Comparison of the expression of P-glycoprotein, Ki-67, and P-53 to technetium-99m tetrofosmin mammoscintigraphic findings

Adjuvant and neoadjuvant chemotherapy is being used increasingly in the treatment of breast cancer patients. However, drug resistance plays an important role in the failure of chemotherapy in breast cancer. The aim of this study was to compare technetium-99m tetrofosmin (Tc-TETRO) mammoscintigraphic findings with the expression of drug resistance proteins (p-glycoprotein [Pgp], Ki-67 and mutant p53) in human breast cancer tissues. Thirty patients diagnosed with infiltrating ductal breast cancer underwent Tc-TETRO mammoscintigraphy before surgery or biopsy. Protein expression was investigated by immunohistochemical analyses on multiple nonconsecutive sections from surgery or biopsy specimens. Tumor to background (T/B) ratios calculated by Tc-TETRO mammoscintigraphic findings were correlated with protein expression determined by immunohistochemical analyses. The Tc-TETRO T/B ratios were significantly lower for tumors in 12 patients with positive Pgp expression than for those in 18 patients with negative expression (1.19 +/- 0.13 and 1.94 +/- 0.33, p value < 0.01). However, differences in Tc-TETRO T/B ratios between the patients with positive and negative Ki-67 or mutant p53 expression were not found in this study. Our data confirmed that Tc-TETRO mammoscintigraphic findings are useful for determination of the presence of Pgp expression in breast cancer patients, but no significant relations between Tc-TETRO mammoscintigraphic findings and Ki67 or mutant p53 were found.     

p53 and P-glycoprotein are often co-expressed and are associated with poor prognosis in breast cancer.

Expression of both P-glycoprotein (P-gp) and mutant p53 have recently been reported to be associated with poor prognosis of breast cancer. The expression of P-gp is associated in vitro and in vivo with cross-resistance to several anti-cancer drugs. p53 plays a regulatory role in apoptosis, and mutant p53 has been suggested to be involved in drug resistance. Interestingly, in vitro experiments have shown that mutant p53 can activate the promoter of the MDR1 gene, which encodes P-gp. We investigated whether p53 and P-gp are simultaneously expressed in primary breast cancer cells and analysed the impact of the co-expression on patients prognosis. Immunohistochemistry was used to investigate P-gp expression (JSB-1, C219) and nuclear p53 accumulation (DO-7) in 20 operable chemotherapy untreated and 30 locally advanced breast cancers undergoing neoadjuvant chemotherapy with doxorubicin and cyclophosphamide. Double immunostaining showed that P-gp expression and nuclear p53 accumulation often occur concomitantly in the same tumour cells. A correlation between p53 and P-gp expression was found in all 50 breast cancers (P = 0.003; Fisher''s exact test). P-gp expression, nuclear p53 accumulation, and co-expression of p53 and P-gp were more frequently observed in locally advanced breast cancers than in operable breast cancers (P = 0.0004, P = 0.048; P = 0.002 respectively. Fisher''s exact test). Co-expression of p53 and P-gp was the strongest prognostic factor for shorter survival by multivariate analysis (P = 0.004) in the group of locally advanced breast cancers (univariate analysis: P = 0.0007). Only 3 out of 13 samples sequentially taken before and after chemotherapy displayed a change in P-gp or p53 staining. In conclusion, nuclear p53 accumulation is often associated with P-gp expression in primary breast cancer, and simultaneous expression of p53 and P-gp is associated with shorter survival in locally advanced breast cancer patients. Co-expression of P-gp and mutant p53 belong to a series of molecular events resulting in a more aggressive phenotype, drug resistance and poor prognosis.     

局部进展期乳腺癌新辅助化疗前后生物标志物表达变化与疗效的相关性

目的：探讨局部进展期乳腺癌行新辅助化疗前后相关生物标志物的表达变化情况与化疗疗效的相关性。方法：采用免疫组化方法检测102例新辅助化疗前后局部进展期乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体－2（HER －2）、p53和增殖细胞核抗原（Ki －67）等表达,分析化疗前后生物标志物表达变化与化疗疗效的相关性。结果：ER 阴性组、PR 阴性组、Ki －67高表达组的新辅助化疗有效率分别为50．0％、49．1％、51．4％,高于 ER 阳性组26．0％、PR 阳性组25．5％、Ki －67低表达组9．4％（P ＜0．05）。Logistic 多因素回归分析显示,ER、Ki －67的表达水平是评估化疗疗效的独立因素（P ＜0．05）。Luminal 型乳腺癌总生存期高于 non －Luminal 型（Long －rank 检验,P ＜0．05）。结论：ER、Ki －67、分子亚型可作为局部进展期乳腺癌新辅助化疗疗效判断的重要预测指标。     

Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours

This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT). Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP. All patients received platinum-based chemotherapy after orchidectomy. Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome. Strong and intermediate expressions of the different MDR-related proteins were: 27 and 41% (Pgp), 54 and 37% (MRP1), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high beta-hCG levels (P=0.003) and stage IV tumours (P=0.029). No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival. In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables. Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome.     

Expression of ras p21, p53 and c-erbB-2 in advanced breast cancer and response to first line hormonal therapy.

Several oncogenes and tumour-suppressor genes have been identified that may have an important role in the development of human breast carcinoma. Furthermore, some of these gene alterations may be linked to the development of invasion and subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumours with rapid cellular proliferation, but the evidence that they are of prognostic importance in patients with breast cancer is conflicting. This study explores the relationship between expression of these oncoproteins and clinical outcome in 92 patients with either locally advanced or metastatic breast cancer treated with primary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hormone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured according to UICC criteria after 6 months of treatment and all patients were followed for time to progression and overall survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progression and overall survival. However, no statistically significant relationship existed between expression of ras p21, p53 or c-erbB-2 and response to treatment, time to progression or overall survival. We conclude that staining for these three oncoproteins has no role in therapeutic decision-making in patients with advanced breast cancer. The negative finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variations in growth characteristics of advanced breast cancer may be influenced by other factors.     

Expression of MRP1, LRP and Pgp in breast carcinoma patients treated with preoperative chemotherapy

Our purpose was to determine the expression of the drug resistance factors multidrug resistance protein (MRP1), lung resistance protein (LRP) and P-glycoprotein (Pgp) in breast carcinoma patients treated with preoperative chemotherapy. We have studied the expression of these proteins in breast carcinomas by immunohistochemistry both prior (n = 80) and after (n = 68) preoperative chemotherapy and compared their expression with response to preoperative chemotherapy. In paired samples prior and after chemotherapy expression of drug resistance factors was significantly lower in prechemotherapy samples as compared with postchemotherapy specimens. This was observed for MRP1 (62% vs. 88%, P < 0.001), LRP (65% vs. 97%, P < 0.001) and Pgp (55% vs. 100%, P < 0.001). Prechemotherapy expression of MRP1 was more frequently observed in patients with distant metastases than in those without (50% vs. 8%, P = 0.02). No associations were observed between LRP expression and clinical parameters. Pgp expression was more frequently detected in lobular carcinomas than in ductal carcinomas (93% vs. 46%, P = 0.001) and in patients with positive lymph nodes than in patients with negative lymph nodes (65% vs. 31%, P = 0.008) but was independent of other clinical parameters. No significant associations were found between the prechemotherapy or postchemotherapy expression of either of these three proteins and response to preoperative chemotherapy. However, prechemotherapy MRP1 expression was significantly associated with shorter progression-free survival of the patients (P = 0.02), whereas no such associations were observed for either LRP or Pgp. In conclusion, preoperative chemotherapy increases the expression of MRP1, LRP and Pgp. Response to chemotherapy is not associated with pre- or postchemotherapy expression levels of these drug resistance proteins but time to progression may be influenced by prechemotherapy MRP1 expression.     

Evaluation of Ki67, p53 and angiogenesis in patients enrolled in a randomized study of neoadjuvant chemotherapy with or without cystectomy: a Southwest Oncology Group Study

In this prospective biomarker study, we evaluated the prognostic significance of Ki67, p53 and angiogenesis in patients with locally advanced bladder cancer. The patients were volunteers from a Southwest Oncology Group trial of locally advanced bladder cancer who were randomized to treatment with neoadjuvant chemotherapy plus cystectomy or cystectomy alone. Tissue specimens were obtained prior to neoadjuvant chemotherapy from 42 patients randomized to receive the combination-treatment arm and 52 randomized to cystectomy alone. The statistical power of the study was quite limited by the small sample size. The biomarkers were assayed by immunohistochemistry. Angiogenesis was determined using anti-CD34 immunostaining. Patients whose tumors had increased Ki67 expression had better progression-free survival that was marginally significant, p=0.063. The median survival in those with higher Ki67 expression was 73 months, and in those with lower expression was 38 months. However, this did not achieve statistical significance, p=0.25. There was a suggestion of worse survival among patients whose tumors exhibited altered p53 staining [hazard ratio (HR) = 1.48; p=0.15], but there was no difference in progression-free survival (HR=1.02; p=0.93). The enumeration of tumor microvessels did not provide prognostic information.     

乳腺癌复发及转移灶分子生物学指标的变化

目的:探讨分析复发转移性乳腺癌患者中原发灶和复发转移灶的肿瘤组织ER、PR、Her-2、Ki67及p53免疫组化表达变化规律及特征.方法:选取我院66例复发转移性乳腺癌患者,分别分析原发灶和复发灶、原发灶和转移灶的肿瘤组织ER、PR、Her-2、Ki67及p53免疫组化表达情况.结果:在原位复发性乳腺癌复发前后表达变化差异经x2检验后提示ER:P =0.615;PR:P =0.497;Her-2:P =0.562;Ki67:P =0.001;p53:P =0.394,仅Ki67表达在原发灶和复发灶之间的变化有统计学意义(P＜0.05).在转移性乳腺癌复发前后表达变化差异经x2检验后提示ER:P=0.711;PR:P =0.538;Her-2:P =0.664;Ki67:P=0.001;p53:P=0.447,仅Ki67表达在原发灶和转移灶之间的变化有统计学意义(P＜0.05).同时得出,复发性和转移性乳腺癌组织中由阳性转阴性比率均高于由阴性转阳性.ER、PR、Her-2、p53在复发性和转移性乳腺癌复发前后表达差异无统计学意义(P＞0.05).结论:复发转移性乳腺癌组织Ki67的变化主要为表达呈衰减趋势(复发转移前的高表达转为复发转移后的低表达),仅Ki67表达在原发灶和转移灶之间的变化有统计学意义,表明Ki67是一项敏感指标,对预测化疗效果有重要的指导意义.ER、PR、Her-2、p53的改变无统计学意义,但是也存在部分病例发生变化,应需对该类病例讨论或修订其后续治疗方案.     

新辅助化疗对乳腺癌患者Ki-67、ER、Her-2和p53的影响及意义

目的探讨新辅助化疗(neoadjuvant chemotherapy,NAC)对乳腺癌Ki-67、ER、Her-2和p53的影响,同时研究上述指标对NAC疗效的预测作用。方法通过免疫组化S-P法检测化疗前经空芯针穿刺标本和化疗后手术切除的30例乳腺癌组织标本的Ki-67、ER、Her-2和p53的表达情况。具体化疗方案为:CAF(CTX600mg/m2,ADM50mg/m2,5-Fu500mg/m2)和TA(艾素75mg/m2,THP30mg/m2),每3周为1疗程,用药2～3个疗程。化疗疗效通过临床体检、乳腺彩超检测及术后病理分析综合判断。结果 30例患者中70%(21/30)获PR,30%(9/30)获SD,全组无恶化病例,总有效率为70%(21/30)。通过对化疗前后各指标的比较发现:NAC能降低Ki67的表达(P<0.01)。化疗前后ER、Her-2和p53表达无明显变化(P>0.05)。Ki67高表达(≥20%)、ER阴性表达及突变型p53阳性表达患者的化疗疗效更明显(P<0.05)。结论 NAC能显著降低乳腺癌组织Ki-67的表达,而对ER、Her-2和p53表达均无显著影响,Ki-67高表达(≥20%)、ER阴性及突变型p53阳性表达的患者对化疗更敏感、短期疗效更显著。     

P7 antigen expression in human breast cancer.

PURPOSE: Evaluate p7 expression in human breast cancer and determine whether chemotherapy and radiation therapy effect a change in p7 expression. EXPERIMENTAL DESIGN: Using a p7-specific monoclonal antibody with immunohistochemistry and Western immunoblot analyses to assess p7 expression in archival, frozen breast cancer specimens both before and after therapy. RESULTS: A novel 7 kDa protein (p7), originally identified in multidrug-resistant ovarian and breast cancer cell lines, was found to be expressed in 21 of 64 (32%) primary, unselected human breast cancer specimens by immunohistochemistry with the use of a p7-specific monoclonal antibody, 1D7. P7 was observed in malignant cells but not in other types of cells in the breast tissue. Western blot analysis confirmed the 7 kDa polypeptide in p7-positive breast carcinomas identified by immunohistochemistry. P7 expression was significantly associated with breast cancers having distant metastasis and/or local recurrence (P = 0.027, Fisher's exact test). In addition, p7 expression was significantly increased in post-treatment breast cancer biopsy specimens compared with pretreatment breast cancer biopsy specimens in patients with locally advanced breast cancer after 5-fluorouracil chemotherapy and radiation therapy [2 of 15 (13%) pretreatment breast cancers compared with 8 of 15 (53%) post-treatment breast cancers; P = 0.016, McNemar's test]. CONCLUSIONS: These findings demonstrate that expression of p7 is associated with malignant tumor cells in primary breast cancers, especially those showing recurrent or metastatic disease. Its specific association with the malignant phenotype suggests it may have potential for novel target-based therapies. The markedly increased expression in patients with locally advanced disease after neoadjuvant therapy suggests a role for p7 in treatment outcome.     

新辅助化疗对乳腺癌p170、Ki67、p53的影响

目的了解乳腺癌对新辅助化疗的反应性以及与相关生物学标志物的关系并探讨其机制。方法37例新诊断为T2-3N0-1M0期的乳腺癌患者术前给予CTF(cyclophosphamide,环磷酰胺;pirarubicin,吡喃阿霉素;5-fluorouracil,氟尿嘧啶)方案化疗2个周期,在化疗前、后分别观察癌组织中p170、Ki67、p53的表达情况及与化疗疗效的关系。结果本组患者经2个周期化疗后,部分缓解和轻度缓解分别为27.0%和54.1%;化疗前p170的表达率为18.9%,经化疗后表达率升高至43.2%(P<0.05);Ki67在化疗前、后表达率分别为32.4%和10.8%(P<0.05);p53无明显变化。结论CTF方案新辅助化疗有一定疗效,经化疗后反映残留癌细胞多药耐药的p170表达呈增加趋势,而反映细胞增殖的Ki67表达呈下降趋势。     

Higher Ki67 Expression is Associates With Unfavorable Prognostic Factors and Shorter Survival in Breast Cancer

Background: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of thisstudy was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2and hormone receptor expression status in breast cancers. Materials and Methods: Clinical and pathologicalfeatures of the patients with breast cancer were retreived from the hospital records. Results: In this study, 163patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20%and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001),estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymphnode positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free andoverall survival compared to those of higher Ki67 levels. Conclusions: High Ki67 expression is associated withER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The levelof Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.     

P-Glycoprotein and multidrug resistance-related protein expressions in relation to technetium-99m methoxyisobutylisonitrile scintimammography findings

The purpose of this study was to retrospectively study 48 patients with infiltrating ductal breast cancer to evaluate the relationship between the degree of accumulation of technetium-99m methoxyisobutylisonitrile (Tc-MIBI) and P-glycoprotein (Pgp) or multidrug resistance-related protein (MRP) expression in breast cancer tissues. Before surgery or biopsy, all 48 patients underwent scintimammography started 10 min after the injection of Tc-MIBI. Tumor:background (T:B) ratios were calculated from the Tc-MIBI scintimammography. Immunohistochemical analysis was performed on the pathological specimens of the 48 breast tumors to determine Pgp and MRP expression. According to the results of immunohistochemical analysis, the 48 breast cancers were separated into four groups: (a) group 1, 12 cancers with both positive Pgp expression and positive MRP expression; (b) group 2, 12 cancers with positive Pgp expression and negative MRP expression; (c) group 3, 12 cancers with negative Pgp expression and positive MRP expression; and (d) group 4, 12 cancers with both negative Pgp expression and negative MRP expression. Among the four groups, the T:B ratio was lowest in group 1 (1.13+/-0.10) and highest in group 4 (2.17+/-0.14), respectively (P < 0.05). The T:B ratios of groups 2 (1.30+/-0.25) and 3 (1.32+/-0.26) were between those of groups 1 and 4. Our data confirmed that Tc-MIBI scintimammography is useful for determining Pgp and MRP expression in patients with breast cancers.     

Prognostic and predictive value of changes in tumour cell proliferation in locally advanced breast cancer primarily treated with doxorubicin

We previously reported that high tumour cell proliferation evaluated by Ki-67 expression, high mitotic frequency and high histological grade were associated with resistance to primary doxorubicin monotherapy in locally advanced breast cancer harbouring wild-type (wt) TP53. The aim of our present study was to evaluate the predictive and prognostic impact of proliferation parameters assessed in tumour tissue obtained after chemotherapy, and alterations induced in tumour cell proliferation. While we found a significant reduction in Ki-67 expression and mitotic frequency in tumours with wtTP53 (p=0.001 and p=0.008, respectively), no significant change was recorded in tumours expressing mutant TP53. For histological grade there was no significant change in either group. There was a direct correlation between pre- and post-treatment values for Ki-67 and mitotic frequency in tumours harbouring wtTP53 (p=0.0001 for both), but no correlation in tumours harbouring mutated TP53. High post-treatment Ki-67 expression and mitotic frequency were found to predict doxorubicin resistance only in patients with wtTP53 (p=0.04 and p=0.03, respectively). The prognostic importance of proliferation markers and histological grade was found to be similar whether they were determined in the pre- or post-treatment samples (Ki-67; pre: p=0.02; post: p=0.03; mitotic frequency; p=0.002 and p=0.01, respectively; histological grade; p=0.0001 and p=0.002, respectively). While the reduction in mitotic frequency was associated with improved survival (p=0.03), no significant associations between changes in other parameters and outcome were recorded.     

子宫颈癌有无HPV感染和PCNA，Ki-67，p53表达与临床病理变化相关性分析

目的：探讨子宫颈癌组织HPV感染与PCNA、Ki-67、p53的表达和临床病理资料的相关性。方法76例子宫颈癌组织,来自2012年3月-2012年8月哈尔滨医科大学附属肿瘤医院,所有的病例均有完整的临床资料。采用组织芯片技术、免疫组织化学技术将检测的HPV、PCNA、Ki-67和p53与各项临床病理指标进行比较分析。结果 HPV在子宫颈癌组织中的表达率为68．4％,与淋巴结转移有关（P＜0．01）;PCNA在90．1％子宫颈癌组织中的表达,在35岁以下的妇女子宫颈癌组织中100％表达,与术前是否经过化疗有关（P＜0．01）。 Ki-67表达率为48．9％,p53表达率为38．2％,Ki-67和p53的表达均与淋巴结转移和术前是否化疗有相关性（ P＜0．05或P＜0．01）。结论在子宫颈癌组织中HPV感染、Ki-67和p53的表达与淋巴结转移有相关性。 HPV促进子宫颈上皮细胞的增殖,致抑癌基因p53功能失活,可促进子宫颈癌的侵袭和转移。子宫颈癌术前经过化疗后再行手术,可降低p53、PCNA和Ki-67的表达。     

多基因蛋白表达判断早期非小细胞肺癌术后化疗疗效的价值

目的 探讨多基因蛋白表达联合检查判断早期非小细胞肺癌(NSCLC)术后化疗疗效的价值.方法 采用组织芯片与免疫组织化学技术(二步法)相结合的方法,义寸86例NSCLC组织中caspase-3、Fas、bax、bcl-2,survivin,PCNA,Ki67,MGMT,p53,063,p73,p16、p27,VEGF、nm23、P-gP、MRP、LRP、GST-π、TopoⅡ、c-myc、cyclin D1、Her-2、Cox-2、Ku70、Ku80、DNA-PKcs、ERCCI、MSH2和BCRP等30种化疗相关蛋白进行检测,并分析其表达与早期NSCLC术后化疗疗效的关糸.结果 30种化疗相关蛋白在肺癌组织中的表达阳性率在27 9%～91.9%间.经过单因素分析,与早期NSCLC术后化疗效果密切相关的基因有8个,即survivin、P-gp、LRP、Ki67、p53、ERCC1高表达和bax、VEGF低表达的NSCLC患者术后化疗效果差.通过Logistic回归分析显示,ERCC1、survivin、bax和VEGF等4个基因联合检测对早期NSCLC术后化疗疗效的预测特异度达96.5%.结论 ERCC1、survivin、bax和VEGF是一组判断早期NSCLC术后辅助化疗效果、指导早期NSCLC的术后治疗的分子指标.     

Potential predictive factors for response to weekly paclitaxel treatment in patients with metastatic breast cancer

The authors compare results obtained from weekly paclitaxel treatment in advanced breast cancer patients with biological and clinical prognostic factors. Expression of c-erbB-2, Ki-67, p53 and hormone receptors (HR) was examined by immunohistochemistry in samples of breast tissue from 30 patients. Univariate analysis showed that Ki-67 positivity and low performance status (PS) were associated with poor outcome (P <0.05). We observed that expression of p53 and c-erbB-2 did not have any negative effect on response to chemotherapy and survival. HR-negative patients had better response and slightly statistically significant overall survival (OS) rates compared to HR-positive patients (P >0.05). In a multivariate analysis low PS was the only significant predictor of shorter survival (P <0.05). In conclusion, while the expression of p53 and c-erbB-2 did not have any effect on treatment results, negative Ki-67 expression and negative HR status were associated with better OS in this patient population. PS was the only significant predictor for OS.     

p53, HER2 and tumor cell apoptosis correlate with clinical outcome after neoadjuvant bevacizumab plus chemotherapy in breast cancer

Bevacizumab, an antibody to vascular endothelial growth factor (VEGF), has been incorporated into chemotherapy regimens in the treatment of several cancer types including breast cancer. The aim of this study was to identify tumor and angiogenic factors that potentially associate with outcome. In a pilot trial, 21 patients with inflammatory breast cancer and locally advanced breast cancer received bevacizumab plus doxorubicin-docetaxel chemotherapy before surgery. Baseline p53, HER2, tumor apoptosis, Ki67, estrogen receptor (ER), VEGF-A, serum VEGF (sVEGF), VEGFR2-Y951 and microvessel density (MVD) were prospectively designed and determined by immunohistochemistry and enzyme-linked immunosorbent assay. Hazard ratios (HR) and 95% confidence intervals for survival and progression-free survival (PFS) were estimated using Cox proportional hazards analyses. With a median follow-up of 65.9 months, patients with low apoptosis or p53-negative tumors had significantly longer survival than those with high apoptosis or p53-positive tumors (median 61.5 vs. 20.2 months; HR 0.22; p=0.011 for apoptosis and median 59.6 vs. 24.2 months; HR 0.27; p=0.016 for p53). Low Ki67 versus high Ki67 exhibited a trend towards association with survival (median 57.1 vs. 17.3 months, HR 0.34, p=0.07). Patients with HER2-negative tumors had significantly longer PFS than those with HER2-positive tumors (median 31.2 vs. 9.4 months; HR 0.23; p=0.03). ER, VEGF-A, sVEGF, VEGFR2-Y951 and MVD were not significantly associated with outcome. Our data suggest that baseline p53, apoptosis and HER2 are each significantly associated with outcome in patients who received bevacizumab plus chemotherapy.     

新辅助化疗对乳腺癌患者survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的影响及其疗效预测意义

目的探讨新辅助化疗对乳腺癌survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的影响,同时研究这些指标对新辅助化疗的疗效预测作用。方法通过免疫组织化学S-P法检测和HE染色对化疗前空芯针穿刺标本和化疗后手术切除的30例乳腺癌组织的survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的表达情况。化疗方案为CAF（CTX 600 mg/m^2,THP 50 mg/m2,5-FU500 mg/m^2）和TA（艾素75 mg/m^2,THP 30 mg/m^2）,每3周1疗程,用药2～3个疗程。化疗疗效通过采用临床体检、乳腺彩超检测及术后病理分析综合判断。结果 30例患者中70.0%（21/30）获PR,SD为30.0%（9/30）,全组无恶化病例,总有效率为70.0%（21/30）。通过对化疗前后的指标比较发现：新辅助化疗能降低Ki-67的表达（P〈0.01）和肿瘤分级（P〈0.05）。化疗前后survivin、ER、C-erbB-2和p53表达无明显变化（P〉0.05）。Ki-67高表达（≥20%）、肿瘤分级高的患者和Ki-67低表达（〈20%）、肿瘤分级较低的患者相比,化疗疗效更明显（P〈0.05）。结论新辅助化疗能显著降低乳腺癌组织Ki-67的表达和肿瘤分级,而对survivin、ER、C-erbB-2和p53表达均无显著影响,Ki-67高表达（≥20%）、肿瘤分级高的患者对化疗更敏感、短期疗效更显著。