Distant Metastasis Status Research Articles

ADAMTS-6 is a predictor of poor prognosis in patients with esophageal squamous cell carcinoma

BackgroundA disintegrin and metalloprotease with thrombospondin motif (ADAMTS) enzymes play important roles in cell functions including adhesion, invasion, migration, and proliferation. ADAMTS-6 is a member of the ADAMTS family; reports of its relationship with esophageal squamous cell carcinoma (ESCC) progression are rare. It is unclear whether ADAMTS-6 could be an independent ESCC biomarker. MethodsADAMTS-6 expression was detected by immunohistochemistry (IHC) in 171 paraffin-embedded ESCC specimens; relationships with patients' clinicopathological features and Twist-1 expression were analyzed by the Pearson Chi-square method, respectively. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan–Meier method and compared using the long-rank test. ResultsADAMTS-6 was expressed mainly in the cytoplasm and nucleus; the expression was significantly higher in tumor tissues. Increased expression of ADAMTS-6 correlated with clinical stage (P = 0.009), pT stage (P = 0.042), lymph node metastasis (P = 0.014) and recurrence (P = 0.033). There were no significant correlations between ADAMTS-6 expression and other clinicopathological parameters including age, sex, tumor size, distant metastasis, differentiation, …chemotherapy, radiotherapy, CD68 expression and epithelial mesenchymal transition (EMT) status. Kaplan–Meier survival curves revealed that upregulated expression of ADAMTS-6 indicated short OS (P = 0.001) and DFS (P = 0.002). Multivariate analysis confirmed that high ADAMTS-6 expression was an independent factor for ESCC prognosis. ADAMTS-6 expression was significantly correlated with Twist-1 expression in ESCC cancer cells (P = 0.007) and stromal cells (P < 0.001). Patients with ESCC revealing expression of both ADAMTS-6 and Twist-1 exhibited significantly reduced OS and DFS rates than other patients. ConclusionsHigh ADAMTS-6 expression is a useful marker of poor prognosis in patients with ESCC.

The expression level of vascular endothelial growth factor receptor-2, vascular endothelial growth factor receptor-3, and insulin-like growth factor II mRNA binding protein 3 in renal cell carcinoma: Can these markers indicate poor prognosis in immunohistochemical examination?

Background: The malignant tumors of the kidney are the most aggressive among urologic cancers. To treat patients with renal cell carcinoma (RCC), it is important to understand the disease's prognostic factors. Angiogenesis is an essential process, responsible for the growing, and spreading of neoplastic tissues. Vascular endothelial growth factor (VEGF), the most potent angiogenetic factor known, and its receptor VEGF (VEGFR) play an important role in angiogenesis. Insulin-like growth factor-II mRNA binding protein 3 (IMP-3) is found in some malignant tumors and contributes to cell growth and cell migration during the early stages of embryogenesis. Material and Methods: The following study retrospectively evaluated 48 radical, 29 simple, and 23 partial nephrectomy specimens with RCC. Pathologic prognostic parameters, including tumor size, tumor stage, Fuhrman nuclear grade, distant metastasis status, and lymph node involvement status were compared with the immunohistochemical expression levels of VEGFR-2, VEGFR-3, and IMP-3. Results: Except the relation between VEGFR-3 and Fuhrman nuclear grade, there was no significant relation with the expressions of VEGFR-2, VEGFR-3, and IMP-3 and the pathologic prognostic parameters such as tumor size, tumor stage, Fuhrman nuclear grade, distant metastasis status, and lymph node involvement status. All three markers showed significant expression in almost all chromophobe and papillary histologic subtypes. The expression rates for chromophobe, papillary type 1, and type 2 RCC were 100%, 90%, and 100% for VEGFR-2, respectively, and 87.5%, 90%, and 100% for VEGFR-3, respectively. The expression rates of IMP-3 were 50% for papillary type 1, 83.3% for papillary type 2, and 100% for chromophobe RCC. Conclusion: Although the limited number of cases, current data gathered from our study shows that these markers have no relation with pathologic prognostic parameters and would not provide additional information in the immunohistochemical examination. Anyway, their tendency of expression in chromophobe and papillary type RCC is remarkable which should be evaluated with a larger number of cases.

A Nomogram for Distinction and Potential Prediction of Liver Metastasis in Breast Cancer Patients.

Liver metastasis from breast cancer has poor prognosis. We aimed at developing a reliable tool for making a distinction and prediction for liver metastasis in breast cancer patients, thus helping clinical diagnosis and treatment. In this study, totally 6238 patients from SEER database with known distant metastasis status and clinicopathologic variables were enrolled and divided randomly into training and validating groups. Logistic regression was used to screen variables and a nomogram was constructed. After multivariate logistic regression, sex, histology type, N stage, grade, age, ER, PR, HER2 status as significant variables for constructing the nomogram. The nomogram for distinguishing and predicting liver metastasis in breast cancer passed the calibration and validation steps and the areas under the receiver operating characteristic curve of the training set and the validation set were 0.6602 and 0.6511 respectively. Our nomogram is a reliable and robust tool for the distinction and prediction of liver metastasis in breast cancer patients, thus helping better choose medical examinations and optimize therapeutic regimen under the cooperation among medical oncologists and surgeons.

The B7 Family Member B7-H6: a New Bane of Tumor

B7-H6 is a ligand of NKp30, which is an activating receptor of natural killer (NK) cells. High expression of B7-H6 is found in certain types of tumor cells, such as lymphoma, leukemia and gastric carcinoma. The expression of B7-H6 can be induced by inflammatory stress in healthy cells. The expression of B7-H6 is significantly correlated with distant metastasis status and post-operative prognosis in cancer patients. The effectiveness of B7-H6 modified antitumor immunotherapy strategies had been verified in tumor-bearing mice, which opened a new door to targeted therapy. In this review, we will focus on the recent development on the roles of B7-H6 in tumor immunity, as well as mechanisms involved in the regulation of B7-H6 expression.

Gene-expression profiles of primary and metastatic lesions in head and neck squamous cell carcinoma

Background: Mechanisms of tumour spread and the deregulation level exisisting in distant metastatic lesions, in comparison with primary disease, are not fully understood in head and neck squamous cell carcinoma (HNSCC). We would test at molecular level the hypothesis that the development of the metastatic disease is linked to the biologic characteristics of the primary tumour more than to the degree of regional nodes involvement Matherials and methods: We identified 27 HNSCC patients with available tissues of either primary tumor and distant metastasis (DM). As control, a series of 26 cases without DM was matched according to subsite, HPV status and TN stage. Whole-transcriptome profiling was performed by microarray analysis using the DASL assay and BeadArray Chips (Illumina). To identify expression pattern related to patients with or without DM, we applied sparse Partial Least Square–Discriminant Analysis (sPLS-DA). We analysed the potential biological pathways differentiating primary tumors and metastases through Gene Set Enrichement Analysis (GSEA) and interrogating the Hallmark Gene Set Collection database. Results: sPLS-DA discloses gene-expression patterns between patients who developed or not DM. sPLS-DA defined a set of genes discriminant for patient’s DM status. Starting from those genes, we developed a signature following the Bayesian Compound Covariate Predictive (BCCP) algorithm. A core including 10-genes entered into our model and was able to predict patients who develop DM reaching AUC=0.85. To investigate the biological patterns associated to primary tumors of patients who developed or not DM, functional analysis was performed and the gene expression matrix was deconvoluted in 18x18 metagenes. We identified two networks involving a number of gene-ontology terms enriched in patients without DM, related to inflammation and keratinocyte differentiation. We investigated the genes differentially expressed between the primary tumors and the corresponding metastatic lesions and a total of 258 genes were identified. Functional pathway analysis was performed by GSEA and hallmark database was investigated resulting in 14 gene-sets enriched in metastasis imposing FDR<0.1. Conclusions: Our analysis of matched HNSCC primary tumours having or not developed DM highlighted a 10-gene signature able to stratify patients whose relevance deserves further validation.

Breast cancers with EGFR and HER2 co-amplification favor distant metastasis and poor clinical outcome.

ErbB signaling serves essential roles in invasive ductal carcinoma (IDC). The aim of the present study was to assess gene amplification in ErbB family members in IDC with clinical implications. Quantitative polymerase chain reaction and fluorescence in situ hybridization were performed on formalin-fixed paraffin-embedded tumor samples for gene amplification detection. The clinical and histopathological characteristics, as well as the prognostic significance, were analyzed. Among the 119 IDC patients evaluated, epidermal growth factor receptor [EGFR; also known as human epidermal growth factor receptor (HER)1], HER2, HER3 and HER4 gene amplification was observed in 30 (25.2%), 44 (36.9%), 0 (0.0%) and 1 (0.8%) patients, respectively. EGFR amplification was associated with estrogen receptor status (P=0.028) and higher possibilities of recurrence (P=0.015) and distant metastasis (following initial surgery) (P=0.011). In survival analysis, EGFR amplification was also associated with disease-free survival (DFS) (P=0.001) and overall survival (OS) (P=0.003). HER2 amplification was associated with larger tumor size (P=0.006), later clinical stage (P=0.003) and distant metastasis (following initial surgery) (P=0.006). In survival analysis, HER2 amplification was also associated with DFS (P=0.011). Notably, the present study identified a group of patients in whom EGFR and HER2 were co-amplified. This group of patients appeared to have a higher possibility of metastasis (when diagnosed) (P=0.014) and distant metastasis (following initial surgery) (P<0.001). In survival analysis, these patients were noticed to be associated with DFS (P<0.001) and OS (P=0.002). With respect to treatment regimen, this was also true for the DFS association with chemotherapy (P<0.001), radiotherapy (P<0.001) and hormonal therapy (P=0.001). The present results suggest that EGFR and HER2 amplification favor distant metastasis following initial surgery and are significantly associated with poor clinical outcome in breast cancer patients.

Epigenetic analysis of FHL1 tumor suppressor gene in human liver cancer.

Liver cancer is one of the most common types of cancer among human malignancies. Four and a half LIM domains 1 (FHL1), as a tumor suppressor gene, is frequently downregulated in multiple types of human cancer. However, the role and specific mechanisms of FHL1 as a tumor suppressor in liver cancer are poorly understood. The present study aimed to investigate the role and associated mechanisms of FHL1 in human liver cancer. The level of FHL1 mRNA in hepatocellular carcinoma (HCC) tissue specimens and cell lines derived from the human liver was determined using reverse transcription polymerase chain reaction and western blot analysis. The association between FHL1 expression and clinicopathological characteristics of patients with liver cancer was analyzed. Western blotting, small interfering RNA (siRNA) and chromatin immunoprecipitation were used to study the expression association of FHL1 and enhancer of zeste homolog 2 (EZH2) in human liver cancer and to explore the regulatory mechanism of FHL1 downregulation. Colony formation and migration assays were performed while FHL1 was overexpressed in Hep3B cells. The results showed that the expression of FHL1 mRNA in tumor tissue decreased, exhibiting a significant difference compared with the adjacent non-cancerous tissue (P<0.05). However, the downregulation of FHL1 was not significantly associated with the sex, age, hepatitis B virus infection status, tumor size, distant metastasis status or level of tumor differentiation of the patients. FHL1 was synergistically silenced by DNA methylation and histone modification, and 3-deanzaneplanocin A (DZNep), an inhibitor of EZH2, which is a histone methyltransferase of the polycomb repressive complex 2, which catalyzes histone H3 lysine 27 tri-methylation (H3K27me3). A significant association between FHL1 and EZH2 expression was identified in the female hepatocellular carcinoma (HCC) samples, but was not in the male HCC samples. FHL1 overexpression and DZNep treatment significantly suppressed the growth and migration of Hep3B cells by restoring FHL1 expression. H3K27me3 was significantly enriched at the FHL1 promoter region, as indicated by a chromatin immunoprecipitation assay, and associated with the epigenetic repression of the FHL1 tumor suppressor gene in HCC cell lines. In conclusion, the present study provides an insight into DNA methylation and EZH2-H3K27me3 epigenetic repression of FHL1 in human liver cancer.

Lymph node metastases in thymic malignancies: a Chinese Alliance for Research in Thymomas retrospective database analysis.

Lymphatic involvement is believed to be relatively rare in thymic epithelial tumours. The incidence and prognostic significance of nodal metastases are still unclear. The goal of this study was to define the incidence and prognostic relevance of nodal metastasis in patients with thymic epithelial tumours, using a nationwide retrospective database of the Chinese Alliance for Research in Thymomas. Patients who underwent upfront surgical resection without preoperative therapy were enrolled for the study. The International Thymic Malignancies Interest Group proposal of a new staging system for thymic epithelial tumours was used to redefine the pathological stage. The incidence of nodal metastasis and its relationship with clinicopathological characteristics and its impact on survival were examined accordingly. A total of 1617 patients were enrolled in this study. Lymph node metastasis was identified in 35 patients (2.2%). No nodal involvement was found in type A, AB or B1 thymomas. The incidence of nodal metastasis in thymoma (B2/B3) and thymic carcinoma was 1.3% and 7.9%, respectively, and it was most commonly seen in patients with neuroendocrine thymic tumours (16.7%, P < 0.001). According to the primary tumour invasion stage, incidences of nodal metastasis were 0.2% in T1, 6.9% in T2, 8.5% in T3 and 7.4% in T4 tumours (P < 0.001). Gender, pleural or distant metastasis and resection status were also correlated with nodal metastasis (P < 0.05) in univariable analysis. Multivariable analysis revealed that patients with non-thymoma histological characteristics (P < 0.001) and tumours in non-T1 stage (P < 0.001) had significantly greater risk of developing nodal metastasis. The overall survival of patients without nodal metastasis was significantly higher than that of patients with nodal involvement (P < 0.001). Disease-free survival of patients after R0 resection without nodal metastasis was also significantly higher than those with nodal metastasis (P < 0.001). On multivariable analysis, overall survival was significantly associated with histology of the tumour (P = 0.019) and complete resection (P = 0.047), and there was a trend towards significance (P = 0.052) in the association between overall survival and nodal involvement. Lymph node metastasis in low-grade, early stage thymic tumours is a rare phenomenon. However, it is not uncommon in tumours with a higher stage or a higher histological grade, especially in neuroendocrine thymic tumours. Nodal involvement as well as tumour invasion and histological grade may denote worse prognosis. Lymph node dissection may be warranted in selected high-risk patients.

The Function and Mechanism of TMEM16A/ANO1 in Pancreatic Cancer

Pancreatic cancer is the eighth leading cause of cancer death and is difficult to treat because clinical presentation is often late, and the disease is resistant to conventional chemotherapy. About 57% of pancreatic cancer patients are diagnosed at distant metastasis status and five-year survival rate is only 2%. More than 90% of pancreatic cancer has activating mutations in KRAS and recent exome sequencing studies have identified additional mutations in several kinds of genes such as AIRD1A, ARID1B, SMARCA1.

Overexpression of Kinesin Family Member 20A Correlates with Disease Progression and Poor Prognosis in Human Nasopharyngeal Cancer: A Retrospective Analysis of 105 Patients.

BackgroundNumerous studies have shown Kinesin family member 20A (KIF20A) may play a critical role in the development and progression of cancer. However, the clinical value of KIF20A in nasopharyngeal carcinoma (NPC) is unknown. Here, we investigated the expression pattern of KIF20A in NPC and its correlation with clinicopathological features of patients.MethodsReal-time PCR and Western blotting were used to quantify KIF20A expression in NPC cell lines and clinical specimens compared with normal controls. KIF20A protein expression was also examined in archived paraffin embedded tumor samples from 105 patients with pathologically confirmed NPC by immunohistochemistry (IHC). Statistical analyses were applied to assess the associations between KIF20A expression and the clinicopathological features and survival outcomes. Effects on migration and invasion were assessed by wound healing and transwell invasion assays after KIF20A silencing.ResultsKIF20A was significantly overexpressed at both the mRNA and protein levels in NPC cell lines and human tumor tissues. 45/105 (42.9%) of NPC specimens expressed high levels of KIF20A among the KIF20A detectable cases. Statistical analysis revealed that high KIF20A expression was significantly associated with gender (P = 0.046), clinical stage (P<0.001), T category (P = 0.022), N category (P<0.001), distant metastasis (P = 0.001) and vital status (P = 0.001). Moreover, Higher KIF20A expression patients had shorter overall survival (OS) and progression-free survival (PFS) (P = 0.001 and P = 0.001; log-rank test). In multivariate analysis, KIF20A was an independent prognostic factor for OS and PFS in the entire cohort (P = 0.033, P = 0.008). Knock down of KIF20A expression significantly suppressed NPC cell’s migration and invasion.ConclusionsKIF20A is overexpressed and may serve as an independent prognostic biomarker in NPC. Targeting KIF20A reduces migration and invasion of NPC cells.

Prognostic value of claudin-4, nm23-H1, and MIB-1 in undifferentiated nasopharyngeal carcinoma

Nasopharyngeal cancer (NPC) is a tumor of epithelial origin with complex etiology, and it is one of the most confusing, commonly misdiagnosed, and poorly understood diseases. Currently, the standard treatment for NPC is radiotherapy, but therapy failure is quite common, making radioresistance an important issue. Claudin-4 is a major tight junction protein that regulates the integrity and function of tight junctions. Aberrant expression of claudin-4 has been shown in various carcinomas with diverse prognostic implications. Ki-67 as a maker of cell proliferation and nm23-H1 as a metastasis marker have been widely used by many studies to indicate their close relationship with the progression and prognosis in many tumors. However, little is known about their prognostic values in undifferentiated NPC. The aim of this study was to evaluate the immunohistochemical staining of claudin-4, nm23-H1 protein, and Ki-67 in human undifferentiated NPC, and the relationship between claudin-4, nm23-H1, and Ki-67 expressions and both metastasis and prognosis of patients with undifferentiated NPC. The results were correlated with sex, age, extent of tumor, lymph node status, the presence or absence of distant metastasis, and patient survival. Low claudin-4 expression, low nm23-H1, and high Ki-67 expression were associated with distant metastasis and poor survival. Claudin-4 may be a novel biomarker for the prediction of distant metastasis and unfavorable prognosis in NPC, especially when combined with nm23-H1 and Ki-67.

Expression of LncRNA AK09398 and Relationship with Prognosis in Patients with Small Cell Lung Cancer

背景与目的小细胞肺癌（small cell lung cancer, SCLC）约占肺癌的15%，由于较早发生血行及淋巴转移，SCLC患者的预后差，其具体机制尚不明确。研究发现LncRNA（noncoding RNA, ncRNA）在肿瘤的发生、发展、转移、凋亡中起着重要的作用。本研究旨在探讨LncRNA AK09398在SCLC组织标本中的表达及临床意义。方法通过qRT-PCR法检测LncRNA AK09398在118例临床资料完整的SCLC肺癌组织及正常肺组织标本中的表达，分析其表达与患者临床病理特征及预后的关系。结果LncRNA AK09398在肺癌癌组织中的平均表达水平为（7.813±0.373），与癌旁组织（1.782±0.116）及正常肺组织（1.209±0.200）比较，差异有统计学意义（F=58.41, P < 0.001）。LncRNA AK09398在SCLC组织标本中的表达较癌旁组织明显增高。LncRNA AK09398的表达与患者的年龄、性别无关，差异无统计学意义（P均 > 0.05）；与疾病分期、淋巴结转移及远处转移、化疗敏感性及生存状态明显相关，差异有统计学意义（P均 < 0.05）。高表达LncRNA AK09398患者的总生存时间及无进展生存时间均较低表达者明显缩短；Cox多因素回归模型分析提示，LncRNA AK09398的表达、远处转移及临床分期是SCLC独立的预后因素（P < 0.05）。结论LncRNA AK09398参与调节SCLC的发生发展，可能作为潜在的SCLC预后评估的分子标志物。

An Algorithm for Creating Prognostic Systems for Cancer.

The TNM staging system is universally used for classification of cancer. This system is limited since it uses only three factors (tumor size, extent of spread to lymph nodes, and status of distant metastasis) to generate stage groups. To provide a more accurate description of cancer and thus better patient care, additional factors or variables should be used to classify cancer. In this paper we propose a hierarchical clustering algorithm to develop prognostic systems that classify cancer according to multiple prognostic factors. This algorithm has many potential applications in augmenting the data currently obtained in a staging system by allowing more prognostic factors to be incorporated. The algorithm clusters combinations of prognostic factors that are formed using categories of factors. The dissimilarity between two combinations is determined by the area between two corresponding survival curves. Groups from cutting the dendrogram and survival curves of the individual groups define our prognostic systems that classify patients using survival outcomes. A demonstration of the proposed algorithm is given for patients with breast cancer from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute.

Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas.

This study is aimed to investigate the BRAF (V600E) and TERT promoter mutation profile of 50 pediatric papillary thyroid carcinomas (PTCs) to refine their clinicopathological correlates. The median age at the time of surgery was 16years (range, 6-18). No TERT promoter mutations were identified in this series. The BRAF (V600E) mutation was present in 15 (30%) tumors. From genotype-histologic variant correlation perspective, 13 of 24 classic variant PTCs and 2 of 7 diffuse sclerosing variant PTCs were found to harbor BRAF (V600E) mutation. One cribriform-morular variant, 3 solid variant, and 15 follicular variant PTCs were BRAF wild type. While tumors with distant metastasis were BRAF wild type, two of five tumors with extrathyroidal extension (ETE) harbored BRAF (V600E) mutation. Nine of 15 BRAF (V600E) harboring tumors had central lymph node metastases. There was no significant correlation with BRAF (V600E) mutation and age, gender, tumor size, ETE, central lymph node metastasis, the status of pT, pN1a-b, and distant metastasis. An adverse correlation between BRAF (V600E) mutation and disease-free survival (DFS) was noted in the entire cohort; however, the predictive value of BRAF (V600E) mutation disappeared within the group of tumors displaying classic architecture as well as classic variant PTCs. The present cohort identifies that the classic architecture with multicentricity and local recurrence are correlates of BRAF (V600E) harboring pediatric PTCs. While the small size of this cohort is one of the limitations, neither the BRAF mutation status nor the classic tumor architecture does seem to be an independent prognosticator of DFS in this series. Evidence also suggests that TERT promoter mutations do not seem to play a major role in the pathogenesis of pediatric PTCs.

Elevated serum apolipoprotein E is associated with metastasis and poor prognosis of non-small cell lung cancer.

Apolipoprotein E (ApoE) is a factor involved in Alzheimer's disease, which recently attracted great attention as an important protein related to tumorigenesis and metastasis. However, serum ApoE levels and its diagnosis and prognosis value in non-small cell lung cancer (NSCLC) patients are still unknown. In 196 NSCLC patients and 203 healthy controls, serum ApoE was measured by turbidimetric immunoassay. The associations of serum ApoE levels with the clinicopathological characteristics and clinical outcomes of NSCLC patients were analyzed. Serum ApoE levels were obviously elevated in NSCLC patients compared with healthy controls (41.6 ± 11.63 vs. 33.8 ± 6.24mg/L) and were associated with TNM stage, lymph node metastasis status, and distant metastasis status (all P < 0.0001). For NSCLC diagnosis, the area under the receiver operating characteristic (ROC) curve was 0.71 at a specificity of 0.90 and sensitivity of 0.47. For lymph node metastasis predicting, the area under the ROC curve was 0.68 at a specificity of 0.56 and sensitivity of 0.73. From ROC/area under curve (AUC) analysis, we used 41.25mg/L as the serum ApoE cut-off value, to divide NSCLC patients into two groups, the median survival was 11.0weeks (95% CI = 8.7 to 13.3) for patients in high serum ApoE group and 20.0weeks (95% CI = 15.0 to 25.0) in low serum ApoE group. Serum ApoE levels elevated in NSCLC patients, which also associated with TNM stages, lymph node metastasis, distant metastasis, and poor prognosis, suggest that serum ApoE may act as a useful clinical serological biomarkers for evaluating the progress of NSCLC.

Apolipoprotein A1 -75 G/A and +83 C/T polymorphisms and renal cancer risk

BackgroundApolipoprotein A1 (ApoA1) is the major apoprotein constituent of high-density lipoprotein that can play important roles in tumor invasion and metastasis. The objective of the present study was to evaluate the association of two genetic variants (−75 G/A and +83 C/T) of APOA1 with predisposition to renal cancer.MethodsA total of 432 subjects, including 216 pathologically-proven renal cancer cases and 216 age- and gender-matched healthy controls, were recruited into this hospital-based case–control study. Genotyping of the APOA1 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsPatients with renal cancer had a significantly higher frequency of APOA1 -75 AA genotype [odds ratio (OR) = 2.10, 95 % confidence interval (CI) = 1.18, 3.75; P = 0.01] and APOA1 -75 A allele (OR =1.40, 95 % CI = 1.05, 1.87; P = 0.02) than controls. When stratifying by the distant metastasis status, patients with distant metastasis had a significantly higher frequency of APOA1 -75 AA genotype genotype (OR =2.20, 95 % CI = 1.04, 4.68; P = 0.04).ConclusionThis study is, to our knowledge, the first to examine prospectively an increased risk role of APOA1 -75 AA genotype and APOA1 -75 A allele in renal cancer susceptibility.

Proposal for selection criteria of secondary cytoreductive surgery in recurrent epithelial ovarian, tubal, and peritoneal cancers.

The selection criteria for secondary cytoreductive surgery (SCS) in recurrent ovarian cancer are yet to be defined. The aim of this study was to propose the selection criteria through identifying predictive factors for successful SCS. All patients who underwent SCS for recurrent epithelial ovarian, tubal, and peritoneal cancers between 1982 and 2012 at our institution were identified through our database. Potential prognostic factors were evaluated in univariate and multivariate analyses. Survival after SCS was examined by the grouping model based on the number of prognostic factors. We performed SCS in 80 consecutive patients, 48 (60%) of whom achieved complete resection. Complete/incomplete resection significantly influenced survival (median 65 vs. 26months; p=0.0005). Among favorable prognostic factors determined before SCS, treatment-free interval >12months, absent distant metastasis, solitary disease, and performance status 0 were independently associated with better survival (p=0.0009, 0.00003, 0.0004, and 0.015, respectively). Patients with 3-4 of those factors had better survival than those with 2 or 0-1 factors (median 79, 26, and 19months; p<0.00001 and <0.0000000001, respectively). Complete resection of visible tumors was achieved in 79% of patients with 3-4 factors, in 40% of those with 2 factors, and in 33% of those with 0-1 factor. Importantly, even when tumor removal was incomplete at SCS, median survival of patients with 3-4 factors was still quite favorable (83 vs. 67.5months for complete/incomplete resection, respectively), while those of patients with 2 factors (41 vs. 25months) and 0-1 factor (19 vs. 19months) were not. We strongly recommend SCS for patients with 3-4 of the above favorable factors at recurrence. As for patients with 2 factors, SCS may be considered if complete resection is expected to be achieved. Prospective studies are warranted to validate our proposal.

Abstract P2-13-04: The role of preoperative MRI in negative margins after breast conserving surgery in patients with invasive breast cancer or purely DCIS

Abstract Introduction Clinical benefit of preoperative MRI in invasive breast cancer (IBC) patients and patients with purely ductal carcinoma-in-situ (DCIS) remains controversial. We aimed to study the role of preoperative MRI in negative margins after breast conserving surgery (BCS) and reexcision rate in a large population-based cohort. Methods Retrospective analyses were performed in women diagnosed with IBC and purely DCIS and surgically treated between 2011-2013 extracted from the Eindhoven Cancer Registry. Patients were excluded in case of: neo-adjuvant systemic therapy, (clinical or pathological) tumor stadium T4, distant metastasis, and unknown resection margin status. According to preoperative MRI use, the study population was divided into a non-MRI and MRI group. All multivariable analyses were adjusted for baseline differences between non-MRI and MRI group with P&amp;lt;0.1. No information was available on the exact reason to perform MRI preoperatively in these patients. Results A total of 3,116 patients were eligible of which 2,238 (71.8%) patients were treated by breast conserving surgery (BCS) and included for analyses. Preoperative MRI was performed in 592 (30.6%) IBC patients and 55 (18.3%) DCIS patients. In IBC patients, differences in non-MRI and MRI group were: median age (62 vs 58), histology (lobular type in 5.7% vs 24.5%), median tumor size (13 mm vs 15 mm), her2neu receptor status and specific tumor locations. Median (interquartile range) time between diagnosis and surgery in the non-MRI and MRI group were 21 (16-28) and 31 (22-40) days respectively (univariable and multivariable P&amp;lt;0.001). Negative margin was attained in 1,135 (84.4%) and 489 (82.6%) patients respectively (OR 0.88 95%CI 0.68-1.14 P=0.326). After adjustment for baseline differences and for factors associated with negative margin with P&amp;lt;0.1 (i.e. histology, tumor size, differentiation grade, progesterone receptor %, her2neu receptor status, regional lymph node stadium, and tumor location) MRI use was not associated with negative margin (OR 1.09 95%CI 0.81-1.45 P=0.587). Reexcision was performed in 96 (7.1%) and 62 (10.5%) patients (P=0.013). In case reexcision was needed, conversion to mastectomy occurred in 32 (2.4%) vs 20 (3.4%) patients (P=0.210). In patients with purely DCIS, only median age differed in non-MRI and MRI group (61 vs 57). Median (interquartile range) time between diagnosis and surgery in the non-MRI and MRI group were 22 (16-31) and 35 (23-49) days respectively (univariable P&amp;lt;0.001 and multivariable P=0.024). Negative margin was attained in 197 (80.1%) and 42 (76.4%) patients respectively (OR 0.80 95%CI 0.40-1.61 P=0.538). After adjustment for baseline differences and for factors associated with negative margin with P&amp;lt;0.1 (i.e. differentiation grade and tumor location) MRI use was not associated with negative margin (OR 1.51 95%CI 0.72-3.16 P=0.280). Reexcision was performed in 39 (15.9) and 10 (18.2) (P=0.672). In case reexcision was needed, conversion to mastectomy occurred in 12 (4.9%) vs 3 (5.5%) patients (P=0.859). Conclusion In both IBC and DCIS patients, preoperative MRI delayed time between diagnosis and surgery, but was not associated with a higher percentage of negative margins after BCS. Citation Format: Elvira L Vos, Adri C Voogd, Cornelis Verhoef, Inge-Marie Obdeijn, Linetta B Koppert. The role of preoperative MRI in negative margins after breast conserving surgery in patients with invasive breast cancer or purely DCIS [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-04.

Matrix Metalloproteinase 14 Overexpression Is Correlated with the Progression and Poor Prognosis of Nasopharyngeal Carcinoma

Matrix metalloproteinase 14 (MMP14) has been identified to play a significant role in several types of cancers, but little is known about the significance of MMP14 in nasopharyngeal carcinoma (NPC) patients. The aim of this study was to explore the association of MMP14 expression with clinicopathologic features and prognosis in NPC. MMP14 mRNA and protein expressions were examined in NPC and nasopharyngeal tissues through real-time PCR and immunohistochemistry. Meanwhile, the relationship of MMP14 expression levels with clinical features and prognosis of NPC patients was analyzed. MMP14 mRNA expression was markedly higher in NPC tissues than in nasopharyngeal epithelium tissues (p = 0.002). Using immunohistochemistry, staining for MMP14 protein was found in the normal nasopharyngeal epithelial cells and malignant epithelial cells, but increased expression of MMP14 was observed in NPC samples compared with normal nasopharyngeal epithelium samples (p = 0.027). In addition, high levels of MMP14 protein were positively correlated with the status of clinical stage (p = 0.009), N classification (p = 0.006), and distant metastasis (p = 0.005) of NPC patients. Patients with higher MMP14 expression had a significantly shorter overall survival time than did patients with low MMP14 expression. Multivariate analysis indicated that the level of MMP14 expression was an independent prognostic indicator (p < 0.001) for the survival of patients with NPC. MMP14 overexpression is a potentially unfavorable prognostic factor for NPC patients.

Correlation between epidermal growth factor receptor and tumor stem cell markers CD44/CD24 and their relationship with prognosis in breast invasive ductal carcinoma.

We studied the correlation between epidermal growth factor receptor (EGFR) and the tumor stem cell markers CD44/CD24 in breast invasive ductal carcinoma (BIDC) and their relationship with prognosis. We analyzed the clinical data of 139 BIDC cases retrospectively, detecting EGFR, CD44, and CD24 expressions in tumor tissue using immunohistochemistry. The proportion of EGFR-, CD44-, and CD24-positive cases was 59.0, 62.3, and 30.9 %, respectively. The proportion of CD44-positive [76.9 % (p < 0.05)] and EGFR-positive [67.2 % (p = 0.108)] cases in the triple-negative breast cancer (TNBC) group was higher than that of the non-TNBC group. In the non-TNBC group, 36.5 % was CD24-positive, higher than that in the TNBC group but not statistically significant. The proportion of CD44-positive cases was significantly higher in the EGFR-positive group than in the EGFR-negative group (p = 0.017). EGFR-positive cases were significantly correlated with premenopausal status (p = 0.036), distant metastasis (p = 0.018), and estrogen receptor-negative status (p = 0.020). CD44-positive status was significantly correlated with human epidermal growth receptor 2 (HER2)-negative (p = 0.023), estrogen receptor-negative (p = 0.021), and progesterone receptor-negative status (p = 0.004). CD24-positive status was significantly correlated with HER2-positive status (p = 0.001). Kaplan–Meier survival analysis showed that TNBC patients had shorter survival. EGFR-positive and CD44-positive status were both correlated with shorter survival in the lymph node- and HR-negative groups, while CD24 positive was significantly correlated with poor survival in lymph node-negative and HR-positive patients. EGFR and CD44 expressions have a significantly positive correlation (p = 0.017) in BIDC. Patients both EGFR and CD44 positive had the worst outcome.