乳腺癌组织中ERCC1、Ki67、PCNA表达与蒽环类化疗药物敏感性的关系

目的:对乳腺癌组织中,核苷酸切除修复交叉互补基因1(Excision repair cross comp-lementing,ERCC1)、Ki67蛋白、增殖细胞核抗原(Proliferating cell nuclear antigen,PCNA)表达与蒽环类化疗药物敏感性的关系进行探讨。方法:通过免疫组化法对93例乳腺癌组织的ERCC1、Ki67和PCNA表达进行检测;观察患者化疗疗效,对ERCC1、Ki67和PCNA表达水平不同患者使用蒽环类药物化疗的效果差异进行比较。结果:ERCC1的阳性率为65.59%,Ki67的阳性率为69.89%,PCNA的阳性率为64.52%。ERCC1阳性组总有效率为50.82%,ERCC1阴性组总有效率为84.38%;Ki67阳性组中,Ki67表达强度为25%~50%患者有效率为73.68%(14/19),50%~75%患者有效率为85.71%(24/28),75%患者有效率为88.89%(16/18),Ki67阴性组总有效率为60.71%;PCNA阳性组中,PCNA表达强度为25%-50%患者有效率为52.94%(9/17),50%~75%患者有效率为62.07%(18/29),75%患者有效率为71.43%(10/14),PCNA阴性组总有效率为81.82%,以上差异均有统计学意义(P0.01,P0.05,P0.05)。结论:乳腺癌患者ERCC1、Ki67和PCNA的表达情况与蒽环类化疗药物的敏感性均有相关关系,而在临床上对多因子的联合检测将更有助于化疗药物的选择以及化疗方案的制定。     

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。     

乳腺浸润性导管癌组织FAK、Ki67的表达及其临床意义

目的：研究乳腺浸润性导管癌组织中黏着斑激酶（Focal adhesion kinase，FAK）和Ki67的表达与肿瘤侵袭转移的关系，探讨FAK介导的细胞信号转导系统在乳腺癌发生发展中的作用机制。方法：应用免疫组化SP法检测88例乳腺浸润性导管癌组织和25例乳腺导管上皮良性增生性病变组织中FAK、Ki67的表达情况。结果：在88例乳腺浸润性导管癌中FAK的阳性表达率为68.2%（60/88），Ki67标记指数为29.6%±22.9%，与良性对照组比较均有显著差异（P〈0.01）；FAK表达与乳腺癌肿瘤大小、腋窝淋巴结转移、临床分期呈正相关（P〈0.01），与患者年龄、组织病理学分级未见显著相关（P〉0.05）；乳腺癌FAK表达与Ki67增殖指数呈正相关（P〈0.01）。结论：FAK和Ki67的高表达与乳腺癌的发生发展密切相关，FAK对肿瘤细胞的Ki67增殖指数具有促进作用，检测这些指标有助于乳腺癌的预后判断及治疗。     

Ki67免疫组化分析在乳腺癌治疗中的临床意义

通过分析Ki67在乳腺癌表达水平与临床病理特征相关性以及研究其在术后新辅助化疗前后的变化,探讨Ki67标记指数在乳腺癌治疗中的临床意义。采取免疫组化法(SP法)检测2012年后该院的246例乳腺癌患者的336例乳腺癌病理组织中Ki67的阳性表达情况,其中包括90例患者新辅助化疗前后的组织标本。Ki67阳性比例为67.5%(166/246),Ki67的表达与肿瘤大小、淋巴结转移、组织细胞学分级和人表皮生长因子受体-2成正相关(为P0.05或P0.01),与年龄、雌激素受体、孕激素受体表达成负相关(均为P0.01),与TNM分期无明显相关性;Ki67在新辅助化疗前后的表达变化值与化疗疗效明显相关(P0.01),新辅助化疗效果越好,Ki67下降越明显。Ki67阳性表达与乳腺癌的临床病理特征有密切的相关性,对乳腺癌的早期诊断、治疗与预后有指导意义,另外术后新辅助化疗影响Ki67的表达,Ki67对预测新辅助化疗的疗效有重要意义,但其是否可以作为乳腺癌诊断预后及新辅助化疗疗效的可靠指标仍需进一步研究。     

乳腺癌细胞动力学指标与相关基因表达、突变的关系

目的 探讨乳腺癌细胞动力学及凋亡与相关基因表达、突变的关系。方法 采用流式细胞术检测54例乳腺癌DNA指数(DI)、S期细胞比例(SPF)、细胞增殖指数(PI)及细胞凋亡指数(AI)，免疫组织化学法检测原癌基因c—erbB-2、Bcl-2、抑癌基因p53，增殖细胞核抗原PCNA、Ki67及托普DNA酶Ⅱ(TopoⅡ)的表达，PCR—SSCP法检测p53点突变及突变部位、类型；结果 高DI、异倍体率、SPF、PI、AI与c—erbB-2、p53、PCNA、Ki67、TopoⅡ高表达相关。低DI、SPF、PI、AI与Bcl-2高表达相关。高DI、SPF、PI、AI与p53高突变相关，高AI与p53突变类型之一——杂合性缺失(LOH)相关。结论 乳腺癌细胞动力学及凋亡的异常与相关基因的异常表达及突变密切相关。     

Ki67、P53、Her-2在乳腺癌中的表达及其相关性

Ki67、P53抗原和Her-2表达与乳腺癌淋巴结转移均密切相关：联合检测Ki67、P53抗原和Her-2表达是衡量乳腺癌预后的重要指标。     

HER2、Ki67表达水平与乳腺癌临床特征及预后的关系分析

目的 探讨HER2、Ki67表达水平与乳腺癌临床特征及预后的关系。方法 回顾性分析我院2016年6月至2019年5月121例乳腺癌患者临床资料,分别使用免疫组织化学（IHC）方法对患者癌组织、癌旁组织及正常组织中HER2、Ki67表达水平进行检测,采用SPSS软件对HER2、Ki67表达水平与乳腺癌病理特征的关系进行分析,并对其与患者预后的关系进行评估。结果 乳腺癌组织HER2(57.85%)、Ki67(61.98%)阳性率明显高于癌旁组织（37.19%、33.88%）与正常组织（4.96%、4.13%）。高表达HER2、Ki67患者淋巴结转移、TNM分期明显高于低表达者。Spearman相关性分析显示,HER2、Ki67表达水平与患者淋巴结转移个数及TNM分期呈正相关,HER2与Ki67表达呈正相关。121例患者随访时间24～48个月,2年内有83例患者生存,生存率为68.60%,中位生存时间为52个月（6～48个月）。高表达HER2(25个月)、Ki67(19个月)中位生存时间明显低于低表达患者（42,44个月）。癌症基因组图谱（TCGA）数据乳腺癌肿瘤组织HER2、Ki67表达量...     

乳腺癌的MRI影像特征与PTEN和PCNA表达的相关性研究

目的探讨乳腺癌动态增强磁共振成像的影像特征及其与癌组织10号染色体上与张力蛋白同源的磷酸酶(PTEN)和增殖细胞核抗原(PCNA)表达的关系。方法纳入2015年5～2017年12月我院乳腺手术患者52例,全部患者均行MRI-弥散加权成像(DWI),将图像进行后处理,并进行ADC值测量。术后病理证实其中43例乳腺癌,9例乳腺纤维腺瘤。所有患者组织采用HE染色观察组织病理学改变,免疫组织化学方法与Western blot方法检测肿瘤组织PTEN和PCNA的表达情况,并将PTEN和PCNA的表达与MRI-DWI成像表观扩散系数(ADC值)进行相关性分析。结果与乳腺纤维腺瘤组织相比,乳腺癌组织中PTEN蛋白阳性表达的平均光密度值显著降低,PCNA蛋白阳性表达的平均光密度值显著升高(P0.01)。乳腺癌ADC值明显低于乳腺纤维腺瘤组织,乳腺癌ADC值与PTEN呈正相关(r=0.619,P0.01);乳腺癌ADC值与PCNA表达结果呈负相关(r=-0.527,P0.01)。结论 PTEN与PCNA的表达与乳腺癌的MRI影像学表现密切相关,可作为患者临床治疗和预后判断的重要参考指标。     

胃肠道类癌中Ki-67、PCNA、Laminin的表达及意义

目的 研究胃肠道类癌Ki-67、PCNA、laminin(LN)的表达与侵袭性和增殖性的关系。方法 应用免疫组织化学S-P法检测36例胃肠道类癌组织中3种指标的表达。结果 36例胃肠道类癌组织中Ki～67、PCNA、LN阳性表达率分别为50．o％、55．5％、55．5％；随肿瘤分化程度降低、浸润深度加深、淋巴结的转移，各指标阳性表达率逐渐升高。结论 Ki-67、PC-NA可作为评估胃肠道类癌预后的指标。Ki-67比PCNA在评价胃肠道类癌增殖性方面更准确；PCNA免疫染色反应性较敏感，其类癌诊断的阳性标准应适当提高。LN的表达可预测胃肠道类癌组织的分化、浸润及转移能力。     

乳腺癌中PCNA的表达及其临床意义

目的:探讨乳腺癌中增殖细胞核抗原(PCNA)的表达与肿瘤病理分级、临床分期及预后的关系。方法:采用免疫组化S-P法,检测63例原发性乳腺癌和11例乳腺小叶增生症中PCNA的表达,并分析其在不同病理分级、临床分期及有无淋巴结转移病例中的表达强度。结果:PCNA在乳腺癌肿瘤组织和小叶增生组织中的表达有显著性差异(P<0.01)。随着乳腺癌病理分级、临床分期的增加,PCNA阳性表达增强,Ⅰ级与Ⅱ、Ⅲ级,Ⅱ级与Ⅲ级,Ⅰ～Ⅱ期与Ⅲ～Ⅳ期,无淋巴结转移与有淋巴结转移比较,差异均有显著性(P<0.05)。结论:PCNA可作为判断乳腺癌恶性程度及预后的指标。     

鼻咽癌细胞增殖因素的检测与预后的相关性

目的：探讨鼻咽癌细胞中细胞增殖因素cyclinD1、c-erbB-2、Ki-67、PCNA蛋白的表达及其与鼻咽癌预后的关系。方法：以免疫组化S－P法检测212例鼻咽癌组织cyclinD1、c-erbB-2,Ki-67和PCNA蛋白的表型。结果：cyclinD1蛋白表达阳性率81．25％,表达程度与临床分期、原发灶范围、鼻咽部复发呈正相关,与患者5年生存率呈负相关。c-erbB-2蛋白表达阳性率为95％,表达程度与临床分期、原发灶、颈部转移灶、局部复发及远处转移呈正相关,与5年生存率呈负相关。Ki-67蛋白表达阳性率为97％,表达程度与临床分期、原发灶、颈部转移灶呈正相关。PCNA蛋白表达阳性率为99％。在cyclinD1,c-erbB-2,Ki-67及PCNA4因素中除Ki-67与PCNA无明显相关性外,其他因素间均存在明显的相关性。多因素分析表明对鼻咽癌颈后有显著影响的因素是cyclinD1、c-erbB-2。结论：cyclinD1、c-erbB-2与鼻咽癌的预后有较好的相关性,对于cyclinD1、c-erbB-2高表达的患者,应采取综合治疗。     

Evaluation of proliferation parameters in in vivo bromodeoxyuridine labelled lung cancers

In a series of 44 bronchial biopsies from patients suspected of having endobronchial lung carcinoma, the validity of proliferating cell nuclear antigen (PCNA) and Ki67 antigen as proliferative indicators was evaluated in ethanol fixed, paraffin embedded tissue. The percentages of cells positive for these markers were compared to the in vivo bromodeoxyuridine (BrdU) labelling index. A good correlation was found between PCNA immunoreactivity and BrdU labelling index, while Ki67-antigen expression showed a significant relation with BrdU labelling index and with PCNA expression. All three parameters showed a trend towards similar values for the individual cases. Based on the fact that Ki67 antigen is expressed in all cycling cells, whereas replicon-associated PCNA and BrdU only reflect the S-phase fraction, the differences between Ki67-antigen scores on the one hand and BrdU and PCNA scores on the other were smaller than expected. In order to determine the degree of concordance between immunohistochemically and flow cytometrically detected proliferation variables, BrdU incorporation was measured using both methods in duplicate bronchial specimens. Discrepancies in labelling indices were observed predominantly in DNA diploid samples, with consistently lower values in the flow cytometrically analysed specimens. In tumour specimens with an aneuploid DNA content, flow cytometric determination of proliferative activity yielded results similar to those obtained by tissue section examination. We conclude that the scores for PCNA and Ki67 antigen, immunohistochemically detected in ethanol fixed, paraffin embedded tissue reflect functional proliferative activity.     

PCNA and Ki67 expression in breast carcinoma: correlations with clinical and biological variables.

AIMS: To investigate the expression of two cell cycle related antigens (proliferating cell nuclear antigen (PCNA) and Ki67 related antigen) in a series of breast cancers; and the possible correlations between the PCNA and Ki67 labelling indexes (PCNA-LI and Ki67-LI) and their associations with other biological and clinicopathological variables. METHODS: Ninety six ductal and 10 lobular carcinoma specimens were investigated. Samples were fixed in formalin and in Methacarnoy for localisation of PCNA. Ki67 was immunostained on frozen sections. The PCNA-LI and Ki67-LI were evaluated in relation to tumour size, mitotic count, histological grade, nodal state as well as receptor content and altered expression of the p53 gene. RESULTS: PCNA-LI did not correlate with Ki67-LI, nor was it associated with any other variable examined. A high KI67-LI (above the median value of 13.5) was associated with high grade and mitotic count, negative receptor content, and altered expression of the p53 gene, but not with other variables. CONCLUSIONS: The PCNA-LI does not seem to be a substitute for the Ki67-LI in evaluating the growth fraction in breast cancer.     

Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms

Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle. A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells. In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated. These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation. However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost. In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours. The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression.     

Proliferation Markers and EGF in ACTH-Secreting Adenomas and Carcinomas of the Pituitary

Pituitary carcinomas are only defined by their metastatic growth, which may be intracranial or systemic. To establish further morphological and immunohistochemical differences between pituitary carcinomas and adenomas, 19 ACTH-secreting adenomas (10 non invasive and 9 invasive) and 2 ACTH-secreting carcinomas with their metastases were studied for expression of the intermediate filaments keratin and vimentin and the tumor-associated antigens Ki67, proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF), cathepsin D, p53, and carcinoembryonic antigen (CEA). Immunohistochemistry was performed using avidin-biotin techniques on formalin-fixed, paraffin-embedded tissue. With the exception of one noninvasive pituitary adenoma, one carcinoma, and the metastases, all tumors contained keratin; none contained vimentin. All tumors stained negative for CEA and p53. Eleven (58.5%) adenomas and both pituitary carcinomas contained Ki67-positive nuclei; 14 (74%) adenomas and one carcinoma revealed PCNA. No correlation was found between the two markers. Seven (38%) adenomas showed a labeling index <1 % for cathepsin D, whereas none of the carcinomas or metastases did so. EGF was found in 7 (38%) adenomas and in both carcinomas. A tendency to a higher rate of EGF positivity in the invasive adenomas was observed. The metastases showed a higher labeling index, and far more intense staining results for Ki67, PCNA, and EGF than the primary tumor. The metastases also had a higher proliferation rate and growth factor content than the carcinoma itself.     

乳腺癌细胞凋亡、增殖与相关基因表达、突变的关系

目的:研究乳腺癌细胞凋亡、细胞增殖及相关基因表达、突变的关系,为乳腺癌细胞凋亡、细胞增殖失衡的基因调控机制提供依据。方法:分别应用TUNEL法、免疫组化S-P法和PCR-SSCP法检测54例乳腺癌标本凋亡指数(AI)和增殖指数(MI),Bcl-2、p53、c-erbB-2、PCNA、Ki67、TopoⅡ蛋白表达和p53基因突变。结果:54例乳腺癌AI平均9.40±3.78,MI平均5.96±2.36,AI与MI呈显著正相关(r=0.46,P＜0.01)。Bcl-2、PCNA、Ki67、TopoⅡ表达与AI、MI均呈显著正相关(P＜0.01)。p53表达、c-erbB-2表达、p53突变与MI呈显著正相关(P＜0.01)。p53基因突变类型与AI呈显著相关(P＜0.05)。结论:乳腺癌细胞凋亡、增殖失衡与相关基因异常表达、突变有关。     

Ki67 antigen and PCNA proliferation markers predict survival in anorectal malignant melanoma

AIMS: To find a possible correlation of Ki67 antigen and proliferating cell nuclear antigen (PCNA) with prognosis in anorectal malignant melanoma. METHODS AND RESULTS: Thirty patients with anorectal malignant melanoma were studied. The percentage of tumour cells stained for Ki67 and PCNA in paraffin sections was assessed. Mode of treatment (local excision or abdominoperineal resection), depth of tumour invasion, attempt at cure as defined by complete tumour excision and absence of distant metastases at presentation, tumour blood vessel invasion, and tumour necrosis, as well as Ki67 and PCNA, were all correlated with survival. By univariate analysis, PCNA, Ki67, attempt at cure, local excision (and not abdominoperineal resection), and depth of invasion were all significantly associated with longer survival. By multivariate analysis, only PCNA was significantly associated with survival, while Ki67 showed a significant positive correlation with PCNA. With a cut-off point of 40%, patients with lower Ki67 scores showed survival advantage over those with higher Ki67 scores (P=0.0004). With a cut-off point of 80%, patients with lower PCNA scores showed survival advantage over those with higher PCNA scores (P=0.0001). The staining for proliferation markers was also associated with depth of tumour invasion. CONCLUSIONS: Ki67 and PCNA immunostaining in paraffin sections may be useful for the prediction of survival in patients with anorectal malignant melanoma. Larger studies are needed to confirm our results.     

DNA topoisomerase IIα expression correlates with cell proliferation but not with recurrence in intracranial meningiomas

AIMS: To assess the value of topoisomerase IIalpha (TopoIIalpha) as a novel proliferation-associated molecule, by correlating its immunohistochemical expression with Ki67 (MIB-1), cell proliferating cell nuclear antigen (PCNA) and mitotic index in meningiomas. Furthermore, to investigate its relation to standard clinicopathological parameters and patients' outcome. METHODS AND RESULTS: This retrospective study comprised a consecutive series of 57 patients with primary intracranial benign and atypical meningiomas. Six tumours recurred (10.5%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months (median 60 months). Archival formalin-fixed paraffin-embedded sections were stained with standard immunohistochemical methods. The lower proliferation indices were obtained with TopoIIalpha and the higher ones with PCNA. TopoIIalpha labelling index (LI) ranged from 0.1% to 10% (median 0.5%) and, along with Ki67 and PCNA LI, increased with malignancy grade (P=0.049, P=0.045 and P < 0.001, respectively), displaying though a significant overlapping between grades. A significant positive correlation was shown between TopoIIalpha and Ki67 (P < 0.001) or PCNA (P=0.032). In univariate and multivariate survival analysis, TopoIIalpha failed to predict meningioma recurrence and did not affect disease-free survival. Only tumour size and Ki67 LI provided significant prognostic information in this regard. CONCLUSIONS: TopoIIalpha expression may be useful as a novel proliferation marker in meningiomas, presenting several advantages over the markers currently in use, notably providing a better estimate of the number of cycling cells and a more uniform nuclear staining pattern. However, it fails to discriminate between benign and atypical neoplasms and does not provide prognostic information beyond that obtained by Ki67.     

Proliferative and apoptotic markers in prostate carcinoma in relation to androgen receptor

Prostate carcinoma, one of the most frequent male malignancies, is in certain stages of its development significantly influenced by androgens. Therefore, we carried out a retrospective study on a set of 130 patients with nongeneralized, localized prostate carcinoma (stage T1-T2, PSA up to 25 ng/ml). We determined immunohistochemically the expression of proliferation markers PCNA and Ki67, Bax, p53, Bcl-2, p21waf1, p27kiP1 and compared them with the expression of the androgen receptor (AR). Multivariation statistical analysis of the results using the chi-square test with Pearson's correction and variability analysis using the SPSS 8.0 software program showed a strong correlation of the PCNA and Ki67 proliferation markers with the expression of hormonal dependence and apoptosis markers. The expression of PCNA correlated strongly with p27 kip1 and Bax, while the expression of Ki67 correlated most strongly with p27 kip1 and Bcl-2. The expression of p27 kip1 correlated with the expression of androgen receptor, PCNA, Ki67 as well as Bcl-2. None of the observed markers correlated significantly with Gleason's score. We did not find substantial significant relation between the observed markers and the expression of p53 and p21 waf1. The results indicate a significant role of the expression of p27 kip1 protein in regulating proliferative activity and hormonal responsiveness in the initial stage of prostate carcinoma.     

Proliferative index in breast carcinoma determined in situ by Ki67 immunostaining and its relationship to clinical and pathological variables

Sixty cases of primary breast carcinoma have been studied using a monoclonal antibody, Ki67, which recognizes an antigen expressed by cells in G1, S, G2, and M phases of the cell cycle but not Go. A Ki67 score (positive cells/total tumour cells) was determined, and possible relationships between this index of cellular proliferation and a number of clinical and pathological parameters were investigated. There was a strong positive correlation between the Ki67 score and mitotic index (p less than 0.001), a weak negative correlation with age (p less than 0.02), and weak positive correlations with histological tumour grade (p less than 0.03), tumour necrosis (p less than 0.01), and cellular reaction (p less than 0.01). No relationship was noted between the Ki67 score and tumour size, nodal status, tumour oestrogen receptor levels, or menopausal status. The Ki67 score may prove to be an objective indicator of biological behaviour and thus be of clinical significance, particularly since it is not strongly related to other clinical and pathological parameters used in predicting outcome in breast carcinoma.