Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may helpto identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determinedby Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: Weobtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes weredefined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive,HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent ofHG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14%separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations betweenKi67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patientswere treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information tobe included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). Weperformed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before andafter chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), bothcategorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patientshad pathologic complete response (cPR). Conclusions: In our experience we did not find associations betweenKi67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.     

Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

Introduction: Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, whichcan be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO donot recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We thereforeaimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymphnode metastasis, ER, PR and HER2neu status. Methods: A total of 194 cases of newly diagnosed breast cancerwere included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed bythe DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated bothas continuous and categorical variables. Results: Mean age of the patients was 51.7 years (24-90). Mean Ki67index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%)and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade,PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size.There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen withHER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as comparedto intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. Conclusion: Ourstudy indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognosticmarkers because we found that tumors with Ki67 higher than 30% have better prognostic profile comparedto tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis andHER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate andlow groups when considering adjuvant chemotherapy and prognostic stratification.     

Pre-treatment Elevated Platelet Count Associates with HER2 Overexpression and Prognosis in Patients with Breast Cancer

Purpose: To research the association between pre-treatment elevated platelet count and clinicopathologiccharacteristics in breast cancer (BC), as well as explore the relationship between pre-treatment elevatedplatelet count and HER2 status and prognosis of BC patients. Materials and Methods: A retrospective cohortof BC patients who were newly diagnosed or treated by surgery only and had pathological detection resultsand platelet values in the Department of Oncology, the First Affiliated Hospital of Liaoning Medical Collegewere enrolled from 1/1/2008 until 31/12/2009, and followed up until 31/12/2014. Age, thrombocyte parametersbefore chemotherapy and/or radiotherapy, immunohistochemical (IHM) indexes, and regional lymph node(LN) involvement and progression-free survival (PFS) were recorded. Results: A total of 447 eligible subjectswere included in this research. As we analyzed, for HER2, positive and negative, the incidence rates of elevatedplatelet count were 25.8% and 14.7% (P<0.05). In the Cox proportional hazards model both variables wereindependent risk factors for BC (for HER2, OR, 0.592, 95% confidence interval, CI, 0.355 to 0.985, P=0.044;f orPLT, OR, 0.998, 95% CI, 0.996 to 1.000, P=0.042). For ER, PR, Ki67 and LN involvement, the differences werenot statistically significant (P>0.05). Conclusions: In this research, pre-treatment elevated level of platelet countdemostrated a significantrelationship with HER2 amplification/overexpression, and both variables significantlyinfluenced the prognosis of BC. However, elevated platelet count did not exhibit any association with ER, PR,Ki67 and LN involvement.     

乳腺浸润性导管癌18F-FDG摄取的影响因素分析

目的:探讨肿瘤大小、病理分级、有无淋巴结转移及病理分子标志物雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体(C-erbB-2)、p53抑癌基因(p53)及增殖细胞核抗原Ki67(Ki67)对乳腺浸润性导管癌18F-FDG摄取的影响。方法:37例病理证实乳腺浸润性导管癌术前18F-FDG PET/CT SUVmax与术后病理免疫组化结果进行综合分析,采用Mann-Whitney U检验进行统计学分析。结果:病灶直径≥2.5cm、肿瘤高分化(III级)、淋巴结转移组平均SUVmax分别高于<2.5cm、低分化(I-II级)及淋巴结未转移有统计学意义(P<0.05)。ER(﹣)组18F-FDG摄取程度高于ER(﹢)组(P<0.05),Ki67(﹢)组18F-FDG摄取程度高于Ki67(﹣)组,差异均有统计学意义(P<0.05)。而PR、C-erbB-2及p53对18F-FDG摄取影响不明显。结论:乳腺浸润性导管癌病灶大小、病理分级、有无淋巴结转移、ER、Ki67的表达影响18F-FDG摄取,18F-FDG PET/CT鉴别诊断及初步分期时应引起重视。     

Correlations between HER2 Expression and Other Prognostic Factors in Breast Cancer: Inverse Relations with the Ki-67 Index and P53 Status

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as 10% positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3 by IHC. For HER2 (2), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor sizealso Ki-6720% as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index 20% in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-6720% had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.     

乳腺癌临床病理指标以及分子分型对TEC新辅助化疗病理完全缓解的预测价值

目的  本研究旨在探讨乳腺癌临床病理指标以及乳腺癌分子分型对多西他赛联合表柔比星、环磷酰胺（TEC）的 新辅助化疗后病理完全缓解率（pathological complete response pCR）的预测价值。方法   对 214例经4周期TEC新辅助化疗的乳腺癌患者的临床病理资料进行回顾性分析;免疫组织化学检测经核心针穿刺 的癌组织雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体-2（HER2）、Ki67、p53表达情况,原位基 因免疫荧光杂交（FISH）检测HER2有无过表达;根据ER、PR、HER2、Ki67的表达情况将乳腺癌分为4种分子分型： LuminalA、 LuminalB、HER2过表达型和三阴性乳腺癌。分析不同的临床病理指标、不同分子分型与pCR的相关性。结果  4周期TEC新辅助化疗后pCR率为14.0%（30/214）;单因素分析：ER、PR、Ki67、乳腺癌分子分型与pCR均具有显 著相关性（P＜0.05）;乳腺癌分子分型各组间显示pCR率不同：LuminalA＜LuminalB＜HER2过表达型＜三阴性乳腺癌 ;多因素分析：与pCR具有显著相关性的分类变量为ER（OR=0.311,95%CI：0.136～0.712;P=0.006）和Ki67 （OR=2.788,95%CI：1.061～7.327;P=0.038）。结论  ER、PR、Ki67以及乳腺癌分子分型可能是TEC新辅助化疗后乳腺癌pCR的预测指标。     

乳腺癌患者人表皮生长因子受体2基因扩增状态与临床病理特征的关系

目的探讨乳腺癌患者人表皮生长因子受体2(HER2)基因的扩增状态与患者临床病理特征相关性,并分析乳腺癌患者腋窝淋巴结转移的影响因素。方法收集2016年1月至2019年3月在滕州市中心人民医院病理科做常规病理检查且HER2免疫组织化学(IHC)结果为++的262例乳腺癌患者病理资料,包括年龄、肿瘤长径、组织学分级、病理类型、是否有淋巴结转移、肿瘤数量、肿瘤部位;用IHC法检测石蜡标本p53、Ki-67、雌激素受体(ER)、孕激素受体(PR)的表达结果;用荧光原位杂交(FISH)法检测HER2基因的扩增状态;分析HER2基因扩增是否与上述临床病理特征相关,以及腋窝淋巴结转移是否与上述特征相关。结果262例乳腺癌患者有69例HER2扩增阳性,阳性扩增率为26.3%;HER2基因扩增与Ki-67增殖指数和ER、PR的表达状态相关,差异有统计学意义(χ^2=13.27,P<0.01;χ^2=34.97,P<0.01;χ^2=38.31,P<0.01);与年龄、肿瘤长径等其余临床病理特征均无关(均P>0.05)。262例乳腺癌患者中发生腋窝淋巴结转移106例(40.5%);淋巴结转移与肿瘤长径显著相关(χ^2=29.10,P<0.01),与其余临床病理特征均无相关(均P>0.05)。结论乳腺癌HER2基因扩增状态与Ki-67增殖指数和ER、PR的表达相关,肿瘤大小为影响乳腺癌患者腋窝淋巴结转移的因素,准确判断上述指标能更好地指导乳腺癌患者的治疗和评估预后。     

p53突变型乳腺癌中Ki67表达水平的临床意义

目的：探讨乳腺癌组织中p53的突变情况及Ki67的表达水平,明确p53与Ki67联合作用在乳腺癌临床病理因素上的体现。方法：应用免疫组化SP法检测165例乳腺癌组织中p53、Ki67的表达,分析其与临床病理因素之间的关系。结果：p53的突变率为55.8%（92/165）,Ki67的阳性表达率为69.1% （114/165）。p53的突变情况与患者年龄、肿块大小、淋巴结转移、TNM分期、ER和PR的表达水平无关,但与HER-2的表达水平呈正相关。在总人群中Ki67的表达水平与肿块大小和淋巴结转移无关。亚组分析显示在p53突变的患者中,Ki67的表达水平与肿块的大小呈正相关（r=0.311,P=0.003）,与淋巴结转移呈正相关（r=0.342,P=0.001）。结论：在p53突变型乳腺癌中Ki67的表达与T分期及N分期均呈正相关,在p53突变人群中Ki67对乳腺癌的生物学行为和患者的预后可能有更高的预测价值,二者联合检测与解读可能更有助于判断乳腺癌患者的预后。     

乳腺浸润性导管癌^（18）F-FDG摄取的影响因素分析

目的：探讨肿瘤大小、病理分级、有无淋巴结转移及病理分子标志物雌激素受体（ER）、孕激素受体（PR）、表皮生长因子受体（C-erbB-2）、p53抑癌基因（p53）及增殖细胞核抗原Ki67（Ki67）对乳腺浸润性导管癌18F-FDG摄取的影响。方法：37例病理证实乳腺浸润性导管癌术前18F-FDG PET/CT SUVmax与术后病理免疫组化结果进行综合分析,采用Mann-Whitney U检验进行统计学分析。结果：病灶直径≥2.5cm、肿瘤高分化（III级）、淋巴结转移组平均SUVmax分别高于〈2.5cm、低分化（I-II级）及淋巴结未转移有统计学意义（P〈0.05）。ER（﹣）组18F-FDG摄取程度高于ER（﹢）组（P〈0.05）,Ki67（﹢）组18F-FDG摄取程度高于Ki67（﹣）组,差异均有统计学意义（P〈0.05）。而PR、C-erbB-2及p53对18F-FDG摄取影响不明显。结论：乳腺浸润性导管癌病灶大小、病理分级、有无淋巴结转移、ER、Ki67的表达影响18F-FDG摄取,18F-FDG PET/CT鉴别诊断及初步分期时应引起重视。     

The Case to Case Comparison of Hormone Receptors and HER2 Status between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis

Background: Nowadays, the adjuvant treatment for breast cancer patients chosen depends on immunohistochemical pattern of Estrogen receptor(ER), Progesterone receptor(PR) and HER2 status of primary breast tumor. Several retrospective studies showed significant discordance in receptor expression between primary and metastatic tumors. The objective of this research was to determine discordant rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis of individual breast cancer patients in Thammasat University Hospital. Methods: A prospective observational study of all breast cancer patients who have axillary metastasis and underwent surgery at Thammasat Hospital between January 2011 to December 2015. Tumor staging, ER, PR, and HER2 status on primary breast tumor were recorded. Synchronous axillary lymph node metastasis was evaluated with immunohistochemistry for ER, PR, and HER2. Results: The ER-positive rate from primary tumor to synchronous axillary lymph node metastasis decreased from 74.7% to 71.7%; the HER2 overexpression rate was decreased from 26% to 24%. In contrast, PR positive rate were 71% in both primary tumor and synchronous axillary lymph node metastasis. In case to case comparison, discordance rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis were 11.1%, 20.2% and 10.1%, respectively. Furthermore, the tumor staging was not significant associated with discordance of ER, PR and HER2. Conclusion: ER, PR and HER 2 biomarkers showed significant concordance between primary tumor and synchronous axillary lymph node metastasis. Hence, if we cannot assess the ER, PR and HER2 status in primary tumor, then synchronous axillary lymph node metastasis can be studied instead. However, the repeat of biomarker testing in node-positive breast cancer patients may be beneficial for tailored adjuvant therapy, especially for patients with negative hormone receptor and/or HER2 profile on primary tumor.     

中国上海地区乳腺癌的临床病理特征分析

目的 研究上海地区乳腺癌患者的临床病理特征。方法统计2008年至2010年上海地区1122例乳腺癌患者的相关临床病理特征,并分析它们之间的联系。结果 男性乳腺癌比例为0.89％,低于其他地区。患者发病平均年龄为53岁（中位55岁）,其中51～70岁人数最多,占43.85％。就诊时绝大多数为Ⅱ期,其中49.02％患者伴有淋巴结转移。病理分型中浸润性非特殊癌占94.47％,其中浸润性导管癌为90.91％,与国内其他地区相比,特殊类型癌比较少,占3.57％。中位肿瘤直径为3cm,巨大型肿瘤较少。三阴性乳腺癌占1881％,ER、PR、HER-2的阳性表达率分别为48.6％、59.4％和23.5％。术后病理分期与ER表达呈负相关,与HER-2呈正相关,与PR、Ki-67、E-cadherin、p53、TOPO-Ⅱ、p27、CK5／6均无关。组织学分级可能与E-cadherin有关（P=0.051）,与其他表达无关。淋巴结转移与HER-2表达呈正相关;肿瘤大小与ER表达呈负相关,与HER-2表达呈正相关。ER表达与PR呈正相关,与HER-2、Ki-67及p53呈负相关。HER-2与ER、PR、CK5／6表达呈负相关,与Ki-67、TOPO-Ⅱ呈正相关。Ki-67与TOPO-Ⅱ、HER-2表达呈正相关,与ER、p53、p27呈负相关。结论 上海地区乳腺癌患者的临床病理特征具有地域性,联合检测ER、PR、HER-2、Ki-67和p53对其诊断并指导治疗具有一定的临床意义。     

Axillary nodal involvement by primary tumor features in early breast cancer: an analysis of 2600 patients

Primary tumor characteristics, which are readily available to all clinicians, may aid in selecting the optimal adjuvant therapy for patients with breast cancer (BC). Herein, we investigated the relationship between tumor size, hormone receptor and HER2 status, Ki67 and age with axillary lymph node metastases (ALNM) in early-BC patients. We analyzed data on consecutive 2600 early-BC cases collected in the registry of Fondazione IRCC Istituto Nazionale dei Tumori, Milano, Italy. Correlation between Ki67 and primary tumor size (T-size) was calculated by Spearman’s rank correlation coefficient. Association of ALNM with Ki67 and other tumor characteristics was investigated by logistic regression. Adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated in all cases, and separately analyzed according to age, T-size and BC subtype. Large tumor size strongly associated to ALNM, with an adjusted odds ratio (OR) for each 5-mm increase of 1.32 (95% CI 1.24–1.41), except for triple-negative BC (TNBC) cases. In tumors =10 mm, without lymphovascular invasion, representing the strongest predictor of ALNM (OR 6.09, 95% CI 4.93–7.53), Ki67 resulted particularly informative, with a fourfold increased odds of ALNM for values > 30%. These results raise the question whether axillary node status is redundant in cases with exceptionally good features, i.e., small tumors with low Ki67, or in those candidate to adjuvant systemic treatment/radiotherapy anyway including TNBC, and support the incorporation of primary BC tumor characteristics as stratification factors in ongoing trials aiming at de-escalating axillary surgical procedures.     

Roles of Ki67 in Breast Cancer - Important for Management?

Background: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer. Materials and Methods: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22. Results: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy. Conclusions: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.     

Influence of tumor biological factors on tumor cell dissemination in primary breast cancer

BACKGROUND: The presence of disseminated tumor cells in the bone marrow (BM) of breast cancer patients is associated with poor prognosis and may therefore be related to aggressive breast cancer as indicated by tumor biological and clinicopathological factors. The aim of this study was to identify those features of the primary tumor related to the presence of disseminated tumor cells in the BM. PATIENTS AND METHODS: Clinical data from 508 primary breast cancer patients were analyzed. Tumor biological features of the primary tumor including HER2, p53, Ki-67, bcl-2 and hormone receptor status, as well as clinicopathological factors including histology, menopausal status, lymph node status, tumor size and grade, were studied for their association with BM involvement by univariate and multivariate analysis. RESULTS: Two-hundred and two out of 508 (40%) primary breast cancer patients had disseminated tumor cells in the BM. p53 expression, hormone receptor status, HER2 and Ki-67 were significantly related to BM involvement. The multivariate analysis revealed that p53 expression (OR: 1.9, 95% CI: 1.2 - 3.0) followed by progesterone receptor status (OR: 1.5, 95% CI: 1.0 - 2.2) were the only independent determinants for BM involvement. CONCLUSION: The presence of disseminated tumor cells in the BM was not influenced by tumor load as reflected by tumor size and lymph node involvement, whereas tumor biological factors were independently correlated to BM involvement. The results substantiate the important role of tumor biological factors of the primary tumor for tumor cell dissemination.     

ER,EGFR,p53在乳腺癌组织中的比较研究

采用免疫组化染色技术,检测７５例原发乳腺癌组织中雌激素受体（ＥＲ）,表皮生长因子受体（ＥＧＦＲ）及ｐ５３的表达。结果表明：ＥＲ、ＥＧＦＲ、ｐ５３的阳性表达率分别为４９．３％、４１．３％和３７．３％。ＥＲ、ＥＧＦＲ的表达与腋淋巴结转移、临床分期有明显相关性（Ｐ＜０．０５）;与年龄及肿瘤大小无明显相关性（Ｐ＞０．０５）。ＥＧＦＲ与ＥＲ有负相关性（Ｐ＜０．０５）。在有４个以上腋淋巴结转移的２１例病例中,ＥＧＦＲ阳性者１４例,占６６．７％。２０例临床Ⅲ期的病例,ＥＧＦＲ阳性者１５例,占７５．０％。ｐ５３的表达与腋淋巴结转移、临床分期、年龄及肿瘤大小均无明显相关性（Ｐ＞０．０５）;与ＥＲ呈负相关性（Ｐ＜０．０５）;与ＥＧＦＲ呈正相关性（Ｐ＜０．０５）。研究认为ＥＧＦＲ蛋白表达阳性的乳腺癌病人预后不良,ｐ５３蛋白表达阳性与乳腺癌病人的预后无明显相关性。     

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.     

JAM-A、p53和Ki67在乳腺癌组织中的表达及其临床意义

目的:观察JAM-A、p53和Ki67在正常乳腺组织和乳腺癌组织中的表达及其临床意义,并探讨其与淋巴结转移和病理分期的关系。方法:采用免疫组织化学染色法检测31例正常乳腺组织和51例乳腺癌组织的JAM-A、p53和Ki67的表达。结果:JAM-A在正常乳腺组织、不伴淋巴结转移的乳腺癌组织和伴淋巴结转移的乳腺癌组织中的阳性表达依次降低,差异有统计学意义(P<0.01)。JAM-A的表达和乳腺癌患者病理分期相关,乳腺癌分期越晚,阳性率越低(P<0.05)。p53和Ki67在正常乳腺组织不表达,在无淋巴结转移的乳腺癌组织、有淋巴结转移的乳腺癌组织中阳性表达逐渐升高,差异有统计学意义(P<0.01),p53在TNBC中阳性率高,差异具有统计学意义(P<0.05)。结论:联合检测JAM-A、p53和Ki67在乳腺癌的治疗决策、预后评估中具有潜在的应用价值。     

E R阳性乳腺癌中FGFR1蛋白的表达与ER及预后的关系

背景与目的：乳腺癌是严重危害女性健康的常见恶性肿瘤之一，内分泌治疗是乳腺癌综合治疗中的重要措施之一。约30%激素敏感型乳腺癌患者并不能从内分泌治疗中获益。成纤维细胞生长因子受体1（fibroblast growth factor receptors 1，FGFR1）的表达与雌激素受体（estrogen receptor，ER）阳性乳腺癌患者内分泌治疗耐药可能有关。该研究旨在探讨ER阳性乳腺癌中FGFR1蛋白的表达水平对乳腺癌临床病理学特征及预后的影响。方法：选取哈尔滨医科大学附属肿瘤医院2008年9月-2011年12月收治的184例ER阳性乳腺癌患者，通过免疫组织化学方法检测FGFR1蛋白的表达；采用χ²检验评估FGFR1蛋白水平与乳腺癌临床病理学特征的关系；采用Spearman相关分析评估变量间是否存在相关性；运用COX回归及Kaplan-Meier法分析FGFR1表达水平对乳腺癌预后的影响。结果：在ER阳性乳腺癌中，FGFR1高表达的患者更易发生区域淋巴结转移（P=0.012，r=0.186），且FGFR1的表达水平与ER的表达水平之间存在显著的负相关关系（P=0.011，r=-0.221）。COX单因素分析显示，TNM分期、区域淋巴结转移情况、Ki-67阳性率及FGFR1表达情况与ER阳性乳腺癌预后有关；进一步进行多因素分析发现，淋巴结转移情况（OR=1.744，95%CI：1.002~3.034，P=0.049）和Ki-67阳性率（OR=1.882，95%CI：1.015~3.491，P=0.045）是ER阳性乳腺癌的独立风险因素。Kaplan-Meier生存分析提示，FGFR1高表达患者预后不良（P=0.036）。结论：在ER阳性乳腺癌中，FGFR1蛋白水平与患者ER的表达水平呈显著负相关，且FGFR1高表达提示患者预后不良。     

Association of Histopathological Markers with Clinico- Pathological Factors in Mexican Women with Breast Cancer

Background: Breast cancer (BCa) is the most common malignancy in Mexican women. A set of histopathological markers has been established to guide BCa diagnosis, prognosis and treatment. Nevertheless, in only a few Mexican health services, such as that of the Secretariat of National Defense (SEDENA for its acronym in Spanish), are these markers commonly employed for assessing BCa. The aim of this study was to explore the association of Ki67, TP53, HER2/neu, estrogenic receptors (ERs) and progesterone receptors (PRs) with BCa risk factors. Materials and Methods: Clinical histories provided background patient information. Immunohistochemical (IHC) analysis was conducted on 48 tissue samples from women diagnosed with BCa and treated with radical mastectomy. The Chi square test or Fisher exact test together with the Pearson and Spearman correlation were applied. Results: On average, patients were 58±10.4 years old. It was most common to find invasive ductal carcinoma (95.8%), histological grade 3 (45.8%), with a poor Nottingham Prognostic Index (NPI; 80.4%). ERs and PRs were associated with smoking and alcohol consumption, metastasis at diagnosis and Ki67 expression (p<0.05). PR+ was also related to urea and ER+ (p<0.05). Ki67 was associated with TP53 and elevated triglycerides (p<0.05), and HER2/neu with ER+, the number of pregnancies and tumor size (p<0.05). TP53 was also associated with a poor NPI (p <0.05) and CD34 with smoking (p<0.05). The triple negative status (ER-/PR-/HER2/neu-) was related to smoking, alcohol consumption, exposure to biomass, number of pregnancies, metastasis and a poor NPI (p<0.05). Moreover, the luminal B subtype was associated with histological type (p=0.007), tumor size (p=0.03) and high cholesterol (p=0.02). Conclusions: Ki67, TP53, HER2/neu, ER and PR proved to be related to several clinical and pathological factors. Hence, it is crucial to determine this IHC profile in women at risk for BCa. Certain associations require further study to understand physiological/biochemical/molecular processes.