Ki67、Her2及EGFR在乳腺癌组织中表达的临床意义

目的 探讨ki67、her2及EGFR在乳腺癌组织中表达的临床意义.方法 对采集的乳腺癌组织标本采用免疫组织化学实验(SP法)进行检测,分析ki67、her2及EGFR在乳腺癌组织、癌旁组织中的表达情况,并分析乳腺癌组织中ki67、her2及EGFR表达和临床病理特征的关系.结果 ki67阳性表达于细胞核上,her2阳性表达于细胞膜上,EGFR阳性表达于细胞膜及细胞质内,阳性细胞均呈现棕黄色或者棕褐色颗粒状.乳腺癌组织中ki67、her2及EGFR阳性表达率分别为72.02%、26.79%及28.57%,均明显高于癌旁组织的阳性表达率,差异均具有统计学意义(P<0.05).乳腺癌组织中ki67阳性表达和年龄、组织学分级、淋巴结转移有关,差异均具有统计学意义(P<0.05),年龄<45岁、组织学分级越高、有淋巴结转移的乳腺癌患者其ki67阳性表达率越高;乳腺癌组织中her2、EGFR阳性表达均和组织学分级、淋巴结转移有关,差异均具有统计学意义(P<0.05),组织学分级越高、有淋巴结转移的乳腺癌患者,其her2、EGFR阳性表达率越高.结论 ki67、her2及EGFR在乳腺癌的发生、发展过程中发挥了重要作用,有望成为重要的乳腺癌生物学行为及预后评估指标.     

Caspase-3及p53预测口腔鳞癌动脉灌注新辅助化疗敏感性的研究

目的：探讨口腔鳞癌在行区域性动脉灌注DF方案新辅助化疗时,Caspase-3及p53预测化疗敏感性的价值。方法：选取76例经区域性动脉灌注DF方案行新辅助化疗及手术的口腔癌患者,检测其癌组织中Caspase-3及p53的表达及化疗后的病理学变化,分析Caspase-3及p53不同表达者与化疗疗效间的关系。结果：1)Caspase-3表达阳性者有效率显著高于表达阴性者(P<0.05),而p53表达阳性者有效率显著低于表达阴性者(P<0.05);2)Caspase-3表达阳性同时p53表达阴性者化疗有效率为92.59%,显著高于其他表达类型(P<0.05);而Caspase-3表达阴性同时p53表达阳性者,化疗有效率为27.78%,显著低于其他表达类型(P<0.05)。结论：在预测口腔鳞癌行动脉灌注DF方案行新辅助化疗时,Caspase-3和p53均可作为敏感性的分子标记物,而且两项指标的表达水平联合预测显著高于单项指标预测。     

p53,Ki-67及E-钙黏蛋白在三阴性乳腺癌中的表达及预后

目的:探讨p53,Ki-67及E-钙黏蛋白(E-cadherin)在三阴性乳腺癌(triple negative breast cancer,TNBC)组织中的表达及预后的关系.方法:采用免疫组织化学法检测52例TNBC和52例非三阴性乳腺癌(non-triple-negative breast cancer,NTNBC)组织中p53,Ki-67及E-cadherin表达情况,观察3个指标与TNBC患者临床病理学特征及预后的关系.结果:TNBC组织中p53,Ki-67及E-cadherin的阳性表达率分别为67.3％,80.8％,26.9％;而在NTNBC组织中为44.2％,61.5％,48.1％(均P＜0.05).在TNBC组织中,p53表达阳性与肿瘤大小、TNM分期及组织学分级有关(均P＜0.05);Ki-67表达阳性与TNM分期、淋巴结转移有关(均P＜0.05);E-cadherin表达阳性与肿瘤大小、TNM分期、淋巴结转移有关(均P＜0.05).在TNBC患者中,p53,Ki-67及E-cadherin表达阳性者与阴性者总体生存率(overall survival,OS)的差异均有统计学意义(P＜0.05).Cox回归分析多因素显示:淋巴结转移、p53、Ki-67及E-cadherin表达是影响TNBC患者总体生存率的独立预后因素(均P＜0.05).结论:TNBC组织中,p53、Ki-67高表达,其表达阳性者预后差,E-cadherin低表达,其表达阳性者预后良好.联合检测p53、Ki-67及E-cadherin表达可为TNBC患者的治疗提供新靶点.     

TIP30与p53、ki67在肺癌中表达的相关性及意义

目的 分析TIP30与p53、细胞核相关抗原(ki67)在肺癌中表达的相关性及意义.方法 回顾性选取2017年1月至2019年4月我院收治的肺癌患者217例,均采用组织芯片(TC)结合免疫组化(IHC)技术检测TIP30、p53、ki67在肺癌组织中的表达、相关性及其与临床病理特征、预后的关系.结果 217例患者,TIP30低表达79例(36.41％)、高表达138例(63.59％),p53阳性表达111例(51.15％)、阴性表达106例(48.85％),ki67低表达102例(47.00％)、高表达115例(53.00％);在肺癌中,TIP30低表达率与p53阳性表达率、ki67高表达率呈正相关(r=0.578、0.499,P<0.05);TIP30表达与性别、年龄、肿瘤大小、临床分期无关(P>0.05),与肿瘤类型、分化程度、是否有淋巴结转移有关(P<0.05),p53表达与肿瘤类型、淋巴结转移有关(P<0.05),与其他病理参数无关(P>0.05),ki67表达与分化程度、淋巴结转移有关(P<0.05),与其他病理参数无关(P>0.05);Kaplan-Meier生存曲线显示,TIP30高表达组2年无瘤生存率87.52％高于TIP30低表达组21.39％(P<0.05),p53阳性表达组2年无瘤生存率36.72％低于阴性表达组76.48％(P<0.05),ki67高表达组2年无瘤生存率44.72％略低于低表达组56.56％,但差异无统计学意义(P>0.05).结论 TIP30低表达及p53阳性表达、ki67高表达均与肺癌有相关性,TIP30表达越低,p53、ki67表达越高,均与病理参数有一定关联.     

Luminal B型乳腺癌TEC新辅助化疗疗效及影响因素分析

目的 探讨Luminal B型乳腺癌TEC新辅助化疗的疗效及其影响因素。方法 对2016年1月~2018年6月于我院行4次TEC方案新辅助化疗的81例Luminal B型乳腺癌患者的临床病历资料进行回顾性分析,分析临床病理特征及相关指标的改变与疗效的相关性。结果 4周期新辅助化疗pCR率为4.94%,临床疗效与临床分期存在统计学意义（P＜0.05）,是否获得pCR与年龄、BMI、绝经状态、原发肿瘤大小、肿瘤部位、确诊时淋巴结状态、PR、P53、Ki67均无统计学意义（P＞0.05）。而除去4例获得pCR的患者,剩余77例乳腺癌患者新辅助化疗前后ER、PR的表达状态、Ki67指数的差异具有统计学意义（P＜0.05）。结论 临床分期晚的患者新辅助化疗疗效相对较差,Ki67可能是乳腺癌新辅助化疗疗效的预测指标。     

cyclin E、pl6ink4、ki67在宫颈脱落细胞中的表达及其与HPV16／18感染的相关性

目的研究cyclin E、p16ink4、ki67在宫颈脱落细胞中的表达水平及其与HPV16/18感染的相关性,探讨其对宫颈癌高危人群筛查的意义.方法采用免疫组织化学方法对78例官颈脱落细胞标本进行cyclin E、p16ink4、ki67检测,同时应用多重引物PCR技术检测HPV16/18.结果cyclin E、p16ink4、ki67在宫颈癌细胞中的表达水平均较鳞状上皮非典型增生(ASCUS)差异有统计学意义(P＜0.005);各级宫颈癌细胞中HPV16的阳性率均较ASCUS差异有统计学意义(x2=25.27,P＜0.005),且随着宫颈上皮细胞损伤程度加重阳性率升高,差异也有统计学意义(P＜0.01).p16ink4和ki67在宫颈癌细胞中的表达水平与HPV16高度相关(rs=1.0,P＜0.05);而cyclin E的表达与HPV16相关性较小(rs=0.4,P＜0.05).HPV18阳性例数较少,在各项分析中差异均无统计学意义(x2=3.68,P＞0.05).结论官颈癌细胞中cyclin E、p16ink4及ki67的高度表达与HPV16感染有关;它们均可能作为有价值的诊断指标应用于宫颈癌高危人群筛查,且cyclin E对宫颈癌的早期诊断意义更大.     

ki67在三阴性乳腺癌中的临床病理意义

目的 通过检测三阴性乳腺癌中细胞增殖抗原ki67的表达情况,分析其与临床病理特征及预后的关系,明确ki67是否可以作为判断三阴性乳腺癌的预后指标.方法 应用免疫组织化学方法检测ki67在三阴性乳腺癌组织中的表达,分析ki67表达与三阴性乳腺癌患者临床病理特征的相关性及与预后的关系.结果 ki67在三阴性乳腺癌组织中的表达与肿瘤大小、TNM分期、组织学分级和淋巴结转移有关(x2=10.536、16.824、11.020、7.180、P＜0.05).单因素生存分析结果显示:肿瘤大小、临床分期、组织学分级、淋巴结转移和ki67与患者总生存均相关(OR=4.211、3.800、0.288、3.502、2.612,P＜0.05).Cox多因素生存分析显示,淋巴结转移与总生存有一定的相关性(OR=2.768,P＜0.05).结论 ki67表达与三阴性乳腺癌中肿瘤大小、TNM分期、组织学分级和淋巴结转移有关,对于三阴性乳腺癌的预后评估具有一定的价值,可作为评价三阴性乳腺癌预后的候选指标.通过Cox多因素生存分析,淋巴结转移可作为与总生存相关的独立预后因素.     

Ki-67和PCNA表达与乳腺癌及乳腺癌化疗敏感性的关系

目的:探讨分析乳腺癌组织中核增殖相关抗原(Ki-67)及增殖细胞核抗原(PCNA)表达变化与乳腺癌的关系及其对乳腺癌化疗敏感性的关系,为临床乳腺癌的有效化疗提供理论依据。方法:实验对象取自于近年来我院收治的、经临床检查确诊为乳腺癌患者84例,利用免疫组化方法分别测量其乳腺癌组织中的Ki-67及PCNA的含量,比较不同Ki-67及PCNA表达水平的患者接受化疗疗效的差异。结果:Ki-67阳性例数为52例,PCNA阳性例数为62例。Ki-67阳性率与患者淋巴结转移及肿瘤分型分期呈正相关,差异有统计学意义,P<0.05。而PCNA阳性率与肿瘤淋巴结转移成正相关,P<0.05,与肿瘤临床分型分期无关,P>0.05。Ki-67+总有效率为80.8%明显高于Ki-67-的56.2%,P<0.05。PCNA-有效率为72.7%明显高于PCNA+的45.2%,P<0.05。结论:Ki-67及PCNA表达与乳腺癌临床资料及其化疗敏感性密切相关,可以作为预测化疗疗效的指标。     

乳腺癌中EZH2和p53蛋白表达及其临床意义

目的探讨乳腺癌组织中EZH2和p53蛋白的表达,分析二者表达与乳腺癌临床病理特征及预后的关系。方法采用免疫组化Max Vision法检测50例乳腺腺病、92例乳腺浸润性小叶癌(invasive lobular carcinoma,ILC)和200例乳腺浸润性导管癌(invasive ductal carcinoma,IDC)组织中EZH2和p53的表达及二者的相关性。结果 EZH2在ILC与IDC中的表达差异无统计学意义(P>0.016 7),其在乳腺腺病组织中的表达低于ILC与IDC组织(P<0.016 7)。EZH2表达与患者年龄、绝经状态、组织学类型、p TNM分期等均无关,与肿瘤直径、淋巴结转移、分子亚型、生存状态及p53表达有关(P<0.05)。p53蛋白在乳腺腺病和ILC组织中的表达差异无统计学意义(P>0.016 7),其在IDC组织中的表达高于ILC与乳腺腺病组织(P<0.0167)。p53表达与患者年龄、绝经状态、肿瘤直径、淋巴结转移等无关,与组织学类型、p TNM分期、分子亚型及生存状态相关(P<0.05)。Kaplan-Meier生存分析示:EZH2及p53蛋白表达与乳腺癌患者无病生存率及总生存率具有相关性(P<0.05);COX多因素回归分析显示:EZH2及p53蛋白表达是乳腺癌患者生存的独立影响因素。结论在乳腺腺病、ILC及IDC组织中,EZH2及p53蛋白表达逐渐升高,二者表达呈正相关。EZH2及p53蛋白表达水平对评价乳腺癌患者预后有重要价值。     

Beclin1、EGFR、cyclinD1在新辅助化疗宫颈癌组织中的表达及临床意义

目的研究自噬标记蛋白Beclin1、表皮生长因子受体(EGFR)、细胞周期蛋白D1(cyclinD1)在新辅助化疗宫颈癌组织中的表达及意义。方法收集2015年3月至2018年2月医院收治的局部晚期宫颈癌80例,术前接受卡铂联合紫杉醇新辅助化疗3个周期,新辅助化疗前后均留取宫颈癌组织标本,并选取行子宫切除的20例患者的正常宫颈上皮组织作为对照组,免疫组化法测定新辅助化疗前后宫颈癌组织Beclin1、EGFR、cyclinD1表达的变化,与正常宫颈上皮组织进行对照,比较不同疗效宫颈癌患者组织Beclin1、EGFR、cyclinD1表达及临床病理资料的差异,多因素Logistic回归分析法筛选宫颈癌新辅助化疗疗效影响因素。结果宫颈癌化疗前后组织Beclin1阳性率低于对照组,EGFR、cyclinD1阳性率高于对照组(P<0.05),化疗后癌组织Beclin1阳性率高于化疗前,EGFR、cyclinD1阳性率低于化疗前(P<0.05);80例患者新辅助化疗3个周期有效55例(68.75%),无效25例(31.25%),有效组癌组织Beclin1阳性率高于无效组,EGFR、cyclinD1阳性率低于无效组(P<0.05);无效组临床分期为Ⅱa1~b1期、组织分化程度为低中分化、伴淋巴结转移所占比例高于有效组(P<0.05);Beclin1、EGFR、cyclinD1、组织分化程度、淋巴结转移均为宫颈癌新辅助化疗疗效影响因素(P<0.05)。结论宫颈癌癌组织EGFR、cyclinD1呈异常高表达,Beclin1呈低表达,新辅助化疗可降低EGFR、cyclinD1阳性率,提升Beclin1阳性率,促成宫颈癌自噬网建立,诱导癌细胞凋亡;Beclin1、EGFR、cyclinD1、组织分化程度、淋巴结转移均为影响宫颈癌新辅助化疗效果的因子。     

Effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese breast cancer patients: A retrospective study of 525 patients

This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese female breast cancer patients. The expression of estrogen receptor (ER), progesterone receptor (PR) and Ki67 among 525 neoadjuvant chemotherapy cases was studied by immunohistochemistry. Differences between specimens made through preoperative core needle biopsy and excised tissue biopsy were observed. The positive rates of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy were 65.3% and 63.2%, 51.0% and 42.6%, 65.6% and 43.4%, respectively. The expression of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy had no statistically significant difference. However, after neoadjuvant chemotherapy, the discordance rates of ER, PR and Ki67 were 15.2% (79/521), 26.9% (140/520) and 44.8% (225/502), respectively. The ER, PR and Ki67 status changed from positive to negative in 7.5% (39/521), 13.3% (69/520) and 21.1% (106/502) of the patients, whereas ER, PR and Ki67 status changed from negative to positive in 7.7% (40/521), 13.6% (71/520) and 23.7% (119/502) of the patients, respectively. These results showed that the status of some biomarkers changes after neoadjuvant chemotherapy and biomarker status needs to be reexamined to optimize adjuvant systemic therapy and better prognosis assessment.     

Dynamic Contrast-Enhanced MR Imaging in a Phase Ⅱ Study on Neoadjuvant Chemotherapy Combining Rh-Endostatin with Docetaxel and Epirubicin for Locally Advanced Breast Cancer

Background: Anti-angiogenesis is a promising therapeutic strategy for locally advanced breast cancer. We performed this phase II trial to evaluate the anti-angiogenesis and anti-tumor effect of rh-endostatin combined with docetaxel and epirubicin in patients with locally advanced breast cancer by dynamic contrast-enhanced magnetic resonance imaging in 70 previously untreated locally advanced breast cancer patients.Methods: The study population was randomly assigned to neoadjuvant chemotherapy with docetaxel and epirubicin (neoadjuvant chemotherapy group) or neoadjuvant chemotherapy combining rh-endostatin with docetaxel and epirubicin (neoadjuvant chemotherapy+rh-endostatin group). The anti-angiogenic and anti-tumor effects of both regimens were evaluated by serial dynamic contrast-enhanced magnetic resonance imaging and microvessel density measurements after final surgery.Results: The results suggested a higher clinical objective response (90.9% vs. 67.7%, P = 0.021) and greater reductions in tumor size (67.2% vs. 55.9%, P = 0.000), Ki-67 proliferation index (32.79% vs. 12.47%, P = 0.000), tumor signal enhanced ratio (64% vs. 48%, P = 0.018), and K^trans (67% vs. 39%, P = 0.026) in neoadjuvant chemotherapy+rh-endostatin group than those in neoadjuvant chemotherapy group. In addition, the microvessel density value in the neoadjuvant chemotherapy+rh-endostatin group was significantly lower than in the neoadjuvant chemotherapy group (18.67 ± 6.53 vs. 36.05 ± 9.64, P = 0.000). Moreover, the microvessel density value was significantly correlated with K^trans after neoadjuvant chemotherapy+rh-endostatin treatment (r=0.88, P = 0.00).Conclusions: The neoadjuvant chemotherapy+rh-endostatin treatment significantly repressed angiogenesis in locally advanced breast cancer and synergistically enhanced the anti-tumor effect of neoadjuvant chemotherapy. Serial dynamic contrast-enhanced magnetic resonance imaging data including reductions in tumor size and K^trans, could provide non-invasive evaluation for chemotherapeutic efficacy and, consequently, optimization of individual chemotherapy for locally advanced breast cancer patients.     

Identification of different subtypes of breast cancer using tissue microarray

Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC) characteristics. The main aim of the present study was to classify breast cancer into molecular subtypes based on immunohistochemistry findings and correlate the subtypes with clinicopathological factors. Two hundred and seventeen primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, EGFR, CK8/18, p53 and Ki67 using tissue microarray technique. All subtypes were significantly associated with Malay ethnic background (p=0.035) compared to other racial origins. The most common subtypes of breast cancers were luminal A and was significantly associated with low histological grade (p<0.000) and p53 negativity (p=0.003) compared to HER2+/ER-, basal-like and normal-like subtypes with high histological grade (p<0.000) and p53 positivity (p=0.003). Luminal B subtype had the smallest mean tumor size (p=0.009) and also the highest mean number of lymph nodes positive (p=0.032) compared to other subtypes. All markers except EGFR and Ki67 were significantly associated with the subtypes. The most common histological type was infiltrating ductal carcinoma, NOS. Majority of basal-like subtype showed comedo-type necrosis (68.8%) and infiltrative margin (81.3%). Our studies suggest that IHC can be used to identify the different subtypes of breast cancer and all subtypes were significantly associated with race, mean tumor size, mean number of lymph node positive, histological grade and all immunohistochemical markers except EGFR and Ki67.     

P-glycoprotein, metallothionein and NM23 protein expressions in breast carcinoma

Cellular drug resistance and increased metastatic potential are the major obstacles in the successful treatment of cancer with chemotherapy. The aim of this study was to investigate whether the immunohistochemical expression of two proteins implicated in drug resistance (P-glycoprotein and metallothionein) and the product of the suppressor gene nm23 could be related to prognosis in breast cancer. Seventy-two patients with palpable or occult breast carcinoma, not treated with chemotherapy or endocrine therapy, were examined. Immunohistochemical methods were used to determine the expression of P-glycoprotein (PG), metallothionein (MT), nm23, as well as the estrogen receptor (ER), the p53 status, and the Ki67 index. The results were correlated with clinical and morphological features. Cytoplasmic and membrane-specific immunostainings of PG were seen exclusively in tumor cells and identified in 14 of 72 cases (19.4%). Only a statistically significant association with metastases, (p = 0.06) and recurrences (p = 0.1) was observed. MT-positive reaction was identified in the cytoplasm of the tumor cells in 47 (65.3%) cases. Statistical significance was associated with metastases (p = 0.07), but not with death or recurrences. Specific immunostaining of nm23 protein was seen only in the cytoplasm of tumor cells. A positive reaction was observed in 55 of 72 (89.3%) cases. Although a significant association between nm23 protein expression and other morphologic and immunohistochemical variables did not exist, we observed a higher morbidity in patients with the MT-positive/nm23-negative tumor phenotype. Univariate analysis for survival selected the following variables: histologic grade (p = 0.001), ER (p = 0.002), mitotic index (p = 0.005), Ki 67 index (p = 0.068), MT (p = 0.046) and PG (p = 0.085). The Cox model provided the following independent variables: histologic grade (p = 0.021) and metallothionein (p = 0.03). These data confirm the prognosis observed in patients with PG or metallothionein expression as well as the independence of these two variables. It also suggests that nm23 is not necessarily involved in the development of an invasive phenotype.     

Prognostic value of Ki67 expression in HR-negative breast cancer before and after neoadjuvant chemotherapy

Background: Immunohistochemical (IHC) expression of Ki67 has been identified as a prognostic and predictive marker in hormone receptor (HR)-positive breast cancer, however, there is little evidence of the association of Ki67 with prognosis in HR-negative patients. We aimed to assess the benefit of Ki67 assessment in HR-negative breast cancers after neoadjuvant chemotherapy (NAC). Methods: In the present study, a total of 183 HR-negative breast cancer patients with Stage II to III that treated with anthracycline and/or taxane-based neoadjuvant chemotherapy between 2004 and 2011 were retrospectively analyzed. Endocrine therapy and trastuzumab was not administered to any patients in this study. Clinical and pathological features of the patients with breast cancer were retrieved from the hospital records. Predictive factors for NAC response and survival were analyzed. Results: Of the 183 patients, 122 (66.6%) were HR- HER2+, and 61 (33.3%) were triple-negative. The clinical response rates were similar across breast cancer subtype. Patients whose tumors contained high Ki67 expression effectively responded to NAC. Ki67 labeling index was a predictive marker for pathologic complete response (pCR). Ki67 expression showed a positive correlation with HER2 status, tumor size, lymph node status, lymphovascular invasion and tumor grade. Furthermore, high Ki67 expression in post-treatment tumors was strongly correlated with poor disease-free survival (DFS), but no correlation of Ki-67 expression with overall survival (OS) was observed. Conclusions: Our results suggest that Ki67 expression in HR-negative breast cancer may improve the assessment of pathological response after NAC, and Ki67 score in residual tumor was an independent prognosticator for DFS in the HR-negative breast cancer patients.     

Aldehyde dehydrogenase 1A1 expression in breast cancer is associated with stage, triple negativity, and outcome to neoadjuvant chemotherapy

Studies have shown that ALDH1A1 expression in the breast is associated with worse clinical outcome. ALDH1A1 inactivates cyclophosphamide, which is an integral agent in breast cancer chemotherapy regimens. The purposes of this study were to verify these results, to correlate ALDH1A1 expression with clinical outcome in patients treated with cyclophosphamide as part of the chemotherapy (adjuvant or neoadjuvant), and to evaluate ALDH1A1 as a useful marker to predict the clinical outcome of breast cancer subsets. A total of 513 primary breast cancers were studied. Tissue microarrays of the studied cases were stained with ALDH1A1. Key clinicopathological information was obtained. Disease-free survival and overall survival were calculated. Patients with neoadjuvant therapy who had substantial residual cancer burden (RCB) were included in the study. Fisher's exact test and Kaplan-Meier methods were used for statistical analysis. ALDH1A1 was expressed in 53 (10%) patients, with a higher frequency in triple negative, followed by HER2+, and finally hormonal receptor+/HER2- (P<0.0001). Tumors with advanced stage, node-positive, or larger tumor size were correlated with ALDH1A1 expression (P=0.006, P<0.0001, and P=0.05, respectively). ALDH1A1 expression was also correlated with worse disease-free survival (P<0.006) and overall survival (P<0.01) in patients who were treated with neoadjuvant chemotherapy. In all, 8 of 22 (36%) received neoadjuvant chemotherapy and died of disease-expressed ALDH1A1 (P=0.008). Similarly, 8 of 23 (35%) who received neoadjuvant chemotherapy and had tumor recurrence expressed this marker (P=0.002). The risk of recurrence was fivefold greater than negative ALDH1A1 tumors. The risk of recurrence became 11-fold greater when cyclophosphamide but not trastuzumab was part of the regimen. Our results are consistent with previous studies. Moreover, we found that ALDH1A1 could be a useful marker to predict worse clinical outcome after chemotherapy in the neoadjuvant setting with substantial RCB. However, a larger cohort is required to verify our results.     

新辅助化疗对局部进展期乳腺癌患者T淋巴细胞亚群及NK细胞免疫功能的影响

目的:探讨局部进展期乳腺癌患者新辅助化疗前、后T淋巴细胞亚群及NK细胞免疫功能的变化。方法:采用流式细胞术检测54例局部进展期乳腺癌患者新辅助化疗前后的静脉血T淋巴细胞亚群及NK细胞免疫功能。美国癌症联合会(American Joint Commitree on Cancer,AJCC)肿瘤分期为Ⅱb期(仅T3N0M0)和Ⅲ期(不包括N3),静脉血于第1周期新辅助化疗治疗前及第3周期化疗后21日抽取,淋巴细胞亚群检测包括:T(CD3+,CD4+,CD8+),NK(CD56+,CD16+),经过3周期新辅助化疗CEF方案(表柔比星、环磷酰胺和5-氟尿嘧啶),根据新辅助化疗临床效果评价分为2组,化疗有效组38例(CR和PR),化疗无效组16例(SD和PD),并与正常体检健康者(40例)作比较。结果:乳腺癌患者治疗前CD4+、CD4+/CD8+明显低于对照组(P<0.01),NK细胞明显低于对照组(P<0.05),新辅助化疗后,有效组总CD3+、CD4+、CD4+/CD8+、NK细胞较治疗前均显著升高(P<0.05),CD8+降低(P<0.05);无效组CD3+、CD4+/CD8+及NK细胞较治疗前显著降低(P<0.05),而CD8+升高(P<0.05)。结论:局部进展期乳腺癌患者免疫功能低下,有效的辅助化疗能提高患者的免疫功能,定期监测免疫功能对指导临床治疗有意义。