Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer

Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.

The expression of Elf-1 and Ki-67 and their correlations in non-small-cell lung cancer

Objective: Elf-1 is a member of the proto-oncogenes Ets-related transcription factor family and over-expressed in many human tumors, Ki-67 is an important nuclear antigen associated with cell proliferation. This study investigated the expression of Elf-1 and Ki-67 in non-small-cell lung cancer(NSCLC) and studied their correlation with the clinicopathological features. Methods: Tissue microarray from 64 cases lung cancer tissue and 10 cases normal lung tissue was constructed, immunohistochemical method was used to evaluate the protein expressions of Elf-1 and Ki-67, correlations of the expression of Elf-1 and Ki-67 to clinicopathological features of NSCLC were analyzed. Results: Expression of Elf-1 and Ki-67 in NSCLC tissues were significantly higher than in normal lung tissues(P < 0.05), the positive rate of Elf-1 and Ki-67 was 73.44% and 64.06% in NSCLC group, Overexpression of Elf-1 in NSCLC was significantly related to histopathological grading, different clinical staging and the intensity of ELF-1 expression was significantly higher in the group with lymph node metastasis than that without(P < 0.05). Overexpression of Ki-67 was also closely related to tumor differentiation, clinical stages and lymph node metastasis(P < 0.05). In addition positive correlation was found between the expressive intensity of Elf-1 and Ki-67(τ = 0.295, P = 0.018). Conclusion: The high expression and positive correlation of Elf-1 and Ki-67 in NSCLC suggest that they probably play a role in onset and progression of lung cancer, united detecting their expression could be used as an valuable molecular biological index for predicting the malignant behavior and early diagnosis of NSCLC.

Ki-67 as a prognostic marker according to breast cancer molecular subtype

Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed.Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Followup ranged from 32 months up to 6 years.Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative(TN),respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than15%(P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15%(P = 0.000).Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients.

Relationship between expression of ER, PR, Her-2, Ki-67 and neoadjuvant chemotherapy effect in breast cancer

Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of neoadjuvant chemotherapy in breast cancer. Methods: The expression of ER, PR, Her-2 and Ki-67 in 45 breast cancers which received neoadjuvant chemotherapy was detected by immunohistochemistry. Results: The effective rates in ER negative and PR negative groups were higher than those in ER positive and PR positive groups(83.3% vs 59. 4%, 82.4% vs 60.6%). There was no significant difference of the effective rate between Her-2 overexpressed group and Her-2 non-overexpressed group(81.8% vs 64.1%), and the same thing happened between Ki-67 negative group and Ki-67 positive group(67.7% vs 63.2%). Conclusion: In the patients with breast cancer, ER, PR negative ones were more sensitive to neoadjuvant chemotherapy. These patients may get more benefits from chemotherapy. ER, PR could be feasible markers for predicting the effective rate of neoadjuvant chemotherapy.

A Meta-Analysis of Lymphatic Vessel Invasion Correlated with Pathologic Factors in Invasive Breast Cancer

Objectives: The invasive breast cancer is divided into four clinical subtypes: Luminal A-like, Luminal B-like, HER-2 positive, and triple-negative according to the expression status of estrogen receptor (ER), progesterone receptor(PR), human epidermal growth factor receptor-2 (HER-2) and Ki-67. The prognosis and treatment strategy vary with subtypes. The current studies have reported the relation between lymphatic vessel invasion (LVI) and the expression status of ER, PR, HER-2, Ki-67 in invasive breast cancer, but the results were debatable. So the meta-analysis was conducted to confirm the relation between LVI and the four factors. Methods: Literature was searched by entering the terms: breast AND (neoplasm OR cancer OR carcinoma) AND (lymphovascular OR “lymph vessel” OR “lymphatic vessel” invasion OR carcinoma embolus) AND (ER OR estrogen receptor OR PR OR progesterone receptor OR HER-2 OR human epidermal growth factor receptor-2 OR Ki-67 OR clinicopathological) in Pubmed. The merged odds ratio (OR) and 95% confidence interval (CI) were estimated using fixed-effect model. Review Manager 5.2 was used to analysis the relation between LVI and the expression status of ER, PR, HER-2, Ki-67 in invasive breast cancer respectively. The fail-safe number was used to estimate publication bias. Results: The analysis included 5 studies, LVI positive rate was significant lower in ER positive, PR positive, HER-2 negative, low Ki-67 expression group statistically. The OR and 95% CI were 0.6(0.44 - 0.81), 0.64(0.43 - 0.95), 1.52(1.03 - 2.24), 5.29(1.53 - 18.35) respectively.Conclusions:?LVI was significantly correlated with the expression status of ER, PR, HER-2 and Ki-67 in invasive breast cancer. Furthermore, LVI was consistent with poor prognostic expression status of the four factors.

三阴性与非三阴性乳腺癌的表观弥散系数与Ki-67指数的相关性研究

目的探讨乳腺扩散加权成像(diffusion weighted imaging,DWI)中平均ADC值(mean apparent diffusion coefficient,ADCmean)、最小ADC值(minimum apparent diffusion coefficient,ADCmin)、最大ADC值(maximum apparent diffusion coefficient,ADCmax)和表观弥散系数差(difference between ratios of apparent diffusion coefficients,ADCDR)的效用,寻找用于鉴别三阴性乳腺癌(triple-negative breast cancer,TNBC)与非三阴性型乳腺癌(non-triple negative breast cancer,nTNBC)的最佳ADC参数并探索ADC值与肿瘤分子生物学指标Ki-67之间的相关性。材料与方法回顾性分析2019年1月至2020年5月收治的145例(共148个病灶)经病理确诊的乳腺癌患者术前磁共振的MRI资料,患者均为女性,年龄25~80(51.4±10.5)岁;其中TNBC 28例(28个病灶),nTNBC 117例(120个病灶)。比较两组间的ADC值定量参数,绘制受试者工作特性(receiver operating characteristic,ROC)曲线,评价ADC值的鉴别精度。测量实体瘤成分的Ki-67增殖指数,探讨其与ADC值的相关性。结果TNBC的ADCmean和ADCmin[(0.769±0.117)×10^(-3)mm^(2)/s、(0.633±0.091)×10^(-3)mm^(2)/s)显著低于nTNBC[(0.897±0.088)×10^(-3)mm^(2)/s、(0.712±0.121)×10^(-3)mm^(2)/s],差异均有统计学意义(P<0.05);TNBC的ADCDR[(0.692±0.082)×10^(-3)mm^(2)/s]显著高于nTNBC[(0.468±0.133)×10^(-3)mm^(2)/s],差异有统计学意义(P<0.05);TNBC的ADCmax[(1.325±0.088)×10^(-3)mm^(2)/s]高于nTNBC[(1.181±0.112)×10^(-3)mm^(2)/s],但差异无统计学意义(P>0.05)。ROC曲线结果显示:ADCDR区分两组效果最好,曲线下面积为0.925,以0.635×10^(-3)mm^(2)/s为作为两组鉴别诊断的最佳阈值,其敏感度及特异度分别为78.6%、93.3%。相关性分析显示:ADCmean(r=-0.321)、ADCmin(r=-0.316)与Ki-67表达呈负相关(P均<0.01),ADCmax(r=0.249)和ADCDR(r=0.447)与Ki-67表达呈正相关(P均<0.01)。结论ADC值定量分析在TNBC与nTNBC鉴别中具有临床诊断价值,可作为常规MRI检查的一种补充的量化分析工具,ADCDR值可能是DWI鉴别两组的最佳单一参数,且ADC值与增殖指数Ki-67之间存在一定的相关性。

ER、PR、Ki-67、VEGF组织表达与乳腺癌患者生存质量的相关性分析

目的探讨ER、PR、Ki-67、VEGF组织表达与乳腺癌患者生存质量的相关性.方法：选择2010年2月至2015年12月来我院就诊的乳腺癌患者120例,均给予新辅助化疗治疗,同时检测所有患者ER、PR、Ki-67和VEGF组织表达程度,比较上述阴性患者与阳性患者治疗前后生活质量评分差异,并计算相关系数R,进行相关性分析.结果：乳腺癌ER、PR、ki67、VEGF阳性表达患者治疗后生存质量评分均明显低于阴性患者,分别经t检验比较,差异均有统计学意义（P〈0.05）.同时针对ER、PR、ki67、VEGF表达与乳腺癌治疗后生存质量进行相关性分析,相关系数均为0〉r≥-1,差异亦有统计学意义（P〈0.05）.结论：ER、PR、Ki-67、VEGF组织表达与乳腺癌患者生存质量呈负相关,表达水平高患者其生存质量较差.

Ki-67、CDK4表达与中晚期乳腺癌新辅助化疗效果的相关性分析

目的:分析Ki-67核抗原(Ki-67)、CDK4表达与中晚期乳腺癌新辅助化疗(NACT)效果的相关性。方法:回顾性选取2016年4月至2018年6月我院的中晚期乳腺癌患者70例,均于新辅助化疗后实施手术,依据化疗效果分为有效组、无效组,采用免疫组化法检测两组化疗前Ki-67、CDK4表达水平,比较不同Ki-67、CDK4表达水平患者病理完全缓解率(pCR)、2年复发转移情况。结果:有效组Ki-67高表达率、CDK4阳性率高于无效组(P<0.05);Ki-67高表达患者pCR率高于Ki-67低表达者,CDK4高表达者pCR率高于CDK4低表达者(P<0.05);Kaplan-Meier曲线显示,Ki-67低表达的乳腺癌患者2年复发转移率低于Ki-67高表达者(P<0.05),CDK4高表达的乳腺癌患者2年复发转移率与CDK4低表达者无明显差异(P>0.05);Spearman相关分析显示,乳腺癌患者Ki-67、CDK4表达变化与化疗效果呈正相关(r=0.569、0.481,P<0.05)。结论:Ki-67、CDK4高表达的乳腺癌患者经NACT后获得pCR率更高,化疗疗效更优,但Ki-67高表达者预后较差,CDK4表达情况与预后相关性不大。

三阴性乳腺癌中AR与Ki-67、CK5/6的表达及相关性分析

目的研究三阴性乳腺癌(triple-negative breastcancer,TNBC)中雄激素受体(androgen receptor,AR)与细胞增殖指数(Ki-67)、细胞角蛋白5/6(CK5/6)的表达及其相关性。方法采用免疫组化法检测回顾性收集的115例TNBC患者已手术切除的肿瘤组织标本中的AR、Ki-67和CK5/6的表达,并对患者的临床病理特征进行相关性分析。结果AR与Ki-67、CK5/6在TNBC的表达均存在显著负相关关系(P<0.05,r值分别为0.467和0.350)。组织学分级在Ki-67分组间的差异存在统计学意义(P<0.05),组织学分级1~2级的TNBC患者在Ki-67低表达组中的占比率高于Ki-67高表达组。患者的年龄、肿瘤最大径、淋巴结转移在Ki-67分组间表达差异均无统计学意义(P>0.05)。患者的年龄、肿瘤大小、组织学分级、淋巴结转移在AR与CK5/6分组间表达差异均无统计学意义(P>0.05)。结论三阴性乳腺癌组织中AR与Ki-67、CK5/6表达存在负相关关系,联合检测这3个抗体的表达,可能有助于TNBC的危险分级,为TNBC潜在的治疗靶点提供一些理论支持。

Soy isoflavone extracts stimulate the growth of nude mouse xenografts bearing estrogen-dependent human breast cancer cells(MCF-7)

We explored the effects of different lifetime exposures to soy isoflavone extracts on the growth of estrogen- dependent human breast cancer cells （MCF-7） implanted into athymic mice of different ovarian statuses. The athymic mice, ovariectomized or not, were implanted with MCF-7 cells. Mice were fed with low, moderate and high doses of soy isoflavone extract, at dietary concentrations of 6.25, 12.5 and 25 g/kg, in different reproductive models, respectively. The expression of ki-67 was detected by immunohistochemistry, pS2 expression in tumors was analyzed by real-time PCR. Estrogen level in the serum was measured by chemiluminescence enzyme im- munoassay. Total genistein and daidzein levels in serum and urine were determined by liquid chromatography- electrospray tandem mass spectrometry （LC-ES/MS/MS）. In Group A, on week 4, nude mice were exposed to different doses of soy iosflavone extracts. In Group B, the experimental diets were given to the nude mice follow- ing ovariectomy and tumor implantation. In both groups, 6.25 and 12.5 g/kg soy isoflavone extracts stimulated the growth of MCF-7 xenografts, increased pS2 expression, proliferation and estrogen level in serum. In both Group B （postmenopausal mouse model） and Group C （premenopausal mouse model）, soy isoflavone extracts at doses of 6.25 and 12.5 g/kg showed stimulatory effects on the growth of MCF-7 tumors. In conclusion, administration of soy isoflavone extracts at doses of 6.25 and 12.5 g/kg during adolescence or later in life stimulated tumor growth in both menopausal and postmenopausal mouse models.

浸润性乳腺癌MRI征象与HER-2及Ki-67表达的相关性

目的:探讨浸润性乳腺癌(IBC)核磁共振成像(MRI)征象与人表皮生长因子受体2(HER-2)、肿瘤增殖抗原Ki-67表达的相关性。方法:选择2015年6月至2017年12月在我院进行治疗的IBC患者65例为研究对象,对所有患者进行MRI扫描检查,采用免疫组化检查患者的HER-2、Ki-67阳性表达。分析MRI征象与HER-2、Ki-67阳性表达的相关性。结果:MRI扫描检查结果显示:边缘毛刺征患者占比63.08%(41/65)、分叶征患者占比58.46%(38/65)、钙化患者占比73.85%(48/65)、淋巴结转移患者占比67.69%(44/65)。免疫组化检查结果显示:HER-2阳性患者占比69.23%(45/65)、Ki-67阳性患者占比58.46%(38/65)。存在边缘毛刺征、分叶征、钙化、淋巴结转移的患者HER-2、Ki-67阳性表达高于无边缘毛刺征、无分叶征、无钙化、无淋巴结转移的患者(P<0.05)。经Spearman相关性分析显示,乳腺癌肿块的边缘毛刺征、分叶征、钙化、淋巴结转移与HER-2、Ki-67阳性表达呈正相关(P<0.05)。结论:IBC的MRI影像学特征与患者的HER-2、Ki-67阳性表达水平呈正相关,可通过对IBC患者细胞生物学因子指标水平的判断,评估患者疾病的严重程度以及预后情况等。

术前MRI影像学检查与乳腺癌KI-67表达的相关性

目的探究术前动态增强磁共振成像(DCE-MRI)检查与乳腺癌患者肿瘤细胞增殖核抗原(KI-67)表达的相关性。方法选择2016年5月至2019年5月我院收治的82例乳腺癌患者为研究组,50例乳腺良性肿瘤患者为对照组,检测两组患者DCE-MRI相关参数[早期增强率(EER)、强化峰值(SImax)、最大线性斜率(Slope)、达峰时间(Tpeak)、MIP图血管计数(NTV)、表观弥散系数(ADC)]及病变组织中KI-67表达水平,分析乳腺癌患者不同DCE-MRI形态学征象之间KI-67表达差异,分析乳腺癌患者DCE-MRI相关参数与KI-67的相关性,分析DCE-MRI对乳腺癌患者KI-67表达状态的预测结果。结果研究组KI-67阳性表达率显著高于对照组(P<0.05);研究组SImax、Tpeak、ADC显著低于对照组(P<0.05);研究组EER、Slope、NTV显著高于对照组(P<0.05);DCE-MRI显示肿瘤直径、肿瘤边界不同的乳腺癌患者病变组织中KI-67表达水平无显著差异(P>0.05);DCE-MRI显示肿瘤内部坏死情况、淋巴结转移情况不同的乳腺癌患者病变组织中KI-67表达水平差异具有统计学意义(P<0.05);乳腺癌患者Slope、SImax与KI-67无相关性(P>0.05);乳腺癌患者EER、NTV与KI-67呈正相关(P<0.05);乳腺癌患者Tpeak、ADC与KI-67呈负相关(P<0.05);DCE-MRI预测乳腺癌患者KI-67表达状态的特异度为90.68%,准确率为85.66%。结论 KI-67在乳腺癌患者中处于高表达状态,乳腺癌患者DCE-MRI扫描各参数与KI-67表达水平密切相关。

The Association between Sentinel Lymph Node Metastasis and Ki-67 Labeling Index

Background: The purpose of this study was to elucidate the association between sentinel lymph node (SLN) metastasis and Ki67 labeling index and to elucidate whether Ki-67 was useful or not for prediction of SLN metastasis in breast cancer. Methods: We identified 343 invasive breast cancer patients with sentinel lymph node biopsy (SLNB) from 2003 to 2012. The association between SLN status and clinicopathological features, molecular subtypes and Ki-67 labeling index were evaluated. Results: SLN metastasis was detected in 79 patients (23.0%). SLN metastasis was significantly associated with clinical T-stage (p = 0.0003), lymphovascular involvement (LVI) (p 0.0001). Ki-67 labeling index of primary tumor was significantly lower in SLN positive patients (p = 0.0331), and Ki-67 cut-off point of 7.5% was useful for dividing SLN positive from negative (p = 0.0197). Conclusion: Low value of Ki-67 labeling index, in addition to progression of clinical T-stage and presence of LVI, is significantly associated with SLN metastasis, and it seems to be useful to consider Ki-67 labeling index for SLN metastasis prediction.

乳腺癌患者不同水平的Ki-67表达及其相关性的临床研究

目的研究乳腺癌患者中不同增殖活性的Ki-67的表达及其表达水平与乳腺癌的临床分期、淋巴结转移的相关性。方法选取已手术的乳腺癌患者67例作为研究对象,根据Ki-67的水平高低分为一组、二组、三组3组,将3组中各研究对象的临床分期及淋巴结转移两项临床指标进行统计学分析,比较乳腺癌患者中不同水平的Ki-67与上述两项临床指标之间的相关性。结果一组中III+IV期临床分期总和所占的百分比为13.3%,二组中临床分期III+IV期所占的百分比为33.3%,三组中临床分期III+IV期所占的百分比为66.7%,经统计学分析,差异具有统计学意义(P<0.05)。一组中经统计淋巴结转移率为16.7%,二组中淋巴结转移率为36.1%,三组中淋巴结转移率为47.2%,统计学分析,差异具有统计学意义(P<0.05)。结论随着Ki-67表达水平的逐渐升高,不同乳腺癌患者的临床分期及淋巴结转移率也随之升高,说明Ki-67表达水平与乳腺癌患者的临床分期及淋巴结转移率之间具有一定的相关性。

Effect of neoadjuvant chemotherapy on expressions of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 in breast cancer

Background This study was designed in an attempt to determine the influence of neoadjuvant chemotherapy on estrogen receptor （ER）, progesterone receptor （PR）, human epidermal growth factor receptor 2 （Her-2）, and Ki-67 expressions in patients with breast cancer. Methods Pre- and post-neoadjuvant chemotherapy, paired-tumor specimens from 103 patients with breast cancer administrated with anthracycline or anthracycline combined taxane regimen were collected. Immunohistochemical staining for ER, PR, Her-2, and Ki-67 was performed by the DAKO EnVision method. Results Among the 103 cases, five patients （4.9%） had a complete response （CR）, 82 （79.6%） partial response （PR）, 15 （14.6%） stable disease （SD）, and one （0.9%） progressive disease （PD）, yielding an overall response rate （CR ＋ PR） of 84.5%. Nine patients achieved pathological CR. There was a significant decrease in the average index of Ki-67 post- neoadjuvant chemotherapy, compared with that before chemotherapy （24.1% vs. 39.7%, P 〈0.001）. After neoadjuvant chemotherapy, the changes of Ki-67 in different subtypes of breast cancer were different （P 〈0.001）, and these changes correlated with response to neoadjuvant chemotherapy （P 〈0.001）. No significant changes in immunohistochemical expression were observed for ER, PR and Her-2. Conclusions Neoadjuvant chemotherapy apparently reduced Ki-67 index in primary breast carcinomas, but profiles for ER, PR and Her-2 were not significantly different before and after neoadjuvant chemotherapy. The change of Ki- 67 correlated with molecular subtypes and response to neoadjuvant chemotherapy, suggesting that Ki-67 index was a surrogate marker to predict the treatment response of neoadjuvant chemotherapy.

Ki-67 index,progesterone receptor expression,histologic grade and tumor size in predicting breast cancer recurrence risk:A consecutive cohort study

Background:The 21-gene recurrence score(RS)assay has been recommended by major guidelines for treatment decision in hormone receptor(HR)-positive early breast cancer(EBC).However,the genomic assay is not accessible and affordable worldwide.Alternatively,an increasing number of studies have shown that traditional immunohistochemistry(IHC)can partially or even completely replace the role of the 21-gene genomic assay.Here,we developed and validated a predictive model(IHC3 model)combining the Ki-67 index,progesterone receptor(PR)expression,histologic grade,and tumor size to predict the recurrence risk of HR-positive EBC.Methods:The data from 389 patients(development set)with HR-positive,human epidermal growth factor receptor 2-negative,lymph node non-metastasized invasive breast cancer were used to construct the IHC3 model based on the Surexam®21-gene RS and the TAILORx clinical trial criteria.An additional 146 patients with the same characteristics constituted the validation set.The predictive accuracy of the IHC3 model was compared with that of Orucevic et al.’s nomogram.Invasive diseasefree survival(IDFS)was analyzed in the IHC3 predictive low-recurrence risk(pLR)group and the predictive high-recurrence risk(pHR)group.The Pearson chi-square test,Fisher exact test,and log-rank test were used for analysis.Results:The pLR and pHR group could be easily stratified using the decision tree model without network dependence.The accuracies of the IHC3 model were 86.1%in the development set and 87.7%in the validation set.The predictive accuracy of the IHC3 model and Orucevic et al.’s nomogram for the whole cohort was 86.5%and 86.9%,respectively.After a 52-month of median follow-up,a significant difference was found in IDFS between of the IHC3 pLR and the pHR groups(P=0.001)but not in the IDFS between the low-and high-recurrence risk groups according to the Surexam®21-gene RS and the TAILORx clinical trial criteria(P=0.556)or 21-gene binary RS group(P=0.511).Conclusions:The proposed IHC3 model could reliably predict low and high recurrence risks in most HR-positive EBC patients.This easy-to-use predictive model may be a reliable replacement for the 21-gene genomic assay in patients with EBC who have no access to or cannot afford the 21-gene genomic assay.

Prognostic value of immunohistochemical stratification of invasive duct carcinoma of the breast

Objective： Gene expression profiling of breast cancer has identified five molecularly distinct subtypes of breast cancer that have different biological behavior and clinical outcomes. These subtypes are termed luminal A, luminal B, luminal HER2, HER2-enriched and triple negative breast cancers （TNBC）. We aimed at identification of breast cancer subtypes among Egyptian population and their clinicopathologic features using ER, PR and HER2, KJ-67 and CK5/6. Methods： Tumors from 100 patients with invasive duct carcinoma were subtyped by immunohistochemistry using ER, PR, HER2, Ki-67 and CK5/6. The prognostic value of the immunohistochemical assignment for breast cancer disease-specific survival was inves- tigated by using Kaplan-Meier curves. Results： Immunohistochemical profiling classified 22 cases as luminal A, 33 cases as luminal B, 9 cases as luminal HER2, 26 cases as HER2-enriched and 10 cases as TNBC. Tumors that measured more than 3.5 cm, showed predominance of HER2-enriched subtype. HER2-enriched and luminal B subtypes dominated the node positive cases （35.4% and 33.8%; respectively）. Large tumor size （〉 3.5 cm）, hormone receptor negative state and HER2 positive state were associated with poor prognosis. Disease free survivals （DFSs） were significantly different （P 〈 0.0001） among different breast subtypes with worst 2-year DFS for HER2-enriched subtype （40.77%） followed by luminal A （63.56%）. DFS was almost similar in the remaining other subtypes, and luminal B, luminal HER2 and TNBC which were 86.85%, 87.5% and 88.89%; respectively. Conclusion： ER, PR, HER2 and Ki-67 constituted a strong surrogate for molecular breast cancer subtypes and can be easily applied. HER2-enriched subtype carries worse features being associated with large tumor size, nodal metastasis and is associated with poor outcome. Luminal A is a heterogeneous subtype with underlying several factors that can turn its prognosis adversely. TNBC subtype may behave unexpected in a favorable way.

PGRMC1在乳腺癌组织中的表达及其与临床病理特征的相关性

目的分析免疫组织化学指标孕激素受体膜组分1(progesterone receptor membrane component 1,PGRMC1)、雌激素受体(estrogen receptor,ER)、孕激素受体(progestogen receptor,PR)、Ki-67和Her-2(human epidermal growth factor receptor-2,Her-2)在乳腺癌组织、乳腺良性肿瘤组织和正常乳腺组织中的表达情况,并分别评估PGRMC1在乳腺癌和乳腺良性肿瘤组织中的表达与其他各指标的相关性。方法选取2015年9月至2017年1月间乳腺癌组织标本60例、乳腺良性肿瘤组织标本30例和正常乳腺组织标本30例(来自经乳腺麦默通微创旋切良性肿瘤周围1cm左右的正常组织,病理证实乳腺组织无异常者)。所有组织来源者在术前经空心针活检或经术后病理组织学检查确诊。采用免疫组织化学方法分别检测乳腺癌组织、乳腺良性肿瘤组织和正常乳腺组织中的PGRMC1、ER、PR、Ki-67和Her-2的表达情况,并分析PGRMC1在乳腺癌和乳腺良性肿瘤组织中的表达与其他各指标的相关性。结果 PGRMC1表达率:乳腺癌组(68.3%)>乳腺良性肿瘤组(26.7%)>正常对照组(6.7%),组间差异有统计学意义(P<0.01)。ER表达率:乳腺癌组(58.3%)>乳腺良性肿瘤组(43.3%)>正常对照组(23.3%),组间差异有统计学意义(P<0.01)。Ki-67表达率:乳腺癌组(66.7%)>乳腺良性肿瘤组(36.7%)>正常对照组(13.3%),组间差异有统计学意义(P<0.01)。乳腺癌组PGRMC1的表达与ER表达呈正相关(OR=3.593,95%CI:1.131~11.418),与PR、Ki-67和Her-2的表达无相关性。结论乳腺癌组PGRMC1的表达水平显著高于乳腺良性肿瘤组和正常对照组;乳腺癌组织中PGRMC1的表达与ER表达呈正相关,与PR、Ki-67和Her-2表达无相关性。

三阴乳腺癌相关性因素研究进展

三阴乳腺癌(triple-negative breast cancer,TNBC)即雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER-2)均为阴性的乳腺癌。是一种特殊类型的乳腺癌,具有独特的生物学行为和临床特征,预后差。对三阴乳腺癌相关性因素的深入研究,将有助于该病的预防、早期诊断、判断疾病的进展和指导治疗。

Reproducibility of the Nottingham modification of the Scarff- Bloom-Richardson histological grading system and the complementary value of Ki-67 to this system

Background The reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson （NSBR） histological grading system for invasive breast cancer （IBC） adopted by the World Health Organization （WHO） has previously not been studied in Chinese hospitals. The proliferation marker, Ki-67, has been widely applied in detecting IBC. The objective of this study was to assess the reproducibility of the NSBR system among Chinese pathologists and the complementary value that Ki-67 brings to this system.Methods Four general pathologists graded 100 IBC cases independently, which had previously been graded by specialists in breast pathology. The interobserver reproducibility among four general pathologists and pairwise reproducibility between each of them and the specialists were assessed. The Ki-67 labeling index （Ki-67LI） was determined by immunohistochemistry, and its correlations with histological grade and survival were determined.Results With respect to interobserver reproducibility, NSBR grading was fairly reproducible （kappa=0.34）; as for the components of NSBR grading, agreement was best for tubule formation （kappa=0.46）, intermediate for nuclear pleomorphism （kappa=0.42）, and poorest for mitotic count （kappa=0.28）. In terms of pairwise reproducibility, agreement was fair to substantial with NSBR grading （kappa=0.30-0.69） and nuclear pleomorphism （kappa=0.28-0.69）, moderate to substantial for tubule formation （kappa=0.51-0.78）, and slight to substantial for mitotic count （kappa=0.19-0.71）.There were characteristic Ki-67LI ranges for grades 1,2 and 3 tumors. Univariate analysis showed that Ki-67 was able to divide grade 2 patients into two different prognostic subgroups. Multivariate analysis of grade 2 patients with negative lymph node demonstrated that Ki-67 was an independent prognosticator for overall survival.Conclusions The reproducibility of grading by general pathologists could be enhanced. Specialization in breast pathology is essential for accurate grading and treatment for IBC. Ki-67, with proven prognostic significance, adds complementary value to the NSBR system.