Prognostic and clinical significance of focal adhesion kinase expression in breast cancer: A systematic review and meta-analysis

BackgroundThe prognostic significance of focal adhesion kinase (FAK) in breast cancer remains controversial. Here, we conducted a meta-analysis to explore the prognostic value of FAK expression in breast cancer.Materials and methodsPossible prognostic significance of protein or mRNA expression of FAK in breast cancer was investigated with searches of electronic databases for relevant publications. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted from eligible studies.ResultsA total of eight eligible studies which included 2604 participants were analyzed in this meta-analysis. Increased expression of FAK protein was found to significantly correlate with shorter overall survival (OS) (HR = 1.43, 95% CI: 1.12–1.83; P = 0.004), and not with disease-free survival (HR = 1.31, 95% CI: 0.92–1.85; P = 0.14). Elevated FAK protein expression was also associated with negative estrogen receptor (ER) expression (OR, 1.34; 95% CI, 1.06–1.68; P = 0.01), negative progesterone receptor (PR) expression (OR, 1.54; 95% CI, 1.22–1.93; P < 0.001), positive human epidermal growth factor receptor 2 (HER2) expression (OR, 1.64; 95% CI, 1.28–2.09; P < 0.001), triple-negative breast cancer (TNBC) (OR, 1.57; 95% CI, 1.14–2.17; P = 0.006), high nuclear grade (OR, 1.70; 95% CI, 1.05–2.78; P = 0.03), high Ki-67 expression level (OR, 2.87; 95% CI, 1.94–4.24; P < 0.001), and positive p53 status (OR, 2.28; 95% CI, 1.58–3.29; P < 0.001).ConclusionOur meta-analysis identifies an association between increased FAK protein expression and worse OS among breast cancer patients. Moreover, enhanced FAK expression is associated with negative ER expression, negative PR expression, positive HER2 expression, TNBC, high nuclear grade, high Ki-67 expression level, and positive p53 status in breast carcinoma.     

Adoptive cellular immunotherapy for the treatment of patients with breast cancer: A meta-analysis

BackgroundTo evaluate the therapeutic efficacy of dendritic cells (DC) alone, cytokine-induced killer (CIK) cells alone and the combination of DC and CIK cells in the treatment of breast cancer, we performed a systemic review of the relevant published clinical studies, collectively referred to as DC-CIK cell therapy.MethodsSix hundred thirty-three patients with breast cancer were assigned to cohorts, and a meta-analysis was conducted.ResultsThe treatment of breast cancer with DC-CIK cells was associated with a significantly improved 1-year survival (P = 0.0001). The Karnofsky performance status scale of the patients treated with DC-CIK cells was significantly improved compared with that of the non-DC-CIK group (P < 0.0001). The percentage of T cells (CD3⁺, CD4⁺ and CD4⁺CD8⁺), CD16⁺ monocytes, and CD3⁺CD56⁺ natural killer T cells in the peripheral blood of cancer patients was significantly increased (P ≤ 0.05), whereas the percentage of CD4⁺CD25⁺ regulatory T cells was not significantly decreased (P = 0.32) in the DC-CIK treatment group compared with the non-DC-CIK group. The levels of interleukin-2, interleukin-12, tumor necrosis factor-α, interferon-γ, and nucleolar organizer region protein in the peripheral blood of cancer patients, which reflect immune function, were significantly increased (P < 0.001) after DC-CIK cell treatment. Furthermore, after DC-CIK treatment, the average levels of the alpha-fetoprotein, cancer antigen embryonic antigen and carbohydrate antigen tumor markers were decreased (P < 0.00001).ConclusionsDC-CIK cell therapy markedly prolongs survival time, enhances immune function, and improves the efficacy of the treatment of breast cancer patients.     

The Prognosis of Breast Cancer Patients after Mastectomy and Immediate Breast Reconstruction: A Meta-Analysis

BackgroundAn increasing number of patients with breast cancer are being offered immediate breast reconstruction (IBR). The aim of this study was to analyze the impact of IBR on the prognosis of patients with breast cancer.MethodsWe searched the electronic databases of Medline (Pubmed), ISI Web of Knowledge, Embase, and Google Scholar databases for studies reporting the overall recurrence, disease-free survival (DFS), and overall survival (OS) of patients after mastectomy only and mastectomy with IBR. With these data, we conducted a meta-analysis of the clinical outcomes.ResultsFourteen studies, including 3641 cases and 9462 controls, matched our criteria. Relevant information was extracted from these 14 studies. There was no significant heterogeneity (P for Q-statistic > 0.10 and I² < 25%). Patients who underwent IBR showed no increased risk of overall recurrence of breast cancer (RR = 0.89; 95% confidence interval [CI]: 0.75, 1.04; P = 0.14). Furthermore, patients receiving IBR had similar DFS (RR = 1.04; 95%CI: 0.99, 1.08); P = 0.10) and OS (RR = 1.02; 95%CI: 0.99, 1.05; P = 0.24)) as those of control patients.ConclusionThis meta-analysis provides evidence that IBR does not have an adverse effect on prognosis. These data suggest that IBR is an appropriate and safe choice for patients with breast cancer.     

Nuclear NHERF1 expression as a prognostic marker in breast cancer

Our purpose was to investigate whether Na⁺/H⁺ exchanger regulatory factor 1 (NHERF1) expression could be linked to prognosis in invasive breast carcinomas. NHERF1, an ezrin-radixin-moesin (ERM) binding phosphoprotein 50, is involved in the linkage of integral membrane proteins to the cytoskeleton. It is therefore believed to have an important role in cell signaling associated with changes in cell cytoarchitecture. NHERF1 expression is observed in various types of cancer and is related to tumor aggressiveness. To date the most extensive analyses of the influence of NHERF1 in cancer development have been performed on breast cancer. However, the underlying mechanism and its prognostic significance are still undefined. NHERF1 expression was studied by immunohistochemistry (IHC) in a cohort of 222 breast carcinoma patients. Association of cytoplasmic and nuclear NHERF1 expression with survival was analyzed. Disease-free survival (DFS) and overall survival (OS) were determined based on the Kaplan–Meier method. Cytoplasmic NHERF1 expression was associated with negative progesterone receptor (PgR) (P=0.017) and positive HER2 expression (P=0.023). NHERF1 also showed a nuclear localization and this correlated with small tumor size (P=0.026) and positive estrogen receptor (ER) expression (P=0.010). Multivariate analysis identified large tumor size (P=0.011) and nuclear NHERF1 expression (P=0.049) to be independent prognostic variables for DFS. Moreover, the nuclear NHERF1(−)/ER(−) immunophenotype (27%) was statistically associated with large tumor size (P=0.0276), high histological grade (P=0.0411), PgR-negative tumors (P<0.0001) and high proliferative activity (P=0.0027). These patients had worse DFS compared with patients with nuclear NHERF1(+)/ER(+) tumors (75.4% versus 92.6% P=0.010). These results show that the loss of nuclear NHERF1 expression is associated with reduced survival, and the link between nuclear NHERF1 and ER expression may serve as a prognostic marker for the routine clinical management of breast cancer patients.     

Development and Validation of Nomograms for Predicting Overall and Breast Cancer–Specific Survival in Young Women with Breast Cancer: A Population-Based Study

INTRODUCTION: The objective of current study was to develop and validate comprehensive nomograms for predicting the survival of young women with breast cancer. METHODS: Women aged <40 years diagnosed with invasive breast cancer between 1990 and 2010 were selected from the Surveillance, Epidemiology, and End Results database and randomly divided into training (n = 12,465) and validation (n = 12,424) cohorts. A competing-risks model was used to estimate the probability of breast cancer–specific survival (BCSS). We identified and integrated significant prognostic factors for overall survival (OS) and BCSS to construct nomograms. The performance of the nomograms was assessed with respect to calibration, discrimination, and risk group stratification. RESULTS: The entire cohort comprised 24,889 patients. The 5- and 10-year probabilities of breast cancer–specific mortality were 11.6% and 20.5%, respectively. Eight independent prognostic factors for both OS and BCSS were identified and integrated for the construction of the nomograms. The calibration curves showed optimal agreement between the predicted and observed probabilities. The C-indexes of the nomograms in the training cohort were higher than those of the TNM staging system for predicting OS (0.724 vs 0.694; P < .001) and BCSS (0.733 vs 0.702; P < .001). Additionally, significant differences in survival were observed in patients stratified into different risk groups within respective TNM categories. CONCLUSIONS: We developed and validated novel nomograms that can accurately predict OS and BCSS in young women with breast cancer. These nomograms may help clinicians in making decisions on an individualized basis.     

Cancer with Diabetes: Prevalence,Metabolic Control,and Survival in an Academic Oncology Practice

ObjectiveTo determine the prevalence of diabetes mellitus, glycemic control, and impact of diabetes on over all survival in an academic oncology practice.MethodsData on cancer patients (1999 to 2008) were retrieved from the institutional cancer registry and linked to electronic files to obtain diabetes status and hemoglobin A1c (A1C) values within the first 6 months of cancer diagnosis. Overall survival by cancer type with and without diabetes was compared using Cox regression.ResultsExcluding skin and hematologic malignancies, 15,951 cancer cases were identified. Overall diabe tes prevalence was 6.8% (n = 1,090), declining over time (P < 0.001). Diabetes was common among patients with pancreatic (9.8% [61 of 624]), colorectal (7.7% [89 of 1,151]), or bladder cancers (7.6% [68 of 899]). Patients with diabetes were older (mean age, 70 versus 66 years; P < 0.001) and more likely to be male (66.3% [723 of 1,090] versus 60.2% [8,949 of 14,858]; P < 0.001). The mean A1C among diabetic cancer patients was 6.8% and did not dif fer across cancer types (P = 0.80). Only 58.6% (331 of 565) of diabetic cancer patients had all A1C < 7.0% during the first 6 months following cancer diagnosis. Pancreatic cancer patients with coexisting diabetes had better overall survival than pancreatic cancer patients without diabetes (hazard ratio, 0.60; 95% confidence interval 0.44 to 0.80; P < 0.001). Conversely, diabetic prostate cancer patients had worse overall survival than prostate cancer patients without diabetes (hazard ratio, 1.36; 95% confidence interval 1.05 to 1.76; P = 0.02).ConclusionIn this academic oncology practice, diabetes was common, glycemic control often was subopti mal, and survival varied by cancer type. Additional study is needed to optimize glucose management and investigate mechanisms underlying age, sex, and survival differences. (Endocr Pract. 2012;18:898-905)     

Detection of ctDNA with Personalized Molecular Barcode NGS and Its Clinical Significance in Patients with Early Breast Cancer

We attempted to detect circulating tumor DNA (ctDNA), taking advantage of molecular barcode next-generation sequencing (MB-NGS), which can be more easily customized to detect a variety of mutations with a high sensitivity than PCR-based methods. Sequencing with a gene panel consisting of the 13 most frequently mutated genes in breast tumors from stage I or II patients revealed 95 somatic mutations in the 12 genes in 62% (62/100) of tumors. Then, plasma DNA from each patient (n = 62) before surgery was analyzed via MB-NGS customized to each somatic mutation, resulting in the detection of ctDNA in 16.1% (10/62) of patients. ctDNA was significantly associated with biologically aggressive phenotypes, including large tumor size (P = .004), positive lymph node (P = .009), high histological grade (P < .001), negative ER (P = .018), negative PR (P = .017), and positive HER2 (P = .046). Furthermore, distant disease-free survival was significantly worse in patients with ctDNA (n = 10) than those without ctDNA (n = 52) (P < .001). Our results demonstrate that MB-NGS personalized to each mutation can detect ctDNA with a high sensitivity in early breast cancer patients at diagnosis, and it seems to have a potential to serve as a clinically useful tumor marker for predicting their prognosis.     

CD44及CD24在乳腺癌组织中的表达及与临床病理特征的关系研究

目的:探讨肿瘤标志因子CD44及CD24在乳腺癌组织中的表达及与临床病理特征的关系。方法:选择从2015年1月到2017年1月在我院接受手术治疗的乳腺癌患者80例纳入本次研究,另选同期在我院治疗的导管原位癌患者30例,小叶增生患者20例及导管单纯增生患者20例的组织提取标本进行对照,分析CD44及CD24在乳腺癌组织和不同病变类型中的表达,并分析CD44~+/CD24~-细胞在癌症免疫分型中的表达以及CD44~+/CD24~-细胞与乳腺浸润导管癌相关病理特征的关系。结果:乳腺癌组织内的CD44阳性率为52.50%,CD24的阳性率为57.50%,均显著高于癌旁组织的11.25%和15.00%,差异均有统计学意义(均P0.05)。CD44及CD24在导管原位癌及乳腺浸润导管癌中的阳性率高于小叶增生和导管单纯增生,导管原位癌的阳性率高于乳腺浸润导管癌,差异均有统计学意义(均P0.05),且CD44在乳腺浸润导管癌不同分化类型中的阳性率差异有统计学意义(P0.05)。CD24在乳腺浸润导管癌不同分化类型中的阳性率差异不显著(P0.05)。CD44~+/CD24~-细胞在不同癌症免疫分型以及不同分化中的阳性率比较差异均有统计学意义(P0.05)。CD44~+/CD24~-细胞与乳腺浸润导管癌患者的年龄、月经状态、肿瘤直径、淋巴结转移以及远处转移之间均无明显关系(均P0.05)。结论:CD44及CD24在乳腺癌组织内存在较高的阳性率,且CD44~+/CD24~-在乳腺原位癌及低分化的乳腺癌组织内具有更高的阳性率,临床上可尝试通过监测CD44~+/CD24~-的阳性表达情况评价患者的病情及预后。     

Kallistatin在乳腺癌中表达的临床病理意义

目的:探讨Kallistatin在乳腺癌中表达的临床病理意义及预后价值。方法:收集乳腺癌档案蜡块及临床资料,分为无淋巴结转移的原发灶(NMBT),有淋巴结转移的原发灶(PBT)及配对的淋巴结转移灶(PMLN),应用免疫组化技术检测Kallistatin表达,统计学分析。结果:结果显示kallistatin在PBT组的表达高于NMBT组合和PMLN组。kallistatin的表达与组织学类型(P=0.003)、淋巴结状态(P0.001)、临床分期(P=0.002)、雌激素受体(ER)表达(P=0.046)有显著相关性。kallistatin在浸润性小叶癌中的阳性表达率高于浸润性导管癌,在PBT组的阳性表达率显著高于NMBT,临床分期越晚期阳性表达率越高,在ER阳性的病历中表达更高。Kaplan-Meier分析显示,kallistatin的阳性表达是乳腺癌患者无病生存时间短(P=0.008)和总生存时间短(P=0.006)的危险因素。在浸润性乳腺导管癌患者中,kallistatin的阳性表达与生存时间短有关(P=0.026)。还与ER阳性表达患者生存时间较短有关(P=0.010)。结论:Kallistatin在乳腺癌中的表达有较为复杂的临床病理意义,其表达提示预后不良。     

Prediction of Poor Prognosis in Breast Cancer Patients Based on MicroRNA-21 Expression: A Meta-Analysis

BackgroundMicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer.MethodsThe meta-analysis was conducted by searching the databases of PubMed, EMBASE, Web of Science and Chinese database-China National Knowledge Infrastructure (CNKI). Data were extracted from studies that investigated the association between miR-21 expression and survival outcomes in breast cancer patients. With respect to survival outcomes, the pooled hazard ratios (HRs) of miR-21 were calculated given a 95% confidence interval (CI).ResultsOur meta-analysis identified a total of 10 studies involving 1,439 cases. Further investigation demonstrated that a high miR-21 expression can predict poor overall survival (OS) (HR = 2.57, 95% CI: 1.37—4.81, P = 0.003) and shortened disease-free/recurrence-free survival (DFS/RFS) (HR = 1.45, 95% CI: 1.16—1.82, P = 0.001) in breast cancer patients. Moreover, high miR-21 expression was significantly correlated with lowered OS in the Asian group (HR = 5.07, 95% CI: 2.89—8.92, P < 0.001), but not in the Caucasian cohort (HR = 1.44, 95% CI: 0.99—2.10, P = 0.058). Furthermore, odds ratios (ORs) showed that up-regulated miR-21 levels were associated with multiple clinical characteristics.ConclusionOur results indicated that miR-21 can predict unfavorable prognoses in breast cancer patients, especially in Asians.     

How do Different Indices of Obesity Correlate with Cardiometabolic Disease Risk Factors in Multiethnic Youths?

ObjectiveTo investigate the relationship between cardiometabolic disease risk factors (CDRFs) among ethnic minorities and anthropometric factors including body mass index z score, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) in Hispanic and non-Hispanic black youths originating primarily from Central America, South America, and the Caribbean.MethodsClinical data of 167 young persons 2 to 19 years of age encountered in an outpatient pediatric endocrinology clinic were analyzed. The CDRFs included fasting insulin and glucose, homeostasis model assessment of insulin resistance (HOMA-IR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), high-density lipoprotein cholesterol, triglycerides, cardiac C-reactive protein (CRP), and apolipoproteins.ResultsFor both the non-Hispanic black and the Hispanic youths, WC was significantly correlated with SBP (r = 0.63; P < .001 and r = 0.50; P < .001, respectively), DBP (r = 0.61; P < .001 and r = 0.47; P < .001, respectively), and cardiac CRP (r = 0.76; P < .001 and r = 0.26; P = .026, respectively). Similarly, WHTR was significantly correlated with SBP, DBP, and cardiac CRP for the non-Hispanic black study subjects, whereas SBP (r = 0.22; P = .01), DBP ( r = 0.34; P < .001), fasting insulin ( r = 0.43; P < .001), HOMA-IR (r = 0.38; P < .001), apolipoprotein A-I (r = 0.30; P = .01), and CRP (r = 0.44; P < .001) were significantly correlated for the Hispanic group. For both groups, body mass index z score was not consistently correlated with CDRFs, and waist-to-hip ratio was not significantly correlated with any CDRFs, except for apolipoprotein B in non-Hispanic black youths.ConclusionOur study shows that WC and WHTR may be useful anthropometric factors for better identification of ethnic minority youths at risk for adult-onset cardiometabolic disease. (Endocr Pract. 2009;15:403-409)     

Inflammatory Breast Cancer: A Distinct Clinicopathological Entity Transcending Histological Distinction

Introduction

Although well recognized in breast oncology literature, histologic subtypes have not been previously described in inflammatory breast cancer (IBC). The purpose of this study was to describe lobular subtype in IBC and assess the impact of histology on patient outcomes.

Methods

We performed a retrospective analysis of 659 IBC patients at MD Anderson Cancer Center between January 1984 and December 2009. Patients with Invasive Lobular, Mixed Invasive Ductal and Lobular, or Invasive Ducal Carcinomas (ILC, MIC, IDC, respectively) comprise the subject of this report. Patient characteristics and survival estimates were compared by using chi-square test and Kaplan-Meier method with log-rank statistic. Cox proportional hazards models were fit to determine association of histology with outcomes after adjustment for other characteristics.

Results

A total of 30, 37, and 592 patients were seen to have invasive lobular, mixed, or ductal histology, respectively. Grade 3 tumors were more common in the ductal group (78%) than in the lobular (60%) or mixed (61%) group (P = 0.01). The 3-year overall survival rates were 68%, 64%, and 62% in the lobular, mixed, and ductal groups, respectively (P = 0.68). After adjustment, histology did not have a significant effect on death in the lobular group (HR = 0.70, 95% confidence interval [CI]: 0.26–1.94; P = 0.50) or mixed group (HR = 0.53, 95% CI: 0.25–1.13; P = 0.10) compared with the ductal group.

Conclusion

In this cohort of IBC patients, lobular histology was seen in 4.5% cases. Histology does not appear to have a significant effect on survival outcomes in IBC patients, unlike in patients with non-inflammatory breast cancer (n-IBC), indicating the distinct biological behavior of the IBC phenotype.     

XPF -673C>T variation is associated with the susceptibility to breast cancer

PurposeXPF variations might decrease the DNA repair capacity and further contribute to cancer development. This study aimed to investigate the association of XPF polymorphisms with risk of developing breast cancer.MethodsTCGA, the Human Protein Atlas and Kaplan-Meier plotter were used to analyze the expression of XPF in breast cancer tissues and its effect on the survival of breast cancer patients. The expression of XPF in breast cancer tissues was detected by qRT-PCR. This case-control study included 467 breast cancer patients and 467 healthy controls. The genotype of genetic variation was detected by polymerase chain reaction restriction fragment length polymorphism. Odds ratios and 95 % confidence intervals were calculated. Correlations between XPF variation and clinicopathological parameters were assessed through Kendall’s Tau-b test. The relationship between XPF gene function variation and XPF gene expression was analyzed by GTEx.ResultsThe expression of XPF in breast cancer tissues is higher than that in normal tissues. Breast cancer patients with high XPF expression have a higher relapse free survival rate (HR = 0.88, 95 % CI = 0.80−0.97), but have no effect on the overall survival rate (logrank P = 0.28). XPF -673C > T variant can reduce the risk of breast cancer patients (OR = 0.35, 95 %CI = 0.20−0.63 for codominant mode; OR = 0.66, 95 %CI = 0.51−0.85 for dominant model; OR = 0.40, 95 %CI = 0.23−0.70 for recessive model). The XPF 11985 GG genotype reduced the risk of early breast cancer (OR = 0.49, 95 %CI = 0.24−0.97), but not the risk of advanced breast cancer (OR = 1.20, 95 % CI = 0.58−2.48). XPF 11985A > G variant can also reduce the risk of ERBB2 expression in patients (OR = 0.50, 95 %CI = 0.27−0.94). There is no correlation between XPF -673C > T/XPF11985A > G variants and ER and PR. XPF -673C > T variant can reduce XPF expression (P < 0.05).ConclusionsGenetic variations of XPF gene may affect its expression and the risk of breast cancer in the Chinese population.     

Clinical implications of activated leukocyte cell adhesion molecule expression in breast cancer

In the study, we enrolled 150 breast cancer cases to investigate the expression status of activated leukocyte cell adhesion molecule (ALCAM), and the relationships between ALCAM expression and clinical-pathological characteristics and prognosis of breast cancer. It was observed that ALCAM was expressed at higher levels in breast cancer tissue compared to levels observed for tumor-adjacent tissue. Compared to cancers with low membranous ALCAM expression, cancers with high membranous ALCAM expression were prone to lymph node metastasis (χ² = 15.910, P = 0.010) and metastasis in general (χ² = 5.211, P = 0.029). High cytoplasmic ALCAM expression was noticeably correlated with local recurrence (χ² = 7.379, P = 0.012), especially for short-term recurrence (interval <2 years) (χ² = 5.562, P = 0.037), while not associated to long-term local recurrence (interval >2 years). The content of ALCAM protein is closely associated with the expression of estrogen receptor (ER) (P = 0.024). The disease-free survival of patients with high cytoplasmic ALCAM expression was significantly shorter compared to the cases with low cytoplasmic ALCAM expression (P = 0.036). In conclusion, ALCAM expressed at high levels in breast cancer. High membranous expression of ALCAM probably resulted in weakened adherent ability and metastasis. In addition, high cytoplasmic ALCAM expression strengthened invasive ability of malignant cells and then promoted tumor development.     

Uveal Melanoma Metastatic to the Liver: The Role of Quantitative Volumetric Contrast-Enhanced MR Imaging in the Assessment of Early Tumor Response after Transarterial Chemoembolization

PURPOSETo determine whether volumetric changes of enhancement as seen on contrast-enhanced magnetic resonance (MR) imaging can help assess early tumor response and predict survival in patients with metastatic uveal melanoma after one session of transarterial chemoembolization (TACE).MATERIALS AND METHODSFifteen patients with 59 lesions who underwent MR imaging before and 3 to 4 weeks after the first TACE were retrospectively included. MR analysis evaluated signal intensities, World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), tumor volume [volumetric RECIST (vRECIST)], and volumetric tumor enhancement [quantitative EASL (qEASL)]. qEASL was expressed in cubic centimeters [qEASL (cm³)] and as a percentage of the tumor volume [qEASL (%)]. Paired t test with its exact permutation distribution was used to compare measurements before and after TACE. The Kaplan-Meier method with the log-rank test was used to calculate overall survival for responders and non-responders.RESULTSIn target lesions, mean qEASL (%) decreased from 63.9% to 42.6% (P = .016). No significant changes were observed using the other response criteria. In non-target lesions, mean WHO, RECIST, EASL, mRECIST, vRECIST, and qEASL (cm³) were significantly increased compared to baseline. qEASL (%) remained stable (P = .214). Median overall survival was 5.6 months. qEASL (cm³) was the only parameter that could predict survival based on target lesions (3.6 vs 40.5 months, P < .001) or overall (target and non-target lesions) response (4.4 vs 40.9 months, P = .001).CONCLUSIONVolumetric tumor enhancement may be used as a surrogate biomarker for survival prediction in patients with uveal melanoma after the first TACE.     

Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer

Purpose

Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.

Methods

Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.

Results

Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively.

Conclusions

This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer.     

Expression of 14-3-3γ in patients with breast cancer: Correlation with clinicopathological features and prognosis

AimProtein 14-3-3γ is an important member of the 14-3-3 family that play important roles in the regulation of various cellular processes. The aim of the study is to investigate the association between 14-3-3γ expression and the clinicopathological features of patients with breast cancer.MethodsThe expression of 14-3-3γ was detected by Western blot in both foci of breast cancer and adjacent non-cancerous tissues. In addition, 14-3-3γ expression was analyzed by immunohistochemistry in 60 clinicopathologically characterized breast cancer cases. The association of 14-3-3γ expression with survival of the patients were analyzed.ResultsThe expression level of 14-3-3γ protein in breast cancer were significantly higher than that in non-cancerous mammary gland tissues. Moreover, high expression of 14-3-3γ correlated with tumor size and tumor grade (all P < 0.05). Patients with high 14-3-3γ expression had worse overall survival rate than that with low expression (P < 0.05). Furthermore, multivariate analysis showed that 14-3-3γ expression was an independent predictor of overall survival (HR, 0.196; 95%CI, 0.043–0.892; P = 0.035).ConclusionsOur data suggest for the first time that the increased expression of 14-3-3γ in breast cancer is associated significantly with tumor progression and poor prognosis. 14-3-3γ may be a novel and potential prognostic marker for breast cancer.     

The Association Between Tumor Tissue Calcification,Obesity, and Thyroid Cancer Invasiveness In A Cohort Study

Objective: We examined the relationships between tumor tissue calcifications of papillary thyroid cancer (PTC), body mass index (BMI), and tumor invasiveness.Methods: This was a retrospective analysis of 13,995 patients with PTC. Comparisons were made between the clinical and pathologic features of the tumor tissue calcifications group and non–tumor tissue calcifications group. Odds ratios (ORs) of tumor tissue calcifications, BMI, and tumor invasiveness features were calculated using a binary logistic regression model. We analyzed the relationship between tumor tissue calcifications and certain characteristics of thyroid cancer based on the pathologic findings.Results: BMI was positively correlated with tumor tissue calcifications in patients with PTC (OR, 1.015; P = .011), and obesity increased the risk of tumor tissue calcifications (OR, 1.374; P = .038). Calcifications were positively correlated with T-size (OR, 1.899; P<.001), multifocality (OR, 1.217; P<.001), extrathyroidal extension (ETE) (OR, 1.287; P<.001), high T-stage (OR, 1.765; P<.001), N+ (OR, 1.763; P<.001), and a higher number of lymph node metastases (OR, 1.985; P<.001). Compared with normal-weight patients with tumor tissue calcifications, obese patients with tumor tissue calcifications had an increased risk of ETE (OR_obesity, 1.765 vs. OR_normal, 1.300) and N+ (OR_obesity, 1.992 vs. OR_normal, 1.784).Conclusion: Tumor tissue calcifications are positively correlated with the invasiveness of PTC. Obesity further promotes the risk of tumor invasiveness in PTC combined with tumor tissue calcifications. These findings suggest that more comprehensive evaluations by trained pathologists may help physicians identify the optimal therapeutic regimens in the postoperative period.Abbreviations: BMI = body mass index; CI = confidence interval; ETE = extrathyroidal extension; FT3 = free triiodothyronine; OR = odds ratio; PTC = papillary thyroid carcinoma; RET = rearranged during transfection; TTC = tumor tissue calcification; US = ultrasonography; USC = ultrasonography calcification; WHO = World Health Organization