Expression of occludin,a tight-junction-associated protein,in human lung carcinomas

Occludin is a tight-junction-associated transmembrane protein, and previous observations suggested that occludin might play a crucial role in the formation and maintenance of organized tubular structures. Based on these observations, we explored the possible role of occludin immunostaining in the diagnosis of lung carcinomas. A total of 68 lung carcinomas and surrounding normal lung tissues were studied. A formalin-fixed, paraffin-embedded section from each tumor was stained with a new anti-occludin monoclonal antibody raised in our laboratory. In normal lung tissues, the anti-occludin antibody strongly stained the apicoluminal borders of the bronchial/bronchiolar epithelia and bronchial glands as a dot or short line. The antibody also stained the intercellular borders of alveolar epithelia. In cancer cells that faced lumina of all adenocarcinomas, regardless of grade, including bronchioloalveolar carcinomas, occludin showed an expression pattern identical to that of the normal bronchial and alveolar epithelia. Occludin reactivity was not noted in any cases of squamous cell carcinoma, large cell carcinoma, small cell carcinoma, or large cell neuroendocrine carcinoma. The results of the present study suggest that occludin can serve as an immunohistochemical indicator of the true glandular differentiation that forms tubulo-papillary structures in human lung carcinoma tissues.     

Different expression of Bcl-2 protein in gastric adenomas and carcinomas

In order to cast light on the possible role of bcl-2 protein (Bcl-2) expression In gastric tumorigenesis, 33 cases of gastric adenomas and carcinomas originating from the same stomachs were immunohistocnemically investigated for Bcl-2 protein (Bcl-2) expression, accumulation of p53 protein and cell proliferation as determined by the KI-67 labeling index (LI). Bcl-2 expression was detected in 24/33 (72.7%) adenomas and in 6/33 (18.2%) carcinomas, the difference being statistically significant (P=0.0O01). Only 4 of 33 (12.1%) cases exhibited expression in both adenoma and carcinoma lesions in the same stomachs. ImmunoreactMty was decreased in areas of cellular and structural atypia in adenoma lesions ( P <0.008), and appeared to be positively linked to the tumor progression and the degree of differentatlon in carcinomas, although It did not reach statistical significance. Accumulation of p53 protein was rare In the adenomas but was found in 15/33 (45.5%) of carcinoma lesions, with a significant dissociation from Bcl-2 immunoreactivity. No apparent relation between Ki-67 U and either adenoma grading or carcinoma typing was noted, although average KI-67 LI of the highest labeling areas in carcinomas was statistically higher than in adenomas ( P =0.0001). These results indicate that the regulation of Bcl-2 expression may differ between gastric adenomas and carcinomas, may be correlated with tumor dlfferentiathre features. In addition, p53 accumulation may play an Important role in the onset of malignancy.     

Expression of 8-hydroxy-2'-deoxyguanosine in gastric carcinomas

Objective: Reactive oxygen species may be involved in the progression of gastric carcinomas. To clarify whether the pathology of gastric carcinoma are related to oxidative DNA damage, the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was examined in 30 patients with gastric carcinomas. Methods: The expression of 8-OHdG and apoptosis in the gastric carcinoma were measured using the methods of immunocytochemistry and deoxynucleartididyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), respectively. Results: Of the 30 cases, 25 (83%) showed stronger immunoreactivity than normal control. The patients with poorly differentiated gastric carcinoma had a larger tumor size and higher labeling indices of TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated gastric carcinoma. Conclusion: Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic gastric injuries and determination of 8-OHdG is useful in assessing high-grade malignancy in gastric carcinomas.     

胃癌组织中NF-κB和COX-2的表达及临床意义

目的：探讨核因子-κB（nuclear factor-kappa B,NF-κB）和环氧合酶-2(cyclooxygenase-2,COX-2)的表达与胃癌发生发展的关系,为开展以NF-κB和COX-2为靶标的胃癌防治提供理论依据。方法：采用免疫组织化学染色法（SP法）检测对照组10例正常胃黏膜及实验组50例胃癌组织中NF-κB和COX-2的表达情况,分析它们在不同组织中的表达、相互关系及与胃癌的关系。结果：实验组NF-κB和COX-2的表达阳性率明显高于对照组（P<0.001）;NF-κB表达与胃癌淋巴结转移、分化程度有关（P<0.05）,COX-2 表达与淋巴结转移有关（P<0.05）;胃癌组织中NF-κB与COX-2的表达呈正相关关系,相关系数r=0.5238 （P<0.01）。结论：NF-κB和COX-2参与胃癌的形成,且与胃癌的侵袭、转移及预后有一定的关系。NF-κB与COX-2表达呈正相关,提示它们在胃癌的发生发展中起协同作用。     

Expression of phosphorylated caspase-9 in gastric carcinomas

Alterations of caspases, the main executioners of apoptosis, have been described in human cancers. Caspase-9 plays a crucial role in the initiation phase of the intrinsic apoptosis pathway. Caspase-9 is phosphorylated at Thr125 through the mitogen-activated protein kinase (MAPK) pathway, and this phosphorylation is associated with inhibition of caspase-9 activation. The aim of this study was to explore whether phosphorylated caspase-9 (p-caspase-9) expression could be a characteristic of gastric carcinomas. We analyzed expression of p-caspase-9 protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. p-caspase-9 was detected in 33 of the 60 carcinomas (55%). Both early and advanced gastric carcinomas expressed p-caspase-9. There was no significant association of p-caspase-9 expression with clinocopathological characteristics, including invasion, metastasis and stage. In contrast to gastric cancer cells, epithelial cells in normal gastric mucosa showed no or only weak expression of p-caspase-9. Taken together, these results indicate that caspase-9 is frequently phosphorylated in gastric carcinomas, and that the phosphorylation of caspase-9 might be an inhibitory mechanism of caspase-9-mediated apoptosis in gastric carcinomas. Increased expression of p-caspase-9 in malignant gastric epithelial cells compared to normal mucosal epithelial cells suggests that p-caspase-9 expression might play a role in gastric carcinoma development.     

Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas,intestinal metaplasia,and non-neoplastic gastric tissues

Trefoil factor family (TFF) domain peptides consist of three members that play a role in intestinal mucosal defence and repair, and in tumourigenesis. The role of the three TFF members in the gastric carcinogenesis cascade remains poorly defined. This study examined seven gastric cell lines, 50 gastric cancers and their adjacent non-cancer tissues, and tissues from 40 non-cancer patients, in order to elucidate the chronology of TFF expression in various stages of gastric carcinogenesis. TFF expression was determined by RT-PCR, immunohistochemistry, and western blot. Aberrant expression of TFF1, TFF2, and TFF3 was frequently detected in gastric cell lines. Specifically, TFF1 was detected in all non-cancer patients, but was detected in only 50% of gastric cancer and 66% of adjacent normal tissues. TFF2 expression was demonstrated in 87.5% of non-cancer patients, 34% of gastric carcinomas, and 58% of adjacent non-cancer tissues. There was a significant correlation between TFF1 and TFF2 expression in gastric cancer and adjacent non-cancer tissues (p<0.001). By contrast, TFF3 was detected in 25% of non-cancer patients and showed a predilection for areas with intestinal metaplasia (p=0.005). Sixty-two per cent of gastric cancers and 24% of neighbouring non-cancer tissues showed TFF3 expression. Immunoreactivity against TFF3 was demonstrated in goblet cells of intestinal metaplasia and within the cytoplasm and nuclei of tumour cells. Progressive loss of TFF1 and TFF2, together with the induction of TFF3, is likely to be involved in the early stage of the multi-step gastric carcinogenesis pathway.     

Expression of vascular endothelial growth factor in human gastric carcinomas

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a secreted protein which may play a pivotal role in tumor-associated microvascular angiogenesis and hyperpermeability. The expression of mRNA for VEGF was examined in eight gastric carcinoma cell lines and 30 gastric carcinoma tissues as well as corresponding normal mucosa. All the cell lines expressed VEGF mRNA at various levels that correlated well with the amounts of VEGF secreted into the condition medium. The expression of VEGF mRNA by TMK-1 cells was increased by the treatment of epidermal growth factor (EGF) or interleukin-1α (IL-1α), whereas it was decreased by the treatment of interferon-β (IFN-β). In gastric carcinoma tissues, the level of VEGF mRNA in primary tumors was higher than that in the corresponding normal mucosas in six (46%) of 13 well-differentiated adenocarcinomas and in two (12%) of 17 poorly differentiated adenocarcinomas, respectively. Vessel counts in well-differentiated adenocarcinomas had a tendency to be higher than those in poorly differentiated adenocarcinomas. In well-differentiated adenocarcinomas, the levels of VEGF mRNA expression tended to be higher in carcinomas of advanced stage than in early stage carcinomas. Both in situ mRNA hybridization and immunohistochemistry demonstrated the presence of VEGF expression within the tumor cells. These results suggest that VEGF may confer angiogenesis and progression of human gastric carcinomas, especially of the well-differentiated type.     

Expression of bcl-2 oncogene protein is prevalent in small cell lung carcinomas

To investigate the frequency of bcl-2 oncogene protein expression in small cell lung carcinoma (SCLC), immunohistochemical staining with a mouse-anti-human monoclonal antibody, bcl-2/124, was carried out on 60 formalin-fixed, paraffin-embedded SCLC samples obtained from surgical biopsy, and autopsy cases. bcl-2 protein was detected in 54 out of the 60 SCLCs. In 47 cases, more than half of the tumour cells stained positively. The staining intensity of the tumour cells was comparable to that of infiltrating lymphocytes in 37 cases, but varied from area to area and even from cell to cell. Negative data in six cases were found to be due to unsuitable fixation or embedding procedures rather than the absence of the antigen. bcl-2 oncogene protein may thus be expressed in most if not all SCLCs. bcl-2 may have potential diagnostic and therapeutic importance in SCLCs and non-SCLCs. Previous cytogenetic and molecular genetic analyses indicate that SCLCs carry a number of chromosomal abnormalities and it would follow from tpresent results that the abnormal expression of bcl-2 may also play a role in the pathogenesis of SCLC, by increasing tumour mass through inhibition of apoptosis as previously proposed. The diagnostic, prognostic, and therapeutic implications of these findings should be studied in greater detail.     

The gastric cytoprotective action of adenosine and prostaglandin E2 in rabbits

The direct protective action of adenosine and prostaglandin E₂ (PGE₂) was examined in an isolated gastric gland preparation in rabbits. Ethanol, (8%, v/v) incubation markedly increased the release of lactate dehydrogenase (LDH) and number of non-viable glands in the preparation. Both effects were prevented by PGE₂ preincubation in a concentration (10^–6, 1.4×10^–5 or 2.8×10^–5 M)-dependent manner. The protective action was smaller in adenosine-treated groups, and yet the highest concentration (10^–4 M) of the compound also significantly inhibited the cytotoxic effects of ethanol. These findings indicate that both adenosine and PGE₂ possess cytoprotective action on gastric glands in rabbits, but the former compound exerts its action beyond physiological concentrations. It is concluded that endogenous PGE₂, but not adenosine may act as an ulcer modulator in the stomach.     

Mutational and expressional analysis of BNIP3, a pro-apoptotic Bcl-2 member, in gastric carcinomas

Cell death deregulation is a hallmark of human cancers. BNIP3 was initially identified as a pro-apoptotic member of the Bcl-2 family and plays an important role in apoptosis, necrosis and autophagy. The aim of this study was to see whether alterations of BNIP3 protein expression and somatic mutation of the BNIP3 gene are characteristics of human cancers. We analyzed the expression of BNIP3 protein in 60 gastric adenocarcinomas by immunohistochemistry. In addition, we analyzed BNIP3 mutation in the DNA sequences encoding BH3 (Bcl-2 homology3) and TM (transmembrane) domains that are important in the cell death function of BNIP3 by single-strand conformation polymorphism (SSCP) in 48 colorectal, 48 gastric, and 48 breast carcinomas, and 48 acute leukemias. By immunohistochemistry, BNIP3 protein was detected in 40 of the 60 carcinomas (67%). Both early and advanced gastric carcinomas expressed BNIP3. There was no significant association between BNIP3 expression and clinicopathologic characteristics, including invasion, metastasis and stage. In contrast to the cancer cells, epithelial cells in normal gastric mucosa showed no or weak expression of BNIP3. Mutational analysis revealed BNIP3 mutation in neither the BH3 nor the TM domain, suggesting that BNIP3 mutation in these domains is not a direct target of inactivation in gastric, colorectal and breast carcinomas, and acute leukemias. Increased expression of BNIP3 in the malignant gastric epithelial cells compared to the normal mucosal epithelial cells suggests that BNIP3 expression might play a role in gastric carcinoma development.     

热休克蛋白70、90在子宫内膜癌中的表达

目的:探讨子宫内膜癌组织中热休克蛋白(HSP)70、90的表达及意义。方法:用免疫组化Envision法及图象分析仪,检测 30例正常子宫内膜、30例增生过长子宫内膜和53例子宫内膜癌中HSP70、HSP90的表达。结果:子宫内膜癌中HSP70表达的灰度值为(209.06±5.36),明显高于正常内膜[(145.21±4.09),P<0.01]和增生过长内膜[(148.59±4.23),P<0.01];子宫内膜癌中HSP90表达的灰度值为(166.98±5.71),明显低于正常子宫内膜[(208.57±31.14),P<0.05]和增生过长子宫内膜[(249.73±4.94),P<0.01]。子宫内膜癌中HSP70的表达随肿瘤病理分级的增加而增强(P<0.01),非内膜样癌(229.90±3.77)较内膜样癌表达强[(198.37±3.15),P<0.01];子宫内膜癌中HSP90表达随肿瘤病理分级的升高而表达减弱,非内膜样癌(140.21±3.22)较内膜样癌表达减弱[(176.59±2.79),P<0.01]。子宫内膜癌中HSP70、90的表达与肌层浸润深度、临床分期及淋巴结转移未见显著相关性(P>0.05)。结论:HSP70、90可能与子宫内膜癌的发生及预后有关。     

Sulglycotide displays cytoprotective activity in rat gastric mucosa

Sulglycotide, a well known antisecretory and antiulcer compound, has been further investigated for its ability to protect rat gastric mucosa against extensive necrosis induced by absolute ethanol, NaOH (0.2N) and NaCl (30%). Sulglycotide, which has been compared with cimetidine, displays a dose-dependent cytoprotective activity against the above necrotizing agents. The results obtained indicate that Sulglycotide requires a normal prostaglandin biosynthetic process in order to manifest its antiulcer activity. In fact gastric mucosa from animals treated with Sulglycotide releases in vitro a greater amount of PGl2-like activity; and furthermore no protection was observed against gastric lesions induced by indomethacin. As far as the mode of action of Sulglycotide is concerned it is tempting to speculate that the compound may interfere with prostaglandin degradation or it may trigger an adaptive cytoprotection which is important in maintaining the cellular integrity of rat gastric mucosa.     

Expression of RNA-binding protein LIN28 in classic gastric hepatoid carcinomas,gastric fetal type gastrointestinal adenocarcinomas,and hepatocellular carcinomas: An immunohistochemical study with comparison to SALL4, alpha-fetoprotein,glypican-3, and Hep Par1

Introduction

Gastric hepatoid carcinomas (GHCs) include type I (classic) and type II (fetal type gastrointestinal adenocarcinoma). The classic type shows overlapping morphologic features with those of hepatocellular carcinoma (HCC). The aim of this study is to investigate expression of LIN28 in GHCs and explore its utility to distinguish classic GHC from HCC.

Increased expression of Gab2, a scaffolding adaptor of the tyrosine kinase signalling, in gastric carcinomas

AIMS: Mounting evidence indicates that alterations of protein kinase signalling pathways play crucial roles in the pathogenesis of cancers. Gab2 (Grb2-associated binding protein 2), a member of the family of Gab scaffolding adaptors, transmits and amplifies the signals from receptor tyrosine kinases. A recent study demonstrated that Gab protein was over-expressed in breast cancers, and the over-expressed Gab2 increased proliferation and invasion of the cells, indicating that Gab2 is an oncogenic protein. However, the roles of Gab in other cancers are largely unknown. METHODS: In this study, to see whether Gab2 expression could be a characteristic of gastric cancers, we analysed the expression of Gab2 in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray. RESULTS: In the normal gastric mucosal epithelial cells, Gab2 protein was expressed in parietal and zymogen cells, but not in other mucosal epithelial cells. In the cancer cells, Gab2 expression was detected in 40 (67%) of the 60 gastric adenocarcinomas. The Gab2 expression was observed in 12 (60%) of the 20 early gastric carcinomas and 28 (70%) of the 40 advanced gastric carcinomas. There was no significant association of Gab2 expression with clinocopathological characteristics, including invasion, metastasis and stage. CONCLUSION: Our data indicate that Gab2 over-expression is a feature not only of breast cancers, but also of gastric cancers. Increased expression of Gab2 in malignant gastric cells compared with normal epithelial cells suggests that Gab2 expression may play a role in gastric cancer development.     

Comparative analysis of protein expressions in primary and metastatic gastric carcinomas

Because metastatic cancers are derived from their primary counterparts, their molecular profiles could reasonably be expected to be similar to those of primary cancers. However, this expectation has been proven to be untrue in several human cancers. To explore protein expressional differences in primary and metastatic gastric carcinoma, we evaluated the expressions of 32 tumor-associated proteins in 250 pairs of primary and metastatic gastric carcinoma tissues by immunohistochemistry using tissue array slides. In metastatic gastric carcinomas, the expressions of epidermal growth factor receptor, c-erbB2, and trefoil factor 1(TFF-1) were higher and those of beta-catenin, E-cadherin, fragile histone triad gene (FHIT), glutathione S transferase-pi (GST-pi), kangai 1 (KAI1), and nuclear factor-kappaB (NF-kappaB) were lower than in primary gastric carcinomas. Furthermore, the expressions of beta-catenin, E-cadherin, KAI1, and NF-kappaB were associated with an advanced T and combined stage. In addition, the loss of E-cadherin expression during lymph node metastasis or E-cadherin immunonegativity in metastatic lesions and epidermal growth factor receptor expression in primary gastric carcinomas were independently associated with a poor prognosis by multivariate analysis. In conclusion, the expression of some tumor-associated proteins and their prognostic significance in metastatic gastric carcinomas differ from those in primary tumors. Consequently, analysis of both metastatic gastric carcinomas and their primary counterparts may be required to fully determine the molecular characteristics of node-positive gastric carcinoma.