鼻咽癌组织与外周血CD4+CD25+调节性T细胞检测及临床意义

 目的 通过检测鼻咽癌患者肿瘤组织及外周血中CD4⁺T、CD8⁺T、CD4⁺CD25^-T、CD4⁺CD25⁺T细胞的频数,寻找客观、全面评价鼻咽癌患者免疫状态的临床指标。方法 采用流式细胞术检测40例初诊鼻咽癌患者及10例正常对照鼻咽部组织和外周血CD4⁺T、CD8⁺T、CD4⁺CD25^-T、CD4⁺CD25⁺T细胞比例。结果 鼻咽癌患者CD4⁺T细胞比例及CD4⁺/ CD8⁺T比值均低于对照组（P<0.05）,而CD8⁺T细胞两组间差异无统计学意义（P>0.05）,但是CD4⁺/ CD8⁺T比值在鼻咽癌组织与外周血间差异无统计学意义（P>0.05）。鼻咽癌组织及外周血中CD4⁺CD25⁺T细胞比例都高于对照组（P<0.05）,同时癌组织中该细胞比例远远高于外周血（P<0.05）。在鼻咽癌组织中CD4⁺CD25⁺T细胞与CD8+ T细胞、CD4⁺CD25^-T细胞呈负相关（r分别为-0.70、-0.675,P<0.05）,而在外周血中没有相关关系（P>0.05）。在不同T(原发肿瘤大小)组间,T4组的鼻咽癌组织中CD4⁺CD25⁺T细胞分别高于T1、T2、T3各组（P<0.05）,而在T1、T2、T3各组间差异无统计学意义（P>0.05）;鼻咽癌中CD4⁺CD25⁺T细胞比例与患者有无淋巴结转移并无关系（P>0.05）;鼻咽癌组织中Ⅲ+Ⅳ期组CD4⁺CD25⁺T细胞比例高于Ⅰ+Ⅱ期组（P<0.05）,而在外周血中两组间差异无统计学意义（P>0.05）。结论 CD4⁺CD25⁺T细胞与鼻咽癌病程进展无相关性,但是联合检测患者肿瘤组织及外周血中CD4⁺CD25⁺T细胞的频数并结合既往CD4⁺/ CD8⁺T比值会全面反应患者免疫状态,为临床治疗提供依据。     

p57kip2与cyclin D1在上皮性卵巢癌中的表达及临床意义

 目的 研究p57^kip2与细胞周期素D1在上皮性卵巢癌中的表达与临床病理特征的关系，探讨其在上皮 性卵巢癌发生发展过程中的作用。 方法 采用免疫组织化学SP法检测p57^kip2与cyclin D1在41例上皮性卵巢癌，12例交界性肿瘤，24例 良性肿瘤与12例正常卵巢组织中的表达。 结果 p57^kip2和cyclin D1在正常卵巢、良性、交界性、恶性肿瘤组织中的阳性率分别为91.7% (11/12)、79.2%(19/24)、 58.3%(7/12)、 46.3%(19/41)和8.3%(1/12)、 29.2%(7/24)、 50%(6/12)、 75.6%(31/41)，其中正常组与恶 性组之间，良性与恶性组之间差异有统计学意义(P＜0.05)。在卵巢癌中p57^kip2和cyclin D1 的表达与肿瘤分化程度，临床分期和有无淋巴结转移有关，且两者的表达呈负相关 (r=-0.311,P＜0.05)。 结论 p57^kip2和cyclin D1可能共同参与了上皮性卵巢肿瘤的发生与发展，p57^kip2的低表达甚至缺 失和cyclin D1高表达对预测卵巢肿瘤的恶性程度及预后有指导意义。     

乳腺浸润性导管癌中cyclinD1 、p57 KIP2的表达及意义

 目的 研究cyclinD1、p57^KIP2在乳腺浸润性导管癌（IDC）中的表达及意义。方法 采用免疫组织化学SP法检测64例113（2、15例乳腺导管内癌（DCIS）和15例癌旁正常乳腺组织中cyclinD1、p57 ^KIP2的表达。结果 cyclinD1、p57 ^KIP2阳性表达率在IDC与在乳腺不同组织之间、腋窝淋巴结有无转移之间差异均有显著性（P≤0．05，P〈0．01）；cyclinD1阳性表达率与IDC组织学分级有关（P〈0．01）；cyclinD1与p57 ^KIP2之间阳性表达率呈负相关（P〈0．01）。结论 cyclinD1与p57 ^KIP2共同参与了乳腺癌的发生发展过程。cyclinD1异常表达是乳腺癌发生的早期事件。联合检测cyclinD1及p57 ^KIP2对预测乳腺癌淋巴结转移有重要意义。     

CD44+/CD24-/low在乳腺癌中的表达及其与含蒽环类药物化疗方案敏感度的关系

目的研究乳腺癌中CD44+/CD24-/low的表达及其与含蒽环类药物化疗方案敏感度的关系。方法 91例乳腺癌接受含蒽环类药物的术前新辅助化疗,2～4个疗程后进行效果评价;采用双染免疫组织化学方法检测化疗前后CD44+/CD24-/low的表达,t检验分析化疗前后CD44+/CD24-/low细胞比例的变化,χ2检验分析乳腺癌CD44+/CD24-/low表型与乳腺癌临床病理参数及化疗疗效的关系。结果乳腺癌中CD44+/CD24-/low阳性表达率为39.6%(36/91),在接受含蒽环类药物的新辅助化疗后乳腺癌中CD44+/CD24-/low细胞比例较化疗前明显增加(P=0.028)。CD44+/CD24-/low阳性组ER阳性率明显低于CD44+/CD24-/low阴性组(25.0%vs.47.3%,P=0.033)。三阴性乳腺癌中CD44+/CD24-/low阳性率明显高于非三阴性乳腺癌(61.9%vs.32.9%,P=0.017)。CD44+/CD24-/low表型与年龄、肿瘤大小、临床分期、病理类型、组织学分级等乳腺癌临床病理参数无明显关系(P>0.05)。CD44+/CD24-/low阳性组的总有效率高于CD44+/CD24-/low阴性组,但两组之间差异无统计学意义(75%vs.69.1%,P=0.542);CD44+/CD24-/low阳性组的病理完全缓解率明显高于CD44+/CD24-/low阴性组(38.9%vs.18.2%,P=0.028)。结论 CD44+/CD24-/low细胞仅存在于部分乳腺癌,CD44+/CD24-/low表型与ER(﹣)、三阴性乳腺癌相关,CD44+/CD24-/low表型与乳腺癌对含蒽环类药物化疗方案的敏感度相关,CD44+/CD24-/low表型可能成为乳腺癌临床化疗疗效的预测指标之一。     

结直肠癌中survivin 、caspase-3 、p21WAF1的蛋白表达及其意义

 目的 探讨结直肠癌中survivin、caspase-3和p21^WAF1的蛋白表达与临床病理参数的联系以及survivin与caspase-3和p21^WAF1蛋白表达之间的关系。方法 采用免疫组织化学SP方法检测15例正常结直肠粘膜和62例结直肠腺癌标本中survivin、caspase-3和p21^WAF1的蛋白表达。结果 结直肠腺癌与正常结直肠粘膜比较,survivin、caspase-3和p21^WAF1的蛋白表达差异均有显著性（P〈0.05）。survivin和caspase-3的蛋白表达与淋巴结转移无明显相关（P〉0.05）;而与分化程度均显著相关（P〈0.05）。survivin蛋白与Dukes分期相关（P〈0.05）;但caspase-3的蛋白表达与Dukes分期无关（P〉0.05）。p21^WAF1蛋白表达与分化程度、淋巴结转移和Dukes分期均显著相关（P〈0.05）。survivin蛋白分别与caspase-3、p21^WAF1蛋白表达之间均呈显著负相关（P〈0.01）。结论 survivin、caspase-3和p21^WAF1蛋白在结直肠癌的发生和进展中都起着重要的作用。p21^WAF1基因与结直肠癌的恶性进展显著相关,此结论鲜见报道。     

p14ARF在宫颈癌中的表达及其与p53 表达相关性的研究

 目的　探讨宫颈癌组织p14^ARF蛋白的表达及其与p53 表达的相关性。方法　应用免疫组化方法检测p14^ARF 、p53 基因在41 例宫颈癌及20 例正常宫颈组织中的表达。结果　p14^ARF在正常宫颈组织中不表达,41 例宫颈癌中35 例表达阳性,占85. 4 %。病理分级为G1 、G2 级的宫颈癌的p14^ARF阳性表达率为68. 4 % ,G3 级为100 % ,两者比较,有显著性差异( P < 0. 05) 。宫颈癌组织中p53 蛋白表达阳、阴性者中p14ARF蛋白表达阳性率分别为75. 0 %(12/ 16) 和92. 0 %(23/ 25) ,两者比较,无显著性差异,p14^ARFF与p53 表达不相关。结论　p14^ARF在宫颈癌中高表达有一定的诊断和估测预后价值,可能是宫颈癌新的肿瘤标志。     

胃癌中Cks1 、p27 Kip1和Skp2 蛋白的表达

 目的 探讨Cks1在胃癌发生及其在Skp2调节p27 ^Kip1降解过程中的作用。方法 应用流式细胞术测定正常胃粘膜和胃癌组织中Cks1、p27^Kip1、Skp2蛋白表达。结果胃癌组织中Cks1、Skp2表达明显高于正常胃粘膜（x²=22．69，P〈0．05；x²=13．42，P〈0．05），而p27 ^Kip1表达则低于正常胃粘膜（x²=14．83，P〈0．05）。胃癌中Cks1、Skp2表达与p27 ^Kip1表达呈负相关（r=-0．649，P〈0．05；r=-0．732，P〈0．05）；而Cks1蛋白表达与Skp2蛋白缺乏相关性（P〉0．05）。胃癌中Cks1的表达与肿瘤分化程度相关（x²=5．05，P〈0．05），而与肿瘤浸润深度、淋巴结转移及临床分期不相关（P〉0．05）。结论Cks1可能参与了胃癌的发生；胃癌中Cks1可能参与了Skp2调节p27 ^Kip1泛素化降解过程。     

89SrCl2 治疗11 例肿瘤骨转移的临床观察

 目的　探讨⁸⁹SrCl₂ 治疗转移性骨肿瘤的临床应用价值。方法　 1 1例经证实为肿瘤骨转移患者接受 ⁸⁹SrCl₂ 4 mci静脉注射治疗 ,治疗后至随访时间为 3个月～ 1年。结果　止痛总有效率72 .8% ;显效 45.5% ( 5/1 1 ) ;有效 2 7.3% ( 3/1 1 ) ;止痛起效时间较快 ,缓解骨痛持续时间较长 ,骨髓抑制不明显。结论　⁸⁹SrCl₂治疗肿瘤骨转移患者有缓解疼痛、提高生存质量的作用.     

应用组织微阵列技术研究胃癌hMSH2 和p16INK4a的表达意义

 目的 探讨错配修复基因hMSH2和抑癌基因p16^INK4a在胃癌组织中表达的意义。方法 构建胃癌组织微阵列(TMA),采用免疫组化法测定hMSH2和p16^INK4a的表达。结果 在胃癌组织中,hMSH2和p16^INK4a的过表达呈正相关(r=0．235,P=0．0134),与有无淋巴结转移及转移程度、生存时间无关。结论 hMSH2和p16^INK4a的过表达呈正相关,两者均不能作为预测有否淋巴结转移、转移程度和预后的分子标志物。     

乳腺癌分子分型的临床意义

目的 利用乳腺癌的3种分子标志物的检测结果将乳腺癌简易分为4种分子亚型,并探讨这4种分子亚型的临床特征及影响预后的因素.方法 依据雌激素受体（ER）、孕激素受体（PR）及人表皮生长因子受体2（HER-2）的免疫组织化学检测结果,采用回顾性方法将本院510例乳腺癌患者分为luminal A、luminal B、HER-2（＋）及basal-like 4种类型.对各型的临床特征采用SPSS13.0 统计软件进行分析,并用Kaplan-Meier法和Cox回归分析各型患者的生存情况及预后因素.结果 在510例乳腺癌患者中,luminal A型、luminal B型、HER-2（＋）型及basal-like型分别占56.86%（290/510）、9.02%（46/510）、3.53%（18/510）和30.59%（156/510）.中位随访66个月,luminal A型、luminal B型、HER-2（＋）型及basal-like型患者的5年总生存率分别为96.21%（279/290）、97.83%（45/46）、83.33%（15/18）和78.85%（123/156）,5年无瘤生存率分别为88.62%（257/290）、95.65%（44/46）、83.33%（15/18）和72.44%（113/156）.basal-like型与luminal A、luminal B型相比,患者无瘤生存率及总生存率较低（P〈0.05）;HER-2（＋）型患者的总生存率比luminal A型患者低（P〈0.05）.经Cox多因素预后分析发现淋巴结状况及分子分型是影响乳腺癌预后的重要因素,淋巴结阳性患者的预后较淋巴结阴性患者差,luminal A型、luminal B型、HER-2（＋）型及basal-like型患者的预后依次变差（P=0.00）.结论 不同分子亚型的乳腺癌患者表现不同的临床特征及预后.淋巴结状况及分子类型是影响乳腺癌患者预后的重要因素,淋巴结阳性及basal-like型患者预后最差.     

Clinical–pathologic significance of cancer stem cell marker expression in familial breast cancers

Human breast cancer cells with a CD44⁺/CD24^?/low or ALDH1+ phenotype have been demonstrated to be enriched for cancer stem cells (CSCs) using in vitro and in vivo techniques. The aim of this study was to determine the association between CD44⁺/CD24^?/low and ALDH1 expression with clinical–pathologic tumor characteristics, tumor molecular subtype, and survival in a well characterized collection of familial breast cancer cases. 364 familial breast cancers from the Ontario Familial Breast Cancer Registry (58 BRCA1-associated, 64 BRCA2-associated, and 242 familial non-BRCA1/2 cancers) were studied. Each tumor had a centralized pathology review performed. TMA sections of all tumors were analyzed for the expression of ER, PR, HER2, CK5, CK14, EGFR, CD44, CD24, and ALDH1. The Chi square test or Fisher’s exact test was used to analyze the marker associations with clinical–pathologic tumor variables, molecular subtype and genetic subtype. Analyses of the association of overall survival (OS) with marker status were conducted using Kaplan–Meier plots and log-rank tests. The CD44⁺/CD24^?/low and ALDH1+ phenotypes were identified in 16% and 15% of the familial breast cancer cases, respectively, and associated with high-tumor grade, a high-mitotic count, and component features of the medullary type of breast cancer. CD44⁺/CD24^?/low and ALDH1 expression in this series were further associated with the basal-like molecular subtype and the CD44⁺/CD24^?/low phenotype was independently associated with BRCA1 mutational status. The currently accepted breast CSCs markers are present in a minority of familial breast cancers. Whereas the presence of these markers is correlated with several poor prognostic features and the basal-like subtype of breast cancer, they do not predict OS.     

CD44+CD24-/low在基底样乳腺癌中过表达与其恶性预后的相关性研究

目的探讨乳腺癌干细胞样标志物CD44⁺CD24^-/low在基底样乳腺癌(basal-like breast carcinoma, BLBC)中过表达与BLBC恶性预后的相关性。方法 在乳腺癌基因表达分型的基础上, 根据雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(Her-2)免疫表型的表达选取乳腺癌组织四组:管腔A组、管腔B/C组、Her-2高表达组及三阴性组;对三阴性组检测CK5/6、EGFR, 分为正常乳腺样型和BLBC型两组;对上述5组进行免疫组化Envision法染色, 选用抗体为CD44、CD24, 观察CD44⁺CD24^-/low表型表达并比较BLBC组与其它各组的差异。结果 (1)三阴性组共60例, CK5/6和或EGFR阳性者41例(68.3%), 确定为BLBC;CK5/6、EGFR阴性者19例(31.7%), 确定为正常乳腺样组;(2)CD44⁺CD24^-/low表型在BLBC组中占78.0%(32/41), 相对于管腔A组37.9%(11/29)、管腔B组25.9%(7/27)、Her-2高表达组17.2%(5/29)、正常乳腺样组26.3%(5/21), 表达增高并具有显著性(P＜0.05);(3)所有150例乳腺癌中(可评价145例)具有CD44⁺CD24^-/low免疫表型者其Ki-67指数增高相对于非CD44⁺CD24^-/low表型具有统计学差异(P＜0.001)。结论 BLBC型乳腺癌表达乳腺癌干细胞样标志物CD44⁺CD24^-/low显著高于其它各型乳腺癌, CD44⁺CD24^-/low与BLBC独特的恶性生物学行为相关。     

Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics

Introduction

Whether cancer stem cells occur in BRCA1-associated breast cancer and contribute to therapeutic response is not known.

Methods

We generated and characterized 16 cell lines from five distinct Brca1deficient mouse mammary tumors with respect to their cancer stem cell characteristics.

Results

All cell lines derived from one tumor included increased numbers of CD44⁺/CD24^- cells, which were previously identified as human breast cancer stem cells. All cell lines derived from another mammary tumor exhibited low levels of CD44⁺/CD24^- cells, but they harbored 2% to 5.9% CD133⁺ cells, which were previously associated with cancer stem cells in other human and murine tumors. When plated in the absence of attachment without presorting, only those cell lines that were enriched in either stem cell marker formed spheroids, which were further enriched in cells expressing the respective cancer stem cell marker. In contrast, cells sorted for CD44⁺/CD24^- or CD133⁺ markers lost their stem cell phenotype when cultured in monolayers. As few as 50 to 100 CD44⁺/CD24^- or CD133⁺ sorted cells rapidly formed tumors in nonobese diabetic/severe combined immunodeficient mice, whereas 50-fold to 100-fold higher numbers of parental or stem cell depleted cells were required to form few, slow-growing tumors. Expression of stem cell associated genes, including Oct4, Notch1, Aldh1, Fgfr1, and Sox1, was increased in CD44⁺/CD24^- and CD133⁺ cells. In addition, cells sorted for cancer stem cell markers and spheroid-forming cells were significantly more resistant to DNA-damaging drugs than were parental or stem cell depleted populations, and they were sensitized to the drugs by the heat shock protein-90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride).

Conclusion

Brca1-deficient mouse mammary tumors harbor heterogeneous cancer stem cell populations, and CD44⁺/CD24^- cells represent a population that correlates with human breast cancer stem cells.     

晚期大肠癌患者化疗前后T淋巴细胞亚群检测的临床价值

目的：探讨晚期大肠癌患者T淋巴细胞亚群免疫功能状态及临床意义。方法：采用流式细胞术检测晚期大肠癌患者化疗前后外周血T淋巴细胞亚群的变化,并与体检健康者作比较。结果：实验组84例晚期大肠癌患者化疗前外周血T淋巴细胞亚群与35例正常对照组比较,CD4⁺、CD8⁺CD28⁺,CD28⁺明显低于对照组（P<0.01）,CD8⁺CD28^-高于对照组（P<0.01）,CD3⁺、CD8⁺、CD4⁺/CD8⁺比值与对照组比较差异无统计学意义（P>0.05）。对于69例接受化疗的患者,临床获益39例,化疗后CD3+较化疗前升高（P<0.05）,CD8⁺、CD8⁺CD28^-较前明显降低（P<0.01）,CD4⁺、CD8⁺CD28⁺、CD28⁺、CD4⁺/CD8⁺较前明显升高（P<0.01）;临床进展30例,化疗后CD8⁺、CD8⁺CD28^-较化疗前明显升高（P<0.01）,CD4⁺、CD4⁺/CD8⁺较前明显降低（P<0.01）,CD28+较前降低（P<0.05）,CD3⁺、CD8⁺CD28⁺较前有所下降,但差异无统计学意义（P>0.05）。结论：晚期大肠癌患者免疫功能低下,有效的化疗能提高患者的T淋巴细胞免疫功能,临床上检测患者外周血T淋巴细胞亚群,特别是联合检测CD8⁺CD28⁺、CD8⁺CD28^-、CD28⁺T细胞对评估晚期大肠癌患者的细胞免疫功能及病情具有更积极的临床价值。     

Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes

Five breast cancer subtypes have been described in sporadic breast cancer (SBC) using expression arrays: basal-like, ERBB2, normal breast-like, luminal A and B. These molecular subtypes show different genomic aberration patterns (GAPs). Recently, our group described these breast cancer subtypes in 50 non-BRCA1/2 familial tumors using immunohistochemistry assays. We extended this study to the other classes of familial breast cancer (FBC), including 62 tumors (18 BRCA1, 16 BRCA2 and 28 non-BRCA1/2), with the same panel of 25 immunohistochemical (IHC) markers and histological grade obtaining a similar classification. We combined these data with results generated by a 1 Mb BAC array-based CGH study to evaluate the genomic aberrations of each group. We found that BRCA1-related tumors are preferentially basal-like, whereas non-BRCA1/2 familial tumors are mainly luminal A subtype. We described distinct GAPs related to each IHC subtype. Basal tumors had a greater number of gains/losses, while luminal B tumors had more high-level DNA amplifications. Our data are similar to those obtained in SBC studies, highlighting the existence of distinct genetic pathways of tumor evolution, common to both SBC and FBC.     

CD44+鼻咽癌细胞的干细胞生物学特性

目的从人鼻咽癌SUNE-1 5-8F细胞株中分离出CD44⁺细胞并探讨其生物学特性。方法常规培养SUNE-1 5-8F细胞,采用流式细胞学技术检测SUNE-1 5-8F细胞中CD44⁺的表达并用流式细胞仪分选CD44⁺细胞;采用四甲基偶氮唑蓝（MTT）法、克隆形成实验等检测并比较CD44⁺、CD44^-细胞在体外增殖、分化等方面的差异;并用反转录聚合酶链反应（RT-PCR）检测干细胞基因Oct4、Bmi-1的表达。结果CD44⁺细胞在鼻咽癌细胞中SUNE-1株所占的比率约为52.5%;新分选的CD44+细胞在无血清培养液和完全培养液中较CD44^-及未分选细胞均显示出较强增殖能力;RT-PCR示Bmi-1和Oct4 mRNA在CD44+细胞中的表达水平明显高于CD44^-细胞。CD44⁺和CD44-细胞在接受2Gy放射处理后,其平均克隆生成效率分别为(23.44±1.90)%和(7.78±1.17)%（P＜0.001）;CD44⁺细胞较CD44^-细胞在相同顺铂和多西他赛药物浓度下显示出更高的细胞存活率。结论CD44⁺细胞具有类肿瘤干细胞特性,可能是鼻咽癌的重要肿瘤干细胞标志之一。     

Tumor-Endothelial Interaction Links the CD44+/CD24- Phenotype with Poor Prognosis in Early-Stage Breast Cancer

Materials and Methods

The genomic effects of tumor-endothelial interactions in cancer are not yet well characterized. To study this interaction in breast cancer, we set up an ex vivo coculture model with human benign and malignant breast epithelial cells with endothelial cells to determine the associated gene expression changes using DNA microarrays.

Results

The most prominent response to coculture was the induction of the M-phase cell cycle genes in a subset of breast cancer cocultures that were absent in cocultures with normal breast epithelial cells. In monoculture, tumor cells that contained the stem cell-like CD44⁺/CD24^- signature had a lower expression of the M-phase cell cycle genes than the CD44^-/CD24⁺ cells, and in the CD44⁺/CD24^- cocultures, these genes were induced. Pretreatment gene expression profiles of early-stage breast cancers allowed evaluating in vitro effects in vivo. The expression of the gene set derived from the coculture provided a basis for the segregation of the tumors into two groups. In a univariate analysis, early-stage tumors with high expression levels (n = 137) of the M-phase cell cycle genes had a significantly lower metastasis-free survival rate (P = 1.8e - 5, 50% at 10 years) and overall survival rate (P = 5e - 9, 52% at 10 years) than tumors with low expression (n = 158; metastasis-free survival, 73%; overall survival, 84%).

Conclusions

Our results suggest that the interaction of endothelial cells with tumor cells that express the CD44⁺/CD24^- signature, which indicates a low proliferative potential, might explain the unexpected and paradoxical association of the CD44⁺/CD24^- signature with highly proliferative tumors that have an unfavorable prognosis.     

PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy

Despite ongoing trials of PARP inhibitors in the treatment of breast cancer (BC), the extent of poly(ADP-ribose)polymerase-1 (PARP-1) protein expression in BCs, which may influence treatment results, is not known. The purpose of this report is to assess expression of PARP-1 in BC including BRCA1-associated, triple negative (TN), and basal-like tumors. Immunohistochemistry with a PARP-1 antibody on tissue microarrays from 130 BRCA1-associated and 594 BRCA1-non-related BCs was used. The vast majority of breast carcinomas expressed high level of nuclear PARP-1 protein and a small percentage of tumors exhibited both nuclear and cytoplasmic PARP-1 expression. There was a significant difference between the mean nuclear PARP-1 quickscore in BRCA1-associated versus BRCA1-non-associated carcinomas in all tumors (P < 0.0001), in the basal-like group (P = 0.0086), TN (P = 0.0015), and non-basal-like groups (P = 0.016) but not in the non-TN group. Among BRCA1-associated BCs, low PARP-1 expression was found in 18.5% of all cases, 18.9% of basal-like and 21% of TN cancers. Among BRCA1-non-related tumors, low PARP-1 expression was found in 8.8% of all cases, 3.1% of basal-like, and 2.7% of TN cancers. PARP-1 expression is significantly associated with BRCA1 status in basal-like and TN BCs. The assessment of PARP-1 expression in tumor samples may improve the selection of BC patients for PARP inhibitor therapy.     

Nuclear CSPP1 expression defined subtypes of basal-like breast cancer

Background:

The multi-exon CSPP1 gene, encoding for centrosome and microtubule-associated proteins involved in ciliogenesis and cell division, is a candidate oncogene in luminal breast cancer but expression of CSPP1 proteins remained unexplored.

Methods:

CSPP1 gene and protein expression was examined in normal mammary tissue, human breast cancer cell lines, and primary breast cancer biopsies from two patient cohorts. Cell type and epitope-dependent subcellular-specific CSPP1 staining pattern in normal mammary gland epithelium and cancer biopsies were correlated to molecular and clinical parameters.

Results:

A novel, nuclear localised CSPP1 isoform was exclusively detected in luminal epithelial cells, whereas cytoplasmic CSPP-L was generally expressed in normal mammary epithelium. Luminal cell-related nuclear CSPP1 expression was preserved in type-matched cell lines and carcinomas, and correlated to gene copy number and mRNA expression. In contrast, basal-like carcinomas displayed generally lower CSPP1 mRNA expression. Yet, a subgroup of basal-like breast carcinomas depicted nuclear CSPP1 expression, displayed luminal traits, and differed from nuclear CSPP1 devoid counterparts in expression of eight genes. Eight-gene signature defined groups of basal-like tumours from an independent cohort showed significant differences in survival.

Conclusions:

Differential expression of a nuclear CSPP1 isoform identified biologically and clinically distinct subgroups of basal-like breast carcinoma.