IL17RB expression might predict prognosis and benefit from gemcitabine in patients with resectable pancreatic cancer

Background(Interleukin 17 Receptor Beta) IL17RB has been implicated in several malignancies. However, its role in the progression of and chemosensitivity in pancreatic cancer remains unknown. We aimed to determine the clinical significance of IL17RB expression in the prognosis of resectable pancreatic cancer and in the benefits from gemcitabine treatment.Materials and methodsWe used microarray and immunohistochemical staining techniques to evaluate IL17RB expression in 91 resectable pancreatic cancer tissues and their respective matched adjacent non-cancerous tissues. Quantitative real-time PCR and Western blotting were used to evaluate IL17RB in human pancreatic cancer cell lines after gemcitabine treatment. The correlation between IL17RB expression and overall survival and disease-free survival times were analyzed.ResultsIL17RB expression correlated with lymph node metastasis and (Vascular endothelial growth factor) VEGF expression. Cox proportional model showed that high IL17RB expression is a significant negative prognostic factor for both (overall survival) OS and (disease-free survival) DFS. Kaplan–Meier survival curves confirmed significantly reduced median overall and DFS time in high IL17RB patients as compared with low IL17RB patients. Furthermore, Cox proportional model confirmed a correlation between adjuvant treatment with gemcitabine-based chemotherapy and IL17RB expression. Kaplan–Meier survival curves showed that low IL17RB expression was associated with longer OS and DFS in patients than high IL17RB expression and gemcitabine-based adjuvant chemotherapy. In human pancreatic cancer cell lines, the messenger RNA and protein levels of IL17RB were signi?cantly enhanced after gemcitabine treatment.ConclusionsIL17RB predicts the prognosis and benefit from gemcitabine in patients with resectable pancreatic cancer.     

ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis

The excision repair cross completing group 1 gene product (ERCC1) and the regulatory subunit of ribonucleotide reductase (RRM1) have been reported as being prognostic of outcome and predictive of therapeutic efficacy in patients with non-small cell lung cancer. Routinely processed surgical specimens from 784 patients from the International Adjuvant Lung Trial were arrayed as tissue microarrays. In situ protein levels were scored with an automated, quantitative analysis system, dichotomized into high and low marker categories, and analyzed for associations with patients' characteristics, survival, and benefit from adjuvant chemotherapy. Scores for both markers were significantly associated with contributing center (P < 0.001) and skewed, with the bulk of scores being low. High scores were more frequent in women for ERCC1 and RRM1 and in older patients and those with adenocarcinoma for RRM1. Low ERCC1 scores indicated significant benefit from adjuvant chemotherapy [hazard ratio (HR) = 0.73 for chemotherapy versus control, P = 0.02]. Although all other survival associations were not statistically significant, low RRM1 scores trended to indicate benefit from adjuvant chemotherapy (HR = 0.84, P = 0.25), and ERCC1 scores were marginally prognostic of survival (HR = 0.77 for high versus low scores, P = 0.10). We conclude that contributing center and specimen quality substantially affect the levels of both markers. Future trials should incorporate the collection and processing of tumor specimens prospectively on standardized protocols to better reveal the impact of biomarkers on clinically relevant outcomes.     

Excision repair cross-complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin-based chemotherapy

Cisplatin has been the cornerstone of the chemotherapy regimen for urothelial carcinoma. Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. Recent reports have suggested that ERCC1 is a predictive and prognostic marker in solid cancers treated with platinum-based chemotherapy. We performed this study to determine whether or not immunohistochemical expression of ERCC1 can predict objective tumor response and cancer-specific survival in patients with advanced urothelial carcinoma treated with cisplatin-based chemotherapy. We performed a retrospective analysis of 89 patients with advanced or recurrent urothelial cancer, who had undergone treatment at Samsung Medical Center between May 2001 and August 2007. Pretherapeutic biopsy samples from 89 patients with a known tumor response were available. ERCC1 expression was assessed by immunohistochemistry. Of the 89 patients, ERCC1 expression was positive in 49 patients (55%). The overall response rate after chemotherapy was 68.5% (95% CI 54.8-74.8%). Among 61 patients who obtained a response, 27 were negative for ERCC-1 expression and 34 were positive (p = 0.61). Median duration of follow-up was 53.7 months (range 14.4-152.3 months). Progression-free survival (PFS) was 10.6 months for ERCC-1-negative patients and 8.4 months for ERCC-1-positive patients (p = 0.03); the difference in overall survival between patients with ERCC-1-negative tumors and ERCC-1-positive tumors (p = 0.73) was not statistically significant. Other than ERCC1 expression, there was no independent prognostic factor for PFS. These results suggest a negative contribution by ERCC1expression to PFS in metastatic urothelial carcinoma patients treated with cisplatin-based chemotherapy.     

The prognostic significance of growth factors and growth factor receptors in gastric adenocarcinoma

We evaluated growth factors/receptors expression in gastric adenocarcinoma. Immunohistochemistry was used to evaluate epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), VEGF‐D, VEGF receptor (VEGFR)‐2, VEGFR‐3, transforming growth factor (TGF)‐α, TGF‐β1, and TGF‐β‐RII in tissue microarrays of adenocarcinoma, dysplasia, metaplasia, and gastritis. In adenocarcinoma, the expression rates of EGFR, VEGF, VEGF‐D, VEGFR‐2, VEGFR‐3, TGF‐α, TGF‐β1, and TGF‐β‐RII were 2.0%, 0%, 10.7%, 4.4%, 11.2%, 26.3%, 9.4%, and 19.5%, respectively. VEGF‐D, TGF‐α, TGF‐β1, and TGF‐β‐RII expression rate were higher in adenocarcinoma than in other groups. TGF‐β‐RII expression was correlated with VEGFR‐3, VEGF‐D, and TGF‐α expression in adenocarcinomas. Tumor location, histologic type, stage, lymphatic invasion, perineural invasion, angioinvasion, VEGF‐D, and VEGFR‐2 expressions were associated with patient survival in a log rank test and advanced stage and positive expression of VEGF‐D were poor prognostic factors using Cox analysis. VEGF‐D expression may be of prognostic value in gastric adenocarcinoma, whereas EGFR and TGF family expression may only have a minor influence.     

结直肠癌术后循环肿瘤细胞检测的临床意义

目的 探讨结直肠癌(CRC)患者术后外周血循环肿瘤细胞(CTCs)阳性率及其计数与临床病理特征、肿瘤复发转移及预后之间的关系及其临床意义。方法 回顾性分析2016年1月—2017年7月上海交通大学医学院附属第九人民医院首诊并经病理确诊的99例CRC患者的临床资料,其中男66例、女33例,年龄37~79岁。检测患者术后4~8周且辅助治疗前CTCs计数和血清癌胚抗原(CEA)水平,随访患者生存情况,比较患者不同临床病理学特征患者间CTCs表达及计数值的统计学差异,包括性别、年龄、原发灶部位、肿瘤分化程度、原发灶浸润深度(T分期)、区域淋巴结侵袭程度(N分期)、远处转移(M分期)、TNM总分期;观察患者生存情况;采用COX比例风险回归模型进行无进展生存期、总生存期的单因素和多因素分析。结果 99例CRC患者CTCs阳性率为60.6%(60/99),CTCs计数值为0~24(4.909±5.518)。患者的CTCs阳性率和CTCs计数值在T1+T2+T3期、N0期、M0期、Ⅰ~Ⅱ期、CEA＜5 ng/mL和中高分化组患者低于T4期、N1+N2期、M1期、Ⅲ~Ⅳ期、CEA≥5 ng/mL、低分化组患者,差异均有统计学意义(P值均＜0.05)。患者随访3~20个月,死亡22例(22/99,22.2%),其中CTCs阳性21例;疾病进展32例(32/99,32.3%),其中CTCs阳性29例。单因素分析显示:CTCs表达、N分期、M分期、肿瘤分期、和高CEA水平是无进展生存期的影响因素(P值均＜0.05);CTCs表达、N分期、M分期、肿瘤原发灶位于直肠、高CEA水平是总生存期的影响因素(P值均＜0.05)。CTCs和远处转移是CRC患者无进展生存期和总生存期的独立预后因素(HR= 5.418、2.254,95%可信区间:1.595~8.403、1.227~7.986,P值均＜0.05)。结论 在术后CRC患者中,CTCs表达与预后不良有关,对肿瘤复发转移评估具有一定的价值和临床意义。     

NKX6.1 hypermethylation predicts the outcome of stage II colorectal cancer patients undergoing chemotherapy

Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the same stage often present with dramatically different clinical scenarios. Thus, robust prognostic biomarkers are urgently needed to guide therapies and improve treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation marker in cervical cancer, functioning as a metastasis suppressor by regulating epithelial–mesenchymal transition. Here, we investigated whether hypermethylation of NKX6.1 might be a prognostic biomarker for CRC. By analyzing the methylation and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using methylation‐specific polymerase chain reaction analysis and found that NKX6.1 was hypermethylated in 35 of 151 CRC tissues (23%). NKX6.1 gene expression was inversely correlated with the DNA methylation level in CRC cell lines in vitro. Then, we analyzed the association of NKX6.1 methylation with clinical characteristics of these CRC patients. Our data demonstrated that patients with NKX6.1 methylation presented poorer 5‐year overall survival (P = 0.0167) and disease‐free survival (P = 0.0083) than patients without NKX6.1 methylation after receiving adjuvant chemotherapy. Most importantly, these data revealed that stage II CRC patients with NKX6.1 methylation had poorer 5‐year disease‐free survival (P = 0.0322) than patients without NKX6.1 methylation after adjuvant chemotherapy. Our results demonstrate that methylation of NKX6.1 is a novel prognostic biomarker in CRC and that it may be used as a predictor of the response to chemotherapy.     

晚期非小细胞肺癌组织中ERCC1、RRM1表达水平与含铂治疗方案疗效及预后相关性分析

目的：探讨ERCC1及RRM1的表达在预测晚期非小细胞肺癌含铂治疗方案疗效及预后中的作用。方法：用免疫组织化学的方法检测124例ⅢB和Ⅳ期非小细胞肺癌患者的石蜡包埋活检组织标本中ERCC1和RRM1的表达水平,并分析其与临床病理特征以及疗效、预后的相关性。124例均为接受以铂类为基础的三代药物联合化疗的初治患者。结果：ERCC1、RRM1表达阳性者分别为43例（35％）和50例（40％）。ERCC1及RRM1的表达与疗效相关,ERCC1表达阴性者疗效达PR的患者（54％）明显高于阳性者（33％）,差异有统计学意义（P=0．022）。同样,RRM1表达阴性患者疗效为PR的明显高于RRM1阳性者（53％VS34％,P=0．042）。ERCC1和RRM1同时阴性表达者的中位生存时问明显长于同时阳性表达者（11．7个月VS9．2个月,P=0．025）,多因素分析表明,ERCC1为独立的预后预测因素（P=0．0066）。结论：ERCC1的表达与晚期非小细胞肺癌预后及含铂治疗方案疗效相关。     

AEG-1 基因在NSCLC 中的表达及其临床病理意义

目的:探讨非小细胞肺癌(NSCLC)组织中星型胶质细胞上调基因1(AEG-1)的表达及其临床意义。方法:选取本院心胸外科手术切除治疗的83 例NSCLC 患者的术后癌组织标本及20 例癌旁组织标本进行研究,采用免疫组化染色法检测两组AEG-1 蛋白的表达水平,并分析AEG-1 蛋白与NSCLC 患者的临床病理学关系。结果:AEG-1 NSCLC 组织中的AEG-1 蛋白高表达46 例(55.42%)显著高于癌旁组织的2 例(10.00%)(P<0.05);NSCLC 组织中的AEG-1 蛋白高表达与患者的T分期、N 分期及发生远处转移具有显著的相关性(P<0.05),与患者年龄、性别、分化程度关系不显著(P>0.05)。AEG-1 高表达NSCLC 患者的中位生存时间15.0 个月显著低于AEG-1 低表达患者的19.0 个月(log-rank 2 =4.19,P<0.05)。结论:NSCLC组织中AEG-1 基因表达上调,并且与患者的临床分期及远处转移有关。     

High Transaldolase 1 expression predicts poor survival of patients with upper tract urothelial carcinoma

Upper tract urothelial carcinoma (UTUC) is a rare tumor with an incidence that varies greatly between Eastern and Western countries. Transaldolase 1 (TALDO1) is a rate-limiting enzyme of the pentose phosphate pathway. In humans, aberrant TALDO1 activity has been implicated in various autoimmune diseases and malignancies; however, the function of TALDO1 in UTUC has not been previously investigated. Here we evaluated the clinical significance of TALDO1 expression in 115 paraffin-embedded tumor samples from patients with UTUC using immunohistochemistry. Our results demonstrated that there was an association between high TALDO1 expression and advanced stage (P = 0.011), tumor size (P = 0.005), tumor location (P = 0.047), distant metastases (P = 0.023), local recurrence (P = 0.002), and cancer death (P = 0.003). Using univariate and multivariate analyses, we found that chemotherapy was an independent factor for bladder recurrence-free survival. Late stage (III/IV) and high TALDO1 expression were independent prognostic factors for progression-free and cancer-specific survival. In summary, increased TALDO1 expression in UTUC was significantly correlated with late stage, tumor size, tumor location, distant metastases, local recurrence, and cancer death. Therefore, high TALDO1 expression could be a predictor of poor survival in patients with UTUC. Further studies are necessary to investigate the role of TALDO1 in UTUC development.     

非小细胞肺癌EGFR基因突变与ERCC1、RRM1、TUBB3 mRNA表达相关性研究

目的：探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变与切除修复交叉互补蛋白1(excision repair cross-complementation 1,ERCC1)、核苷酸还原酶亚单位M1(ribonucleotide reductase subunit M1,RRM1)及3型β-微管蛋白基因(classⅢβ-tubulin,TUBB3)表达的关系。方法：回顾性分析我院经病理诊断的69例NSCLC患者的手术切除的肿瘤标本,利用扩增受阻突变系统(amplification refractory mutation system,ARMS)进行EGFR基因突变检测,应用实时荧光定量PCR检测ERCC1、RRM1及TUBB3 mRNA的表达水平。结果：69例患者中,EGFR突变率为33.33%(23/69),在性别、吸烟史、病理类型组间突变率有显著性差异。ERCC1低、高表达率分别为59.42%(41/69)、40.58%(28/69),EGFR突变与ERCC1表达呈负相关性,EGFR无突变时ERCC1趋向于高表达(P=0.024);RRM1低、高表达率分别为31.88%(22/69)、68.12%(47/69),EGFR突变与RRM1表达无相关性(P>0.05);TUBB3低、高表达率分别为8.70%(6/69)、91.30%(63/69),EGFR突变与TUBB3表达无相关性(P>0.05)。ERCC1、RRM1、TUBB3三者间的基因表达均无相关性。结论：NSCLC患者肿瘤组织中EGFR突变患者ERCC1倾向低表达,这类患者可能更能从铂类化疗和靶向药物中受益。     

The distribution pattern of ERα expression,ESR1 genetic variation and expression of growth factor receptors: association with breast cancer prognosis in Russian patients treated with adjuvant tamoxifen

Identification of additional biomarkers associated with ER genomic and nongenomic pathways could be very useful to distinguish patients who will benefit from tamoxifen treatment. The aim of this study was to analyze the prognostic significance of the distribution pattern of ERα expression, ESR1 gene single-nucleotide polymorphisms and expression levels of growth factor receptors in Russian hormone receptor-positive breast cancer patients treated with adjuvant tamoxifen. Formalin-fixed paraffin-embedded tumor tissue samples from 97 patients were examined for the distribution pattern of ERα expression, as well as for EGFR and TGF-βR1 expression by immunohistochemistry. Genotypes for ESR1 +30T>C (rs2077647) and ESR1 2014G>A (rs2228480) were analyzed using a TaqMan assay. Progression-free survival (PFS) was used as an endpoint for the survival analyses. We found that patients with the heterogeneous distribution of ERα expression had poor prognosis on tamoxifen treatment (P = 0.021). We identified a high EGFR expression in patients who developed distant metastasis or recurrence during tamoxifen treatment (a tamoxifen-resistant group—TR) in contrast to the distant metastasis-free patients (a tamoxifen-sensitive group—TS) (80.0 vs. 41.9 %, respectively, P = 0.009). Carriers of the ESR12014A mutant allele were more prevalent among the TR patients compared to the TS patients (26.3 vs. 8.0 %, respectively, P = 0.009). EGFR expression and the distribution pattern of ERα expression were associated with the response to tamoxifen by both univariate and multivariate logistic regression analyses. The presence of these markers either alone or in combination was correlated with the worse PFS for all patients. Analysis of the distribution pattern of ERα expression and the EGFR status in tumor tissue may be valuable for patient selection for tamoxifen adjuvant therapy.     

Cyclooxygenase-2 expression correlates with uPAR levels and is responsible for poor prognosis of colorectal cancer

Considering recent findings that cyclooxygensase-2 (COX-2) is involved in the progression of colorectal carcinoma (CRC), the role of COX-2 in promoting invasion and angiogenesis was investigated by evaluating the relationship of COX-2 expression to various clinicopathological variables, including plasminogen activating system (PA system) and vascular endothelial growth factor (VEGF). Tumor tissues from 71 patients with CRC were assayed to determine the antigen levels of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2), as well as immunohistochemical expression of VEGF. COX-2 was assayed immunohistochemically in 56 patients. COX-2 expression was detected in cancer cells and it was also expressed by stromal cells in some patients. Fourteen patients (25%) were COX-2 positive, whereas 42 were negative. COX-2 expression was significantly related to lymphatic invasion (P=0.0317), but was not related to microvessel density or VEGF expression. In the PA system, uPAR antigen levels were significantly higher in tumors with COX-2 expression than in tumors without (P=0.0233). Univariate analysis showed that significant prognostic variables for survival were tumor size, lymph node involvement, lymphatic invasion, vascular invasion, liver metastasis, high uPAR level, and COX-2 expression, but only liver metastasis was an independent prognostic factor (P=0.0065) in multivariate analysis. COX-2 expression was a more important prognostic indicator than any other factor except liver metastasis (P=0.0526). The significant relationship between the presence of COX-2 protein and uPAR antigen levels contributed to the enhancement of tumor invasion and the poor outcome in patients with CRC. This revised version was published online in July 2006 with corrections to the Cover Date.     

Expression profiling of 21 biomolecules in locally advanced nasopharyngeal carcinomas of Caucasian patients

Background

Since scarce data exist on the pathogenesis of nasopharyngeal carcinoma in Caucasian patients, we attempted to elucidate the responsible molecular pathways in this patient population.

Methods

Formalin-fixed paraffin-embedded tumor tissue samples from 107 patients, diagnosed with locally-advanced nasopharyngeal carcinoma and treated with chemotherapy or chemo-radiotherapy, were analyzed by immunohistochemistry for the expression of the following proteins: E-cadherin, P-cadherin, Fascin-1, Cyclin D1, COX-2, EGFR, VEGF-A, VEGF-C, VEGFR-2, VEGFR-3, ERCC1, p53, p63, Ki67, MAPT, phospho-p44/42MAPK, PTEN, phospho-AKT, phospho-mTOR, and phospho-GSK-3β. EBER status was assessed by in situ hybridization. The majority of the cases were included in tissue microarray. All stains were performed and assessed centrally by two pathologists. The median follow-up time was 76.8 (42.3 – 99.2) months.

Results

Biomolecules expressed in >90% of cases were: p53, COX-2, P-cadherin, EBER, phospho-GSK-3β, and Fascin-1. WHO II+III tumors were more frequently EBER & PTEN positive and VEGF-A negative. Advanced age was significantly associated with positive phospho-GSK-3β and ERCC1 expression; male gender with positive phospho-AKT and phospho-p44/42MAPK; and worse performance status (1 or 2) with negative Ki67, ERCC1, PTEN, and phospho-mTOR expression. Earlier disease stage was closely associated with p63, MAPT, PTEN, and Cyclin D1 positivity. Univariate Cox regression analysis highlighted Cyclin D1 as a negative prognostic factor for disease-free survival (p=0.034) and EBER as a positive one for overall survival (p=0.048). In multivariate analysis, advanced age and stage, poor performance status, and positive ERCC1 emerged as predictors of worse disease-free and overall survival, as opposed to positive phospho-mTOR. Clustering analysis defined two protein-expression groups being predictive of better overall survival (p=0.043).

Conclusions

Our study is the first to examine the activation and interaction of established biomolecules and signaling pathways in Caucasian NPC patients in an effort to reveal new therapeutic targets.     

Correlations between expression levels of thymidylate synthase,thymidine phosphorylase and dihydropyrimidine dehydrogenase,and efficacy of 5-fluorouracil-based chemotherapy for advanced colorectal cancer

The efficacy of 5-fluorouracil (5-FU)-based chemotherapy for colorectal cancer (CRC) widely varies among patients; therefore, it is difficult to accurately predict chemotherapeutic responses. Some recent studies have found that key enzymes in the various metabolic pathways activated by 5-FU present potential predictors of treatment outcome. Of these enzymes, thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) are known to play important roles in the efficacy of therapeutic agents. Here, we measured expression levels of TS, TP, and DPD in formalin-fixed, paraffin-embedded, CRC specimens and paracancerous tissue with normal mucosa by immunohistochemical and fluorescence real-time quantitative polymerase chain reaction techniques. We found no significant differences in TS, TP, and DPD expression levels between CRC specimens and paracancerous tissues (P > 0.05), although overall survival and the chemotherapeutic effect were relatively poor in CRC patients with relatively high expression levels of TS, TP, and DPD, as compared to those with comparatively low expression levels (P < 0.05). Therefore, TS, TP, and DPD mRNA levels appear to be suitable indicators of the efficacy of 5-FU-based chemotherapy and prognosis of CRC.     

Expression and prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor (FLT-1) in nephroblastoma

AIMS: To investigate the prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor Flt-1 in nephroblastoma and whether tumour microvessel density (MVD) immunoreactivity, determined by the CD31 antigen, is related to the expression of VEGF and Flt-1. METHODS: The expression of VEGF and Flt-1 and MVD were investigated by means of immunohistochemical analysis in 62 Wilms's tumours. Patients were treated preoperatively with chemotherapy and had a mean follow up of 5.7 years. RESULTS: In general, VEGF and Flt-1 were expressed in normal kidney parenchyma and to a variable extent in the three main components of Wilms's tumour, namely: the blastemal, epithelial, and stromal cells. In tumour tissue, 52% and 47% of blastemal cells were positive for VEGF and Flt-1, respectively. A non-significant correlation was found between the expression of VEGF and Flt-1 in blastemal and epithelial cells and the clinicopathological stage. MVD was significantly higher in VEGF and Flt-1 positive tumours than in VEGF and Flt-1 negative tumours. Univariate analysis showed that the expression of VEGF and Flt-1 in blastemal cells was indicative of clinical progression and tumour specific survival. In addition, MVD expression was indicative of clinical progression. Epithelial staining was of no prognostic value. In a multivariate analysis, VEGF protein expression by blastemal cells was an independent prognostic marker for clinical progression. CONCLUSIONS: These results indicate that VEGF and Flt-1 protein expression are closely related to MVD and seem to be an important predictor for poor prognosis in treated patients with Wilms's tumour. Therefore, the expression of these molecules in primary Wilms's tumour may be useful in identifying those patients at high risk of tumour recurrence and in guiding antiangiogenic treatment.     

结直肠癌中Keratin 17的表达及其临床预后价值

目的 分析角蛋白17(Keratin 17,KRT17)在结直肠癌(colorectal cancer,CRC)中的表达及其临床预后价值.方法 采用生物信息学方法分析KRT17在CRC数据库中的表达及预后价值;进一步,采用免疫组织化学技术检测KRT17蛋白在95对CRC临床样本组织中的表达水平,并分析其表达与患者临床病...     

Prognostic value of vascularity and vascular endothelial growth factor expression in non-small cell lung cancer

AIMS: High expression of the angiogenic factor vascular endothelial growth factor (VEGF) in tumours has been found to be associated with poor prognosis in some studies, but not in others. The aims of this study were to determine the prognostic value of VEGF in operable non-small cell lung cancer (NSCLC) and its possible association with vascularity. METHODS: Sections from 81 NSCLC archival specimens were stained with antibodies to von Willebrand factor (vWF) and VEGF. Vascularity was measured by the average density of vWF positive vessels. VEGF expression in tumour cells was assessed by consensus of two independent observers according to three indices, namely: (1) percentage of area stained, (2) intensity of staining, and (3) final score (product of area and intensity). RESULTS: VEGF immunoreactivity was present in all tumours and adjacent normal lung tissue. None of the three VEGF indices was associated with vascularity or the clinical parameters examined. Mean survival times were shorter in patients with high VEGF expression, but the difference was not significant. This applied to the full cohort of patients, or when analysed separately according to tumour type or stage. However, high VEGF expression was associated with poor survival in patients with high vascularity (p = 0.02). VEGF had no discriminant value among patients with low vascularity. Vascularity had no prognostic value, except for late stage patients (UICC stages II and IIIa combined; n = 36), where high vascularity was associated with longer survival (p = 0.01). CONCLUSIONS: VEGF on its own has no prognostic value in NSCLC, but may become a useful indicator when combined with vascularity. VEGF may play a physiological role in the normal lung.     

Different subtypes of epithelioid sarcoma and their clinical implication: long‐term multi‐institutional experience with a rare sarcoma

Epithelioid sarcoma (ES) is a very rare soft‐tissue sarcoma with a high tendency of recurrence and metastasis. We analyzed clinical features of ES and aimed to identify the potential role of radio‐ and chemotherapy in ES. Fifty‐five patients diagnosed with ES between 1997 and 2014 were enrolled from seven tertiary hospitals in Korean Cancer Research Group. The clinical variables were retrospectively reviewed and analyzed. Forty‐six (84%) patients underwent surgical resection of ES, and among them, 27 experienced recurrence. In these patients, resection margin status and adjuvant radiotherapy were independent prognostic factors for longer recurrence‐free survival (RFS), while adjuvant chemotherapy did not influence RFS. Twenty‐two (40%) patients received palliative chemotherapy for metastatic or recurrent ES, and in these patients, palliative chemotherapy was the only independent prognostic factor for longer overall survival. Intriguingly, the clinical benefit of radio‐ and chemotherapy was observable only in proximal ES, but not in extremity ES, indicating that subtypes of ES might respond to radio‐ or chemotherapy differently. Proximal ES seems to benefits more from active anticancer treatment than conventional extremity ES. The aggressive characteristics of proximal ES could be overcome with an optimal multimodal treatment.