淋巴结阴性乳腺癌p21waf1、c-erbB-2和p53蛋白表达及其临床意义

目的：探讨腋淋巴结阴性乳腺癌组织中p21^waf1、c-erbB-2和p53基因蛋白表达及其与临床病理参数和预后的关系。方法：应用免疫组化LSAB方法检测121例腋淋巴结阴性乳腺部石蜡切片中p21^waf1、c-erbB-2和p53蛋白的表达情况;同时应用Kaplan-Meier法及多变量Cox比例风险模型,分析3种蛋白表达与预后的关系。结果：（1）p21^waf1蛋白表达率为48．8％,与病理组织学分级、ER状态有关;p53蛋白表达率为36．4％,c-erbB－2蛋白表达率为26．4％,与组织学分级有关;（2）p21^waf1阳性表达与p53表达呈负相关（P＜0．01）;Cox阳性组患者无瘤生存率高于阴性组（P＜0．05）;c-erbB－2阳性组患者无瘤生存率明显低于阴性组（P＜0．01）;Cox模型分析显示仅有c-erbB－2表达对预后有显著影响。结论：乳腺癌组织p21^waf1、c-erbB-2表达与病理组织学分级有相关性;p^21waf1表达依赖于p53途径刺激;p^21waf1、c-erbB－2表达与腋淋巴结阴性乳腺癌预后有关,且c-erbB-2表达是一个独立的预后指标。     

乳腺癌组织中c-erbB-2 p53 PCNA及bcl-2蛋白的表达及其临床意义

目的:探讨生物学指标c-erbB-2、p53、PCNA及bcl-2在乳腺癌中的表达与乳腺癌病理生物学行为的关系.方法:应用免疫组织化学方法对56例乳腺癌组织切片c-erbB-2、p53、PCNA及bcl-2的表达进行检测.结果:c-erbB-2表达41.1%,与组织学分级呈正相关,与临床分期、病理类型、患者年龄(≥35岁)、ER、PR受体关系不密切;p53蛋白表达48.2%,与组织学分级、ER、PR受体呈正相关,与患者年龄(≥35岁)、临床分期、病理类型呈负相关;全组PCNA表达100%;bcl-2表达50.0%,与组织学分级、病理类型、ER、PR受体呈负相关,与临床分期呈正相关,与患者年龄(≥35岁)关系不密切.结论:生物学指标c-erbB-2、p53、PCNA及bcl-2应与临床预后因素临床期别、组织学分级等联合应用,提高对乳腺癌预后评价的正确性.     

乳腺癌组织p53、bel-2、PCNA和雌激素水平与临床病理及预后的关系

目的：研究乳腺癌组织中p53、bcl-2、PCNA的表达及ER、PR的水平与其病理分期、组织学分级和预后的关系。方法：应用免疫组织化学S-P法检测57例术后乳腺癌标本p53、bcl-2、PCNA的表达和ER、PR的水平。结果：乳腺癌组织学分级低，bel-2的阳性表达率高；乳腺癌的临床分期晚和组织学分级高，p53和PCNA呈高表达，而ER、PR则呈低表达。结论：乳腺癌患者bcl-2、ER的过度表达者预后好，p53、PCNA的过度表达则预后不良。     

乳腺癌组织中c-erbB-2、p53、PCNA和nm23蛋白的表达及其临床意义

目的探讨生物学指标c-erbB-2、p53、PCNA、nm23在乳腺癌中的表达及其与临床乳腺癌预后因素的关系.方法应用免疫组织化学方法对1180例乳腺癌组织切片c-erbB-2、p53、PCNA、nm23的表达进行检测.结果 c-erbB-2表达与患者年龄(≥35岁)、临床期别、腋淋巴结状态、组织学分级呈负相关,与ER、PR受体呈正相关;p53蛋白的表达与患者临床期别、组织学分级、病理类型呈负相关,与腋淋巴结状态呈正相关;PCNA的表达与患者临床期别、腋淋巴结状况呈负相关,与ER、PR呈正相关;nm23蛋白的表达与患者腋淋巴结状态呈负相关,与病理类型、ER、PR呈正相关.结论生物学指标c-erbB-2、p53、PCNA、nm23应与临床预后因素(临床期别、组织学分级、腋淋巴结状态及病理类型等)联合应用,有助于提高对乳腺癌预后评价的正确性.     

乳腺癌ER、PR、p53及C—erbB-2癌基因的多因素分析

目的:探讨乳腺癌组织ER、PR、 p53及c-erbB-2 癌基因蛋白表达与淋巴结转移、患者年龄及组织学类型的相关性.方法: 采用乳腺组织免疫组化SP法检测124例乳腺癌患者中ER、PR、 p53及c-erbB-2的表达,并分析其临床意义.结果:ER、 PR 的阳性表达率与淋巴结转移、患者年龄及组织学类型的无关.(P>0.05),ER、 PR 与 p53及c-erbB-2、表达之间存在负相关性,p53、 c-erbB-2 阳性表达率与有无淋巴结转移、年龄有关(P<0.05),与组织学类型无关(P> 0.05).结论:ER、PR、 p53及c-erbB-2 的检测对乳腺癌治疗方案的制定和预后估计有重要临床意义.     

乳腺癌组织中c-erbB-2、p53、PCNA和nm23蛋白的表达及其临床意义

目的探讨生物学指标c-erbB-2、p53、PCNA和nm23在乳腺癌中的表达及其与临床乳腺癌预后因素的关系.方法应用免疫组织化学方法对1180例乳腺癌组织c-erbB-2、p53、PCNA和nm23的表达进行检测.结果 c-erbB-2表达与患者年龄(≥35岁)、肿瘤临床期别、腋淋巴结状态、组织学分级呈负相关,与雌激素受体(ER)、孕激素受体(PR)呈正相关;p53蛋白表达与患者临床期别、组织学分级、病理类型呈负相关,与腋淋巴结状态呈正相关;PCNA表达与患者临床期别、腋淋巴结状况呈负相关,与ER、PR呈正相关;nm23蛋白表达与患者腋淋巴结状态呈负相关,与病理类型、ER、PR呈正相关.结论生物学指标c-erbB-2、p53、PCNA、nm23与临床期别、组织学分级、腋淋巴结状态及病理类型等联合应用,有助于提高对乳腺癌预后评价的正确性.     

p53 、bcl-2 和CD44v6 蛋白表达与乳腺癌转移的相关性研究

 目的 探讨乳腺癌及癌旁正常乳腺组织中p53、bcl—2和CD44v6蛋白的表达及意义。方法 采用免疫组化法检测96例乳腺癌及其癌旁正常乳腺组织中p53、bcl—2和CD44v6蛋白的表达，并分析其与淋巴结转移和c-erbB-2表达状态的相关性，从而评价这些指标在预测乳腺癌转移方面的价值。结果 正常乳腺组织中p53蛋白为阴性，在乳腺癌中阳性表达率为65．63％；随着组织学分级的增高，阳性率逐渐增高；淋巴结转移组阳性表达率明显高于无淋巴结转移组，并与c-erbB-2表达状态呈正相关。乳腺癌组织中bcl-2阳性表达率明显低于周围正常乳腺组织，随着组织学分级的增高，阳性率逐渐降低，淋巴结转移组中的表达率明显低于淋巴结非转移组，与c-erbB-2的表达呈负相关。CD44v6在乳腺癌组织中的阳性表达率明显高于正常乳腺组织，随着组织学分期的增加，CD44v6的阳性表达率亦增高，但差异无显著性，淋巴结转移组的阳性率略高于无淋巴结转移组，差异也无显著性，与c-erbB-2表达无相关性。结论 p53和bcl-2蛋白可作为预测乳腺癌转移的指标，CD44v6的阳性表达可能与乳腺癌的发生、进展有一定关系，但尚不能把它作为预测乳腺癌转移的稳定的生物学指标。     

乳腺癌组织p53、bcl-2、PCNA和雌激素水平与临床病理及预后的关系

目的:研究乳腺癌组织中p53、bcl-2、PCNA的表达及ER、PR的水平与其病理分期、组织学分级和预后的关系。方法:应用免疫组织化学S-P法检测57例术后乳腺癌标本p53、bc1-2、PCNA的表达和ER、PR的水平。结果:乳腺癌组织学分级低,bc1-2的阳性表达率高;乳腺癌的临床分期晚和组织学分级高,p53和PCNA呈高表达,而ER、PR则呈低表达。结论:乳腺癌患者bc1-2、ER的过度表达者预后好,p53、PCNA的过度表达则预后不良。     

ER、PR、p53及c-erbB-2癌基因在乳腺癌中的表达及预后意义

目的:探讨乳腺癌组织ER、PR、p53及c-erbB-2癌基因蛋白表达与患者年龄、肿瘤体积、淋巴结转移及组织学类型的相关性。方法:采用免疫组化SP法检测126例乳腺癌患者乳腺组织中ER、PR、p53及c-erbB-2的表达,并分析其与临床意义的关系。结果:126例乳腺癌中,ER、PR、p53及c-erbB-2的阳性表达率分别为44.4%(56/126)、47.6%(60/126)、64.3%(81/126)、68.3%(86/126)。ER、PR的阳性表达率与患者年龄、肿瘤体积、有无淋巴结转移、肿瘤分期及组织学类型的差异无统计学意义(P>0.05);p53及c-erbB-2阳性表达率与有无淋巴结转移、年龄的差异有统计学意义(P<0.05),与肿瘤体积及组织学类型的差异无统计学意义(P>0.05)。结论:在乳腺癌患者中ER、PR、p53及c-erbB-2的联合检测可以用来指导临床用药和判断预后。     

ERβ、C-erbB-2及bcl-2蛋白在乳腺癌组织的表达及意义

目的:检测乳腺癌组织中雌激素受体β(ERβ)、C-erbB-2和bcl-2蛋白的表达情况,并分析ERβ蛋白的表达与组织学分级、C-erbB-2及bcl-2蛋白表达的关系.方法: 采用免疫组化S-P法检测96例乳腺癌组织标本中ERβ、C-erbB-2及bcl-2蛋白的表达情况,并作统计学分析.结果: 96例乳腺癌组织标本中,ERβ、C-erbB-2及bcl-2蛋白阳性表达率分别为64.6%、36.5%和51.0%;ERβ蛋白的表达与组织学分级、C-erbB-2蛋白的表达呈负相关(P<0.05),与bcl-2蛋白的表达呈正相关,与腋淋巴结状态无关(P>0.05).结论: ERβ蛋白表达可能是乳腺癌患者预后良好的指标.     

The prognostic value of p53 and c-erbB-2 expression, proliferative activity and angiogenesis in node-negative breast carcinoma

AIMS AND BACKGROUND: p53, c-erbB-2 and Ki-67 protein expression and microvessel density (MVD) determined by CD34 antibody were evaluated by immunohistochemistry and their correlation with clinicopathological parameters including estrogen (ER) and progesterone (PR) receptor status and survival were investigated in patients with axillary lymph node-negative infiltrating ductal breast carcinoma. METHODS: The study population consisted of 47 patients with axillary lymph node-negative infiltrating ductal breast carcinoma. RESULTS: p53 and c-erbB-2 expression was detected in 36.2% and 31.9% of patients, respectively. Median Ki-67 expression was 10%. There were no statistically significant differences in the distribution of p53, Ki-67 and c-erbB-2 protein expression in relation to the age of the patients or to the size, histological grade or ER and PR status of the tumors. p53 protein expression correlated positively with c-erbB-2 and Ki-67 protein expression (P < 0.05). The mean MVD was 63.65 +/- 29.1 and it correlated positively with histological grade and Ki-67 expression (P < 0.05). Survival analysis revealed that age, tumor size, p53 and c-erbB-2 expression and PR status had no significant prognostic impact, whereas histological grade, proliferative activity and angiogenic activity were significant prognostic factors. Although ER-positive patients had a statistically significant overall survival advantage, the difference in disease-free survival was not significant. CONCLUSION: In axillary lymph node-negative breast carcinoma the histological grade and the proliferative and angiogenic activity of the tumor could be useful prognostic indicators.     

Relative effects of immunohistochemical expressions of c-erbB-2, p53, and bcl-2 oncoproteins on the survival of advanced breast cancer patients after endocrine therapy

c-erbB-2, p53, and bcl-2 oncoproteins were detected immunohistochemically in 92 recurrent or advanced breast cancer tumors just before an endocrine therapy, adreno-oophorectomy. Estrogen receptors (ER) and partly progesterone receptors were concomitantly assayed in the same tumor tissues. Twenty-eight percent (26/92) of c-erbB-2, 16% (15/92) of p53, and 11% (10/92) of bcl-2 expressions were shown to be positive. There were no significant correlations of these oncoproteins with clinical background characteristics of the patients, except the inverse relation between p53 expression and ER status (p=0.0033). Of these covariates, ER status was shown to be the only predictor of response to endocrine therapy. In the absence of ER measurement, p53 expression was a significant predictor of the response. Kaplan-Meier curves showed that ER had a significant and p53 expression had a marginal effect on the overall survival length of the patients, c-erB-2 or bcl-2 were indifferent to survival or response. It is concluded that p53 immunohistochemical expression might be a supplementary predictor next to ER status of the overall survival as well as response of advanced breast cancer patients treated with endocrine therapy, and that p53 alteration might modify the ER dependent hormone-responsiveness of breast cancer.     

p53 and c-erbB-2 but not bcl-2 are predictive of metastasis-free survival in breast cancer patients receiving post-mastectomy adjuvant radiotherapy in Taiwan

BACKGROUND: Patients with breast cancer often receive radiotherapy after mastectomy if they are at a high risk of local recurrence, but the prognosis varies among patients. We conducted a study to evaluate p53, bcl-2 and c-erbB-2 as predictors of prognosis in breast cancer patients receiving post-mastectomy radiotherapy, which has not been well defined in the Taiwanese population. METHODS: We recruited 74 consecutive patients with primary operable breast cancer who were treated with mastectomy followed by locoregional radiotherapy and studied the presence of p53, bcl-2 and c-erbB-2 expressions in tumor tissues by immunohistochemical staining. Associations between the protein expressions and clinical outcomes, including local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS), were evaluated. RESULTS: The median follow-up time was 55 months. Expressions of p53, bcl-2 and c-erbB-2 were observed in 14 (19%), 28 (38%) and 39 (53%) patients, respectively. Both p53 and c-erbB-2 were significant predictors of MFS. The 5-year MFS for p53-negative and p53-positive tumors were 61.2 and 35.7% (P = 0.01) and 5-year MFS for c-erbB-2-negative and c-erbB-2-positive tumors were 71.3 and 42.4% (P = 0.01). Whereas expression of bcl-2 protein is associated with favorable clinicopathological features, it was not related to LRFS, MFS or OS. Multivariate analyses confirmed c-erbB-2 and p53 expressions as predictors of MFS independent of tumor size, histological grading and lymph node involvement. CONCLUSION: Expressions of p53 and c-erbB-2 are independent predictors of MFS in this Taiwanese population. Further research should be conducted on their application in the treatment and follow-up of patients.     

Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins

Patients with primary breast carcinoma with one to three axillary lymph node metastases but without distant metastases (n1-3) in Japan have been shown to have a 10-year disease-free survival rate of > 60%. It would be reasonable to divide n1-3 Japanese breast cancer patients into groups with high- or low-risk for recurrence and to consider post-operative adjuvant therapy. In the present study, we analyzed 228 consecutive Japanese patients with n1-3 breast cancer who underwent radical mastectomy and were followed up for a median time of 11.0 years. The expression of bcl-2, p53 and c-erbB-2 proteins in the primary tumors was examined immunohistochemically and their prognostic roles were also analyzed along with conventional clinicopathologic indicators. bcl-2 expression was correlated with positive estrogen receptor status and inversely correlated with p53, c-erbB-2 and histologic grade. Univariate analysis showed that bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the patient's group as well as node status, histologic grade, tumor size, age at diagnosis, menopausal status and estrogen receptor status. Cox's regression analysis demonstrated that the number of nodes involved, menopausal status, p53 and bcl-2 were independent predictors for overall survival and that histologic grade and the number of nodes involved were independent predictors for disease-free survival. These results suggest that bcl-2 expression in combination with p53 and c-erbB-2 expression, the number of lymph node metastases, histologic grade and menopausal status are useful in selecting subgroups of n1-3 breast cancer patients with good or poor prognoses.      

淋巴结阴性乳腺癌p21~(waf1)、c-erbB-2和p53蛋白表达及其临床意义

目的：探讨腋淋巴结阴性乳腺癌组织中ｐ２１ｗａｆ１、ｃ－ｅｒｂＢ－２和ｐ５３基因蛋白表达及其与临床病理参数和预后的关系。方法：应用免疫组化ＬＳＡＢ方法检测１２１例腋淋巴结阴性乳腺癌石蜡切片中ｐ２１ｗａｆ１、ｃ－ｅｒｂＢ－２和ｐ５３蛋白的表达情况;同时应用Ｋａｐｌａｎ－Ｍｅｉｅｒ法及多变量Ｃｏｘ比例风险模型,分析３种蛋白表达与预后的关系。结果：（１）ｐ２１ｗａｆ１蛋白表达率为 ４８． ８％,与病理组织学分级、ＥＲ状态有关; ｐ５３蛋白表达率为 ３６． ４％, ｃ－ｅｒｂＢ－２蛋白表达率为 ２６． ４％,与组织学分级有关;（２）ｐ２１ｗａｆ１阳性表达与 ｐ５３表达呈负相关（ Ｐ＜ ０． ０５）;（３）ｐ２１ｗａｆ１阳性组患者无瘤生存率高于阴性组（Ｐ＜０．０５）;ｃ－ｅｒｂＢ－２阳性组患者无瘤生存率明显低于阴性组（Ｐ＜０ ０１）;Ｃｏｘ模型分析显示仅有ｃ－ｅｒｂＢ－２表达对预后有显著影响。结论：乳腺癌组织ｐ２１ｗａｆ１、ｃ－ｅｒｂＢ－２表达与病理组织学分级有相关性;ｐ２１ｗａｆ１表达依赖于ｐ５３途径刺激; ｐ２１ｗａｆ１、、ｃ－ｅｒｂＢ－２表达与腋淋巴结阴性乳腺癌预后有关,且ｃ－ｅｒｂＢ－２表达是一个独立的预后指标。     

Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer

TP53 status [mutations, immunostaining, and loss of heterozygosity (LOH)], expression of c-erbB-2, bcl-2, and histological grading were correlated to the response to doxorubicin monotherapy (14 mg/m2) administered weekly to 90 patients with locally advanced breast cancer. Mutations in the TP53 gene, in particular those affecting or disrupting the loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy (P = 0.063 for all mutations and P = 0.008 for mutations affecting L2/L3, respectively). Similarly, expression of c-erbB-2 (P = 0.041), a high histological grade (P = 0.023), and lack of expression of bcl-2 (P = 0.018) all predicted chemoresistance. No statistically significant association between either p53 immunostaining or TP53 LOH and response to therapy was recorded, despite the finding that both were associated with TP53 mutation status (p53 immunostaining, P < 0.001; LOH, P = 0.021). Lack of immunostaining for p53 despite mutation of the TP53 gene was particularly seen in tumors harboring nonsense mutations or deletions/splices (7 of 10 negative for staining compared with 4 of 16 with missense mutations). TP53 mutations (total/affecting L2/L3 domains) were associated with expression of c-erbB-2 (P < 0.001 for both), high histological grade (P = 0.001 and P = 0.025), and bcl-2 negativity (P = 0.003 and P = 0.002). TP53 mutations, histological grade, and expression of bcl-2 (but not LOH or c-erbB-2 expression) all predicted for relapse-free as well as breast cancer-specific survival in univariate analysis (Ps between <0.0001 and 0.0155), but only tumor grade was found to be predictive in multivariate analysis (P = 0.01 and P = 0.0007, respectively). Our data are consistent with the hypothesis that certain TP53 mutations predict for resistance to doxorubicin in breast cancer patients. However, the observation that the majority of patients with TP53 mutations affecting or disrupting the L2/L3 domains with LOH in addition (n = 12) obtained a partial response (n = 4) or stabilization of disease (n = 5) during chemotherapy suggests redundant mechanisms to compensate for loss of p53 function. Our findings are consistent with the hypothesis that other defects may act in concert with loss of p53 function, causing resistance to doxorubicin in breast cancers.     

Relationship between c-erbB-2 and other tumor characteristics in breast cancer prognosis.

The aim of this study was to evaluate c-erbB-2 overexpression by means of a quantitative biochemical technique in 488 primary breast cancer patients with long-term follow-up (median, 10 years) and its relation to other biochemical prognostic factors (uPA, p53, and epidermal growth factor receptor) and adjuvant therapy. High levels of c-erbB-2 (>500 IU/mg protein) were associated with estrogen receptor (ER) and progesterone receptor negativity, high histoprognostic SBR grade and high levels of uPA and p53. Univariate analyses showed shorter metastasis-free survival (MFS) and overall survival (OS) in patients whose tumors overexpressed c-erbB-2 in the overall population, in subgroups defined by ER and uPA status, and in patients with positive pathological nodal status, SBR grade II, progesterone receptor, and p53-negative tumors. Patients with ER-positive, c-erbB-2-positive tumors had a shorter MFS and OS than those patients with c-erbB-2-negative tumors. No difference was observed between adjuvant-treated and untreated patients (chemotherapy and/or hormone therapy) in the c-erbB-2-negative subgroup. There was a trend toward a longer short-term MFS in c-erbB-2-positive patients treated with chemotherapy, whereas an opposite effect was observed with hormone therapy. Cox multivariate analyses showed that high levels of c-erbB-2 negatively influenced MFS in the overall population as well as in node-positive patients and in tamoxifen-treated patients, along with pN and uPA. Results for OS were comparable with those obtained for MFS. These results suggest that c-erbB-2 overexpression in breast cancer may be a better predictor of the response to tamoxifen than is ER status alone.     

bcl-2和p53的表达在膀胱癌预后判断中的意义

以免疫组织化学染色的方法,研究ｐ５３和ｂｃｌ－２蛋白在膀胱癌中表达,以及与病理临床表现之间的关系。方法：应用抗ｐ５３和ｂｃｌ－２的单克隆抗体,以标准的ＬＳＡＢ方法,共分析了１３１例患者的肿瘤标本。结果：ｐ５３染色阳性的肿瘤为８６例（６５．６％）,Ｇ３级阳性的比例（８４．１％）,明显高于Ｇ１－２级（５６．３％）,Ｐ＝０．００１２）;浸润型（Ｔ２－４）肿瘤阳性的比例（７５．８％）明显高于浅型肿瘤（５５