双侧乳腺癌中Ki67和VEGF的表达及临床分析

随着乳腺癌发病率的增加,双侧乳腺癌的发病率也在逐年上升.Ki67作为目前较为肯定的细胞增殖标记物,与恶性肿瘤的增殖活性有关,它的表达对乳腺癌预后判断有重要意义.VEGF是一种重要的血管生成因子,在恶性肿瘤的形成中发挥重要的作用,与肿瘤的生长、浸润和转移有关.本文回顾及叙述了近几年来对Ki67和VEGF的研究及进展,包括二者的基本生物学特性,作用机理以及在双侧乳腺癌中的表达和临床分析.     

桑葚花色苷对乳腺癌裸鼠肿瘤组织中VEGF、p53 及Ki67 表达的影响

目的：探究桑葚花色苷对乳腺癌裸鼠肿瘤组织中VEGF、p53 及Ki67 表达的影响。方法：选择60 只健康BALB/c 裸鼠,按随 机数字表分为5 组,即对照组、桑葚花色苷低剂量组(SL组)、桑葚花色苷中剂量组(SM组)、桑葚花色苷高剂量组(SH 组)以及阳性 药(氟尿嘧啶)组,每组12 只裸鼠。以注射乳腺癌MDA-MB-231细胞悬液到裸鼠右肩皮下的方法建立移植乳腺癌模型,分别检测 和比较各组裸鼠的癌瘤湿重、癌重系数以及肿瘤组织中VEGF与p53、Ki67 的表达。结果：治疗后,与对照组相比,各治疗组的癌 瘤湿重水平及癌重系数均明显下降;与阳性药组相比,SM组及SH 组的癌瘤湿重以及癌重系数下降程度更为明显,差异均具有统 计学意义(P＜0.05);治疗后,与对照组相比,各治疗组的VEGF与p53、Ki67 阳性表达率均明显下降;且与阳性药组相比,SM组及 SH 组的VEGF与p53、Ki67 阳性率下降程度更为明显,差异均具有统计学意义(P＜0.05)。结论：桑葚花色苷能够明显抑制乳腺癌 的发展,这可能与其抑制P53、Ki67 在和VEGF的表达有关。     

乳腺浸润性导管癌组织中AIB1 与Ki67的表达及临床意义

目的:探讨乳腺浸润性导管癌(IDC)中乳腺癌扩增性抗原1(AIB1)和增殖细胞核抗原(Ki67)蛋白的表达及临床意义。方法:选择2012年6月到2014年6月在我院经病理检查确诊为IDC患者的组织石蜡标本160例,采用链霉素-生物素(SP)免疫组化法检测标本中AIB1和Ki67蛋白的表达,多因素Logistic回归分析二者与IDC临床病理学特征的相关性。结果:AIB1、Ki67的阳性表达率分别为75.63%和80.63%。AIB1、Ki67的表达与淋巴结转移、组织学分级及TNM分期存在相关性(P0.05),且随组织学分级和TNM分期的增高,阳性表达率逐渐增高(P0.05),Ki67的表达水平随肿瘤变大,阳性率逐渐增加(P0.05)。淋巴结阳性组AIB1、Ki67的阳性表达率显著高于淋巴结阴性组(P0.05)。多因素Logistic回归分析显示,AIB1、Ki67的阳性表达是淋巴结转移、病理组织学分级及TNM分期的危险因素(P0.05)。结论:在IDC组织中AIB1和Ki67的阳性表达均增高,二者与IDC临床病理学特征有密切关系。     

HR-MAS MR Spectroscopy of Breast Cancer Tissue Obtained with Core Needle Biopsy: Correlation with Prognostic Factors

The purpose of this study was to examine the correlation between high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy using core needle biopsy (CNB) specimens and histologic prognostic factors currently used in breast cancer patients. After institutional review board approval and informed consent were obtained for this study, CNB specimens were collected from 36 malignant lesions in 34 patients. Concentrations and metabolic ratios of various choline metabolites were estimated by HR-MAS MR spectroscopy using CNB specimens. HR-MAS spectroscopic values were compared according to histopathologic variables [tumor size, lymph node metastasis, histologic grade, status of estrogens receptor (ER), progesterone receptor (PR), HER2 (a receptor for human epidermal growth factor), and Ki-67, and triple negativity]. Multivariate analysis was performed with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA). HR-MAS MR spectroscopy quantified and discriminated choline metabolites in all CNB specimens of the 36 breast cancers. Several metabolite markers [free choline (Cho), phosphocholine (PC), creatine (Cr), taurine, myo-inositol, scyllo-inositol, total choline (tCho), glycine, Cho/Cr, tCho/Cr, PC/Cr] on HR-MAS MR spectroscopy were found to correlate with histologic prognostic factors [ER, PR, HER2, histologic grade, triple negativity, Ki-67, poor prognosis]. OPLS-DA multivariate models were generally able to discriminate the status of histologic prognostic factors (ER, PR, HER2, Ki-67) and prognosis groups. Our study suggests that HR-MAS MR spectroscopy using CNB specimens can predict tumor aggressiveness prior to surgery in breast cancer patients. In addition, it may be helpful in the detection of reliable markers for breast cancer characterization.     

乳腺癌组织中ER、PR、C-erbB-2、CD44V6、Ki67表达的相关分析及临床意义

目的：探讨乳腺癌组织中ER、PR、C-erbB-2、CD44V6和Ki67的表达与年龄、肿瘤大小、临床分期、淋巴结转移的关系以及它们相互之间的线性关系,同时分析其在乳腺癌的发生、发展中所表现出的临床作用和意义。方法：采用免疫组化S—P法检测103例乳腺癌标本中ER、PR、C-erbB-2、CD44V6和Ki67的表达,并与临床病理因素进行相关性分析。结果：103例患者中ER阳性的有57例（55．34％）,PR阳性的有49例（47．57％）,C-erbB．2阳性的有39例（37．86％）,CD44V6阳性的有68例（66．02％）,Ki67阳性的有例（90．29％）,其中以Ki67的表达率最高,C—erbB．2的表达率最低;不同年龄、淋巴结是否转移对ER、PR、C—erbB-2、CD44V6和Ki67表达量的差异。无统计学意义（P〉0．05）;PR的表达与乳腺癌临床分期相关（P〈0．05）,临床分期越高,PR的表达量越低;C．erbB．2的表达与肿瘤大小相关（P〈0．05）,肿瘤组织越小,C—erbB-2的表达量越低;ER的表达量和CD44V6的表达量的差异,有统计学意义（P〈0．05）。结论：在乳腺癌发病率越来越高的中国以至世界,免疫组化检测ER、PR、C—erbB-2、CD44V6和Ki67的阴阳性表达,可以作为乳腺癌发生、发展的评价指标,联合检测更加有助于早期乳腺癌患者的临床治疗和预后判断,减轻乳腺癌患者的身体和心理的痛苦,为临床医生选择和评估乳腺癌患者的治疗方案提供一些参考,更为下一步的个体化治疗和基因治疗做了一些前序工作。     

术前空芯针穿刺与开放性手术活检对乳腺癌患者临床预后的影响

目的:探讨术前空芯针穿刺与开放性手术活检对乳腺癌患者临床预后的影响,为乳腺癌相关临床研究提供参考。方法:选取2010年12月至2014年12月我院临床收治的早期乳腺癌患者380例为研究对象,根据诊断方法不同将患者分为术前针穿刺组(n=92)和手术活检组(n=288),观察并比较两组患者的相关临床指标及无病生存率水平进行观察和比较。结果:两组患者的年龄、淋巴结转移发生率、肿瘤分级情况、ER阳性表达率、PR阳性表达率和HER-2阳性表达率水平差异不大,且组间比较无统计学意义(P0.05);研究组患者的肿瘤直径≥2 cm患者的比例显著高于对照组,且差异有统计学意义(P0.01);研究组和对照组术后24个月的无病生存率分别为98.91%和99.65%,组间比较差异无统计学意(P0.05);研究组和对照组术后36个月的无病生存率分别为95.65%和96.18%,组间比较差异无统计学意义(P0.05)。结论:早期乳腺癌患者术前采用空芯针穿刺活检对于患者的预后没有显著影响,可以作为临床诊断患者病情的有效方法之一。     

Risk of Breast Cancer in Females With Hypothyroidism: A Nationwide,Population-Based,Cohort Study

ObjectivesThe results of studies investigating the relationship between breast cancer and hypothyroidism vary greatly from study to study. In this study, we analyzed a large and reliable, population-based database to gain a better understanding of the correlation.MethodsThis retrospective cohort study analyzed patients with hypothyroidism between January 1, 2000 and December 31, 2012 (hypothyroidism cohort) from the Longitudinal Health Insurance Database 2000 in Taiwan. For each woman with hypothyroidism, 1 woman without a history of breast cancer was randomly selected from the Longitudinal Health Insurance Database 2000 and frequency matched (1:4) with women without hypothyroidism by age and index year of hypothyroidism. The study outcome was the diagnosis of breast cancer during a 12-year follow-up period.ResultsIn this study, 6665 women with hypothyroidism and 26 660 women without hypothyroidism were identified. The hypothyroidism cohort had a significantly higher risk of breast cancer than the nonhypothyroidism cohort (adjusted hazard ratio [aHR] 1.69 [95% CI, 1.15-2.49]; P = .01), especially in the group aged 40 to 64 years (aHR 2.07 [95% CI, 1.32-3.23]; P = .01). Women in the hypothyroidism cohort taking levothyroxine for a duration ˃588 days showed a significantly decreased risk of breast cancer (aHR 0.37 [95% CI, 0.19-0.71]; P = .003).ConclusionWomen with hypothyroidism are at a higher risk of breast cancer than those without hypothyroidism. Levothyroxine may reduce the risk of breast cancer in a woman with hypothyroidism.     

三阴性乳腺癌中Ki-67 的表达及其临床病理意义

目的:探讨三阴性乳腺癌中Ki-67的表达及其临床病理意义。方法:回顾性分析2010年11月1日至2015年12月31日辽宁省肿瘤医院收治的110例行乳腺癌根治术的三阴性乳腺癌患者的临床病理资料,检测其乳腺癌组织中Ki-67的表达,并分析其与患者年龄、绝经情况、组织学分型、临床分期、淋巴结转移、肿瘤大小等临床病理资料的关系。进一步采用Kaplan-Meier生存分析法绘制生存曲线,比较高表达Ki-67和低表达Ki-67患者的3年、5年生存率。结果:Ki-67在三阴性乳腺癌患者50岁以下和50岁以上相比较,差异具有统计学意义(P0.05);Ki-67在三阴性乳腺癌患者绝经情况、组织学分型、临床分期、淋巴结转移、肿瘤大小的表达相比较,差异不具有统计学意义(P0.05);高表达Ki-67组3年生存率为79.49%,5年生存率为30.77%;低Ki-67组的3年生存率为85.92%,5年生存率为46.48%;两组3年生存率相比较差异不具有统计学意义(P0.05);两组5年生存率相比较差异具有统计学意义(P0.05);两组总生存时间相比较,差异具有统计学意义(P0.05)。结论:三阴性乳腺癌中Ki-67呈高表达,可作为乳腺癌预后不良的危险因素。     

Hospital Recorded Morbidity and Breast Cancer Incidence: A Nationwide Population-Based Case-Control Study

Introduction

Chronic diseases and their complications may increase breast cancer risk through known or still unknown mechanisms, or by shared causes. The association between morbidities and breast cancer risk has not been studied in depth.

Methods

Data on all Danish women aged 45 to 85 years, diagnosed with breast cancer between 1994 and 2008 and data on preceding morbidities were retrieved from nationwide medical registries. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression associating the Charlson comorbidity score (measured using both the original and an updated Charlson Comorbidity Index (CCI)) with incident breast cancer. Furthermore, we estimated associations between 202 morbidity categories and incident breast cancer, adjusting for multiple comparisons using empirical Bayes (EB) methods.

Results

The study included 46,324 cases and 463,240 population controls. Increasing CCI score, up to a score of six, was associated with slightly increased breast cancer risk. Among the Charlson diseases, preceding moderate to severe renal disease (OR = 1.25, 95% CI: 1.06, 1.48), any tumor (OR = 1.17, 95% CI: 1.10, 1.25), moderate to severe liver disease (OR = 1.86, 95% CI: 1.32, 2.62), and metastatic solid tumors (OR = 1.49, 95% CI: 1.17, 1.89), were most strongly associated with subsequent breast cancer. Preceding myocardial infarction (OR = 0.89, 95% CI: 0.81, 0.99), connective tissue disease (OR = 0.87, 95% CI: 0.80, 0.94), and ulcer disease (OR = 0.91, 95% CI: 0.83, 0.99) were most strongly inversely associated with subsequent breast cancer. A history of breast disorders was associated with breast cancer after EB adjustment. Anemias were inversely associated with breast cancer, but the association was near null after EB adjustment.

Conclusions

There was no substantial association between morbidity measured with the CCI and breast cancer risk.     

Association between Oestrogens Receptor Expressions in Breast Cancer and Comorbidities: A Cross-Sectional,Population-Based Study

Background

Breast cancer with oestrogen receptor expression is common in older women. Several factors, such as age and reproductive hormone exposure, have been associated with oestrogen receptor expression in breast cancer. However, the association between comorbidities and the oestrogen receptor expression has been poorly studied. We hypothesized that there was an association between burden comorbidity and breast cancer with oestrogen receptor expression in older women.

Objective

To determine whether oestrogen receptor expression in breast cancer was associated with burden comorbidity in community-dwelling women.

Methods

A total of 1,707 women with breast cancer registered on the list of a breast cancer registry were included. The recorded data included: age, Charlson Comorbidity Index score≥1, breast cancer characteristics (coded according to the International Classification of Diseases for Oncology), and breast cancer pathological stage (the pathological-tumour-node-metastasis, Scarff Bloom Richardson, and hormonal status of oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor).

Results

Breast cancer with oestrogen receptor expression was identified in 1,378 patients (80·7%). The fully-adjusted logistic regression showed that oestrogen receptor expression was associated with Charlson Comorbidity Index score≥1 (odds ratio [OR] = 1·91,95%confidence interval [CI] = [1.01–3.61], P = 0·048), progesterone receptor expression (OR = 16·64, 95%CI = [11.62–23.81], P<0·001), human epidermal growth factor receptor (OR = 0·54, 95%CI = [0.34–0.84], P = 0·007), age (OR = 1.02, 95%CI = [1.00–1.03], P = 0.008), Scarff Bloom Richardson grade II and grade III (OR = 0·21with 95%CI = [0.10–0.44] and OR = 0·06 with 95%CI = [0.03–0.12], P<0·001).

Conclusion

Our findings provide new data showing an independent positive association between burden comorbidity and breast cancer with oestrogen receptor expression. This result confirms that evaluation of oestrogen receptor expression in breast cancer should not be limited to hormonal factors stratified by age.     

Fracture Risk and Adjuvant Therapies in Young Breast Cancer Patients: A Population-Based Study

Background

Breast cancer survivors have an increased risk of bone fracture. But the risk among young patients with adjuvant therapies remains unknown. This population-based study is aimed to assess the incidence and risk of fracture among young (age of 20 to 39 years) breast cancer patients who received adjuvant therapies.

Methods

From January 2001 to December 2007, 5,146 newly diagnosed breast cancer patients were enrolled from the National Health Insurance Research Database (NHIRD) in Taiwan. Patients were observed for a maximum of 6 years to determine the incidence of newly onset fracture. Kaplan Meier and Cox regression analyses were used to evaluate the risk of fracture in young breast cancer patients who received adjuvant treatments.

Results

Of the total 5,146 young (age of 20 to 39 years) breast cancer patients, the Cox multivariate proportional hazards analysis showed that AIs, radiotherapy, and monoclonal antibodies were significantly associated with a high risk of fracture. Moreover, patients who received AIs for more than 180 days had a high hazard ratio (HR) of 1.77 (95% CI = 0.68–4.57), and patients who received more than four radiotherapy visits had a high HR of 2.54 (95% CI = 1.07–6.06). Under the site-specific analysis, young breast cancer patients who received AIs had the highest risk of hip fracture (HR = 8.520, 95% CI = 1.711–42.432, p < 0.04), whereas patients who received radiotherapy had the highest risk of vertebral fracture (HR = 5.512, 95% CI = 1.847–16.451, p < 0.01).

Conclusion

Young breast cancer patients who are receiving AIs, radiotherapy or monoclonal antibody need to be more careful for preventing fracture events. Breast cancer treatment plans are suggested to incorporate fracture prevention interventions.     

A Comparison of Visual Assessment and Automated Digital Image Analysis of Ki67 Labeling Index in Breast Cancer

Background

Ki67 labeling index (LI) is critical for treatment options and prognosis evaluation in breast cancer. Visual assessment (VA) is widely used to assess Ki67 LI, but has some limitations. In this study, we compared the consistency between VA and automated digital image analysis (DIA) of Ki67 LI in breast cancer, and to evaluate the application value of DIA in Ki67 LI assessment.

Methods

Ki67 immunostained slides of 155 cases of primary invasive breast cancer were eyeballing assessed by five breast pathologists and automated digital image analyzed by one breast pathologist respectively. Two score methods, hot-spot score and average score, were used to choose score areas. The intra-class correlation coefficient (ICC) was used to analyze the consistency between VA and DIA, and Wilcoxon signed-rank test was used to compare the median of paired-difference between VA and DIA values.

Results

(1) A perfect agreement was demonstrated between VA and DIA of Ki67 LI by ICC analysis (P<0.0001) in the whole cohort. A perfect agreement between VA and DIA of Ki67 LI was also showed in G2-G3, ER positive/HER2 negative cases. Average score and hot-spot score methods both demonstrated a perfect concordance between VA and DIA of Ki67 LI. (2) All cases were classified into three groups by VA values (≤10%, 11%-30% and >30% Ki67 LI). The concordance was relatively lower in intermediate Ki67 LI group (11%-30%) compared with high (>30%) Ki67 LI groups according to both methods. (3) All cases were classified into three groups by paired-difference (d) between VA values of hot-spot score and average score (d<5, 5≤d<10, d≥10) to evaluate the correlation between Ki67 staining distribution (heterogeneous or homogenous) and reproducibility of assessment. A perfect agreement was all demonstrated in three groups, and a slightly better Ki67 LI agreement between VA and DIA was indicated in homogenous staining slides than in heterogeneous staining ones. (4) VA values were relatively smaller than DIA values (average score: median of paired-difference -3.72; hot-spot score: median of paired-difference -9.12).

Conclusions

An excellent agreement between VA and DIA of Ki67 LI in breast cancer was demonstrated in the whole mixed cohort, suggesting that VA and DIA both could be used to assess Ki67 LI in clinical practice. Average score and hot-spot score methods both demonstrated a perfect concordance between VA and DIA of Ki67 LI. The almost perfect agreement between VA and DIA was observed in high Ki67 LI cases, displaying a homogenous staining pattern. The consistency between VA and DIA was relatively low in intermediate Ki67 LI group. The heterogeneity of tumors may slightly affect the concordance between VA and DIA of Ki67 LI. Assessment of VA provides lower Ki67 values than DIA, the biological importance of these values are not known at the moment.     

Risks of Breast and Endometrial Cancer in Women with Diabetes: A Population-Based Cohort Study

Objective

We investigated the overall and age-specific risks of developing breast and endometrial cancer among women with diabetes in a population-based cohort study.

Methods

Women with diabetes (n = 319310) and age-matched controls (n = 319308), selected from ambulatory care claims and beneficiary registry in 2000, respectively were linked to the in-patient claims (2000–2008) to identify admissions due to breast (ICD-9-CM: 174) and endometrial (ICD-9-CM: 182) cancer. The person-year approach with Poisson assumption was used to estimate the incidence density rate. The age-specific hazard ratios (HRs) of above malignancies in relation to diabetes with multivariate Cox proportional hazard regression.

Results

The overall incidence density rate of breast and endometrial cancer was estimated at 1.21 and 0.21 per 10,000 patient-years, respectively, for diabetes. The corresponding figures for controls were lower at 1.00 and 0.14 per 10,000 patient-years. Compared with the controls, the covariate adjusted HR for breast and endometrial cancer was 1.42 (95% confidence interval (CI) 1.34–1.50) and 1.71 (95% CI 1.48–1.97), respectively in women with diabetes. Elderly (> = 65 years) diabetes had the highest HR (1.61) of breast cancer, while the highest HR (1.85) of endometrial cancer was observed in diabetes aged < = 50 years.

Conclusions

Diabetes may significantly increase the risks of breast and endometrial cancer in all age stratifications. Health education for strict adherence of cancer screening program in women with diabetes is essential.     

Phospho-Akt Immunoreactivity in Prostate Cancer: Relationship to Disease Severity and Outcome,Ki67 and Phosphorylated EGFR Expression

Background

In the present study, we have investigated the prognostic usefulness of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well-characterised tissue microarray from men who had undergone transurethral resection due to lower urinary tract symptoms.

Methodology/Principal Findings

pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal anti-pAkt (Ser⁴⁷³) antibody. Immunoreactive intensity was determined for 282 (tumour) and 240 (non-mlignant tissue) cases. Tumour pAkt-IR scores correlated with Gleason score, tumour Ki67-IR (a marker of cell proliferation) and tumour phosphorylated epidermal growth factor receptor (pEGFR)-IR. For cases followed with expectancy, a high tumour pAkt-IR was associated with a poor disease-specific survival, and the prognostic information provided by this biomarker was additive to that provided by either (but not both) tumour pEFGR-IR or Ki67-IR. Upon division of the cases with respect to their Gleason scores, the prognostic value of pAkt-IR was seen for patients with Gleason score 8–10, but not for patients with Gleason score 6–7.

Conclusions/Significance

Tumour pAkt-IR is associated with both disease severity and disease-specific survival. However, its clinical use as a biomarker is limited, since it does not provide prognostic information in patients with Gleason scores 6–7.     

Use of Primary Care during the Year before Childhood Cancer Diagnosis: A Nationwide Population-Based Matched Comparative Study

Objective

Childhood cancer is rare and symptoms tend to be unspecific and vague. Using the utilization of health care services as a proxy for symptoms, the present study seeks to determine when early symptoms of childhood cancer are seen in general practice.

Methods

A population-based matched comparative study was conducted using nationwide registry data. As cases, all children in Denmark below 16 years of age (N = 1,278) diagnosed with cancer (Jan 2002-Dec 2008) were included. As controls, 10 children per case matched on gender and date of birth (N = 12,780) were randomly selected. The utilization of primary health care services (daytime contacts, out-of-hours contacts and diagnostic procedures) during the year preceding diagnosis/index date was measured for cases and controls.

Results

During the six months before diagnosis, children with cancer used primary care more than the control cohort. This excess use grew consistently and steadily towards the time of diagnosis with an IRR = 3.19 (95%CI: 2.99–3.39) (p<0.0001) during the last three months before diagnosis. Children with Central Nervous System (CNS) tumours had more contacts than other children during the entire study period. The use of practice-based diagnostic tests and the number of out-of-hours contacts began to increase four to five months before cancer diagnosis.

Conclusions

The study shows that excess health care use, a proxy for symptoms of childhood cancer, occurs months before the diagnosis is established. Children with lymphoma, bone tumour or other solid tumours had higher consultation rates than the controls in the last five months before diagnosis, whereas children with CNS tumour had higher consultation rates in all twelve months before diagnosis. More knowledge about early symptoms and the diagnostic pathway for childhood cancer would be clinically relevant.     

Major Depressive Disorder and Stroke Risks: A 9-Year Follow-Up Population-Based,Matched Cohort Study

Background and Purpose

Major depressive disorder (MDD) is characterized by recurrent depressive episodes and one of the treatment choices is antidepressants. Patients with MDD are at greater risk of developing major metabolic diseases that may in turn lead to stroke. Moreover, both depressive symptoms and taking antidepressant medications are associated with higher risk of stroke. However, whether and how clinical depression increases stroke risk remains an unanswered question. Our aim was to provide answers to this question.

Methods

A matched cohort study of 5015 subjects (1003 MDD patients and 4012 control subjects) was conducted using a nationwide database. Subjects were followed to a maximum of 9 years to determine rates of newly-developed strokes, and controls and MDD groups with different levels of antidepressant refractoriness were compared to determine the temporal relation between stroke and three major metabolic comorbidities (i.e., diabetes mellitus, hypertension and hyperlipidemia). The levels of depressive symptoms and the antidepressant medications before stroke onset were investigated.

Results

Patients with MDD had significantly higher rates of stroke (4.3% vs. 2.8%, p<0.05) during the follow-up. Mediation regression analyses revealed that the occurrence of stroke in the MDD subjects was significantly mediated by the development of major metabolic diseases. Greater severity of depression, but not greater use of antidepressants, preceded the occurrence of stroke.

Conclusions

A clinical diagnosis of major depression leads to stroke indirectly through more intense depressive symptoms and the development of major comorbidities.     

Prognostic Value of Molecular Breast Cancer Subtypes based on Her2, ESR1, PGR and Ki67 mRNA-Expression in Muscle Invasive Bladder Cancer

INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n = 57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P = 0.0009) and ESR1 (P = 0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR = 2.11, CI 1.11-4.21, P = 0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P = 0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR = 4.41, CI 1.53-18.71, P = 0.004) and Luminal B (HR = 1.96, CI 0.99-4.08, P = 0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.     

A Probable Risk Factor of Female Breast Cancer: Study on Benign and Malignant Breast Tissue Samples

The study reports enhanced Fe, Cu, and Zn contents in breast tissues, a probable risk factor of breast cancer in females. Forty-one formalin-fixed breast tissues were analyzed using atomic absorption spectrophotometry. Twenty malignant, six adjacent to malignant and 15 benign tissues samples were investigated. The malignant tissues samples were of grade 11 and type invasive ductal carcinoma. The quantitative comparison between the elemental levels measured in the two types of specimen (benign and malignant) tissues (removed after surgery) suggests significant elevation of these metals (Fe, Cu, and Zn) in the malignant tissue. The specimens were collected just after mastectomy of women aged 19 to 59 years from the hospitals of Islamabad and Rawalpindi, Pakistan. Most of the patients belong to urban areas of Pakistan. Findings of study depict that these elements have a promising role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu, and Zn was observed. The results showed the excessive accumulation of Fe (229?±?121 mg/L) in malignant breast tissue samples of patients (p?<?0.05) to that in benign tissues samples (49.1?±?11.4 mg/L). Findings indicated that excess accumulation of iron in malignant tissues can be a risk factor of breast cancer. In order to validate our method of analysis, certified reference material muscle tissue lyophilized (IAEA) MA-M-2/TM was analyzed for metal studied. Determined concentrations were quite in good agreement with certified levels. Asymmetric concentration distribution for Fe, Cu, and Zn was observed in both malignant and benign tissue samples.     

The Reliability of Endoscopic Biopsies in Assessing HER2 Status in Gastric and Gastroesophageal Junction Cancer: A Study Comparing Biopsies with Surgical Samples

AIM: The aim of this study is to validate the accuracy of HER2 assessment on biopsies by comparing matched biopsy/surgical material from the same patients. METHODS: HER2 status was evaluated by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 103 cases of gastric and gastroesophageal junction cancers in coupled biopsy and surgical material. RESULT: Complete concordance between IHC and FISH results on biopsy versus surgical samples was noted in 80% and 95% of cases, respectively. At comprehensive comparison, including IHC and FISH data on biopsy and surgical samples, 89% of biopsies were predictive of HER2 status in surgical samples, whereas 11% showed variable inconsistencies. The majority of these (10 of 12 cases) showed IHC score 0/1+ on biopsy but were all IHC positive and amplified at surgery; in particular, three (3 of 35; 8.5%) IHC score 0 and four (4 of 16; 25%) IHC score 1+ cases were FISH amplified on biopsy material also, whereas the remaining three cases were FISH non-amplified on biopsy. The percentage of cases, which were FISH amplified with IHC score 1+ or 2+ on biopsies, were similar (25% and 33%, respectively) and they also shared a similar grade of amplification. These data suggest that both IHC score 1+ and 2+ on biopsy material represent “equivocal cases” that may merit further investigation. CONCLUSIONS: The predictive value of HER2 IHC in biopsies is high. FISH analysis should be considered for IHC score 2+ and 1+ biopsy cases. Approximately 8% of cases will not be accurately predicted by biopsy evaluation.