Prognostic Value of P-gp and p27 in Patients with Esophageal Squamous Cell Carcinoma

Objective： To evaluate the prognostic value of P-gp and p27 expression in patients with esophageal squamous cell carcinoma （ESC）. Methods： The expressions of P-gp and p27 were detected by immunohistochemistry in 104 cases of ESC, and the clinicopathological characteristics were analyzed as well. Results： The positive rate of P-gp expression in 104 cases of ESCs was 32.7%. The positive rate of P-gp expression in the group that survived over 3 years （17.5%） was significantly lower than that in the group died within 3 years （53.3%） （x^2=14.227, P〈0.001）. The positive rate of p27 expression in 104 cases of ESCs was 67.3%. The positive rate of p27 expression in the group that survived over 3 years （75.8%） was significantly higher than that in the group died within 3 years （56.5%） （x^2=4.361, P〈0.05）. The patients with poorer differentiation whole wall invasion, lymph node metastasis and more advanced TNM stage had a shorter survival than did those with better differentiation, more superficial invasion, no lymph node involvement and earlier TNM stage; and it was statistically significant （P〈0.05）. However, tumor size, macropathologic type, age and gender had no prognostic impact on ESC patients （P〉0.05）. Conclusion： P-gp and p27 expression levels had a clinical prognostic significance in ESC. It could provide a reference basis for selecting the chemotherapy projection. The tumor differentiation degree, depth of invasion, lymph node involvement and TNM stages all were correlated to ESC patients＇ survival.     

Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-Differences in Etiology,Epidemiology and Prevention

In Germany,esophageal carcinoma is one of the ten most frequent causes of death.Normallythe disease is found in men over the age of 50.Although squamous cell carcinoma (SCC) of the esophagushas been more commonly diagnosed over the past 30 years,there is increasing incidence of esophagealadenocarcinoma (AC) in Western industrialized countries.For SCC the known etiological risk factorsare nicotine and alcohol abuse.For AC,they are moderate nicotine and alcohol consumption as well asgastro-esophageat reflux and obesity.     

β-Catenin Alterations in Squamous Cell Carcinoma of the Lip

This study aimed to investigate the correlation between ß-catenin immunoexpression and histopathologicalgrades of lower lip squamous cell carcinoma (LSCC). β-Catenin abnormal expression was found in 29% of thesquamous cells of well differentiated LSCC, 63% of moderately differentiated and 86% of poorly differentiated,and therefor was significantly associated with histological grade (p=0.000). Nuclear β-catenin expression appearedin 5% of the cells and was also correlated with the histological grades (p=0.000). In 14.7% of the cells it waslocalized in the cytoplasm, again correlating with histology (p=0.002). According to this study the expressionof β-catenin is an independent prognostic factor for histological grade and to the tumor differentiation. Thisappears to reflect a structural association and the role of β-catenin in tumor progression.     

Change and Significance of Mitochondrial DNA Copy Number in Esophageal Squamous Cell Carcinoma

OBJECTIVE To compare the differences of mitochondrial DNA (mtDNA) copies among the tissues of esophageal squamous cell carcinoma (ESCC), para-neoplastic tissue and normal mucous membrane of the esophagus, and to study the relationship between the mtDNA and the occurrence and devel- opment of esophageal squamous cell carcinoma. METHODS The mtDNA copies of 42 specimens with the ESCC, paraneoplastic mucous tissue and normal mucous membrane of the esophagus were determined using real-time fluorescence quantitative PCR. The mtDNA was analyzed using agarose gel electrophoresis. RESULTS The mtDNA from all of the tissues (42/42) from the ESCC, para-neoplastic tissue and normal esophageal mucous membranes was analyzed, showing that there were an average mtDNA copy number of 27.1894×106 μg DNA, 9.4102×106 μg DNA and 5.9347×106 μg DNA, from the respective tissues. There were signifi cant differences (F=27.83, P<0.05) in mtDNA copy number among the three. A positive band was shown at 403 bp after gel electrophoresis of the PCR products, and the lane where the ESCC mtDNA located was rather bright, which was in accordance with the result of the real-time PCR determination. CONCLUSION An increase in the mtDNA copy number is related to the occurrence and development of ESCC.     

Prognostic Value of Ki67 and VEGF Expression in Laryngeal Squamous Cell Carcinoma

OBJECTIVE To investigate the prognostic value of measuring Ki67 and VEGF expression in laryngeal squamous cell carcinoma （LSCC）. METHODS The expression of Ki67 and VEGF in 32 LSCC tissues was studied by immunohistochemical staining. Of these cases, 5 recurred （recurrent group）, 3 cases metastasized （metastatic group）, 8 cases died （deceased group） and 24 cased survived （survival group） over a 3 year period of follow-up after their operation. RESULTS The expression of Ki67 and VEGF in the deceased group was higher compared to that in the survival group （P〈0.01）. Overexpression of Ki67 was found in the recurrent group and in the metastatic group （P〈0.05）. VEGF expression was higher in the recurrent group than in the non recurrent group （P〈0.05）. With Cox-regression of multivariate analysis, Ki67 （RR：3.236; P=0.001）, the clinical T stage （RR：1.382; P=0.029） and metastasis in lymph nodes （RR：0.316; P=0.033） were shown to be independent prognostic factors for survival of LSCC patients. CONCLUSION Ki67 and VEGF expression is related to the prognosis of LSCC. Overexpression of the 2 markers indicated poor prognosis of the disease, a finding which might be helpful for the treatment of laryngocarcinoma.     

Patterns of Presentation and Treatment Outcomes of Non–clear-cell Renal Cell Carcinoma and Sarcomatoid Renal Cell Carcinoma Patients in 2 Tertiary Referral Centers in Sydney,Australia

BackgroundNon–clear-cell renal cell carcinoma (nccRCC) and renal cell carcinoma with sarcomatoid features (scRCC) are rare, and represent subtypes with less defined treatment strategies. The aim of this study is to describe the patterns of care and outcomes of these patients in 2 tertiary referral centers in South Western Sydney Local Health District over a 10-year period.Patients and MethodsPatients with RCC seen at South Western Sydney Local Health District from January 1, 2005 to December 31, 2015 were identified from electronic medical records. For each patient, we extracted details regarding demographics, tumor characteristics, treatment, recurrences, and survival, which was analyzed using the Kaplan-Meier method.ResultsOf 178 patients with RCC identified between 2005 and 2015, 23% (n = 41) had nccRCC and 8% (n = 15) had scRCC. Twenty-five patients in total had de novo metastatic disease or disease recurrence. The median follow-up was 46 and 16 months for nccRCC and scRCC, respectively. The median overall survival for nccRCC with metastatic disease was 34 months (range, 14 months to not reached). Seventy percent of these patients received systemic therapy. By contrast, the median overall survival for scRCC with metastatic disease was 10 months (range, 1.6-89 months). Less than one-half of the patients with scRCC received systemic therapy in our cohort, with only 34% receiving no more than 1 line of treatment.ConclusionsOur data confirm the rapid and aggressive course of scRCC, highlighting the need for more effective therapeutic strategies in this rare patient population.     

Outcome of Cervical Cancer in Iranian Patients According to Tumor Histology,Stage of Disease and Therapy

Background: Cancer of cervix, the second most common cancer of women overall, is a leading cause ofcancer death in developing countries. The purpose of this study was to measure outcome of treated cervicalcancer cases in Yazd since 2002 to 2009, according to pathology, stage of disease, lymph node involvement andtherapy. Materials and Methods: 100 cases were enrolled and survival was determined through phone calls togenerate 3 and 5- year-survival rates, evaluated by long-rank test with SPSS software. Results: Mean age of thepatients was 53.6 years, and 3 -year survival was 75.9 %( mean of 59.4 months). In first months, survival wasthe same in both pathology types, but because of the higher stages of squamous cell carcinomas in comparisonwith adenocarcinomas, their overall rate was lower. Stage IIB and IIIB survival rates were 90.9% and 30.8%,respectively, and rates with and without lymph node involvement were 64.8% and 80.1%. With para-aorticlymph node involvement, the rate was 85.8% (mean of 65.3 months). In patients who underwent surgery andchemoradiation, the respective figures were 71.6% and 54.9%. Anemic and non-anemic rates were 50% and78%. Conclusion: 3-5 year survival of cervical cancer fluctuates in the range of 70 to 93%. The relationship withlymph node involvement is weak. Survival of women receiving chemotherapy was lower than after surgery. Ourfindings showed an importance of diagnosis in primary stages and surgical resection of pelvic and para-aorticlymph nodes.     

The Expression of RECK mRNA and Protein in Esophageal Squamous Cell Carcinoma and Its Clinical Significance

目的:探讨食管鳞癌组织中RECK mRNA和蛋白的表达情况及其与临床病理因素的关系。方法:应用RT-PCR和免疫组化SP法检测62例食管鳞癌组织、31例癌旁不典型增生组织及62例正常食管粘膜组织中mRNA和蛋白的表达。结果:在食管鳞癌癌变过程中RECK在癌组织、癌旁不典型增生组织及正常粘膜组织中mRNA的含量依次增高,分别为1.052±0.078、1.274±0.235、1.306±0.121,组间比较有明显差异(F=49.936,P<0.05);不同分化程度、不同浸润深度及有无淋巴结转移的食管鳞癌组织之间RECK mRNA相对含量差异均有统计学意义(F=5.081,F=26.084,U=24.011,P均<0.05)。食管鳞癌组织及癌旁不典型增生组织中RECK蛋白表达均低于正常粘膜组织,表达量分别为59.7%(37/62)、71.0%(22/31)、85.5%(53/62),组间比较有明显差异(χ2=10.331,P<0.01);食管鳞癌组织中RECK蛋白表达与癌组织的分化程度、不同浸润深度及有无淋巴结转移密切相关(P<0.05)。结论:食管鳞癌组织中RECK mRNA和蛋白表达均降低,其低表达可能与食管鳞癌发生有关。检测RECK mRNA及蛋白的表达可望成为食管鳞癌早期诊断和判断预后的分子指标之一。     

Italian Nivolumab Expanded Access Program in Nonsquamous Non–Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients

Introduction

Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC.

Prognostic Value of Ki67 and VE6F Expression in Laryngeal Squamous Cell Carcinoma

OBJECTIVE To investigate the prognostic value of measuring Ki67 and VEGF expression in laryngeal squamous cell carcinoma (LSCC). METHODS The expression of Ki67 and VEGF in 32 LSCC tissues was studied by immunohistochemical staining. Of these cases, 5 recurred (recurrent group), 3 cases metastasized (metastatic group), 8 cases died (deceased group) and 24 cased survived (survival group) over a 3 year period of follow-up after their operation. RESULTS The expression of Ki67 and VEGF in the deceased group was higher compared to that in the survival group (P<0.01). Overexpression of Ki67 was found in the recurrent group and in the metastatic group (P< 0.05). VEGF expression was higher in the recurrent group than in the non recurrent group (P<0.05). With Cox-regression of multivariate analysis, Ki67 (RR:3.236; P=0.001), the clinical T stage (RR: 1.382; P=0.029) and metastasis in lymph nodes (RR:0.316; P=0.033) were shown to be independent prognostic factors for survival of LSCC patients. CONCLUSION Ki67 and VEGF expression is related to the prognosis of LSCC. Overexpression of the 2 markers indicated poor prognosis of the disease, a finding which might be helpful for the treatment of laryngocar-cinoma.     

A Tuft Cell–Like Signature Is Highly Prevalent in Thymic Squamous Cell Carcinoma and Delineates New Molecular Subsets Among the Major Lung Cancer Histotypes

IntroductionIn-depth genomic characterization of thymic epithelial tumors (TETs), comprising thymomas and thymic carcinomas (TCs), failed to identify targetable mutations and suggested unique biology of TETs, including KIT expression in most TCs. Recently, tuft cell–like medullary thymic epithelial cells were identified in the murine thymus, and our reanalysis of the published gene expression data revealed that these cells express KIT. In addition, recently, a minor subset of SCLCs with tuft cell–like features was described.MethodsWe interrogated mRNA expression data from our tumor cohorts (N = 60) and publicly available, independent data sets from TETs and NSCLC (N = 1199) for expression of tuft cell genes and KIT. Expression of KIT and of POU2F3 protein, the master regulator of tuft cells, was analyzed in cancer tissue (N = 344) by immunohistochemistry.ResultsNormal human thymic tuft cells and most TCs coexpressed KIT and known tuft cell genes, particularly POU2F3 and GFI1B. Unexpectedly, small subsets of tuft cell–like tumors coexpressing POU2F3, GFI1B, and KIT were also identified among pulmonary squamous cell carcinomas, adenocarcinomas, and large cell neuroendocrine carcinoma and clustered together in each histologic cohort. In addition to the tuft cell–like signature, both thymic and lung tuft cell–like carcinomas had distinct genetic, pathologic, and clinical features in each cohort.ConclusionsWe suggest that the tuft cell–like phenotype defines novel subsets of thymic and pulmonary carcinoma. Its high prevalence in thymic squamous cell carcinomas that have no known toxic or viral etiologies suggests a new mechanism of carcinogenesis that may lead to specific drug susceptibilities.     

Elevated Renin Levels in Patients with Liver Cirrhosis and Hepatocellular Carcinoma

Liver fibrosis is the common consequence of chronic liver injury of any etiology, disrupting the normalarchitecture,and causing hepatocellular dysfunction and portal hypertension. Since the renin-angiotensin system(RAS) may be involved in chronic liver diseases, in the present study we assayed renin levels using ELISA in groupsof Egyptian patients with liver cirrhosis (N=32) and hepatocellular carcinoma (HCC) (N=67), for comparisonwith twenty five healthy controls. The results showed significant differences between the control and liver cirrhosispatients (P<0.001) and also the controls and HCC patients (P<0.001), without significant variation between thepatient groups. Furthermore, in HCC patients, it was found that the renin levels negatively correlated with serumalbumin and prothrombin time (P=0.003 for each) and positively with α-fetoprotein (P=0.04). Thus, it is concludedthat renin levels are elevated in patients with liver cirrhosis and HCC and suitable medical intervention shouldbe placed for management of such alteration. Moreover, further studies are warranted to explore its prognosticsignificance.     

Receptor-type Protein Tyrosine Phosphatase �� Regulates Met Phosphorylation and Function in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and has a high rate of mortality. Emerging evidence indicates that hepatocyte growth factor receptor (or Met) pathway plays a pivotal role in HNSCC metastasis and resistance to chemotherapy. Met function is dependent on tyrosine phosphorylation that is under direct control by receptor-type protein tyrosine phosphatase β (RPTP-β). We report here that RPTP-β expression is significantly downregulated in HNSCC cells derived from metastatic tumors compared to subject-matched cells from primary tumors. Knockdown of endogenous RPTP-β in HNSCC cells from primary tumor potentiated Met tyrosine phosphorylation, downstream mitogen-activated protein (MAP) kinase pathway activation, cell migration, and invasion. Conversely, restoration of RPTP-β expression in cells from matched metastatic tumor decreased Met tyrosine phosphorylation and downstream functions. Furthermore, we observed that six of eight HNSCC tumors had reduced levels of RPTP-β protein in comparison with normal oral tissues. Collectively, the results demonstrate the importance of RPTP-β in tumor biology of HNSCC through direct dephosphorylation of Met and regulation of downstream signal transduction pathways. Reduced RPTP-β levels, with or without Met overexpression, could promote Met activation in HNSCC tumors.     

Immunohistochemical Assessment of E-cadherin and β-catenin in the Histological Differentiations of Oral Squamous Cell Carcinoma

The aim of this study was to establish the expression and localization of E-cadherin and β-catenin inoral squamous cell carcinomas (OSCC) so that we could correlate the findings with prognostic-relevanthistopathological variables. E-cadherin and β-catenin expression in normal oral epithelia and in oral squamouscell carcinomas was examined immunohistochemically, and associations with histopathological differentiationand prognosis were then analyzed in 33 patients who had been operated on for OSCC. E-cadherin expressionwas found in (82%) of the squamous cells of well differentiated OSCC, (61%) of moderately differentiatedand (39%) of poorly differentiated. E-cadherin expression was significantly associated with histological grade(p=0.000). No nuclear staining was detected. In (19.5%) of the cells E-cadherin localized in the cytoplasm, withno correlation to the histological grade (p=0.106). β-Catenin expression was found in 87% of the squamous cellsof well differentiated OSCC, 67% of moderately differentiated and 43% of poorly differentiated, the expressionwas significantly associated with histological grade (p=0.000). the nuclear β-Catenin expression appeared in 3.3%of the cells and it was correlated to the histological grade (p=0.000). In (23.5%) of the cells β-Catenin localizedin the cytoplasm, with correlation to the histological grade (p=0.002). According to this study the expression ofβ-catenin and E-cadherin were independent prognostic factors for histological grade. E-cadherin was closelylinked to β-catenin expression in OSCC (p=0.000) and to tumor differentiation. That reflects a structuralassociation and the role of both in tumor progression.     

Salivary Tumour Necrosis Factor-α as a Biomarker in Oral Leukoplakia and Oral Squamous Cell Carcinoma

Background: Oral cancer is one of the life threatening disease which requires an availability of a biomarker for itsearly detection and also for effective treatment strategies. The current study is done to evaluate the efficacy of one suchbiomarker i.e. TNF- α as an indicator for oral precancer and oral cancer. Objectives: To evaluate the efficacy of Tumournecrosis factor - alpha (TNF)-α as a salivary biomarker in histopathologically diagnosed cases of oral leukoplakia andOral squamous cell carcinoma. To correlate the levels of TNF- α with varying histologic grading in Oral SquamousCell Carcinoma and dysplasia grading in Oral leukoplakia or Hyperkeratosis. Materials and Methods: The studygroup included 90 subjects that were divided into three groups. OSCC (n=30), leukoplakia (n=30) and controls (n=30).Cases were selected based on inclusion and exclusion criteria of the study. Salivary samples were then collected fromall three groups. Salivary levels of TNF-α were estimated using Enzyme Linked Immunosorbent Assay (ELISA). Thedata on concentration gradients obtained were subjected to appropriate statistical analysis. Results: The results of thepresent study demonstrated higher levels of salivary TNF-α in individuals with OSCC compared to leukoplakia andhealthy control subjects with a high level of statistical significance. ROC curve analysis along with diagnostic parametercalculation also revealed that salivary TNF-α to be a better medium for detecting OSCC. There is also an increase inthe salivary TNF-α levels with increase in the histological grade of differentiation in OSCC as well as leukoplakia.Conclusion: The present study concludes that salivary TNF – α can be used as a prognostic biomarker of OSCC. Inview of the elevated levels of TNF – α in saliva of individuals with severe dysplasia, it can also be used to monitor themalignant transformation to leukoplakia to OSCC.