Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic,periampullary/ampullary,and choledochal adenocarcinomas

BACKGROUND Pancreatic,periampullary/ampullary,and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis.Immune checkpoint blockade is a promising treatment option for several tumor types.H long terminal repeatassociating 2(HHLA2),which is analogous to programmed death-ligand 1(PDL1),is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many malignancies.AIM To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to immunotherapy.METHODS Ninety-two adenocarcinoma cases located in the pancreas,ampulla,and distal common bile duct were identified.This study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and 2021.Immunohistochemistry was conducted to examine the expression of DNA mismatch repair(MMR),PD-L1,and HHLA2 proteins.RESULTS Patients with high HHLA2 expression had a higher mean age than those with low expression.Low HHLA2 expression was associated with high perineural invasion.HHLA2 expression was low in pathological stage T3(pT)3 cases and high in pathological stage T1,T2,and T4 cases.There was no correlation between HHLA2 expression and the expression of MMR proteins and PD-L1.CONCLUSION Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.

Radiomic features from computed tomography to differentiate invasive pulmonary adenocarcinomas from non-invasive pulmonary adenocarcinomas appearing as part-solid groundglass nodules

Objective:We aim to investigate radiomic imaging features extracted in computed tomography(CT)images to differentiate invasive pulmonary adenocarcinomas(IPAs)from non-IPAs appearing as part-solid ground-glass nodules(GGNs),and to incorporate significant radiomic features with other clinically-assessed features to develop a diagnostic nomogram model for IPAs.Methods:This retrospective study was performed,with Institutional Review Board approval,on 88 patients with a total of 100 part-solid nodules(56 IPAs and 44 non-IPAs)that were surgically confirmed between February 2014and November 2016 in the First Affiliated Hospital of China Medical University.Quantitative radiomic features were computed automatically on 3D nodule volume segmented from arterial-phase contrast-enhanced CT images.A set of regular risk factors and visually-assessed qualitative CT imaging features were compared with the radiomic features using logistic regression analysis.Three diagnostic models,i.e.,a basis model using the clinical factors and qualitative CT features,a radiomics model using significant radiomic features,and a nomogram model combining all significant features,were built and compared in terms of receiver operating characteristic(ROC)curves.Decision curve analysis was performed for the nomogram model to explore its potential clinical benefit.Results:In addition to three visually-assessed qualitative imaging features,another three quantitative features selected from hundreds of radiomic features were found to be significantly(all P<0.05)associated with IPAs.The diagnostic nomogram model showed a significantly higher performance[area under the ROC curve(AUC)=0.903]in differentiating IPAs from non-IPAs than either the basis model(AUC=0.853,P=0.0009)or the radiomics model(AUC=0.769,P<0.0001).Decision curve analysis indicates a potential benefit of using such a nomogram model in clinical diagnosis.Conclusions:Quantitative radiomic features provide additional information over clinically-assessed qualitative features for differentiating IPAs from non-IPAs appearing as GGNs,and a diagnostic nomogram model including all these significant features may be clinically useful in preoperative strategy planning.

Sonic hedgehog-Gli1 pathway in colorectal adenocarcinomas

AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, Gli3 and PDGFRα. METHODS： Expression of Shh in 25 colorectal adenocarcinomas was detected by RT-PCR,in situ hybridization and immunohistochemistry. Expression of Ptchl was observed by in situ hybridization and immunohistochemistry. Expression of Hip, Gil1, Gli3 and PDGFRα was analyzed by in situ hybridization. RESULTS： Expression of cytokeratin AE1/AE3 was observed in the cytoplasm of colorectal crypts. Members of the Hh signaling pathway were expressed in colorectal epithelium. Shh was expressed in cytoplasm of dysplastic epithelial cells, while expression of Ptchl, Hip and Gill were mainly detected in the malignant crypts of adenocarcinomas. In contrast, PDGFRα was expressed highly in aberrant crypts and moderately in the stroma. Expression of Gli3 could not be detected in colorectal adenocarcinomas. CONCLUSION： These data suggest that Shh-Ptchl-Gli1 signaling pathway may play a role in the progression of colorectal tumor.

Survivin isoforms and clinicopathological characteristics in colorectal adenocarcinomas using real-time qPCR

AIM:To investigate three isoforms of survivin in colorectal adenocarcinomas.METHODS:We used the LightCycler Technology(Roche),along with a common forward primer and reverse primers specific for the splice variants and two common hybridization probes labeled with fluorescein and LightCycler-Red fluorophore(LC-Red 640).Real time quantitative polymerase chain reaction(PCR) was performed on cDNAs from 52 tumor specimens from colorectal cancer patients and 10 unrelated normal colorectal tissues.In the patients group,carcinoembryonic antigen(CEA) and CA19-9 tumor markers were also measured immunochemically.RESULTS:Wild type survivin mRNA isoform was expressed in 48%of the 52 tumor samples,survivin-2b in 38%and survivin-ΔΕx3 in 29%,while no expression was found in normal tissues.The mRNA expression of wild type survivin presented a significant correlation with the expression of the ratio of survivin-2b,survivin-ΔΕx3,survivin-2b/wild type survivin and survivin-ΔΕx3/wild type survivin(P<0.001).The mRNA expression of wildsurvivin and survivin-ΔΕx3 was related with tumor size and invasion(P=0.006 and P<0.005,respectively).A significant difference was found between survivin-2b and morphologic cancer type.Also,the ratio of survivin-ΔEx3/ wild-survivin was significantly associated with prognosis.No association was observed between the three isoforms and grade,metastasis,Dukes stage and gender.The three isoforms were not correlated with CEA and CA19-9.CONCLUSION:Survivin isoforms may play a role in cell apoptosis and their quantification could provide information about clinical management of patients suffering from colorectal cancer.

Inducible nitric oxide synthase, nitrotyrosine and apoptosis in gastric adenocarcinomas and their correlation with a poor survival

AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma.METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression wasdetected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOSexpression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P＜0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high Ais (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low Ais (0.79%; 47.14%) (P= 0.001). COX's multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69).CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival.

Association between Helicobacterpylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas

AIM TO correlate Helicobacter pylori （H. pylorli）, EpsteinBarr virus （EBV） and human papillomavirus （HPV） with gastric cancer （GC） cases in Para State, Brazil.METHODS Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eberl RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.RESULTS The majority of the 302 samples analyzed were obtained from men （65%） aged 55 years or older （67%） and were classified as the intestinal subtype （55%）. All three pathogens were found in the samples analyzed in the present study （H. pylori： 87%, EBV： 20%, HPV： 3%）. Overall, 78% of the H. pylori-positive （H. pylorl＋） samples were cagA＋ （H. pylori-cagA＋）, and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA＋ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.CONCLUSION HPV was not involved in gastric tumorigenesis. Prophy- lactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

Associations Between Epidermal Growth Factor Receptor Gene Mutation and Serum Tumor Markers in Advanced Lung Adenocarcinomas: A Retrospective Study

Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGlaR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 （43%） advanced lung adenocarcinoma patients. Gender （P=0.003）, smoking status （P=0.001）, and abnormal serum status of carcinoembryonic antigen （CEA, P=0.028） were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation （P=0.046） with an odds ratio of 2.613 （95% Ch 1.018-6.710）. However, receiver operating characteristic （ROC） curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma （the area under the ROC curve was 0.608, P=0.069）. Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.

Significance and prognostic value of lysosomal enzyme activities measured in surgically operated adenocarcinomas of the gastroesophageal junction and squamous cell carcinomas of the lower third of esophagus

AIM： To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction （GEJ） and the squamous cell carcinomas of the lower third of the esophagus （LTE）. METHODS： Between February 1, 1997 and February 1, 2000, we obtained tissue samples at the moment of resection from 54 patients for biochemical analysis. The full set of data could be comprehensively analyzed in 47 of 54 patients＇ samples （81%）. Of these, 29 were adenocarcinomas of the GEJ Siewert type Ⅰ （n = 8）, type Ⅱ （n = 12）, type Ⅲ （n = 9）, and 18 presented as squamous cell carcinomas of the LTE. We evaluated the mean values of 11-lysosomal enzyme and 1-cytosol protease activities of the tumorous and surrounding mucosae as well as their relative activities, measured as the ratio of activity in tumor and normal tissues from the same patient. These data were further analyzed to establish the correlation with tumor localization, TNM stage （lymph-node involvement）, histological type （papillary, signet-ring cell, tubular）, state of differentiation （good, moderate, poor）, and survival （≤24 or ≥24 mo）. RESULTS： In adenocarcinomas, the activity of α-mannosidase （AMAN）, cathepsin B （CB） and dipeptidyl-peptidase Ⅰ （DPP Ⅰ） increased significantly as compared to the normal gastric mucosa. In squamous cell carcinomas of the esophagus, we also found a significant difference in the activity of cathepsin L and tripeptidyl-peptidase Ⅰ in addition to these three. There was a statistical correlation of AMAN, CB, and DPP Ⅰ activity between the level of differentiation of adenocarcinomas of the GEJ and lymph node involvement,because tumors with no lymph node metastases histologically confirmed as well-differentiated, showed a significantly lower activity. The differences in CB and DPP Ⅰ activity correlated well with the differences in survival rates, since the CB and DPP Ⅰ values of those who died within 24 mo following surgical intervention were significantly higher than of those who survived for 2 years or more. CONCLUSION： Adenocarcinomas of the GEJ form a homogenous group from a tumor-biochemical aspect, and differ from the biochemical characteristics of squamous cell carcinomas of the LTE on many points. When adenocarcinomas of the GEJs are examined at the preoperative phase, the ratio of the performed AMAN, CB, and DPP Ⅰ enzymatic activity of the tissue sample from the tumor and adjacent intact mucosa within 2 cm of the tumor may have a prognostic value even in the preoperative examination period, and may indicate that ranking of these patients into the neo-adjuvant treatment group should be considered.

Adenocarcinomas after Prophylactic Surgery for Familial Adenomatous Polyposis

The incidence of familial adenomatous polyposis (FAP) is one in 7,000 to 12,000 live births. Virtually, all surgically untreated patients with FAP inevitably develop colorectal-cancer in their lifetime because they carry the adenomatous polyposis coli gene. Thus prophylactic proctocolectomy is indicated. Surgical treatment of FAP is still controversial. There are however, four surgical options: ileorectal anastomosis, restorative proctocolectomy with ileal pouch-anal anastomosis, proctocolectomy with ileostomy, and proctocolectomy with continent-ileostomy. Conventional proctocolectomy options largely lie between colectomy with ileorectal anastomosis or ileal pouch-anal anastomosis. Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis because of better functional results and quality of life. The functional outcome of total colectomy with ileorectal anastomosis is undoubtedly far superior to that of the ileoanal pouch;however, the risk for rectal cancer is increased by 30%. Even after mucosectomy, inadvertent small mucosal residual islands remain. These residual islands carry the potential for the development of subsequent malignancy. We reviewed the literature (1975-2012) on the incidence, nature, and possible etiology of subsequent ileal-pouch and anal transit zone adenocarcinoma after prophylactic surgery procedure for FAP. To date there are 24 studies reporting 92 pouch-related cancers;15 case reports, 4 prospective and 5 retrospective studies. Twenty three of 92 cancers (25%) developed in the pouch mucosa and 69 (75%) in anal transit zone (ATZ). Current recommendation for pouch surveillance and treatment are presented. Data suggest lifetime surveillance of these patients.

Meta-analysis of lymph node metastasis in Siewert type Ⅰ and Ⅱ T1 adenocarcinomas

AIM To evaluate the incidence of lymph node metastasis （LNM） and its risk factors in patients with Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas.METHODS We enrolled 85 patients [69 men, 16 women; median age （range）, 67 （38-84） years] who had undergone esophagectomy or proximal gastrectomy for Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas. Predictive risk factors of LNM included age, sex, location of the tumor center, confirmed Barrett’s esophageal adenocarcinoma, tumor size, macroscopic tumor type, pathology, invasion depth, presence of ulceration, and lymphovascular invasion. Multivariate logistic regression analysis was used to identify factors predicting LNM. We also evaluated the frequencies of LNM for Siewert type Ⅰ and type Ⅱ pT1 adenocarcinomas in meta-data analysis.RESULTSLNMs were found in 11 out of 85 patients （12.9%, 95%CI： 5.8-20.0）. Only 1 of the 15 patients （6.6%, 95%CI： 0.0-19.2） who had a final diagnosis of pT1a adenocarcinoma had a positive LNM, whereas 10 of the 70 patients （14.2%, 95%CI： 6.0-22.4） with a final diagnosis of pT1b adenocarcinoma had positive LNM. Furthermore, only one of the 30 patients （3.3%, 95%CI： 0.0-9.7） with a tumor invasion depth within 500 μm from muscularis mucosae had positive LNM. Poor differentiation and lymphovascular invasion were independently associated with a risk of LNM. In meta-data analysis, 12 of the 355 patients （3.3%, 95%CI： 1.5-5.2） who had a final diagnosis of pT1a adenocarcinoma had a positive LNM, whereas 91 of the 438 patients （20.7%, 95%CI： 16.9-24.5） with a fnal diagnosis of pT1b adenocarcinoma had positive LNM.CONCLUSIONWe consider endoscopic submucosal dissection （ESD） is suitable for patients with Siewert type Ⅰ and type Ⅱ T1a adenocarcinomas. For patients with T1b adenocarcinoma, especially invasion depth is within 500 μm from muscularis mucosae with no other risk factor for LNM, diagnostic ESD could be a treatment option according to the overall status of patients and the presence of comorbidities.

Infrequent p53 gene mutation and expression of the cardia adenocarcinomas from a high-incidence area of Southwest China

INTRODUCTIONAdenocarcinomas of the cardia are the lesionsarising from the proximal stomach or within 3 cm ofthe gastroesophageal junction.These cancerstended to be advanced at the time of presentation,usually with poor prognosis.In recent decade,the incidence of adenocarcinoma of gastric eardiaand esophagus are increasing steadily,while therehas been a decrease in the proportion of the cancersarising from the distal stomach.The

Identification of biomarkers of human pancreatic adenocarcinomas by expression profiling and validation with gene expression analysis in endoscopic ultrasound-guided fine needle aspiration samples

AIM： To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR （RT-QPCR） in endoscopic ultrasound-guided fine needle aspiration （EUS-guided FNA） specimens.METHODS： Commercially dedicated cancer cDNA macroarrays （Atlas Human Cancer 1.2） containing 1176 genes were used. Different statistical approaches （hierarchical clustering, principal component analysis （PCA） and SAM） were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.RESULTS： RT-QPCR validated the increased expression of LCN2 （lipocalin 2） and for the first time PLAT （tissue-type plasminogen activator or tPA） in malignant pancreas as compared with normal pancreas. Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.CONCLUSION： Expression profiling is a useful method to identify biomarkers and potential target genes. Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.

Alterations of tumor-related genes do not exactly match the histopathological grade in gastric adenocarcinomas

AIM:To investigate the diverse characteristics of different pathological gradings of gastric adenocarcinoma (GA) using tumor-related genes.METHODS:GA tissues in different pathological gradings and normal tissues were subjected to tissue arrays.Expressions of 15 major tumor-related genes were detected by RNA in situ hybridization along with 3' terminal digoxin-labeled anti-sense single strandedoligonucleotide and locked nucleic acid modifying probe within the tissue array.The data obtained were processed by support vector machines by four different feature selection methods to discover the respective critical gene/gene subsets contributing to the GA activities of different pathological gradings.RESULTS:In comparison of poorly differentiated GA with normal tissues,tumor-related gene TP53 plays a key role,although other six tumor-related genes could also achieve the Area Under Curve (AUC) of the receiver operating characteristic independently by more than 80%.Comparing the well differentiated GA with normal tissues,we found that 11 tumor-related genes could independently obtain the AUC by more than 80%,but only the gene subsets,TP53,RB and PTEN,play a key role.Only the gene subsets,Bcl10,UVRAG,APC,Beclin1,NM23,PTEN and RB could distinguish between the poorly differentiated and well differentiated GA.None of a single gene could obtain a valid distinction.CONCLUSION:Different from the traditional point of view,the well differentiated cancer tissues have more alterations of important tumor-related genes than the poorly differentiated cancer tissues.

Clinicopathologic significance of GLUT1 expression and its correlation with Apaf-1 in colorectal adenocarcinomas

AIM:To investigate the role of glucose transporter 1 (GLUT1) expression in colorectal carcinogenesis and evaluate the correlation with clinicopathological parameters and apoptosis-activating factor-1 (Apaf-1) expression in colorectal adenocarcinomas. METHODS:We used tissue microarrays consisting of 26 normal mucosa,50 adenomas,515 adenocarcinomas,and 127 metastatic lesions. Medical records were reviewed and clinicopathological analysis was performed. RESULTS:GLUT1 expression was absent in normal mucosa and low or moderately apparent in 19 cases (38.0%) of 50 adenomas. However,GLUT1 expression was detected in 423 (82.1%) of 515 adenocarcinomas and in 96 (75.6%) of 127 metastatic lesions. GLUT1 expression was significantly correlated with female gender (P = 0.009),non-mucinous tumor type (P = 0.045),poorer differentiation (P = 0.001),lymph node metastasis (P < 0.001),higher AJCC and Dukes stage (P < 0.001 and P < 0.001,respectively). There was a significant inverse correlation between GLUT1 expression and Apaf-1 expression (P = 0.001). In univariate survival analysis,patients with GLUT1 expression demonstrated poor overall survival and disease-free survival (P = 0.047 and P = 0.021,respectively,log-rank test). CONCLUSION:GLUT1 expression was frequently increased in adenocarcinomas and metastatic lesions. GLUT1 expression was significantly correlated with poorer clinicopathologic phenotypes and survival of patients with colorectal adenocarcinomas.

Chromodomain-helicase-DNA binding protein 5, 7 and pronecrotic mixed lineage kinase domain-like protein serve as potential prognostic biomarkers in patients with resected pancreatic adenocarcinomas

Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.

MicroRNA-22E Inhibits HER-3 Protein Expression to Facilitate Metastasis of Lung Adenocarcinomas

MicroRNA-22 (miR-22), a short non-coding RNA that post-transcriptionally regulates mRNA stability and protein synthesis, has been shown to enhance metastatic potential and to suppress HER-3, an important mRNA marker for non-small cell lung cancer (NSCLC). However, the effect of miR-22 has not been investigated in lung adenocarcinoma (LADC), the most common type of NSCLC in the Far East. In this study, we analyzed the role of miR-22 expression in LADC patients. Expression of miR-22 was detected by reverse-transcription polymerase chain reaction (RT-PCR), and confirmed by cDNA sequencing. Signals of miR-22 in LADC sections were identified using in situ hybridization (ISH). The association between miR-22 expression and survival was evaluated by the log-rank test. Induction of miR-22 expression and the effect on HER-3 levels, as well as the subsequent cell behavior were also investigated In vitro. Two types of miR-22: miR-22 and miR-22H, were detected by RT-PCR. The miR-22H had extra 13 bases, 5’-TGTGTTCAGTGGT-3’, at the 3’-end, and this segment was named miR-22E. Using ISH, miR-22E overexpression was detected in 225 (83.0%) of 271 LADC patients. A significant difference was found in cumulative survival between patients with high miR-22E levels and those with low miR-22E levels (p In vitro, epidermal growth factor induced miR-22, but reduced HER-3 expression. Expression of miR-22 increased cell movement ability. In conclusion, expression of miR-22 is closely associated with tumor recurrence, metastasis and overall survival in LADC patients by suppressing HER-3 protein expression to enhance epithelial-mesenchymal transition and metastasis.

Loss of fragile histidine triad and amplification of 1p36.22 and 11p15.5 in primary gastric adenocarcinomas

AIM: To investigate the genomic copy number alterations that may harbor key driver genes in gastric tumorigenesis. METHODS: Using high-resolution array comparative genomic hybridization (CGH), we investigated the genomic alterations of 20 advanced primary gastric adenocarcinomas (seventeen tubular and three mucinous) of Chinese patients from the Jilin province. Ten matching adjacent normal regions from the same patients were also studied. RESULTS: The most frequent imbalances detected in these cancer samples were gains of 3q26.31-q27.2, 5p, 8q, 11p, 18p, 19q and 20q and losses of 3p, 4p,18q and 21q. The use of high-resolution array CGH increased the resolution and sensitivity of the observed genomic changes and identified focal genetic imbalances, which included 54 gains and 16 losses that were smaller than 1 Mb in size. The most interesting focal imbalances were the intergenic loss/homozygous deletion of the fragile histidine triad gene and the amplicons 11q13, 18q11.2 and 19q12, as well as the novel amplicons 1p36.22 and 11p15.5. CONCLUSION: These regions, especially the focal amplicons, may harbor key driver genes that will serve as biomarkers for either the diagnosis or the prognosis of gastric cancer, and therefore, a large-scale investigation is recommended.

Preliminary Study of the Lectin Receptor Expression in Adenocarcinomas of the Gastrointestinal Tract

Ten cases of gastrointestinal adenocarcinomas were histochemically investigated fortheir lectin receptors by avidin—biotin-peroxidase complex(ABC)method.Results showed thatgastric adenocarcinomas expressed more types of lectin receptors than large boweladenocarcinomas.Positive rates of Glc/Man-and GlcNAc-specific lectin receptors in these tu-mors were kigher than those of Gal/GalNAc-and Fuc-specific lectin receptors.From the stom-ach to rectum,the spectrum of the lectin receptors in pericarcinomatous tissues graduallychanged from the gastric type to the rectal type.The expression of lectin receptors ingustrointestinal adenocarcinomas was obviously different Jrom that in their correspondingpericarcinomatous tissues.The increase and decrease of lectin receptor expression,theappearance and disappearance of some types of lectin receptors as well as the change of thereceptor distribution are indirectly regulated by cellular genome.

Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine

The frequency of primary small intestinal adenocarcinoma is increasing but is still low.Its frequency is approximately 3%of that of colorectal adenocarcinoma.Considering that the small intestine occupies 90%of the surface area of the gastrointestinal tract,small intestinal adenocarcinoma is very rare.The main site of small intestinal adenocarcinoma is the proximal small intestine.Based on this characteristic,dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis.Since most nutrients are absorbed in the proximal small intestine,the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine.The proportion of aerobic bacteria is high in the proximal small intestine,but the absolute number of bacteria is low.In addition,the length and density of villi are greater in the proximal small intestine.However,the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas.On the other hand,the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there.Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma.In carcinogenesis experiments in which the positions of the small and large intestines were exchanged,tumors still occurred in the large intestinal mucosa more often.In other words,the influence of the intestinal contents is small,and there is a large difference in epithelial properties between the small intestine and the large intestine.In conclusion,small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium.It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.

Does St.John's Wort cause regression in gastrointestinal system adenocarcinomas?

St.John's Wort(SJW) is an old herb which has long been consumed widely for its anti-inflammatory,antiviral,and anti-depressive properties.Here we present a detailed clinical evaluation of three cases(two colon and one duodenal adenocarcinoma) with remarkable and intensive lymphoplasmocytic host reaction,at the basal part of tumor,intensive fibrosis,giant cells,plasma cell increase in lymph nodes and few giant cells in germinal centers in resection specimens.The observation of similar host reaction in those tumors having otherwise usual appearance was interesting.None of the cases received neoadjuvant chemoradiotherapy or additional treatment before surgery but only SJW.These cases are presented to increase the awareness about such cases.Further research is needed to reveal the possible effect of SJW,which has long been consumed for different treatment purposes,on human tumors.