Nuclear accumulation of beta-catenin in intestinal-type gastric carcinoma: correlation with early tumor invasion

Mutation of the adenomatous polyposis coli gene, which is known to be an early event in the carcinogenesis of intestinal-type gastric carcinoma, leads to accumulation of beta-catenin. In addition, beta-catenin has been found to activate down stream signaling molecules in the wingless/Wnt pathway. In this study, the clinical significance of nuclear accumulation of beta-catenin was evaluated in gastric carcinoma. Immunohistochemical staining showed nuclear localization in 16 (12%) of 139 (94 intestinal-type and 45 diffuse-type) gastric carcinomas, and all 16 lesions with nuclear staining were intestinal-type adenocarcinomas. Of the 16 cases, 15 were in the early clinical stage. In the remaining case, the lesion had invaded the subserosal layer and showed strong nuclear staining at the invasive front. In 14 of the 16 cases with nuclear localization, there were no abnormal mobility shifts detected using polymerase chain reaction-single strand conformational polymorphism analysis. This was confirmed using direct sequencing analysis, which revealed the wild-type sequence in the 12 cases tested. Nuclear accumulation of beta-catenin did not correlate with lymph node metastasis or 5-year survival. These findings suggest that high intranuclear levels of beta-catenin protein play an important role in early tumor growth and may function in initiation of invasive processes in intestinal-type gastric carcinoma.     

Expression of PRL-3 phosphatase in human gastric carcinomas: close correlation with invasion and metastasis.

OBJECTIVE: High expression of PRL-3, a protein tyrosine phosphatase, has been reported to be associated with metastasis of colorectal carcinoma. The aim of this study is to investigate the significance of PRL-3 expression in tumor progression and metastasis of gastric carcinoma. METHODS: The levels of PRL-3 mRNA expression in 8 gastric cancer cell lines were examined by RT-PCR. Ninety-four human gastric carcinomas and 54 matched lymph node metastases were employed in this study. The expression of PRL-3 was detected by immunohistochemistry and the relationship with clinicopathological parameters was analyzed. RESULTS: The expression of PRL-3 mRNA was clearly detected in 7 of 8 gastric cancer cell lines (87.5%) by RT-PCR. In tumor samples, PRL-3 expression was detected in 68% of primary gastric carcinoma (with nodal metastasis 81.5%, without nodal metastasis 50%; p = 0.004). The incidence of PRL-3 expression in lymph node metastasis was significantly higher than that in primary gastric cancers (p < 0.001). Moreover, PRL-3 expression was closely associated with lymphatic invasion (p = 0.002), extent of lymph node metastasis (p = 0.002) and tumor stage (p = 0.045). CONCLUSIONS: These results strongly suggest that PRL-3 expression may play a significant role in invasion and metastasis of gastric carcinoma. PRL-3 might be a novel molecular marker for aggressive gastric cancer.     

Neural invasion in gastric carcinoma.

AIMS--To determine whether neural invasion in advanced gastric cancer is of clinicopathological significance. METHODS--The study population comprised 121 cases of primary advanced gastric carcinoma. Two paraffin wax embedded blocks taken from the central tissue slice in each primary tumour were used. For definitive recognition of neural invasion, immunostaining for S-100 protein was applied to one slide; the other slide was stained with haematoxylin and eosin. RESULTS--Neural invasion was recognised in 34 of 121 (28%) primary gastric carcinomas. There were significant differences in tumour size, depth of tumour invasion, stage, and curability between patients with and without neural invasion. The five year survival rates of patients with and without neural invasion were 10 and 50%, respectively. Multivariate analysis, however, demonstrated that neural invasion was not an independent prognostic factor. CONCLUSIONS--Neural invasion could be an additional useful factor for providing information about the malignant potential of gastric carcinoma. This may be analogous to vessel permeation which is thought to be important, but is not an independent prognostic factor.     

胃癌组织中钙网织蛋白的表达及其与临床病理特征的关系

目的 观察钙网织蛋白(CRT)在胃癌组织中的表达水平及其与临床病理的关系.方法 收集2009年4月至2010年8月本院外科手术切除并经病理确诊的44例新鲜胃癌组织及癌旁正常胃组织,采用实时荧光定量PCR和免疫组织化学方法分别检测44例胃癌及癌旁正常胃组织中CRT的mRNA和蛋白表达水平,分析其表达情况与临床病理学特征之间的关系.结果 胃癌组织中CRT的mRNA表达水平低于正常胃组织[36.50(21.72,71.47)比48.19(20.84,139.20),P=0.031].CRT蛋白主要定位于细胞质中,在胃癌组织中其阳性表达率明显低于正常胃组织[34.09％(15/44)比77.27％ (34/44),P=0.000].胃癌组织中CRT mRNA和蛋白的低表达均与胃癌的分化程度、淋巴结转移等临床病理因素密切相关(均P＜0.05),与患者的年龄、性别、肿瘤大小、TNM分期无关(均P＞0.05).结论 胃癌组织中CRT低表达,且与淋巴结转移、胃癌分化程度密切相关,是一项有潜在价值的肿瘤相关标志物.     

Overexpression of Ets-1 proto-oncogene in latent and clinical prostatic carcinomas

AIMS: The high incidence of clinically diagnosed prostatic cancer is exceeded by the frequency of tumours detected at autopsy. The Ets-1 proto-oncogene is expressed by a variety of malignant and normal tissues. Therefore, in this study, expression of Ets-1 protein was investigated in 'latent' prostatic cancer detected at autopsy, compared with benign prostatic hyperplasia, normal prostatic tissues and clinical prostatic cancer. METHODS AND RESULTS: Using immunohistochemistry, we analysed Ets-1 expression in 95 prostatic specimens including 19 cases of latent prostatic carcinoma (LPC) and 55 cases of clinical prostatic carcinoma (CPC), 11 cases of benign prostatic hyperplasia (BPH) and 10 cases of normal prostate (NP). Differences in the incidence of LPC and CPC suggest different courses for the biological progression of prostatic cancer. There was a significant difference in the degree of Ets-1 expression in CPC and LPC (P < 0.05). Ets-1 was not expressed in BPH and NP, but in malignant cases (57 of 74; 77.0%) commonly demonstrated immunoreactivity in the tumour cells. In our study the expression of Ets-1 between benign and malignant, and well, moderately and poorly differentiated adenocarcinomas of prostatic cancer showed significant differences. The presence of Ets-1 mRNA was confirmed by in-situ hybridization in human prostatic tissues. CONCLUSION: Our results suggest that Ets-1 might play an important role in carcinogenesis and/or the progression of human prostatic carcinomas.     

Expression of thrombospondin-1 in pancreatic carcinoma: correlation with microvessel density

Thrombospondin-1 (TSP-1) is a multifunctional platelet and extracellular matrix protein that is involved in angiogenesis. Under certain pathological conditions, e.g., malignant tumors, high concentrations of TSP-1 work as an angiogenic agonist. Here we examined 98 pancreatic carcinomas with respect to TSP-1 immunoreactivity and its correlation to intratumoral microvessel density (MVD), a representation of the overall degree of angiogenesis in carcinomas. Northern blot analysis for TSP-1 mRNA was performed in seven additional cases. Eighty-seven tumors showed strong TSP-1 immunoreactivity, nine carcinomas were only weakly positive, and two lesions were negative for TSP-1. TSP-1 immunoreactivity was detected in the extracellular matrix, mostly at the invasion front of the tumor. Using Northern blot analysis, we observed high levels of TSP-1 mRNA in three out of seven pancreatic carcinomas. The mean MVD in pancreatic carcinoma was 38.8 vessels per mm2. Tumors with a high expression of TSP-1 showed a higher MVD and the correlation between TSP-1 immunoreactivity and microvessel density was highly significant (P=0.003). As a modulator of angiogenesis, TSP-1 is strongly expressed in most pancreatic adenocarcinomas and is likely to contribute to the extensive neovascularization and spread of this highly aggressive tumor.     

bFGF和Ets-1表达与原发性卵巢癌的关系

目的检测碱性成纤维细胞因子（bFGF）和E26转录因子（Ets—1）在卵巢癌中的表达，为评估卵巢癌的生物学行为提供新的依据。方法应用免疫组织化学链霉素抗生物素—过氧化物酶复合法（SP）检测有2002年6月-2006年1月在哈医大二院病理科的50例卵巢癌组织中bFGF和Ets—1的表达，观察其与肿瘤组织学分级、临床分期、有无淋巴结转移及相互之间的关系。结果bFGF和Ets—1表达与原发性卵巢癌的FIGO分期、组织学分级密切相关（P＜0.05）；有大网膜淋巴结转移的病例bFGF和Ets—1阳性表达率显著高于无淋巴结转移的病例（P＜0．05和P＜0．05）。结论bF—GF和Ets—1的表达与原发性卵巢癌发生和转移有密切关系，检测bFGF和Ets—1的表达可作为了解卵巢癌生物学行为的参考指标。     

Renal expression of proto-oncogene Ets-1 on matrix remodeling in experimental diabetic nephropathy

The molecular mechanisms of glomerulosclerosis and tubulointerstitial fibrosis in diabetic nephropathy (DN) have received scant attention. Ets-1 proto-oncogene plays a role in matrix remodeling by regulating matrix-degrading enzymes. We investigated the possible role of Ets-1 in the pathogenesis of DN. 6-week-old male Sprague-Dawley rats were divided into two experimental groups as follows: control group (n = 30) and a Diabetes mellitus group (n = 40) induced by injection of streptozotozin (STZ). The rats were investigated at 1, 4, 8, 12 and 16 weeks after STZ-treatment. By means of immunohistochemistry, the expression of Ets-1 in glomeruli was significantly increased in STZ-treated rat kidneys from week 1 (P < 0.05) and reached the peak at week 4 (P < 0.05), followed by a downward trend at subsequent time points. Similarly, the expression of Ets-1 in the tubulointerstitium was also markedly increased from week 1 (P < 0.05) and reached a maximum at week 8 (P < 0.05). By double immunostaining, Ets-1-positive cells were frequently found to co-express matrix metalloproteinase-2 (MMP-2) in STZ-treated rat kidneys. Increased expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) coincided with increased expression of α-smooth muscle actin (α-SMA) in STZ-induced DN. A positive relationship was observed between the expression of Ets-1 in glomeruli or tubulointerstitium and the expression of MMP-2 (P < 0.01; P < 0.01, respectively) in STZ-treated rat kidneys. The ratio of MMP-2 and TIMP-2 in glomeruli or tubulointerstitium was negatively correlated with deposition of type IV collagen (P < 0.01; P < 0.01, respectively). These findings suggest that Ets-1 may play a critical role in fine-tuning matrix remodeling of STZ-induced DN.     

胃癌MT1-MMP、RECK蛋白的表达及其意义

目的探讨胃癌组织中膜型基质金属蛋白酶一1（MT1一MMP）和RECK蛋白表达状况和两者之间的关系,及其表达与胃癌临床诊断之间的关系。方法采用免疫组织化学法（两步法）对胃癌切除标本进行研究。结果在44例胃癌标本中,有37（84．1％）例MT1-MMP表达呈阳性反应,31（70．5％）例RECK免疫组化为阳性。MT1-MMP表达与胃癌分化具有一定的关系,低分化组织标本中,MT1一MMP表达较多,而中、高分化组织标本中,MT1-MMP表达相对较弱,具有统计学意义（P=0．015）。胃癌中MT1-MMP表达与肿瘤细胞浸润深度相关（P=0．007）。但MT1-MMP表达与性别以及有无淋巴结转移之间未见统计学差异。与此相反,在胃癌标本中,高分化标本中RECK蛋白表达相对较多,中分化标本其次,在低分化标本中表达较少。RECK表达与肿瘤分化具有统计学意义（P：0．006）。RECK表达与性别、肿瘤细胞浸润深度以及有无淋巴结转移无关,且与MT1-MMP表达之间亦无统计学意义。结论MT1-MMP过表达在胃癌分化、转移中发挥着重要的作用,而RECK的表达有益于胃癌向高分化发展。     

Expression of the RET proto-oncogene in human Embryos

The patterns of RET proto-oncogene expression in mouse, rat, and chicken and the anomalies observed in targeted RET mutants suggest that RET plays a major role in development of mouse enteric nervous system and in kidney organogenesis. Here, we report on in situ hybridization studies describing the pattern of RET proto-oncogene expression during early development of human embryos between 23 and 42 days. We show that the RET gene is expressed in the developing kidney (nephric duct, mesonephric tubules, and ureteric bud), the presumptive enteric neuroblasts of the developing enteric nervous system, cranial ganglia (VII+VIII, IX, and X) and in the presumptive motor neurons of the spinal cord. Yet, despite the high level of RET gene expression in the kidney and in the motor neurons of the developing central nervous system in human embryos, only rare cases with renal agenesis have been reported in Hirschsprung disease patients, and no clinical evidence of spinal cord involvement has been shown in patients carrying RET germline mutations (i.e., multiple endocrine neoplasia syndromes and Hirschsprung disease). Am. J. Med. Genet. 80:481–486, 1998. © 1998 Wiley-Liss, Inc.     

FHL1在人胰腺癌族中的表达及其与胰腺癌的侵袭及转移的相关性研究

目的:探讨FHL1蛋白在胰腺癌组织中的表达及其与胰腺癌临床病理特征的关系.方法:利用Western blot检测62例胰腺癌手术切除标本与其相对应的癌旁胰腺组织中FHL1蛋白的表达.用Log-rank检验分析FHL1蛋白表达与预后的关系.结果:FHL1的蛋白表达在胰腺癌中与对应癌旁胰腺组织相比下降明显(0.197±0.042 vs. 0.508±0.272,P<0.01).同时,FHL1在胰腺癌中的表达与临床分期、病理分级、淋巴结转移、肿瘤累及范围、远处转移均有明显差异(P<0.05),与高表达FHL1组相比,低表达FHL1组患术后生存时间明显缩短(P<0.01).结论:FHL1的异常表达很可能与胰腺癌的侵袭、转移等密切相关,而这种异常表达又影响了胰腺癌患的预后.     

凝血酶受体-1在肺癌组织中的表达及其与转移的关系

目的研究凝血酶受体（PAR）-1在肺癌组织中的表达及其与肺癌侵袭、转移的关系。方法免疫组织化学sP法、形态学计量及逆转录-聚合酶链反应（RT-PCR）检测肺癌原发灶和转移灶组织（36例液氮冻存肺癌组织、80例石蜡包埋肺癌组织）中PAR-1的表达。结果具有侵袭和转移部位的癌巢、脉管内癌栓、癌周围的肺泡上皮不典型增生灶及支气管腺导管上皮不典型增生灶均呈现较强的阳性反应。肺癌组织PAR-1蛋白表达阳性率为73．8％（59／80例）;转移组85．7％（48／56）与非转移组45,8％（11／24）之间差异有统计学意义（P〈0．05）。转移和非转移（P〈0．05）、原发灶和转移灶（P〈0．05）、肿瘤组织和肺组织（P〈0．01）各组之间PAR．1蛋白含量差异有统计学意义;而肿瘤大小、组织学类型和组织学分化各组间差异无统计学意义（P〉0．05）。肺癌组织PAR．1mRNA表达阳性率63．9％（23／36例）;转移组78．3％（18／23例）与非转移组38．5％（5／13）之间差异有统计学意义（P〈0．05）。结论PAR-1过度表达与肺癌的转移表型、组织发生及恶性表型有关;PAR-1可能是肺癌转移过程中发挥重要作用的因素之一。     

TGF-β1在子宫内膜异位症与子宫内膜癌中的表达及生物学行为相关性研究

目的研究转化生长因子β-（TGF-β1在子宫内膜异位症、子宫内膜癌中的表达，探讨其表达与子宫内膜异位症发生及子宫内膜异位症和子宫内膜癌生物学行为的相关性。方法采用免疫组织化学方法检测10例子宫内膜异位症在位内膜、异位内膜，10例子宫内膜癌，10例对照组正常子宫内膜TGF-β1表达。结果TGF-β1在子宫内膜异位症异位内膜组中的表达显著高于子宫内膜异位症在位内膜组及对照组（P〈0．05、P〈0．05）；TGF—β1在子宫内膜癌组中的表达显著高于对照组（P〈0．05）；TGF-β1在子宫内膜异位症异位内膜组中的表达与子宫内膜癌组中的表达差异无显著性（P〉0．05）。结论TGF-β1的异常表达可能与子宫内膜异位症的发生有关；且可能与子宫内膜异位症具有和子宫内膜癌相似的生物学行为有关。