Overexpression of E-cadherin and beta-catenin proteins in metastatic prostate cancer cells in bone

BACKGROUND: The expression of E-cadherin in the intercellular adhesion of metastatic prostate cancer cells in bone, which is the most prevalent site of metastatic growth, remains elusive. METHODS: The aim of the study was to compare the concurrent membranous expression of E-cadherin and beta-catenin proteins, the state which is known to be associated with the cellular adhesion function of E-cadherin, in prostate biopsy tissue specimens by immunohistochemical staining method. The expression patterns of E-cadherin or beta-catenin were classified as homogeneous (most cells exhibiting positively), heterogeneous (a few scattered patches of cells with positivity) or negative. RESULTS: Benign prostate hyperplasia cells exhibited homogeneous expression of both E-cadherin and beta-catenin in 9 of 11 (82%), whereas the primary prostate cancer cells were homogeneously positive for both proteins only in 4 of 22 (18%) of the cases. The results are similar to those reported in literature. However, in contrast to the primary cancer, a significantly increased frequency of the metastatic prostate cancer cells in bone exhibited homogeneous expression of E-cadherin and beta-catenin in 12 of 17 (71%) of the cases. A statistically significant association was observed between the overexpression of both proteins and the metastatic prostate cancer cells in bone (Fisher's exact P < 0.001). CONCLUSIONS: The result of the study demonstrated for the first time that the membranous overexpression of E-cadherin and beta-catenin are significantly associated with the metastatic prostate cancer cells in bone and that the high frequency of expression suggest their involvement in the intercellular adhesion of the metastatic cells in bone.     

Understanding oral cancer in the genome era

Completion of the human genome project approximately 15 years ago was followed closely by advancements in array technology. Investigators quickly applied this new powerful tool to the genomic and proteomic study of oral squamous cell carcinoma (OSCC). Resultant publications documented chromosome, gene, mRNA, and protein alterations that characterize oral cancer. In this review, we summarize how the genomic, proteomic, and epigenetic array studies have provided insight into the process of oral carcinogenesis. We discuss the significant limitations and requirement for validation of these array studies. We also review the manner in which state‐of‐the‐art, high‐throughput approaches are being used to search for salivary and serum oral cancer biomarkers. © 2010 Wiley Periodicals, Inc. Head Neck, 2010     

Tumor-specific genetic expression profile of metastatic oral squamous cell carcinoma

BACKGROUND: Metastasis is the most important predictor of survival in patients with oral squamous cell carcinoma (OSCC). We tested the hypothesis that there is a genetic expression profile associated with OSCC metastasis. METHODS: We obtained samples from 6 OSCC node-positive primary tumors and their matched metastatic lymph nodes, and 5 OSCC node-negative primary tumors. Using laser capture microdissection, we isolated OSCC cells from metastatic lymph nodes and compared them with those from matched primary tumors and unmatched node-negative primary tumors using Affymetrix Human Genome Focus arrays. RESULTS: Comparison of tumor cells from the lymph nodes with those from the unmatched, node-negative primary tumors revealed differential expression of 160 genes. Hierarchical clustering and principal component analysis using this 160-gene set showed that the node-negative samples were distinguishable from both, node-positive primary tumors and tumors in the lymph nodes. Many of the expression changes found in the metastatic cells from the lymph nodes were also found in the node-positive primary tumors. Immunohistochemical analysis for transglutaminase-3 and keratin 16 confirmed the differential genetic expression for these genes. CONCLUSION: These preliminary results suggest that there may be a metastatic gene expression profile present in node-positive primary OSCC.     

Expression of PCNA, p53, Bax, and Bcl-X in oral poorly differentiated and basaloid squamous cell carcinoma: relationships with prognosis

BACKGROUND: The aim of this study was to compare the clinical features and proliferating cell nuclear antigen (PCNA), p53, Bcl-X, and Bax expression in primary oral basaloid squamous cell carcinoma (BSCC) and poorly differentiated squamous cell carcinoma (PDSCC) matched by stage and site and to assess the possible prognostic significance of these variables. METHODS: Seventeen cases of oral BSCC were compared with 27 PDSCCs matched by stage and tumor site. In addition, PCNA, p53, Bax, and Bcl-X expression in both carcinomas were evaluated in relation to their clinicopathologic features and prognostic values using the Kaplan-Meier method and Cox regression models. RESULTS: No statistically significant differences were found between the groups (BSCC and PDSCC) in regard to clinical features and immunohistochemical reactivity for antibodies PCNA, p53, and Bcl-X. In comparison with PDSCC, the BSCC group exhibited a higher Bax score (p = .031). The 5-year and 10-year overall survival, cancer-specific survival, and disease-free survival rates demonstrated no significant differences between the BSCC and PDSCC groups, and the PCNA, p53, Bax, and Bcl-X also showed no prognostic value. CONCLUSIONS: These results suggest that the clinical and biologic course of BSCC is similar to PDSCC in the oral cavity when clinical stage and site are matched.     

Resection margins in oral cancer surgery: Room for improvement

The purpose of this review was to identify publications on resection margins in oral cancer surgery and compare these with the results from 2 Dutch academic medical centers. Eight publications were considered relevant for this study, reporting 30% to 65% inadequate resection margins (ie, positive and close margins), compared to 85% in Dutch centers. However, clinical outcome in terms of overall survival and recurrence seemed comparable. The misleading difference is caused by lack of unanimous margin definition and differences in surgicopathological approaches. This prevents comparison between the centers. Data from Dutch centers showed that inadequate resection margins have a significantly negative effect on local recurrence, regional recurrence, distant metastasis, and overall survival. These results confirm the need for improvement in oral cancer surgery. We underline the need for consistent protocols and optimization of frozen section procedures. We comment on development of optical techniques for intraoperative assessment of resection margins. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E2197–E2203, 2016     

Hypermethylation of GSTP1, CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites

BACKGROUND: In the US, the incidence and mortality of prostate cancer is about twofold higher among US Blacks compared to Whites, suggesting racial differences in prostate tumor occurrence and aggressiveness. The reason for these racial differences is unknown. Epigenetic events such as promoter-region gene hypermethylation may be influenced by environmental exposures and have been implicated in prostate carcinogenesis (by the silencing of tumor suppressors and other regulatory genes). METHODS: Using real-time methylation-sensitive PCR, we assessed differences in DNA hypermethylation of GSTP1, CD44, and E-cadherin (three genes thought to be important in the progression of prostate cancer) in archival tumor tissue of black (n = 47) and white men (n = 64). RESULTS: We found a high prevalence of GSTP1 hypermethylation overall (84%) but no differences by race (89 and 83% in black vs. white men, respectively), tumor stage, or grade. Although CD44 hypermethylation was less prevalent overall (found in 32% of tumors), we observed a 1.7-fold higher frequency among black men (43 vs. 25% in black vs. white men, P = 0.05) and a correlation with tumor grade (CD44 was hypermethylated in 10, 42, and 52% of well, moderate, and poorly differentiated tumors, respectively, P = 0.003) but not disease stage. The E-cadherin gene was not hypermethylated in any of the tumors. In summary, of the three genes examined, only CD44 hypermethylation differed by race and correlated with tumor grade, independent of race. CONCLUSIONS: These preliminary findings suggest that differences in gene promoter hypermethylation may potentially underlie racial differences in prostate cancer pathogenesis and should be explored in larger studies.     

上皮型钙黏附素基因表达及启动子甲基化与胃癌家族遗传性

目的通过检测家族遗传性胃癌和伴胃癌家族史和肿瘤家族史胃癌及散发性胃癌的E-cd的表达和启动子甲基化情况,探讨E-cd与我国家族遗传性胃癌家系的关系。方法采用免疫组织化学方法检测符合ICG-HGC诊断标准的家族性遗传性胃癌8例和伴胃癌家族史胃癌的30例,伴肿瘤家族史胃癌的30例,散发性胃癌20例的E-cd蛋白表达情况及基因启动子甲基化情况,进行分析,探讨家族性胃癌发生的分τ遗传学基础。结果E-cd在各组胃癌中表达均下调,与正常组织的差异具有统计学意义。家族性遗传性胃癌中E-cd表达下调与其他胃癌组相比差异具有统计学意义。在各组中均不同程度发生E-cd基因启动子甲基化,在家族遗传性胃癌、伴胃癌家族史胃癌与其他组相比差异具有统计学意义。结论E-cd蛋白表达抑制在胃癌中较常见 且在家族遗传性胃癌组降低最明显,同时E-cd基因启动子区甲基化可能是导致E-cd基因表达下调的重要原因 E-cd基因可能是家族遗传性胃癌的分子遗传学基础。     

Pattern of nonspecific (or global) DNA methylation in oral carcinogenesis

BACKGROUND: Although alterations in nonspecific (or global) DNA methylation (GDM) in specific cells are known to be involved in the process of lung carcinogenesis, similar associations have not been evaluated in other smoking-related cancers of the head and neck. METHODS: We evaluated the status of GDM by using monoclonal antibodies specific for 5-methylcytosine (5-mc) in oral squamous cell carcinoma (SCC) specimens of 48 cigarette smokers who had SCC develop and in 93 age-, race-, and sex-matched smokers who did not. RESULTS: Percentages of cells positive for 5-mc immunostaining of DNA of SCC and dysplastic lesions were significantly higher than those of normal oral epithelial cells from cancer subjects and from noncancer subjects. The degree of DNA methylation was unrelated to DNA content. CONCLUSIONS: The pattern of GDM in oral SCCs is different from that of lung SCCs. The differences in nutrient risk factor profiles that are related to GDM and differential activity of DNA methyltranferases between oral and lung SCCs may explain these observations.     

膀胱癌细胞中DAPK基因启动子甲基化状态分析

目的 分析DAPK抑癌基因在T24、5637、ScaBER三种膀胱癌细胞中的表达情况及该基因启动子区的甲基化状态。方法 采用半定量RT-PCR和Westernblot分别检测三种膀胱癌细胞中DAPK基因的表达，用甲基化特异PCR（MSP）方法检测三种细胞中的DAPK基因启动子甲基化状态。观察甲基转移酶（DMNT）抑制剂5-aza-2’-deoxy．cytidine（5-aza-CdR）对各细胞中的基因表达和甲基化状态的影响。结果 T24细胞中未检测到DAPK基因的表达，也未检测到启动子甲基化；5637细胞中该基因表达水平极低，在SeaBER细胞中该基因的表达较前两者要高。5637细胞和ScaBER细胞中均有甲基化改变。2．5μmol／l浓度的5-aza-CdR可以有效上调5637和ScaBER细胞的DAPK基因的表达。结论 抑癌基因DAPK的表达异常与移行细胞癌的发生发展有重要联系，且基因启动子区CpG岛的异常甲基化在调节DAPK基因的表达中发挥重要作用。