p21,p185,p53蛋白的卵巢浆液性肿瘤中表达的临床意义

目的：探讨ｒａｓ、ｎｅｕ、ｐ５３基因在肿瘤演地过程中的作用。方法：采用链蛋白生物素免疫组化法（ＬＳＡＢ）检测了ｒａｓ、ｎｅｕ、ｐ５３基因产物ｐ２１、ｐ１８５、ｐ５３蛋白在卵巢浆液肿瘤中的表达情况。结果：三种蛋白在良性、交界性恶性肿瘤组织中阳经呈递增趋势，联合表达率呈递增趋势，差异显著，Ｐ２１表达与患者生存期有关，过度表达组低于非过度表达组，结论：联合检测Ｐ２１、Ｐ１８５、Ｐ５３蛋白在卵巢浆液性肿瘤     

大肠癌p185^erbB2,p21^ras,p53的表达及其临床病理意义

目的：研究大肠癌中ｐ１８５＾ｅｒｂＢ２、ｐ２１＾ｒａｓ、ｐ５３的表达及其临床病理意义。方法采用Ｓ－Ｐ法检测８０例大肠癌组织中ｐ１８５＾ｅｒｂＢ２、ｐ２１＾ｒａｓ、ｐ５３的表达。结果大肠癌原发病灶中ｐ１８５＾ｅｒｂＢ２、ｐ２１＾ｒａｓ、ｐ５３的阳性表达率分别为５８．８％、７１．３％及５３．８％。癌组织同时有２种以上蛋白表达者占６３．７％（５１／８０）,有３种蛋白同时表达者占３０％（２４／８０）。ｐ１     

卵巢上皮性癌p53基因改变,蛋白过度表达及临床意义

目的：检测卵巢上皮性癌ｐ５３基因改变、蛋白过度表达，探讨其与临床病理和预后的关系。方法：应用ＡＢＣ免疫组化法检测５６例卵巢上皮性肿瘤ｐ５３蛋白表达，对其中４０例应用聚合酶链反应单链构象多态性（ＰＣＲＳＳＣＰ）溴乙锭染色法检测ｐ５３基因５～８外显子突变及杂合性缺失（ＬＯＨ）。结果：（１）ｐ５３蛋白表达阳性率：良性肿瘤０／１０；交界性肿瘤１／４；卵巢上皮性癌２２／４２（５２．３８％），浆液性与粘液性癌表达相似，且３例原发灶与转移灶表达一致。（２）ｐ５３基因突变率：良性肿瘤０／１０；交界性肿瘤１／３；卵巢上皮性癌１３／２７（４８．１５％），其中８例杂合型基因的病例中４例基因突变伴等位基因杂合性缺失。本研究１３例ｐ５３基因突变者中１２例ｐ５３蛋白过度表达。ｐ５３蛋白过度表达与卵巢上皮性癌组织学类型、临床分期及预后无关（Ｐ＞０．０５）。而与卵巢上皮性癌病理有关（Ｐ＜０００５）。结论：ｐ５３基因改变及蛋白过度表达在卵巢癌中较常发生，且与卵巢上皮性癌病理分级有关，这些改变可能是卵巢上皮性癌的早发事件，亦在卵巢上皮性癌的发生发展过程中起重要作用。     

ras p21和p53的表达与尿路上皮肿瘤临床预后的关系

目的 研究ｒａｓ ｐ２１和ｐ５３的表达与尿路上皮肿瘤临床与预后的关系。方法 采用免疫组织化学ＡＢＣ法检测６６例尿路上皮肿瘤ｒａｓ ｐ２１和ｐ５３的表达。结果 ｒａｓ ｐ２１阳性表达４０例（６０．６％）,ｐ５３阳性表达３６例（５４．５％）,ｒａｓ ｐ２１和ｐ５３共同阳性表达２７例（４０．９％）;ｒａｓ ｐ２１和ｐ５３阳性表达随肿瘤病理分级和分期的上升而增强,与肿瘤复发及预后呈正相关性（Ｐ〈０．０１）     

胃肠道间质瘤p53蛋白和p21蛋白的免疫组化研究

目的 探讨抑癌基因产物ｐ５３蛋白和ｒａｓ基因产物ｐ２１蛋白在胃肠道间质瘤（ＧＩＳＴ）中的表达及意义。方法 应用免疫组织化学Ｓ－Ｐ法。检测了６２例胃道间质瘤这两种蛋白的表达。结果 １０例良性间质瘤ｐ５３和ｐ２１均呈阴性表达,１０例交界性间质瘤中ｐ５３阳性表达者３例（３０．０％）,ｐ２１阳性表达者４例（４０．０％）,４２例胃肠道间质肉瘤中阳性表达者３５例（８３．３％）,ｐ２１阳性表达者３１例（７３．８     

幽门螺杆菌感染在胃癌及癌前病变中p21和p53同步检测的对比分析

用ＬＳＡＢ免疫组化法，对２０例胃癌、２２例异型增生、３０例肠化生及１３例正常组织进行了ｒｓａ－ｐ２１和突变型ｐ５３蛋白表达的检测。结果发现，胃癌、异型增生及肠化生，ｒａｓ－ｐ２１和ｐ５３阳性率较高，正常组织全部阴性；在所有病变组织中，ＨＰ阳性病人的ｐ２１和ｐ５３阳性率分别为４１．６％（３０／７２）和２７．７％（２０／７２），明显高于ＨＰ阴性病人，有统计学意义（Ｐ＜０．０１；Ｐ＜０．０５）。结果表明，ＨＰ感染与ｒａｓ－ｐ２１和突变型ｐ５３过度表达存在着明显的相关性，提示ＨＰ感染参予了ｒａｓ原癌基因激活和ｐ５３抑癌基因的失活，基因突变可能是ＨＰ致胃癌作用的机制之一。     

儿童白血病脑脊液p53蛋白和ras癌基因蛋白表达及比值分析

目的 探讨ｐ５３蛋白和ｒａｓ癌基因蛋白在白血病儿童脑脊液（ＣＳＦ）中的表达水平及与白血病化疗的关系。方法 应用Ｗｅｓｔｅｒｎ斑点印迹法检测５４例儿童急性白血病ＣＳＦ中ｐ５３蛋和ｒａｓ癌基因蛋白表达水平，并计算ｐ５３／ｒａｓ比值。结果 白血病儿童危象期ＣＳＦ中ｐ５３蛋白明显高于非肿瘤对照水平（Ｐ〈０．０１）。缓解期ｐ５３蛋白和ｒａｓ癌基因蛋白与危象期比有增高趋势（Ｐ〈０．０１），同时高于非肿瘤对照水     

卵巢肿瘤中癌基因 nm23Hl,c-erbB-2,ras 和 p53 的蛋白表达与腹膜后淋巴结转移关系的研究

目的本研究旨在结合腹膜后淋巴结切除术，探讨癌蛋白ｎｍ２３Ｈ１，ｐ１８５，ｐ２１，ｐ５３在卵巢癌中的表达与卵巢癌腹膜后淋巴转移（ＬＮＭ）的关系。方法采用免疫组化方法测定石腊包埋标本中ｎｍ２３Ｈ１，ｐ１８５，ｐ２１和ｐ５３的表达，单因素、多因素分析它们的表达与淋巴结转移关系。结果在３１例（３１．６％）患者中ｎｍ２３Ｈ１蛋白表达阳性；ｐ２１的表达与组织分化程度及残留癌相关。病理证实４９例（５５．１％）有淋巴结转移；ｎｍ２３Ｈ１蛋白表达阳性的ＬＮＭ率低（３５．７％ｖｓ６３．９％，Ｐ＝０．０１２）；ｐ２１表达与ＬＮＭ正相关（Ｐ＜０．００１）；ｐ１８５（～）病例ＬＮＭ率（６４．４％）高于ｐ１８５（＋）或ｐ１８５（－）的转移率（４５．９％），但差异无统计学意义；ｐ５３表达与ＬＮＭ无关。与ＬＮＭ相关的临床因素是伴有腹水、组织分化不良、残留灶和分期晚。经Ｌｏｇｉｓｔｉｃ回归多因素分析，影响淋巴结转移的独立危险因素是ｎｍ２３Ｈ１蛋白阴性表达，ｐ２１的阳性表达、有残留灶和分化差。结论在卵巢恶性肿瘤中，ｎｍ２３Ｈ１蛋白和ｐ２１的表达对腹膜后淋巴结转移有独立的联合作用，而ｐ１８５和ｐ５３的表达则无关。     

p16蛋白在卵巢上皮性浆液性肿瘤中的表达及其临床意义

目的探讨ｐ１６蛋白在正常卵巢和卵巢上皮性浆液性肿瘤中的表达及其临床意义。方法应用免疫组化法检测ｐ１６蛋白在８４例卵巢上皮性浆液性肿瘤组织（良性２０例，交界性１２例，癌５２例）及１２例正常卵巢组织常规石蜡标本的表达。结果ｐ１６蛋白在卵巢浆液性癌中的检出率５０．０％，低于良性浆液性瘤８５．０％及正常卵巢组９１．７％，均Ｐ＜０．０５。ｐ１６蛋白低表达与卵巢浆液性癌的恶性程度高，临床分期晚、肿瘤分化差、癌瘤播散、淋巴结转移及患者预后有关（Ｐ＜０．０１或Ｐ＜０．０５）。结论ｐ１６蛋白作为细胞周期的负性调节子具有抑制细胞增殖的作用。ｐ１６抑癌基因异常导致ｐ１６蛋白合成障碍，可引起细胞无限性生长即恶变。对卵巢浆液性癌ｐ１６蛋白表达的测定，有助于确定肿瘤的恶性度，判断其癌瘤播散、转移的能力，并估计患者的预后     

p53和p21基因蛋白表达与胃癌侵袭力的关系

采用免疫组织化学方法研究了６８例胃癌中癌细胞ｐ５３和ｐ２１基因蛋白表达与癌细胞侵袭力的关系。结果表明：６８例胃癌中有３６例ｐ５３基因蛋白染色阳性（５２．９％）,４８例ｐ２１基因蛋白染色阳性（７０．６％）;浸润于浆膜层和肌层的癌细胞ｐ５３蛋白染色的阳性程度明显高于粘膜层癌细胞（Ｐ＜０．０５）;浸润性生长的癌细胞中ｐ５３和ｐ２１蛋白阳性程度均明显强于膨胀性生长的癌细胞（Ｐ＜０．０５）;淋巴结转移病例的癌细胞其ｐ５３和ｐ２１蛋白染色阳性率（分别为５４．３％和７３．９％）与无淋巴结转移的病例（分别为５０．０％和６３．６％）无显著性差异（Ｐ＞０．０５）;有淋巴结转移的病例中,原发癌ｐ５３蛋白阳性强度与转移癌正相关（γ＝０．６８,Ｐ＜０．０１）。结果提示：ｐ５３和ｐ２１基因蛋白染色阳性程度较高的胃癌细胞具有较强的侵袭力。     

卵巢癌细胞DNA倍体、p21及p53基因表达产物定量分析

目的　探讨卵巢癌DNA倍体、p2 1及 p5 3基因定量表达情况及其临床意义。 方法　应用流式细胞术 (FCM )和荧光免疫技术 ,对 3 9例卵巢癌组织的卵巢癌细胞和 9例正常卵巢组织的卵巢细胞的染色体倍体、p2 1基因和 p5 3基因表达产物进行定量分析。结果　在卵巢癌组织中DNA的异倍体率、p2 1、p5 3基因蛋白产物的阳性表达率均明显高于对照组 ,两者比较均有非常显著性差异 (P <0 .0 1)。结论　应用FCM定量测定卵巢癌细胞中的DNA倍体、p2 1及 p5 3基因表达产物 ,在临床上具有重要的参考价值     

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.     

Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer.

PURPOSE: Dysregulation of cell cycle control, in particular G(1)-S-phase transition, is implicated in the pathogenesis of most human cancers, including epithelial ovarian cancer (EOC). However, the prognostic significance of aberrant cell cycle gene expression in EOC remains unclear. EXPERIMENTAL DESIGN: The expression of selected genes from the pRb pathway that regulates G(1)-S-phase progression, including cyclin D1, p16(Ink4a), cyclin E, p27(Kip1), p21(Waf1/Cip1), and p53, was examined in a consecutive series of 134 serous EOC using immunohistochemistry and the results correlated to disease outcome. RESULTS: Molecular markers predictive of reduced overall survival in univariate analysis were overexpression of cyclin D1 (P = 0.03) and p53 (P = 0.03) and reduced expression of p27(Kip1) (P = 0.05) and p21(Waf1/Cip1) (P = 0.02), with the latter three also being prognostic for a shorter progression-free interval. In addition, patients displaying overexpression of p53 with concurrent loss of p21(Waf1/Cip1) had a significantly shorter overall (P = 0.0008) and progression-free survival (P = 0.0001). On multivariate analysis, overexpression of cyclin D1 and combined loss of p21(Waf1/Cip1) in the presence of p53 overexpression were independent predictors of overall survival. Similarly, the combination of p21(Waf1/Cip1) loss and p53 overexpression was independently predictive of a shorter progression-free interval. Overexpression of p53 and cyclin E and reduced expression of p27(Kip1) and p21(Waf1/Cip1) were significantly associated with increasing tumor grade. CONCLUSIONS: This study confirms that dysregulation of cell cycle genes is common in EOC, and that aberrant expression of critical cell cycle regulatory proteins can predict patient outcome in serous EOC.     

P糖蛋白在胰腺癌中的表达及其与p21^ras和p53蛋白表达的关系

为了解Ｐ糖蛋白在原发和复发胰腺癌组织中的表达及其临床意义，并分析其表达与Ｐ２１＾ｒａｓ和Ｐ５３蛋白表达的关系，采用免疫组化泽４８例原发胰腺导管癌和１５例复发胰腺癌的石蜡包埋标本进行Ｐｇｐ，ｐ２１＾ｒａｓ蛋白和ｐ５３蛋白单抗的免疫组化染色。     

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.     

The effect of cyclooxygenase-2 expression on tumor vascularity in advanced stage ovarian serous carcinoma

BACKGROUND: Cyclooxygenase-2 (COX-2) seems to be involved at various steps in the processes of malignant transformation and tumor progression. Investigations have shown that COX-2 overexpression is associated with increased proliferation, reduced apoptosis, and angiogenesis. METHODS: Specimens from 125 patients with high-grade, advanced-stage (Stage III-IV) serous ovarian carcinoma were evaluated by immunohistochemistry for COX-2, p53, bcl-2, epidermal growth factor receptor (EGFR), and Her-2/neu expression and for CD34-stained microvessel density (MVD). Statistical analysis was performed to investigate the correlations between COX-2 expression and 1) clinicopathologic characteristics, 2) tumor MVD, and 3) expression of other molecular markers. The effect of COX-2 expression on survival was determined using survival analysis. RESULTS: Increased COX-2 expression was significantly correlated with tumor MVD (Spearman rank correlation test: r = 0.41; P < 0.001). There was no association observed between COX-2 expression and expression levels of EGFR, Her-2/neu, bcl-2, or p53. Patients who had tumors that showed high COX-2 expression had a worse prognosis compared with patients who had tumors with low expression (death hazard ratio, 2.0; 95% confidence interval, 1.2-3.5; P < 0.001). A multivariate analysis revealed that COX-2 expression was the strongest predictor of survival among the different prognostic factors analyzed. CONCLUSIONS: The current study demonstrated that COX-2 expression was correlated significantly with survival in patients with high-grade, high-stage serous ovarian carcinoma. Expression of COX-2 also was correlated with tumor angiogenesis but not with EGFR, Her-2/neu, or p53 expression. In addition to their prognostic significance, a better understanding of the biology of these molecular changes may help identify new targets for therapy in patients with ovarian carcinoma.     

p16、p53、BRAF、Bcl-2在卵巢浆液性肿瘤组织中的表达及临床意义

目的:探讨卵巢浆液性肿瘤组织中p16、p53、BRAF、Bcl-2的表达及临床意义。方法:收集宁夏医科大学总医院病理科2017年至2018年确诊的卵巢浆液性肿瘤136例，其中浆液性囊腺瘤52例，交界性囊腺瘤22例，低级别浆液性癌18例，高级别浆液性癌44例；另收集卵巢良性肿瘤和卵巢癌手术切除标本各30例。分别采用免疫组织化学SP法检测p16、p53、BRAF、Bcl-2的表达，实时定量PCR法检测p16、p53在卵巢良恶性肿瘤组织中的表达。结果:卵巢浆液性囊腺瘤、交界性囊腺瘤、低/高级别浆液性癌组织中p16的阳性率分别为3.8%、45.5%、88.9%、81.8%，p53为0、9.1%、55.6%、45.5%，BRAF为46.2%、45.5%、22.2%、31.8%，Bcl-2为46.2%、45.5%、38.9%、47.7%。不同类型浆液性肿瘤组织中p16、p53表达均有显著性差异（P＜0.001），但BRAF、Bcl-2表达未见明显差异。与卵巢良性肿瘤相比，p16在交界性肿瘤、卵巢癌中的阳性表达明显升高，差异有显著统计学意义（P＜0.012 5）；p53在卵巢癌中的阳性表达明显高于良性肿瘤（P＜0.001）；p16和p53的表达呈正相关（P＜0.05）。p53、Bcl-2与卵巢癌淋巴结转移有相关性（P＜0.001），p16、p53、Bcl-2与盆腔侵犯有关（P＜0.05），p53、BRAF、Bcl-2与CA125表达有不同程度相关性（P＜0.05）。p16、p53联合检测对卵巢癌诊断的敏感性和特异性为90.0%、76.7%。结论:p16、p53、BRAF、Bcl-2参与卵巢癌的发生发展，p16和p53基因突变可能在卵巢浆液性肿瘤的恶性进展中发挥作用，联合检测p16、p53对卵巢癌诊断有指示意义。     

p53、p21ras、nm23-H1基因在子宫内膜癌中表达与临床病理关系研究

目的　研究p53、p2 1ras、nm2 3 H1基因在子宫内膜癌中的表达与临床病理学关系。方法　应用免疫组织化学方法 (SABC法 )研究 18例正常增生期子宫内膜、12例子宫内膜非典型性增生过长、78例子宫内膜癌的p53、p2 1ras、nm2 3 H1基因的表达情况。结果　 12例增生期子宫内膜中p53和p2 1ras基因表达阴性 ,3例子宫内膜非典型性增生过长中p53阳性 ;p53、p2 1ras、nm2 3基因在子宫内膜癌中表达率分别为 57 69% ,55 12 % ,71 79% ;p53的表达在不同的临床分期 ,病理学分级 ,有无淋巴结转移和是否绝经之间差异有显著性意义 (P <0 0 1) ;p2 1ras基因表达与病理学分级及有无淋巴结转移有关 (P <0 0 5) ,但与临床分期无关 ;nm2 3 H1的表达与病理学分级 ,临床分期 ,有无淋巴结转移有关。结论　p53、p2 1ras、nm2 3基因在子宫内膜癌中均高表达 ,p53的表达和肿瘤发生 ,发展有关 ,p2 1ras基因表达与肿瘤的进展有关 ,nm2 3的表达与淋巴结转移呈负相关。