The present study aimed to clarify the association between macrophages, tumor neo-vessels and programmed cell death-ligand 1 (PD-L1) in the tumor microenvironment and the clinicopathological features of patients with non-small cell lung cancer (NSCLC), and to explore the prognostic factors of stromal features in NSCLC. To determine this, tissue microarrays containing samples of 92 patients with NSCLC were studied using immunohistochemistry and immunofluorescence. The quantitative data demonstrated that in tumor islets, the number of CD68+ and CD206+ tumor-associated macrophages (TAMs) was 8-348 (median, 131) and 2-220 (median, 52), respectively (P<0.001). In tumor stroma, the number of CD68+ and CD206+ TAMs was 23-412 (median, 169) and 7-358 (median, 81), respectively (P<0.001). The number of CD68+ TAMs in each location of the tumor islets and tumor stroma was significantly higher than that of CD206+ TAMs, and they were significantly correlated (P<0.0001). The quantitative density of CD105 and PD-L1 in tumor tissues was 19-368 (median, 156) and 9-493 (median, 103), respectively. Survival analysis revealed that a high density of CD68+ TAMs in tumor stroma and islets and a high density of CD206+ TAMs and PD-L1 in tumor stroma were associated with worse prognosis (both P<0.05). Collectively, the survival analysis demonstrated that the high-density group was related to a worse prognosis regardless of combined neo-vessels and PD-L1 expression with the CD68+ TAMs in tumor islets and stroma, or CD206+ TAMs in tumor islets and stroma. To the best of our knowledge, the present study was the first to provide a multi-component combined prognostic survival analysis of different types of macrophages in different regions with tumor neo-vessels and PD-L1, which demonstrated the importance of macrophages in tumor stroma.

Purpose The present study was performed to clarify the correlation between macrophages, tumor neo-vessels and programmed cell death-ligand 1 (PD-L1) in the tumor microenvironment (TME) and the clinicopathological features of non-small cell lung cancer (NSCLC) and to explore the prognostic factors of stromal features in NSCLC. Methods Tissue microarrays containing 92 NSCLC patients were studied with immunohistochemistry (IHC). The distribution and quantitative data of CD68- and CD206-positive tumor-associated macrophages (TAMs) in tumor islets and tumor stroma, and the expression of tumor neo‑vessels and PD-L1, were analyzed by inverted microscopy and Image-Pro Plus 6.0 software. Prognostic analyses with the clinicopathological characteristics and tumor microenvironment features were performed. Results The number of CD68-positive macrophages in each location of the tumor islets and tumor stroma was significantly higher than that of CD206-positive macrophages, and they were significantly correlated (P < 0.0001). Survival analysis revealed that CD68- and CD206-positive TAMs in the tumor stroma and tumor islets were significant prognostic factors (P < 0.05, respectively). Comprehensive analysis of CD206-positive stromal TAMs showed that CD105 and PD-L1 were significant prognostic factors (P=0.045). Moreover, CD68-positive TAMs in tumor islets and the expression of PD-L1 were independent predictors of poor prognosis for NSCLC. Conclusion Thus, the key elements in the tumor microenvironment, including tumor neo‑vessels, macrophages and PD-L1, were heterogenic in NSCLC tissues and had significant roles in cancer invasion and metastasis. The combined analysis of key components in the tumor microenvironment was an important prognostic factor.

BACKGROUND:Immune checkpoint inhibitors play a vital role in triple-negative breast cancer (TNBC) immunotherapy. A recent study showed that chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) has a crucial role in programmed death-ligand 1 (PD-L1) stability. The aim of this study was to investigate the relationship between CMTM6 and PD-L1 in TNBC and the association with clinical characteristics.METHODS:A total of 143 patients, including 75 with human epidermal growth factor receptor 2 (HER2)-driven breast cancer and 68 with TNBC, were included in this study. In 83 paired primary breast cancers (PBCs) and metastatic breast cancers (MBC) comprising 45 HER2-driven breast cancers and 38 TNBC, CMTM6 and PD-L1 were detected based on immunohistochemistry (IHC) with FFPE tissues. Another 60 PBCs comprising 30 HER2-driven breast cancers and 30 TNBC in order to detect CMTM6 and PD-L1 mRNA expressions based on real-time polymerase chain reaction (RT-PCR) using frozen tissues. Furthermore, 153 patients comprising 30 TNBC and 123 HER2-driven breast cancer based on The Cancer Genome Atlas (TCGA) database were used to confirm the difference mRNA expression.RESULTS:The expression of CMTM6 in patients with TNBC was significantly higher than in those with HER2-driven PBC (IHC, P=0.036, mRNA, P=0.036, TCGA dataset, P=0.039). CMTM6 was correlated with PD-L1 based on IHC in triple-negative MBC (P=0.004); the same result was found based on mRNA data in triple- negative PBC (P=0.021). Moreover, a high expression of CMTM6 in TNBC was associated with poor progression-free survival (PFS) (P=0.030, 95% CI: 1.08-4.57, HR =2.22). After multiple Cox regression analysis, CMTM6 in TNBC emerged as an independent risk factor for PFS (P=0.027, 95% CI: 1.11-5.20, HR =2.40). The expression of PD-L1 was negatively correlated with lymph node metastasis (P=0.026) and was not associated with PFS.CONCLUSIONS:The expression of CMTM6 was higher in TNBC than in HER2-driven breast cancer. In TNBC, CMTM6 was correlated with PD-L1 expression, and potentially could be used as an independent risk factor for predicting PFS.

目的 探讨成纤维细胞生长因子受体4(FGFR4)在膀胱肌层浸润性尿路上皮癌(MIBUC)中的表达及意义.方法 采用免疫组化EnVision两步法以及Western blot方法检测50例MIBUC组织及其配对癌旁正常膀胱黏膜组织中FGFR4蛋白的表达,并分析其与MIBUC病理及预后的关系.结果(1)MIBUC组织中FGFT4蛋白表达高于癌旁正常膀胱黏膜组织(P<0.05);(2)FGFR4阳性表达与神经侵犯、淋巴结转移、肿瘤T分期有关(P<0.05),与患者的年龄、性别、肿瘤大小、脉管侵犯和组织学分级无明显关系(P>0.05);(3)FGFR4的表达上调可导致β-catenin异常表达.结论(1)FGFR4蛋白在MIBUC组织中呈高表达,其在MIBUC发生、发展中起重要作用;(2)β-catenin参与了上皮间质转化(EMT)的过程;(3)FGFR4蛋白阴性表达者预后好于阳性表达者,可作为临床上MIBUC预后的评价指标.

BACKGROUND:Micropapillary-predominant adenocarcinoma (MPA) of the lung is associated with extensive lymph node involvement and rapid terminal metastasis. However, this subtype has been recognized for only a few years, and there have been few studies of the molecular mechanisms associated with its highly invasive behaviors.METHODS:The present study utilized immunohistochemical staining of surgically resected tissue blocks of MPA and lepidic-predominant lung adenocarcinoma to quantify the expression of specific biological markers in the WNT/β-catenin pathway and evaluate their influence on the lymph nodes invasion of these two types of lung adenocarcinomas.RESULTS:Our findings revealed that disruption of the cell membrane cadherin-catenin complex, which weakens the tumor cell adherence of MPA, was caused by the dissociation of β-catenin from the cadherin-catenin complex and the subsequent accumulation of β-catenin in the cytoplasm. This caused abnormal activation of the WNT/β-catenin pathway. We also found that Wnt-1-specific overexpression and Axin1 inhibition in MPA could explain the redistribution and cytoplasmic retention of β-catenin. Collectively, these findings suggest that an abnormality in the WNT/β-catenin pathway could enhance the invasiveness of MPA through the overexpression of Wnt-1 and downregulation of Axin1 molecules.CONCLUSIONS:Our data support the need for further research regarding the WNT/β-catenin pathway and the need to develop novel targeted therapies for restoration of tumor cell adherence and improvement of the prognosis of MPA.

目的 探究组织内星形胶质细胞活化基因-1(AEG-1)表达情况对葡萄膜恶性黑色素瘤(UM)病理特征的影响.方法 选取2016年3月～2018年8月我院眼科诊治的62例(62眼)于病理室存放的UM石蜡组织标本纳入研究组.并选取同期20例(20眼)因外部原因受伤采取眼球摘除术但少量UM或绝大部分葡萄膜组织正常的石蜡组织标本作为对照组.对比分析两组患者AEG-1基因表达情况以及AEG-1表达情况与UM病理特征的相关性.结果 UM组织中AEG-1 mRNA相对表达量为(1.09±0.05),正常葡萄膜膜组织中AEG-1 mRNA相对表达量为(1.01±0.12),差异有统计学意义(P<0.05);研究组62例(62眼)AEG-1阳性表达为37眼(59.68％),阴性表达为25眼(40.32％);对照组20例(20眼)AEG-1均呈阴性表达,差异有统计学意义(P<0.05);肿瘤高度>8 mm、累及睫状体、侵犯巩膜导管、眼外生长、视盘受累以及继发视网膜脱落与AEG-1高表达均有明显相关性(P<0.05).结论 UM高度>8 mm、累及睫状体、侵犯巩膜导管、眼外生长、继发视网膜脱落及视盘受累病理特征均与AEG-1的高表达具有密切联系,显著影响UM转移风险和预后,为UM临床诊断和治疗提供有效参考.

BACKGROUND Tumor microenvironment is a complex and dynamic community, which plays a crucial role in tumor progression via the co-evolution of cancer cells and tumor stroma. Among them, tumor-associated macrophages (TAMs) and tumor neo-vessels are two key components in the tumor microenvironment during cancer invasion. In addition, programmed cell death ligand 1/programmed cell death ligand 1 (PD-1/PD-L1) also plays an important role in tumorigenesis and development, and the clinical strategies to block PD-1/PD-L1 pathway could have great benefits for cancer patients. This study was aimed at analyzing the quantitative expression and prognostic significance of TAMs, tumor neo-vessels and PD-L1 in tumor microenvironment and exploring the relations between the expression of above components with the patients' prognosis of non-small cell lung cancer (NSCLC). METHODS Clinico-pathological data and surgical specimens of 92 patients with NSCLC were collected, and immunohistochemistry was used to stain the expression of TAMs, tumor neo-vessels and PD-L1 on tumor tissue and peri-tumor tissues. The inverted microscopy was used to take pictures and Image-pro Plus 6.0 software was used for quantitative analysis. The clinicopathological characteristics and overall survival (OS) were analyzed. RESULTS The median OS of 92 NSCLC cases was 22.5 month. The expression of TAMs, tumor neo-vessels and PD-L1 in tumor tissue and peri-tumor tissues were not statistically significant (P>0.05). According to the cutoff of above key three components in tumor microenvironment, all the cases could be classified into high, middle and low expression groups. The survival analysis demonstrated that the OS in high expression group of TAMs (P=0.016) and PD-L1 (P=0.002) was shorter than the other two groups, respectively, with statistical significance. The OS in high tumor neo vessels group was shorter than the other two groups. However, there was no statistical significance between these three group (P=0.626). Combined with above the three components, all the cases could be classified into low, middle and high density groups. The survival analysis demonstrated that the median OS of combined high density group was shorter than the other two groups (P=0.001). Multivariate analysis by Cox regression indicated that pathological type, TAMs and PD-L1 expression were the independent prognostic factors. CONCLUSIONS The key components of TAMs and PD-L1 in tumor microenvironment are closely related to the prognosis of NSCLC patients.

In this meta-analysis on correlation between schizophrenia and breast cancer (BC), we found that the incidence of schizophrenia is positively correlated with BC, and the incidence of BC in schizophrenia patients is increased in a certain degree. Because of the effects of potential bias and publication bias, the conclusion needs more high-quality studies to increase the strength of evidence. Purpose: To determine the correlation between schizophrenia and breast cancer (BC). Methods: We searched relevant articles indexed in the PubMed, Embase, and Cochrane Library databases; managed the data in Endnote X7 software; evaluated literature quality by Newcastle-Ottawa quality evaluation criteria; designed tables; and extracted relevant data. The main outcome measure was BC incidence. Effect values were risk ratio and 95% confidence intervals. We used Stata 13.1 software to perform the meta-analysis, choosing a corresponding combination model according to heterogeneity test results and carrying out subgroup analyses in order to better understand the stability of results through sensitivity analysis. Results: On the basis of 15 studies that assessed patients in different geographic regions, meta-analysis results showed that BC incidence between the exposure group (patients with schizophrenia) and the control group (nonschizophrenia population or general population) had statistical difference (risk ratio =1.18; 95% confidence interval, 1.05, 1.32), thus showing that BC incidence in patients with schizophrenia is higher than in the nonschizophrenia or general population. Subgroup analysis indicated that gender and geographic region may be sources of the assessed studies' heterogeneity. Conclusion: The incidence of schizophrenia is positively correlated with BC, and the incidence of BC in patients with schizophrenia is increased to a certain degree. Because of the effects of potential and publication bias, this conclusion needs more high-quality studies to increase the strength of evidence. (C) 2018 Elsevier Inc. All rights reserved.

Background Young patients are rarely diagnosed with non-small cell lung cancer (NSCLC), and little is known about its predisposing genomic alterations and survival. Methods This retrospective study was conducted to evaluate the genomic alterations, treatment and prognosis of young patients under 40 years old from a cohort of 640 lung adenocarcinoma and squamous carcinoma cases from Zhejiang Cancer Hospital. All patients were examined for EGFR, KRAS, NRAS, PIK3CA, BRAF and HER2 mutations and ALK, ROS1 and RET fusion genes. Results In total, 54 patients were aged under 40 years. The frequencies of genomic alterations in younger (≤40 years) and older (>40 years) patients were 68.5% and 54.8%, respectively (P=0.05). Younger patients harbored a higher frequency of fusion genes (22.2% vs. 4.1%, P<0.001) but not gene mutations (46.3% vs. 45.6%, P=0.92). There was a general trend toward shorter recurrence-free survival (RFS) (35.2 vs. 43.8 months, P=0.050), while no overall survival (OS) difference existed between younger and older patients (50.2 vs. 51.4 months, P=0.112). Conclusions Younger patients with NSCLC had a higher frequency of gene fusions than older patients and had a trend of worse OS.

Tumor-infiltrating lymphocytes (TILs) play a critical role in tumor immune surveillance and immune suppression. Understanding tumor infiltrating T cell subset density, location and PD-1/PD-L1 expression might provide insight for the prediction of tumor therapeutic response and clinical outcome. The purpose of this study was to evaluate the expression and localization of CD8, FoxP3, PD-1, and PD-L1 in primary tumor tissues and their effects on prognosis of stage IV M0 locally advanced nasopharyngeal carcinoma (NPC) patients. Sixty NPC patients with stage IV M0 locally advanced disease were treated with definitive chemoradiation. Tumor biopsies from primary lesion were analyzed for the expression and localization of CD8, FoxP3, PD-1, and PD-L1 by immunohistochemistry. Their associations with local disease control and survival of NPC were analyzed. The average follow-up time was 43 months (range from 14 to 61 months). High expression of CD8+, FoxP3+, PD-1+ and PD-L1+ was observed in 60, 86.7, 56.7, and 91.7% of patients, respectively. There was no correlation between clinicopathological features and the expression of these immune markers. High PD-1 expression was found to be associated with lower local disease control (5-year LRFS 23.2% vs 96.8%, p < 0.001) and unfavorable clinical outcome (5-year OS 47.4% vs 73.3%, p = 0.014). In multivariate analysis, PD-1 expression was also an adverse prognostic factor for 5-year OS (HR: 3.68, P = 0.023) and LRFS (HR: 16.89, 1.27–11.84, P = 0.007). Those with PD-1 distribution in both stroma and tumor region had the poorest prognosis. However, PD-1 expression has no significant correlation with 5-year RRFS (p = 0.980) and DMFS (p = 0.865). Patients with both PD-1 and PD-L1 high expression had significant poor local disease control (5-year LRFS 96.0% vs 43.0%, p < 0.001) and overall survival (5-year OS 80.8% vs 45.1%, p < 0.001) compared with the others. Other immune markers were not found having corrections with disease control and survival. PD-1 high expression, especially with PD-L1 co-expression, is associated with high local recurrence and unfavorable clinical outcome for stage IV M0 NPC patients, and might be a potential target for immunotherapy.

Checkpoint kinase 1 (CHK1) and p53 are involved in cell-cycle checkpoint, and cellular response to DNA damage. CHK1 and p53 are overexpressed in bladder urothelial carcinoma (BUC); however, a clear elucidation on their interaction and influence in the progress of BUC is absent. The aim of the present study was to examine the correlation between CHK1 and p53 in BUC, and analyze their value as therapeutic targets and prognostic indicators in BUC. A clinically annotated cohort of 110 patients with BUC was identified retrospectively. EnVision-based immunohistochemistry and western blot analysis of the aforementioned DNA repair proteins were conducted on formalin-fixed-paraffin-emb edded or frozen tissues from the primary tumor. A total of 45 peritumoral tissue cases were assessed similarly as the control group. In the cohort of 110 patients with BUC, a significant overexpression of CHK1 and p53 was observed in primary compared with the peritumoral tissues (P<0.05). CHK1 and p53 demonstrated a positive correlation in BUC, and both were positively associated with the histological grade, clinical pathological staging, lymphatic metastasis and the 5-year survival rate (P<0.05). However, CHK1 and p53 were not associated with sex, age, tumor diameter, single/multiple sites or incipient/recurrence. The overexpression of CHK1 and p53, and their synergistic interaction were putatively correlated with the physiology of BUC that may be deemed as potential therapeutic targets and prognostic indicators.

Some progresses have been made in research of long non-coding RNA (hereunder referred to as LncRNA) related to breast cancer. Lots of data about LncRNA transcription concerning breast cancer have been obtained from large-scale omics research (e.g. transcriptomes and chips). Some LncRNAs would become indices for detecting breast cancer and judging its development and prognosis. LncRNAs may affect genesis and development of breast cancer in multiple ways. Perhaps they could develop into potential targets for treating breast cancer if they are carcinogenic. Like those from other studies of breast cancer, many data gained from omics research remain to be validated by much experimental work. For instance, it is still necessary to demonstrate reliability of LncRNAs as indices for diagnosing breast cancer and judging its prognosis (particularly for various subtypes of breast cancer), effectiveness and feasibility of these genes for treating breast cancer as targets. In this paper, recent years' literatures about LncRNAs which are related to breast cancer are summarized and sorted out to review the research progresses in relationships between LncRNAs and breast cancer.

Some progresses have been made in research of long non-coding RNA (hereunder referred to as LncRNA) related to breast cancer. Lots of data about LncRNA transcription concerning breast cancer have been obtained from large-scale omics research (e.g. transcriptomes and chips). Some LncRNAs would become indices for detecting breast cancer and judging its development and prognosis. LncRNAs may affect genesis and development of breast cancer in multiple ways. Perhaps they could develop into potential targets for treating breast cancer if they are carcinogenic. Like those from other studies of breast cancer, many data gained from omics research remain to be validated by much experimental work. For instance, it is still necessary to demonstrate reliability of LncRNAs as indices for diagnosing breast cancer and judging its prognosis (particularly for various subtypes of breast cancer), effectiveness and feasibility of these genes for treating breast cancer as targets. In this paper, recent years’ literatures about LncRNAs which are related to breast cancer are summarized and sorted out to review the research progresses in relationships between LncRNAs and breast cancer.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are one of the most common observed genetic events in lung adenocarcinoma. The present study aimed to characterize treatment patterns and to estimate survival for patients in China with advanced lung adenocarcinoma and KRAS mutation. We identified KRAS-mutant lung adenocarcinoma between February 2013 and June 2017 in Zhejiang Cancer Hospital. Patients' characteristics and treatment outcomes were analyzed. A total of 159 lung adenocarcinoma were included, and 26 (16.4%) patients harbored KRAS mutations. Compared to KRAS-wild patients, patients with KRAS-mutant tumors were more likely to be smokers (76.9% vs. 51.9%, P = 0.029). Median tumor mutation burden (TMB) was significantly higher in the KRAS-mutant cohort than in the KRAS-wild cohort (5.4 vs. 4.2 mutations/megabases; P=0.041). Of the 93 patients receiving first-line chemotherapy, the median progression-free survival (PFS) in the KRAS-mutant group was significantly shorter than in the KRAS-wild group (1.5 vs. 7.2 months; P<0.001). The median overall survival (OS) in the KRAS-mutant group was also significantly shorter than in the KRAS-wild group (hazard ratio for progression or death for patients with KRAS mutation, 3.260; 95% CI, 1.516 to 7.013; P=0.001). In summary, our findings have several important implications for the molecular characterization and therapeutic outcome of lung adenocarcinoma initiated by oncogenic KRAS. Since the number of KRAS-mutant lung cancer is considerable, it should be taken seriously in clinical diagnosis and treatment. KRAS-mutant lung adenocarcinoma was not sensitive to chemotherapy, new and effective drugs targeting the KRAS pathway are in urgent need.

Objective To detect the frequency of BRAF/ KRAS and PIK3CA mutations in the small cell lung cancer (SCLC) specimens from a large population of Chinese patients and to analyze the gene mutation and clinical characteristics. Methods A total of 557 samples were collected from SCLC patients from 2009 to 2014.BRAF,KRAS,PIK3CA,NRAS and MEK1 gene mutations were detected by the dideoxy sequencing. Chi-square test was adopted to analyze the correlation between clinical factors and gene mutation. Kaplan-Meier method was utilized for survival analysis. Cox model was used for multivariate prognostic analysis. Results BRAF mutations were detected in 13 out of 557 specimens. The mutation types included V600E (n= 5) ,V600A (n= 2) ,V600M (n= 1) ,D594G (n= 1),G464E (n= 1),K601R (n= 2) and S605N (n= 1).KRAS mutation was detected in 6 cases including G12C (n= 3),G12A (n= 1),G12D (n=1) andG13D (n= 1).PIK3CA mutation was observed in 4 samples including E545G (n= 2) and H1047R (n= 2).Besides,NRAS mutation (Q61R) was detected in 1 case and MEK1 mutation (D61Y) was noted in 1 case. These gene mutations were not significantly correlated with the age, gender, smoking status and clinical staging of the patients. Univariate survival analysis demonstrated the median survival time of patients with gene mutation was (10.30±0. 751) months (95％CI:8. 829-11. 771 months),significantly shorter than (12.80±0. 543) months (95％CI:11. 736-13. 864 months) of their counterparts without gene mutation (P=0. 011). Conclusions BRAF/ KRAS and PIK3CA gene mutation is detected in a small proportion of SCLC patients. These gene mutations are not significantly correlated with the clinical characteristics. Univariate survival analysis demonstrates that negative these gene mutations are negatively correlated with the clinical prognosis of SCLC patients.

BACKGROUND:Esophageal sarcomatoid carcinoma (ESC) is a rare disease with a mixture of both carcinomatous and sarcomatous components in the tumor. Its genetic background and mechanisms of oncogenesis remain largely unknown.METHODS:Here we performed targeted next generation sequencing (NGS) on a pan-cancer gene panel in 15 ESC tumors to explore their genetic alterations, and aimed to identify clinically actionable mutations for future treatment instructions.RESULTS:TP53 alterations were identified in all patients. Alterations in receptor tyrosine kinases (RTK) were identified in 10 out of 15 patients. Members of downstream RAS and PI3-kinase pathways are also mutated in 10 patients, and PIK3CA is the top mutated gene in these pathways. In addition, we identified mutations on histone modification genes in 5 patients, including histone acetyltransferase gene EP300 and its homologue CREBBP, lysine methyltransferase genes KMT2A and KMT2B, and lysine demethylase gene KDM5A. Finally, mismatch repair (MMR) genes and proofreading gene POLE all together were mutated in one third of the ESC patients.CONCLUSIONS:This is the first study to unravel the mutational profile of ESC tumors. Our findings could match 9 patients to the targeted therapies currently available in clinical practice or in active clinical trials, suggesting the potential utility of targeted therapies for this rare disease in the future.

Background: As a type of new targets for prognosis of malignancies, long non-coding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcription 1) is associated with proliferation and metastatic abilities of several malignancies. However, its relations to development and migration of triple negative and human epidermal growth factor receptor 2 (Her-2) positive breast cancers haven't been reported. Objectives: In this paper, we aimed to discuss how MALAT1 is connected with and affects proliferation and invasion abilities of cells in Her-2 positive and triple-negative breast cancers (TNBC). Methods: The expression of MALAT1 in clinical samples with TNBC and Her-2 positive breast cancers was tested by qRT-PCR. The statistical analysis was performed to unveil the potential relationships between the expression of MALAT1 and prognostic factors of breast cancer such as OS (overall survival), RFS (relapse-free survival), number of metastatic lymph nodes and pTNM staging in patients with TNBC or Her2 positive breast cancer. MALAT1 and XBP1 were knockdown respectively in Her-2 positive cell line MDA-MB-231, and MALAT1 and Her-2 were knockdown respectively in TNBC cell line MDA-MD-435 using siRNA. The alterations of expressions of MALAT1 and related genes were detected by qRT-PCR in two breast cancer cell lines. The changes of proliferation abilities in two cell lines were observed using CCK8 assays. Furthermore, transwell assays were performed to detect changes to invasion abilities of the cells. Results: The expression of MALAT1 in triple negative and Her-2 positive breast cancers was positively correlated to the number of metastatic lymph nodes in patients with breast cancer. MALAT1 promotes proliferation and invasion abilities of breast cancer cells through XBP1 (X-box binding protein 1)-HIF (hypoxia-inducible factor)-1 alpha pathway in MDA-MB-231 and through Her-2 pathway in MDA-MD-435. Moreover, MALAT1 could possibly be involved in regulation of MYC gene and CD47 (an immune checkpoint gene) in both cell lines. Conclusions: Our study suggested that MALAT1 is a core signaling molecule for promoting development and migration of triple negative and Her-2 positive breast cancers. It would be employed as common markers for prognosis of the two types of breast cancer mentioned above and potential targets for treating them.

Background: This study aimed to examine the clinical and pathological characteristics of surgically resected lung adenocarcinoma patients harboring uncommon epidermal growth factor receptor (EGFR) mutations and provide a rational basis to provide postoperative adjuvant treatment for these patients. Methods: Data from 13 patients with lung adenocarcinomas harboring uncommon EGFR mutations were retrospectively collected, and the clinicopathological parameters and disease-free survival (DFS) data analyzed. Results: EGFR uncommon mutations commonly occurred in acinar predominant adenocarcinomas, females, and never smokers. Despite treatment, six patients relapsed. Conclusion: Patients with EGFR 20 insertion mutations relapsed quickly. Postoperative adjuvant treatment with chemotherapeutic drugs or new tyrosine kinase inhibitors for lung adenocarcinoma patients harboring EGFR 20 insertion mutations requires further evaluation.

Objective To analyze the quantitative expression and prognostic significance of tumor neo-vessels, macrophages and fibroblasts in tumor microenvironment of hepatocellular carcinoma (HCC).Methods The clinic-pathological features and tissue samples for 101 HCC cases were collected.Immunohistochemistry was used to stain the tumor neo-vessels, macrophages and fibroblasts on tumor tissue.The distribution results and quantitative data of above key components were acquired by inverted microscopy equipped with CRi Nuance multispectral analysis system.The number of tumor neo-vessels and macrophages on HCC tissue were counted and the thickness of cancer stroma based on the expression of fibroblasts was measured.The clinic-pathological characteristics and overall survival were analyzed.Results The median disease free survival (DFS) of 101 HCC cases was 5 month.The quantitative analysis of tumor neo-vessels, macrophages and fibroblasts showed that the expression range was 51-429 with median 218, 110-555 with median 259, 35.61-555.35 with median 246.98, respectively.To take the median as cutoff, all the cases could be classified into high and low expression group.The survival analysis demonstrated that the high density group of macrophages (P=0.022) and fibroblasts (P<0.001) has shorter DFS than low density group, with statistical significance.The high tumor neo-vessels group has shorter DFS with median 5 month than low density group with median 7 month.However, there was no statistical significance between these two group (P=0.197).Combined with above the three stromal components, all the cases could be classified into low, middle and high group.The survival analysis demonstrated that the high density group of stromal components has shorter DFS than the other two groups with median 3 month (P=0.001).Multivariate analysis by Cox regression indicated that cirrhosis, metastasis status, macrophages and fibroblasts density were the independent prognostic factors.Conclusion The key elements in tumor microenvironment including tumor neo-vessels, macrophages and fibroblasts were heterogenic in HCC tissues and played significant roles in HCC invasion and metastasis.

Objective To conduct a large-scale survey of the epidermal growth factor receptor (EGFR) mutations among Chinese small cell lung cancer (SCLC) patients, and to analyze the genetic heterogeneity and clinical characteristics of EGFR mutations in primary SCLC. Methods From 2009 to 2014, tissue specimens were collected from a total of 557 patients with SCLC.A total of 45 surgery and 512 biopsy samples are included. Dideoxy sequencing was used to determine the EGFR mutations. The chi-square test was used to analyze the correlation between clinical variables and EGFR mutations. Survival analysis was performed using the Kaplan-Meier method. Multivariate prognostic analysis was made by the Cox model. Results In the 557 specimens, 38 had EGFR mutations (6.8%), containing 3 with E19 deletion, 3 with E21 L858R, 1 with E20 T790M, and others with non-classical mutations. There was no correlation of EGFR mutations with gender, age, or clinical stage. There was no significant difference in proportion of non-smokers between patients with and without EGFR mutations (11/36 vs. 86/398, P=0.080). After the patient-treatment history matching, patients with EGFR mutations had a significantly longer median overall survival time than those without EGFR mutations (24.43±9.46 vs. 14.17±0.84 months, P=0.020), indicating a better prognosis in patients with EGFR mutations. The Cox regression analysis suggested that limited stage disease, age of<65 years, and EGFR mutations were prognostic predictors (HR=2.610, 1.476, 0.576, P=0.000, 0.010, 0.039). Conclusions EGFR mutations with high genetic heterogeneity can be found among the patients newly diagnosed with SCLC. EGFR mutations are positively correlated with the survival of patients with SCLC. Key words: Neoplasm, small cell lung; Epidermal growth factor receptor; Heterogeneity; Prognosis