The distribution of extracellular matrix proteins and CD44S expression in human astrocytomas

Aims of the study were: 1. to establish the prevalence of CD44 protein expression in human astrocytomas; 2. to compare the distribution of the extracellular matrix in these tumors; 3. to investigate the relation between CD 44, the extracellular matrix proteins and the histological grade of the tumor. CD44, Type IV Collagen (Col IV), Laminin (LN), Fibronectin (FN), and Tenascin (TN) expression were detected by immunohistochemistry in formalin fixed paraffin embedded tissue samples of 52 astrocytic tumors: 35 glioblastomas (GB), 7 Anaplastic astrocytomas (AA) and 10 astrocytomas (A). The localization of Col IV was observed in the basement membrane of the vessel walls in most of the astrocytomas (88.4%) with a similar pattern obtained with LN staining. 7 of 10 A (70%), 2 of 7 AA (28%) and 9 of 35 GB (25.7%) showed LN positivity. There was a negative correlation between LN expression and tumor grade (p=0.03). FN was either localized in the basement membrane or showed thick multi-layered immunoreactivity of the vessel walls. FN expression was seen in 6 A (60%), 4 AA (57%) and all of 35 GB (100%). The FN distribution was not uniform and its staining intensity showed decrease in GB. 3A (30%), 3 AA (42%), 27 GB (77.1%) showed TN expression in the vessel walls and in some tumor cells of 19 GBs. TN expression was positively correlated with the degree of vascular endothelial proliferation in GB (p<0.05). The expression of CD44s wasseen as plasma membrane positivity of glioma cells in 5 of 10A (50%), 3 of 7AA (42.3%) and 29 of 35 GB (82.8%). The intensity of immunoreaction was quite strong especially near the vessels. There was a good correlation between TN and CD44s expression in human astrocytic tumors (p=0.005). No relationship was observed between GFAP, ECM proteins and CD44s expression. Both CD44s and TN expression showed increase with malignancy in astrocytomas. These findings indicated that the histological malignancy of the astrocytomas was correlated with expression of TN and CD44s. It was suggested that in astrocytomas there was a biological relationship only between CD44 and TN, but none with the other ECM proteins. TN may play a role in angiogenesis in human astrocytic tumors.     

C-erbB-2、p53、Ki-67及VEGF在乳腺癌中的表达及相关性

目的探讨C-erbB-2、p53、Ki-67及VEGF在乳腺癌组织中的表达及其与乳腺癌临床病理特征之间的相关性。方法采用免疫组化SP法检测72例乳腺癌组织中C-erbB-2、p53、Ki-67及VEGF表达情况,并结合临床病理特征进行相关性分析。结果乳腺癌患者C-erbB-2、p53、Ki-67及VEGF阳性表达率分别为47.2%、48.6%、56.9%、65.3%。C-erbB-2、p53表达与淋巴结转移、雌激素受体、孕激素受体相关(P<0.05);Ki-67、VEGF与肿瘤直径、淋巴结转移相关(P<0.05);ER和PR呈正相关(P<0.05);C-erbB2与ER、PR呈负相关(P<0.05);p53与ER和PR呈负相关(P<0.05);p53、Ki-67、VEGF之间均呈正相关(P<0.05)。结论 C-erbB-2、p53、Ki-67及VEGF检测对判断乳腺癌预后有重要意义。     

Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast carcinoma

Ecto-5'-nucleotidase (ecto-5'-NT) is a phosphatidylinositol anchored membrane structure recently defined as the lymphocyte differentiation antigen CD73. Using CD73 (1E9.28.1) monoclonal antibody, normal mammary gland and breast carcinoma were immunohistochemically investigated for ecto-5'-NT expression. In normal breast epithelium, CD73 was differentially expressed in lobular, ductal and myoepithelial cells and was most frequently detected in the myoepithelial compartment. The glandular stroma contained fibrocytes, a subset of which was also CD73-positive. Among 102 unselected breast carcinoma primary lesions, only 9 contained CD73-positive tumour cells, whereas in 95 cases, stromal fibroblasts and fibrocytes showed variable degrees of CD73 expression. The extent of stromal CD73 expression correlated positively with the estrogen receptor (ER) status of the tumour (P less than 0.038). We conclude that ecto-5'-NT-expression reflects a still unknown state of activity of normal breast epithelium which is lost in the majority of carcinomas derived therefrom. It may also be indicative of some functional activity of stromal fibroblasts which is significantly enhanced in ER-positive carcinomas.     

ER，PR，Her-2及Ki-67在乳腺癌原发灶和前哨淋巴结转移灶中的表达对比研究

目的:探讨ER、PR、Her-2及Ki-67在乳腺癌原发灶和前哨淋巴结转移灶中的表达变化及其临床病理意义。方法:收集50例具有乳腺癌原发灶和前哨淋巴结转移灶的病例,采用免疫组化及原位杂交分析原发灶和前哨淋巴结转移灶中ER、PR、Her-2及Ki-67的表达有无差异。结果:ER在乳腺癌原发灶和SLN转移灶中表达一致率为100%。PR原发灶和转移灶一致率为92%,变化率为8%,Her-2原发灶和转移灶一致率为96%,变化率为4%,表达变化均无统计学意义（P＞0.05）。Ki-67在乳腺癌原发灶表达率为（30.3±20.2）%,SLN转移灶表达率（25.1±17.6）%,差异具有统计学意义（P＜0.05）;Ki-67原发灶和转移灶表达一致率为70%,变化率为30%,但表达变化无统计学意义（P＞0.05）。补充腋窝淋巴结阳性率在原发灶高表达、SLN转移灶中变为低表达组22.2%（2/9）明显低于无变化组62.5%（15/24）,差异具有统计学意义（P=0.04）。结论:原发灶基本能反应SLN转移灶ER、PR、Her-2表达状态,但针对个体而言,SLN转移灶分子状态重新评价仍有益。Ki-67在SLN转移灶表达率降低,原发灶高表达而SLN转移灶变为低表达可能预测补充腋窝淋巴结的低转移率。     

乳腺癌DCE-MRI表现特征与生物因子表达及淋巴结转移的相关性研究

目的探索乳腺癌动态增强磁共振成像(DCE MRI)表现特征与生物因子雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体 2(Her 2)、Ki 67表达状态及淋巴结转移的关系。方法选取2015年6月至2019年5月连云港市第一人民医院收治的经病理确诊为乳腺癌的80例患者(80个病灶),分析患者的DCE MRI特征:肿瘤直径、肿瘤形态、肿瘤边缘、强化方式、时间 信号强度曲线(TIC)及早期强化率(ΔSI)。采用免疫组织化学染色分析ER、PR、Her 2、Ki 67的表达情况。分析乳腺癌患者的DCE MRI表现特征与ER、PR、Her 2、Ki 67阳性表达状态及淋巴结转移之间的关系。结果直径≤2 cm、2 cm<直径≤5 cm及直径>5 cm肿瘤的PR阳性表达率组间差异具有统计学意义（P=0024）;形态为类圆形、分叶状及不规则形肿瘤的PR阳性表达率组间差异有统计学意义（P=0040）;直径>5 cm肿瘤发生淋巴结转移的概率较直径≤2 cm肿瘤及2 cm<直径≤5 cm肿瘤高（均P<005）。肿瘤边缘与Her 2表达水平呈正相关(r=0276,P=0013),早期强化率与Ki 67表达水平呈正相关(r=0254,P=0023)。结论乳腺癌DCE MRI表现特征在一定程度上可以初步评估乳腺癌细胞的生物学行为,为指导临床综合治疗及评估患者预后提供客观依据。     

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.     

乳腺癌组织中ER、PR、cerbB-2、Ki-67表达及其意义

目的探讨乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、cerbB-2和Ki-67基因的表达及其临床意义。方法采用S-P免疫组化方法,检测107例乳腺癌组织中ER、PR、cerbB-2、Ki-67的表达水平,并结合其患者的相关临床资料进行分析。结果乳腺癌组织中ER、PR、cerbB-2、Ki-67阳性表达率分别为56.1%、82.2%、71.0%、67.3%。ER、PR、cerbB-2、Ki-67阳性表达与乳腺癌腋窝淋巴结转移和临床分期显著相关（P〈0.05）。而与患者年龄、肿瘤大小无相关性（P〉0.05）。相关分析结果显示ER与PR表达呈正相关（P=0.000）,与Ki-67表达呈负相关（P=0.000）;PR与cerbB-2、Ki-67表达呈负相关（P=0.012、0.006）。结论 ER、PR和cerbB-2、Ki-67与乳腺癌的发生、发展有关,联合检测ER、PR、cerbB-2和Ki-67,有助于客观评估乳腺癌的生物学行为,从而指导临床治疗和预后判断。     

ER、PR与C-erbB-2、Ki-67在乳腺癌中的表达及其临床意义

目的 探讨乳腺癌组织中ER、PR与C-erbB-2、Ki-67的表达及它们的相关性.方法 采用免疫组化检测,对356例乳腺癌患者ER、PR、C-erbB-2及Ki-67的表达、临床病理特征以及它们的相关性进行回顾性分析.结果 ER、PR、C-erbB-2及Ki-67的表达与淋巴结转移相关(P<0.05);乳腺癌组织分级...     

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.     

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.     

CD44v6在乳腺浸润性导管癌组织中的表达及其临床意义

背景与目的:近年研究表明,CD44v6与乳腺癌的发生、侵袭和转移密切相关,但其与乳腺癌预后关系的报道结果并不一致。本研究探讨CD44v6在乳腺癌和乳腺癌旁非癌组织中的表达及其与乳腺癌临床病理因素的关系以及对乳腺癌患者预后的预测意义。方法:采用免疫组织化学SP法检测84例乳腺浸润性导管癌和20例癌旁非癌乳腺组织中CD44v6的表达。采用SPSS10.0软件统计分析CD44v6表达与各病理因素的关系,采用Cox比例风险模型分析影响预后的因素。结果:CD44v6在乳腺浸润性导管癌上皮细胞的表达(78.6%)明显高于癌旁非癌乳腺组织上皮(5.0%),差异有显著性(P<0.05);CD44v6的表达与乳腺癌的TNM分期、肿瘤大小、淋巴结转移状况密切相关;中位随访时间为60个月,CD44v6阴性组的总体生存情况优于CD44v6阳性组,有显著性差异(P<0.05),而且随着CD44v6表达的增强,总体生存曲线有逐渐下降的趋势。Cox比例风险模型多因素的预后分析结果显示,ER、TNM分期、CD44v6均是影响预后的独立因素(P<0.05)。结论:CD44v6在乳腺癌组织中的表达明显升高;CD44v6的表达与乳腺癌患者的TNM分期、肿瘤大小、淋巴结转移呈正相关;CD44v6表达升高可作为预测乳腺癌预后的独立指标之一。     

Expression of ERalpha, ERbeta and Ki-67 in primary tumors and lymph node metastases in breast cancer

The success of current hormonal therapies used in breast cancer patients often depends on estrogen receptor (ER) status. The simultaneous pathological assessment of primary breast tumors (PTs) and metastases to regional lymph nodes (MRLNs) could improve the effectiveness of this treatment, but is rarely performed. Consequently, we studied by immunohistochemistry the expression of ERalpha (ERalpha), ERbeta (ERbeta), and the proliferation marker (Ki-67) in PTs and matching MRLNs. The expression of each ERalpha, ERbeta, and Ki-67 positively correlated between PTs and MRLNs (r=0.751, p<0.0001; r=0.391, p<0.03; and r=0.707, p<0.0001, respectively). A negative correlation between the expression of ERalpha and Ki-67 was found in PTs (r=-0.678, p<0.001) and MRLNs (r=-0.501, p<0.005). A negative correlation between ERalpha and Ki-67 was also observed in PTs vs. MRLNs (r=-0.619, p<0.0001). Moreover, the expression of ERalpha and Ki-67 was not associated with nodal status, contrary to ERbeta expression, which correlated with negative axillary node status. The results indicated that the associations among ERalpha, ERbeta, and Ki-67 are maintained in PTs and MRLNs. Thus, simultaneous assessment of selected markers in PT and MRLN might help in understanding the mechanisms of breast cancer progression as well as result in the development of new principles for diagnosis and individual therapy planning of estrogen dependent cancer.     

乳腺浸润性癌MRI表现与生物因子表达的相关性研究

目的 探讨乳腺浸润性癌MRI表现与生物因子雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)、肿瘤增殖抗原Ki-67、肿瘤抑制蛋白p53表达的相关性及临床意义.方法 回顾性分析69例乳腺浸润性癌患者的MRI表现及生物因子ER、PR、HER2、Ki-67、p53的表达情况,采用Spearman相关分析和分类回归树(CART)算法分析MRI表现与各生物因子表达的相关性.结果 HER2表达与淋巴结转移呈正相关(r=0.299,P﹤0.05),p53表达与病变表现为肿块呈负相关(r=-0.261,P﹤0.05);肿块分叶征象与Ki-67(r=0.472,P﹤0.01)、p53(r=0.25,P﹤0.05)阳性表达呈正相关.根据MRI表现分析各生物因子表达的CART决策树,分类准确度依次为:Ki-67(0.797)﹥ER(0.754)﹥PR(0.725)﹥HER2(0.478)﹥p53(0.464).结论 乳腺浸润性癌的MRI表现与生物因子ER、PR、HER2、Ki-67、p53的表达有一定的相关性,可作为乳腺癌的重要诊断指标.     

CD44 variant expression and estrogen receptor status in breast cancer

To understand the relationship between CD44 gene expressionand an established variable associated with aggressive behaviourin human breast cancer, we have studied apanel of 6 breast cell lines and 40breast tumors selected primarily on the basis ofestrogen receptor (ER) status. CD44s (standard form) mRNAwas assessed by semi-quantitative RT-PCR, and CD44 variantsincorporating exon v7 or v10 were studied byRT-PCR and Southern blot. While CD44 expression wasnot influenced by estrogen in ER+ve MCF-7 cells,CD44s expression was slightly higher (up to 2fold) in ER–ve cells but there was amarked decrease in the range of CD44 variantsincorporating exons v7 or v10. In microdissected tumors,the levels of CD44s showed no correlation withER status but the pattern of expression oflarger forms of CD44 incorporating variant exons v7and v10 was significantly different (p=0.005and p=0.015, respectively) between ER+ve andER–ve tumors, reflecting the pattern seen in thecell lines. These findings suggest that the profileof CD44 expression in breast cancer may reflectcellular differentiation as indicated by the ER phenotype.The influence of these differences in CD44 expressionon the increased metastatic potential of ER negativebreast cancer remains to be determined.     

Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome

The aim of this study was to provide a better insight into breast cancer response to chemotherapy. Chemotherapy improves outcome in breast cancer patients. The effect of cytotoxic treatment cannot be predicted for individual patients. Therefore, the identification of tumour characteristics associated with tumour response and outcome is of great clinical interest. We studied 97 patients, who received anthracycline-based neoadjuvant chemotherapy. Tumour samples were taken prior to and after chemotherapy. We quantified the response to chemotherapy clinically and pathologically and determined histological and molecular tumour characteristics. We assessed changes in the expression of Bcl-2, ER, P53 HER2 and Ki-67. Association with response and outcome was tested for all parameters. The experimental results showed 15 clinical (17%) and three (3%) pathological complete remissions. There were 18 (20%) clinical vs 29 (33%) pathological nonresponders. The expression of most markers was similar before and after chemotherapy. Only Ki-67 was significantly decreased after chemotherapy. Factors correlated with response were: large tumour size, ER negativity, high Ki-67 count and positive P53 status. Tumour response and marker expression did not predict disease-free or overall survival. In conclusion, clinical and pathological response assessments are poorly associated. Proliferation decreases significantly after chemotherapy. ER negativity and a high proliferation index are associated with better response. HER2 status does not predict response, and outcome is not related to tumour response.     

乳腺癌患者原发灶与复发转移灶中ER、PR、HER-2及Ki-67表达异质性的回顾性分析

目的:探讨ER、PR、HER-2及Ki-67在乳腺癌患者原发灶及复发转移灶中的表达差异,并分析其对乳腺癌患者预后的影响。方法:统计2012年01月01日2021年12月31日我院肿瘤科收治的复发转移性乳腺癌患者,除外病理及临床资料缺失的患者后,共计89例患者纳入本研究。采用回顾性队列研究方法,比较乳腺癌原发灶及复发转移灶中ER、PR、HER-2及Ki-67的表达差异。结果:本研究纳入患者的平均年龄为53.14岁(20~84岁)。其中有34例患者接受术前新辅助治疗,所有患者均行乳腺癌根治术或改良根治术,并进行了相应的术后辅助治疗。乳腺癌原发灶中ER及PR阳性表达率均高于转移灶;而HER-2阳性及Ki-67高表达的情况在转移灶中更常见。乳腺癌原发灶与复发转移灶中ER、PR、HER-2、Ki-67表达差异比例分别为:24.72%、42.70%、11.24%、13.48%。乳腺癌原发灶及转移灶中ER、PR表达的异质性与患者无病生存期相关。结论:乳腺癌患者的ER、PR、HER-2和Ki-67表达状态在原发灶与复发转移灶中存在一定的异质性,进而影响患者的治疗策略及预后。     

纤维连接蛋白及层黏连蛋白在食管癌表达的研究

目的研究纤维连接蛋白、层黏连蛋白在食管癌中的表达及意义。方法采用免疫组化法分别检测60例食管癌患者纤维连接蛋白、层黏连蛋白的表达,正常食管组织标本、不典型增生食管组织标本各15例作为对照。结果在正常食管组织向恶性转化过程中,连续线状表达减少,碎片状表达增加;纤维连接蛋白(FN)、层黏连蛋白(LN)表达与食管癌病理分级、淋巴结转移有关;FN、LN在癌细胞胞质中阳性表达与食管癌病理分级、有无淋巴结转移无关;癌细胞胞质中FN与LN表达之间有明显的正相关性。结论基底膜FN、LN表达可作为临床判断食管癌分化程度及有无转移的有用指标;癌细胞胞质中FN与LN表达之间的正相关性提示在食管癌发展中两者有内在关联性;FN、LN表达异常对食管癌预后评估有一定意义。     

Prostate-specific antigen and gross cystic disease fluid protein-15 are co-expressed in androgen receptor-positive breast tumours.

Androgens regulate breast cancer cell proliferation via androgen receptor (AR)-mediated mechanisms. To investigate further the androgen-responsiveness of human breast tumours, we examined the immunohistochemical expression of the AR and two androgen-regulated proteins, prostate-specific antigen (PSA) and gross cystic disease fluid protein-15 (GCDFP-15), in 72 primary breast tumours. AR immunoreactivity was present in the nuclei of breast tumour cells and was correlated with oestrogen receptor (ER; P < 0.05) and progesterone receptor (PR; P < 0.01) status. PSA and GCDFP-15 immunoreactivity was present in the cytoplasm of tumour cells but not the adjacent stromal cells. AR-positive cells were present in 85% (61/72) of breast tumours, and 98% (43/44) of PSA-positive and 92% (44/48) of GCDFP-15-positive tumours were also positive for AR. Positive immunoreactivity for both PSA and GCDFP-15 in breast tumours was highly dependent on AR status (odds ratios of 24.0 and 4.5 respectively), but unrelated to age, ER and PR status and axillary lymph node involvement. PSA immunoreactivity was more frequently observed in moderate and well-differentiated tumours and was significantly (P < 0.001) associated with GCDFP-15 immunoreactivity. In conclusion, PSA and GCDFP-15 immunoreactivity was dependent on the presence of AR, but not ER or PR in primary breast tumours.     

层粘连蛋白和纤维粘连蛋白在癌组织中的分布及其意义

目的:探讨在浸润、分化程度、组织学类型和转移中,癌组织细胞外基质(LN和FN)的含量改变和分布规律.方法:采用S-P免疫组化染色法观察了257例癌组织的LN和FN的含量分布.染色程度分为(-)、( )和( ),将癌按浸润程度,分化程度、组织学类型和有否转移进行分组.结果:基底膜LN和FN在非浸润癌时连续完整,微浸润区可见分段或缺失,浸润癌时含量明显减少,分布不规则.两者在分化好组和分化差组的表达具有显著性差异(P<0.01).在已分化的各组织学类型之间,LN和FN的表达无明显差异(P<0.05),在转移和未转移组的表达也无明显差异(P>0.05).97%以上的癌间质中存在FN阳性物.结论:基底膜LN和FN是否完整对于鉴别癌是否有浸润有重要的参考价值,其含量随肿瘤细胞分化程度的降低而减少,而与组织学类型和转移无明显关系.间质FN的存在和分布与肿瘤的分化程度、组织学类型及淋巴结转移均无明显关系,可能反映机体对肿瘤的防御和抵抗功能的状态.     

An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer

Background:

The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer.

Methods:

Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (n=92) undergoing PST with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24− or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.

Results:

A higher proportion of CD44+/CD24− tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24− and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24− tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.

Conclusion:

The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.