膀胱上皮癌△Np63、p53及ki-67基因表达与预后的相关性研究

目的 探讨△Np63在膀胱移行细胞癌(transitional cell carcinoma of bladder,TCCB)中作用及联合检测△Np63、p53和ki-67与膀胱上皮癌预后的相关性.方法 用免疫组化检测56例膀胱移行细胞癌组织△Np63、p53和ki-67的表达,分析免疫染色结果与病理分级、分期和预后的关系.佶果膀胱移行细胞癌中△Np63、p53和ki-67阳性表达率明显高于正常膀胱黏膜,在高级别、浸润性癌组织中的阳性表达率明显高于低级别、浅表性癌组织,各组阳性表达率差异有统计学意义(P<0.05)△Np63与p53、Ki-67均呈正相关,rs'分别为0.298、0.316,相关性有统计学意义(P<0.05).结论 △Np63可能是TCCB发生和发展的重要促进因素,与膀胱癌的预后密切相关,联合检测△Np63、p53和ki-67可以更好地判断TCCB的预后.     

TOPⅡ联合Ki-67和p53表达对局部晚期乳腺癌化疗敏感性的预测分析

目的探讨TOPⅡ联合p53和Ki-67的表达对局部晚期乳腺癌化疗敏感性的预测价值。方法采用免疫组化方法检测90例乳腺癌患者不同分子分型的TOPⅡ、p53和Ki-67的表达状况,比较不同TOPⅡ、p53及Ki-67表达状况患者接受新辅助化疗的疗效差异。结果 Ki-67表达阳性率在HER2过表达型、Basal-like型、腺腔A型和腺腔B型之间的差异具有统计学意义(χ2=38.877,P=0.000),其中HER2过表达型和Basal-like型高于腺腔A型和腺腔B型;TOPⅡ及p53的表达表达阳性率在4种分子分型间的差异无统计学意义(χ2=7.105,P=0.069;χ2=7.105,P=0.069)。TOPⅡ和Ki-67表达阳性者的新辅助化疗疗效优于表达阴性者χ2=18.28,P=0.000;χ2=6.64,P=0.009;而p53的表达状况与新辅助化疗的敏感性无关。结论 HER2过表达型和Basal-like型乳腺癌患者对新辅助化疗敏感,疗效好;TOPⅡ表达阳性并Ki-67表达阳性可作为乳腺癌临床化疗患者敏感性生物学指标。     

Her-2阴性乳腺癌中激素受体、Ki-67、P53的表达与蒽环类新辅助化疗疗效的关系

目的探讨Her-2阴性乳腺癌中激素受体、Ki-67、P53的表达与蒽环类新辅助化疗疗效的关系。方法应用免疫组化法测定78例Her-2阴性乳腺浸润性导管癌蒽环类新辅助化疗前ER、PR、Ki-67、P53的表达。四个周期CEF或AC方案化疗后进行临床及病理疗效评价。结果激素受体双阳或单阳组与激素受体双阴组相比,临床总有效率及术后病理有效率有显著性差异(P0.05);Ki-67阳性组与Ki-67阴性组相比,临床总有效率无显著性差异(P0.05),术后病理有效率有显著性差异(P0.05);P53阳性组与P53阴性组相比,临床总有效率及术后病理有效率均未见显著性差异(P10.05)。结论激素受体阴性、Ki-67阳性对Her-2阴性乳腺癌患者蒽环类新辅助化疗的敏感性较高,激素受体状态、Ki-67可能成为判断Her-2阴性乳腺癌蒽环类新辅助化疗疗效的重要指标。     

乳腺癌组织ABCG2与Ki-67的表达与化疗敏感性的相关性研究

探讨乳腺癌耐药相关蛋白(ABCG2)、增殖细胞核抗原(Ki-67)的表达与乳腺癌化疗敏感性的关系。选取我院60例女性乳腺癌新辅助化疗患者化疗前乳腺癌标本,免疫组化SP法检测ABCG2、Ki-67蛋白的表达情况。60例乳腺癌组织ABCG2、Ki-67的阳性表达率分别为56.7%和61.7%。ABCG2、Ki-67的表达水平与肿块的大小和淋巴结转移情况呈正相关(P0.01);ABCG2、Ki-67表达与ER、PR表达无明显相关性(P0.05);ABCG2表达水平与化疗疗效呈负相关(P0.01),Ki-67的表达水平与化疗疗效呈正相关(P0.01)。ABCG2、Ki-67表达水平是与乳腺癌化疗敏感性相关,是评估乳腺癌新辅助化疗的重要指标。     

分子标记物表达预测乳腺癌蒽环类新辅助化疗疗效价值研究

目的探讨局部晚期乳腺癌病人肿瘤组织分子生物学标记物的表达及其与新辅助化疗有效率的关系。方法采用免疫组化的方法检测2000年1月至2010年12月复旦大学附属肿瘤医院乳腺外科收治的420例乳腺癌新辅助化疗病人化疗术后标本中雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER-2)/neu、p53、Cathepsin-D、p27、cyclinD1、Bax、Ki67、TOPOII、GSTπ、MDR和Bcl-2等分子标记物的表达情况,分析这些分子标记物的表达与新辅助化疗疗效之间的关系。结果 p53或cathepsin-D或GSTπ阴性的病人化疗疗效要显著优于阳性的病人,多因素回归分析提示GSTπ和p53是独立的新辅助化疗疗效预测指标。结论 GSTπ和p53可作为判定乳腺癌蒽环类新辅助化疗方案敏感性的两个独立预测指标。     

乳腺癌术前新辅助化疗对p53和Ki-67表达的影响

目的:研究分析乳腺癌组织p53和Ki-67表达及其与术前新辅助化疗(NAC)的相关性。方法:2014年1月—2015年9月,乳腺癌患者73例,给予3周NAC治疗后进行手术,分别在化疗前以及手术后取穿刺组织及切除组织标本进行病理检测,分析患者的疗效及p53及Ki-67的表达。结果:73例患者中CR 24例(32.88%)、PR39例(53.42%)、OR 63例(86.30%)。术后病理分级5级13例,4级26例,3级22例,2级9例,1级3例。化疗前后,全部患者的p53表达率差异无统计学意义(P0.05)。化疗后患者Ki67的表达率显著低于化疗前(P0.05)。化疗后的OR患者中,p53阳性表达率34.92%,显著低于阴性表达率65.08%;Ki-67阳性表达率71.43%,显著高于阴性表达率28.57%(P均0.05)。乳腺癌组织中p53的阴性表达与化疗疗效呈正相关(r=0.689,P0.05);Ki-67个阳性表达与化疗疗效呈正相关(r=0.714,P0.05)。结论:乳腺癌组织内p53以及Ki-67表达及其与术前NAC疗效具有紧密的相关性,临床上可通过监测p53以及Ki-67的表达用于辅助判定NAC疗效。     

膀胱上皮癌ΔNp63、p53及ki-67基因表达与预后的相关性研究

目的探讨ΔNp63在膀胱移行细胞癌（transitional cell carcinoma of bladder,TCCB）中作用及联合检测ΔNp63、p53和ki-67与膀胱上皮癌预后的相关性。方法用免疫组化检测56例膀胱移行细胞癌组织ΔNp63、p53和ki-67的表达,分析免疫染色结果与病理分级、分期和预后的关系。结果膀胱移行细胞癌中ΔNp63、p53和ki-67阳性表达率明显高于正常膀胱黏膜,在高级别、浸润性癌组织中的阳性表达率明显高于低级别、浅表性癌组织,各组阳性表达率差异有统计学意义（P〈0.05）;ΔNp63与p53、Ki-67均呈正相关,rs′分别为0.298、0.316,相关性有统计学意义（P〈0.05）。结论ΔNp63可能是TCCB发生和发展的重要促进因素,与膀胱癌的预后密切相关,联合检测ΔNp63、p53和ki-67可以更好地判断TCCB的预后。     

新辅助化疗对结肠癌细胞凋亡及相关调控蛋白表达的影响

目的 观察新辅助化疗(NACT)对结肠癌细胞凋亡及相关调控蛋白表达的影响.方法 收集结肠癌患者114例,采用原位末端标记法和免疫组织化学方法分别观察经NACT的FOLFOX4方案治疗前后结肠癌细胞凋亡和癌组织中B细胞淋巴瘤/白血病-2相关X蛋白(bax)、B细胞淋巴瘤/白血病-2(bcl-2)、环氧合酶-2(COX-2)、p53蛋白的表达,并判定NACT的近期疗效.结果 NACT化疗后结肠癌细胞发生典型凋亡形态学变化,细胞凋亡系数(3.87％比1.17％)和凋亡阻性率(59.65％比23.68％)显著高于化疗前.经NACT治疗后患者结肠癌细胞bcl-2(54.39％比70.15％)、COX-2(28.07％比50.00％)和p53(45.61％比70.05％)的阳性表达率与化疗前比较均有不同程度降低,差异有统计学意义(P＜0.05或P＜0.01),而bax阳性表达率(22.81％比50.88％)显著增强,差异有统计学意义(P＜0.01).同时bcl-2/bax比值(3.08比1.07)也显著降低.NACT治疗组的总有效率(39.47％)显著高于对照组(1.75％),治疗后患者无严重药物不良反应.结论 结肠癌患者经NACT化疗后癌组织中bcl-2、COX-2和p53蛋白表达明显降低,而bax蛋白的表达显著增加,促进癌细胞凋亡,且NACT的近期疗效显著.     

小鼠乳腺癌中p53与bcl-2/bax基因表达的相关性研究

目的探讨p53基因和bcl-2/bax基因在乳腺癌发病机制中的作用以及它们之间的相互关系。方法以小鼠乳腺癌BCML-TA299可移植模型为研究对象,用免疫组织化学染色法观测α-干扰素(INF-α)干扰后p53基因与bcl-2/bax表达的关系。结果实验性乳腺癌BCML-TA299治疗组荷瘤鼠生存期较对照组延长,且随着时间的推延治疗组肿瘤的体积明显低于对照组的肿瘤体积;治疗组与对照组比较,肺转移率低。对照组p53蛋白阳性表达率为92.01±0.48,而治疗组中p53呈阴性表达。对照组瘤组织bcl-2蛋白表达为50.21±0.52,bax蛋白表达为12.08±0.13;治疗组瘤组织bcl-2蛋白表达为12.01±0.2,bax蛋白表达为48.19±0.57。对照组p53蛋白表达与bcl- 2呈正相关,而与bax呈负相关(P<0.05);治疗组中p53呈阴性表达,bcl-2和bax表达与对照组结果相反。结论bcl-2和bax的表达受p53调节。p53、bcl-2/bax在乳腺癌发病机制中起着较重要的作用。     

乳腺癌ER、PR、p53、Her-2表达与新辅助化疗有效率的关系

目的探讨乳腺癌患者ER、PR、p53、Her-2的表达及其与新辅助化疗有效率的关系。方法采用免疫组化的方法检测178例乳腺癌新辅助化疗患者化疗前ER、PR、p53、Her-2的表达情况,观察新辅助化疗的效果。结果178例乳腺癌新辅助化疗病例中,ER、PR、p53阴性率、Her-2过度表达率分别为33.15、23.60%、60.67%、35.39%。ER(+)组与ER(-)组、PR(+)组与PR(-)组、p53(+)组与p53(-)组化疗有效率差异均有统计学意义(P<0.05),Her-2过度表达组与非过度表达组化疗有效率差异无统计学意义(P>0.05)。结论ER、PR、p53阴性的乳腺癌病人对化疗更敏感,化疗后获益更多,ER、PR、p53可作为乳腺癌新辅助化疗(TE或CET方案)敏感性的预测指标。     

Apoptotic and proliferative indexes in esophageal cancer: predictors of response to neoadjuvant therapy [corrected].

Altered expression of the genes that control apoptosis and proliferation may influence the response of cancer cells to cytotoxic agents. The primary aim of this study was to determine the role of the novel antiapoptotic and cell cycle gene, survivin, in apoptotsis and proliferation in esophageal cancer and to evaluate whether the survivin, p53, and bcl-2 status were able to predict a patient's response to neoadjuvant therapy. A total of 104 patients with esophageal tumors were studied. Tumor tissue was immunostained for survivin, p53, and bcl-2 proteins. Proliferative and apoptotic activity was measured using ki-67 immunohistochemical analysis and the TUNEL method, respectively. Forty-eight patients whose pretreatment biopsies were analyzed received neoadjuvant chemoradiation therapy or chemotherapy followed by surgery. Outcome was graded as a complete response, a partial response, or no response according to the results of histologic examination and CT imaging. Expression of survivin was found to correlate significantly with the proliferative index but not the apoptotic index. Patients who received neoadjuvant treatment were more likely to achieve a complete response if their tumors had high proliferative activity, and p53 positive tumors were more likely to contain residual tumor after treatment. In conclusion, survivin expression appears to foster proliferative activity in esophageal cancer, and tumors with a high proliferative index or a functioning p53 gene are more responsive to neoadjuvant chemoradiation therapy.     

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目的　探讨乳腺癌新辅助化疗中Ki- 6 7、bcl- 2和AI表达率与临床疗效的关系。方法　2 0 0 2年1月至2 0 0 3年6月对5 8例可手术女性乳腺癌病人采用CEF方案新辅助化疗3个周期。对资料完整的4 2例,检测化疗前后Ki -6 7、bcl- 2及肿瘤细胞凋亡指数(AI)的变化。结果　化疗有效率为6 2. 1%。Ki 6 7高表达乳腺癌有效率高(P <0 .0 5 )。疗效与bcl- 2表达及AI值无明显关系。结论　可手术乳腺癌采用CEF方案新辅助化疗,Ki- 6 7表达情况对预测化疗效果具有重要价值。     

Apoptotic and proliferative indexes in esophageal cancer: Predictors of response to neoadjuvant therapy apoptosis and proliferation in esophageal cancer

Altered expression of the genes that control apoptosis and proliferation may influence the response of cancer cells to cytotoxic agents. The primary aim of this study was to determine the role of the novel an-tiapoptotic and cell cycle gene, survivin, in apoptotsis and proliferation in esophageal cancer and to evaluate whether the survivin, p53, and bcl-2 status were able to predict a patient’s response to neoadjuvant therapy. A total of 104 patients with esophageal tumors were studied. Tumor tissue was immunostained for survivin, p53, and bcl-2 proteins. Proliferative and apoptotic activity was measured using ki-67 immu-nohistochemical analysis and the TUNEL method, respectively. Forty-eight patients whose pretreat-ment biopsies were analyzed received neoadjuvant chemoradiation therapy or chemotherapy followed by surgery. Outcome was graded as a complete response, a partial response, or no response according to the results of histologic examination and CT imaging. Expression of survivin was found to correlate significantly with the proliferative index but not the apoptotic index. Patients who received neoadjuvant treatment were more likely to achieve a complete response if their tumors had high proliferative activity, and p53 positive tumors were more likely to contain residual tumor after treatment. In conclusion, survivin expression appears to foster proliferative activity in esophageal cancer, and tumors with a high proliferative index or a functioning p53 gene are more responsive to neoadjuvant chemoradiation therapy. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation). Supported by grants from the Royal College of Surgeons of England and Yorkshire Cancer Research.     

新辅助化疗对乳腺癌ER、PR、C-erbB-2、P53、Ki-67表达的影响

目的　探讨新辅助化疗对乳腺癌ER、PR、C-erbB-2、P53、Ki-67表达的影响。方法　通过免疫组化检测化疗前后38例乳腺癌ER、PR、C-erbB-2、P53、Ki-67的表达。结果　新辅助化疗前后ER、PR状态各有9例发生变化,C-erbB-2状态各有8例发生变化,P53状态各有10例发生变化,比较差异均无统计学意义;Ki-67状态有17例发生改变,比较差异有统计学意义。结论　新辅助化疗对ER、PR、C-erbB-2、P53表达状态无显著影响,而能显著降低Ki-67的表达。     

The role of bcl-2, p53, and ki-67 index in predicting tumor recurrence for low grade superficial transitional cell bladder carcinoma

PURPOSE: We assess the prognostic significance of bcl-2 expression, p53 mutation and ki-67 index for low grade, superficial transitional cell bladder carcinoma. MATERIALS AND METHODS: The medical records of 93 cases of primary, low grade (24 G1, 69 G2), superficial (70 pTa, 23 pT1) transitional cell carcinoma of the bladder were reviewed. Association of bcl-2, p53 and ki-67 index immunoreactivity with tumor grade and stage was examined. Prognostic significance of tumor grade, pathological stage, bcl-2 expression, p53 mutation and ki-67 index in predicting tumor recurrence was assessed. RESULTS: Of the tumors 60 (70%) had p53 mutation and 9 (10.5%) expressed bcl-2. These 2 markers did not relate to tumor grade or pathological stage. Median ki-67 index was 10.9% and positively correlated with tumor grade. Recurrence was noted in 34.9% of patients with a median followup of 26 months (range 1 to 84). The ki-67 index was the only significant prognostic indicator in univariate and multivariate analyses. This marker can further distinguish grade 2 tumors with a favorable prognosis from those with an unfavorable outcome. CONCLUSIONS: The ki-67 labeling index is an independent predictor of tumor recurrence for patients with primary superficial, low grade bladder cancers.     

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??Expression of molecular markers predict breast cancer to neoadjuvant anthracycline chemotherapy value CHEN Yi-zuo*, CHEN Can-ming, FEI Fei, et al. *Department of Breast Surgery, Fudan University Shanghai Cancer Center,Shanghai 200032, China
Corresponding author: WU Jiong, E-mail??wujiong1122@vip.sina.com
Abstract Objective To investigate the predictive value of biological markers for responsiveness to anthracyline-based regimen in neoadjuvant systemic therapy for local advanced breast caner. Methods Postoperative paraffin-embedded tumor samples from 420 breast cancer patients admitted between January 2000 and December 2010 in Department of Breast Surgery of Fudan University Shanghai Cancer Center were examined for expression of ER, PR, Her-2/neu and other 15 markers by immunohistochemistry, to analyze the predictive value of the biological markers for response to neoadjuvant chemotherapy. Results Negative p53, cathepsin-D and loss of GSTπwere significantly predictive for an effective response to anthracycline-based neoadjuvant chemotherapy. In multivariate logistic regression analysis, the GSTπand p53 status were found with independent predictive value. Conclusion Loss of GSTπand p53 independently predict the response to anthracycline-based regimen.     

新辅助化疗对乳腺癌生物学指标表达的影响

目的 探讨新辅助化疗对评估原发性乳腺癌空心针穿刺活检（CNB）和手术切除标本（SES）生物学指标的影响.方法 152 例原发性乳腺癌患者纳入本研究.其中化疗组99 例,手术组53 例.采用免疫组织化学（IHC）方法 比较152 例CNB 和SES 采样组织标本中雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子2（Her2）、Ki67、p53 和TopoⅡ的表达,评估CNB 在乳腺癌生物学指标检测中的准确性.结果 CNB 和SES 在评估是否接受过新辅助化疗乳腺癌生物学指标方面具有良好的一致性,K 值〉 0.6.手术组CNB 对生物学指标评估的准确性达到87% ~ 91%,化疗组的准确性78% ~ 95%.但新辅助化疗对ER、PR、Her2、p53 和Ki67 表达的影响差异无统计学意义（P 〉 0.05）,两组间比较TopoⅡ表达差异有统计学意义（P 〈 0.05）.结论 CNB 和SES 在评估乳腺癌生物学指标上的一致性较好,CNB 评估乳腺癌生物学指标的准确性高.新辅助化疗对乳腺癌生物学指标的影响较小.     

P53和Ki-67的表达变化与三阴性乳腺癌pCR的关系研究

目的探讨三阴性乳腺癌新辅助化疗前后P53和Ki-67的表达变化,及其与病理完全缓解率(pCR)间的关系。方法选取2016-01-2018-12间就诊的73例三阴性乳腺癌患者的病史及病理资料,均经空心针穿刺病理确诊,并接受表柔比星联合多西他赛新辅助化疗。8周期化疗后行乳腺癌改良或保乳根治术。探讨新辅助化疗前后P53和Ki-67表达变化及其与pCR间的关系。结果73例患者总体pCR为30.1%(22/73),其中P53阳性组pCR为38%(19/50)、Ki-67高表达组pCR为39.2%(20/51)、Ki-67高表达且P53阳性组pCR高达48.6%(17/35),明显高于其他组。化疗后P53阳性表达率及Ki-67表达率均明显下降,其中P53阳性组有21例转为阴性组,pCR达71.4%。结论结合化疗前后P53及Ki-67的表达变化有助于预测三阴性乳腺癌新辅助化疗的pCR。     

凋亡相关基因 bcl-2、bax、bad与乳腺癌

目的探讨乳腺癌发生、发展过程中bcl-2、bax及bad基因表达水平变化及与乳腺癌其他生物因素的相关性。方法复习国内、外相关文献并进行综述。结果在从正常乳腺组织到乳腺癌逐渐演化的过程中凋亡抑制基因bcl-2的表达水平变化尚有待进一步研究,而凋亡促进基因bax、bad的表达水平呈递减趋势。bcl-2基因表达水平与乳腺癌中一些公认的正性因子如雌激素受体(ER)、孕激素受体(PR)呈正相关,与其他一些负性因子如p53、表皮生长因子受体、c-erbB-2、腋窝淋巴结转移情况等呈负相关。bax基因的表达水平与乳腺癌ER、PR水平以及p53表达水平等无关。对于bad基因与乳腺癌其他生物因素的相关性尚未见报道。结论乳腺癌中bcl-2基因表达水平的变化对乳腺癌预后以及治疗的作用尚存在争议,bad基因与乳腺癌预后的关系亦不清楚,而bax基因表达水平与乳腺癌的预后呈正相关。对于它们的研究将为我们评价乳腺癌的预后提供新的指标,为乳腺癌的治疗开辟新的思路。