　研究 p5 3、p2 1WAF1、p16在胃癌前病及胃癌发生发展中的作用 ,探讨他们之间的相互关系。方法　采用SP免疫组化法检测慢性萎缩性胃炎 6 5例、肠化 93例、胃上皮不典型增生94例、胃癌 6 0例中三者的表达。结果　随着病变的发展三者均有较明显失活 (P <0 .0 5 )。结论　p5 3、p2 1WAF1及 p16的失活对于胃癌的发生有重要作用 ,p5 3和 p2 1WAF1的失活有协同性属于癌症发生的相对晚期事件 ,p16的失活发生于病变早期。     

Relations between immunologically different p53 forms,p21(WAF1) and PCNA expression in ovarian carcinomas

The role of tumor suppressor p21WAF1 expression in epithelial ovarian cancer has not been definitely explained and the clarification of mutual p53 and p21WAF1 relations considering proliferative activity seems to be very important for understanding of a functional link between p53 and cell-cycle control. Therefore the expression of p53 and p21WAF1 was assessed immunohistochemically in a series of 50 ovarian carcinomas considering clinicopathological variables. The reactivity of three anti-p53 monoclonal antibodies (DO-7, PAb240, PAb1620) recognizing immunologically distinct forms of p53 were analysed in relation to p21WAF1 level in individual patients. p21WAF1 was expressed in 24 (48%) of all cases. The detection of p53 protein was related to the antibody applied and DO-7 antibody appears to be better than both PAb240 and PAb1620. However, independently of antibody used significant inter- and intratumoral heterogeneity in p53 and p21WAF1 expression was revealed. The identification of different p53/p21WAF1 phenotypes reflect the complex and multiple relations between these two cell-cycle regulators indicating that in ovarian carcinomas p21WAF1 activation may be both p53-dependent and p53-independent. High cell proliferation was usually accompanied by undetectable or weak p21WAF1 staining. There was no significant correlation between p53 and p21WAF1 expression and histology, stage and grade of ovarian carcinomas (p>0.05).     

P33~(ING1)和Survivin及Ki67蛋白在食管癌发生发展中的作用

目的 检测P33ING1、Survivin和Ki67蛋白在食管正常黏膜、单纯增生、不典型增生、浸润癌中的表达情况,分析这三种蛋白在食管癌不同病变区域中的表达及与食管癌病理特征的关系.方法 采用免疫组化方法 检测P33ING1、Survivin和Ki67蛋白在51例食管癌大体标本中的不同病变区域的表达.结果 P33ING1蛋白从正常黏膜、单纯增生、不典型增生增生、浸润癌呈渐进性低表达,而Survivin和Ki67蛋白则呈渐进性高表达.三种蛋白在正常黏膜中的表达与不典型增生及浸润癌中的表达差异有显著性(P<0.01);P33ING1蛋白在食管癌中的表达与癌肿浸润深度(肌层至全层)呈负相关(P<0.05),与分化程度(G1、G3)呈正相关(P<0.05 );Survivin蛋白表达与食管癌分化程度、淋巴结转移有关(P<0.05);P33ING1蛋白在浸润癌中的低表达与Survivin和Ki67蛋白高表达呈负相关(P<0.01).结论 Survivin功能的激活、Ki67增殖及P33ING1功能的下调可能共同对抗细胞凋亡,参与食管癌的发生发展.三者有可能为临床上食管癌早期诊断、相关治疗及预后研究提供新的手段.