Staging Of Gastric Carcinoma Research Articles

Prognostic Significance of VEGF Expression in Correlation With COX-2, Microvessel Density, and Clinicopathological Characteristics in Human Gastric Carcinoma

Many studies have shown that angiogenesis plays an important role in the process of cancer development and progression. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity, and cyclooxygenase-2 (COX-2) supports angiogenesis by regulated production of angiogenic factors, including VEGF. The purpose of this study was to examine the expression of VEGF in combination with COX-2 and CD34, their correlation with various clinicopathological factors, and their prognostic significance in human gastric carcinoma. Specimens from 169 patients with different grade and stage gastric carcinoma were investigated by immunohistochemistry for COX-2 and VEGF expression. Tumor microvessel density was assessed with CD34 immunostaining. Correlations between the expression of VEGF, COX-2, CD34, and various clinicopathological factors were studied. The effect of these proteins on patient survival was determined. COX-2 and VEGF were positively expressed in 36.7% and 50.3% of the patients, respectively. Positive correlation was found between VEGF and COX-2 and between VEGF and CD34. VEGF expression was correlated with depth of invasion; metastatic lymph nodes; lymphatic and venous invasion; and tumor, node, metastasis system stage. Patients with positive staining for VEGF showed far lower disease-free (64.9% vs. 81.3%) and overall (58.3% vs. 76.9%) survival rates than VEGF-negative patients. In multivariate analysis, only tumor location, depth of invasion, and lymph node metastasis were shown to be independent prognostic factors. VEGF expression correlates with angiogenesis and tumor progression and is a valuable prognostic factor in patients with gastric carcinoma.

Clinical application of multi-slice spiral computed tomography in the preoperative staging of gastric carcinoma

To evaluate the application of multi- slice spiral computed tomography (MSCT) in the preoperative staging of gastric carcinoma. Eighty- nine cases of gastric carcinoma confirmed by endoscopic biopsy (including 49 men and 40 women) were collected between June 2004 and March 2006. MSCT was performed one week before operation and all the images were read by two radiologists. The results were compared with the postoperative pathologic findings. In general, the accuracy of MSCT in determining the T stage of gastric carcinoma was 68.7% based on axial and MPR images. The accuracy of diagnosis for T (1) was 90.0% (9/10), for T(2) was 82.8% (24/29), for T(3) was 69.6% (16/23) and for T(4) was 52.4% (11/21) respectively. The accuracy for MSCT in determining the N stage of gastric carcinoma was 51.8% in general. The accuracy of diagnosis for N(0) was 44.0% (11/25), for N(1) was 72.0% (18/25), for N(2) was 46.4% (13/28) and for N(3) was 40.0% (2/5) respectively. The accuracy of diagnosis for distant metastasis (M(1)) was 90% (9/10). The accuracy of MSCT in preoperative staging of gastric carcinoma is relatively high. It is easily accepted by the patients as a practical and noninvasive technique of gastric carcinoma staging.

Magnetic Resonance Imaging for Local Staging of Gastric Carcinoma

Preoperative staging of gastric carcinoma is limited by the fact that available imaging modalities do not enable accurate evaluation of the depth of infiltration of the gastric wall. The aim of this study was to evaluate the efficiency of conventional magnetic resonance imaging (MRI) in local staging of gastric carcinoma. Sixty-five specimens of patients with proven gastric carcinoma were examined immediately after gastrectomy. Examination was performed with a 1-T MRI and included T1-weighted, T2-weighted, and opposed phase images. Images were analyzed for the number of visible wall layers and their signal intensity characteristics, for tumor localization and depth of infiltration. T-stage was classified according to the TNM system. Finally, the staging by MRI was compared with the histopathological staging of the specimens. The mucosal, submucosal, and proper muscle layers could be differentiated by the typical signal intensities. Depiction of the subserosa or serosa was not possible. In 65 specimens, 67 carcinomas were found by the pathologist. Sixty-four of 67 (96%) histologically proven carcinomas were correctly localized by MRI; T-staging accuracy was 50% only, mainly because of overstaging pT2 tumors as T3. MRI enables differentiation of gastric wall layers and, therefore, technically allows the evaluation of the local tumor stage of gastric carcinomas. However, infiltration of the subserosal and serosal layer cannot be proved accurately. Overstaging pT2 tumors is one of the most predominant problems. Yet further technical developments in high-resolution imaging of the gastric wall may improve T-staging in the near future and overcome today's staging limitations.

Study on the correlation between spiral CT features and expression of phosphatase and tensin homlogy deleted on chormosome ten, basic fibroblast grouth factor in gastric carcinoma

目的 探讨胃癌浸润转移的螺旋CT表现及与磷酸酶基因(PTEN)、碱性成纤维细胞生长因子(bFGF)表达的相关关系.方法 对83例进展期胃癌行螺旋CT平扫及三期动态增强扫描.术后标本常规石蜡包埋及5 μm切片后行HE及PTEN、bFGF免疫组织化学染色.将螺旋CT征象与PTEN、bFGF的表达相对照.结果 (1)CT对T2与T3～4明胃癌诊断正确率为94.0%(78/83),淋巴结有无转移正确率为89.2%(74/83).(2)胃癌组织中PTEN表达率为47.0%(39/83),T3～4(40.8%,29/71)、淋巴结转移组(38.3%,23/60)PTEN表达率明显低于T2(10/12)、非淋巴结转移组(16/23),差异有统计学意义(χ2=7.439,P=0.006;χ2=6.511,P=0.011).(3)胃癌组织中bFGF高表达率为63.9%(53/83),T3～4(70.4%,50/71)、淋巴结转移组(71.7%,43/60)bFGF高表达率明显高于T2(3/12)、非淋巴结转移组(10/23),差异有统计学意义(χ2=7.314,P=0.007;χ2=5.724,P=0.017).(4)16例PTEN表达同时bFGF高表达,PTEN(41.0%,16/39)与bFGF(30.2%,16/53)表达呈负相关(r=-0.447,P=0.000).结论 螺旋CT增强扫描与分子生物学相结合可提高对胃癌侵袭、转移和预后评估的准确性。

Endoscopic ultrasonography for gastric cancer

This study aimed to evaluate the utility and shortcomings of endoscopic ultrasound (EUS) in tumor node metastasis (TNM) staging of gastric cancer and its influence on treatment. The series included 126 patients (65 men and 44 women) with gastric cancer who underwent EUS from July 1997 to June 2003 at the National University Hospital, Singapore. The final analysis included 109 patients ranging in age from 29 to 97 years (mean, 63.13 years). EUS staging for primary disease: Specimen histology was available for 102 of the 109 patients who underwent surgery. The accuracy was 79% for T1, 73.9% for T2, 85.7% for T3, and 72.7% for T4. The overall accuracy was 80.4%. EUS staging for nodes: The sensitivity of EUS for detecting nodal disease was 74.2% for N0, 78% for N1, 53.8% for N2, and 50% for N3. Overall, the N staging by EUS showed a sensitivity of 82.8%, a specificity of 74.2%, a positive predictive value of 85.4%, a negative predictive value of 70.2%, and an accuracy of 77.7%. Radical gastrectomy was proposed for 95 patients on the basis of the staging with EUS and computed tomography (CT) scan, and 87 patients (91.6%) underwent the surgery. Preoperative staging accurately predicted the operative strategy for 89% of the patients. No significant predictor for accuracy was achieved by performing a logistic regression analysis for the correct staging of T stage using EUS and adjusting for tumor location (middle part/distal third/whole stomach vs proximal/cardioesophageal) (p = 0.873), operator (p = 0.546), and subject's sequence (initial 50 vs last 50 cases) (p = 0.06). Ultrasound is the most accurate and reliable method for the preoperative staging of gastric carcinomas, and it is mandatory if a tailored therapeutic approach is planned according to stage.

Expression of insulin-like growth factor binding protein-2 in gastric carcinoma and its relationship with cell proliferation

To investigate the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in gastric carcinoma and its clinical significance and to explore its relationship with cell proliferation. Expressions of IGFBP-2 and Ki-67 in 118 cases of gastric carcinoma and 40 cases of normal gastric mucosa were detected by EnVision immunohistochemical technique. Expression of IGFBP-2 in gastric carcinoma was higher than that in normal gastric mucosa (P < 0.01). There was no difference between high- and low-grade gastric carcinoma (P > 0.05). Expression of IGFBP-2 in advanced gastric carcinoma was higher than that in early gastric carcinoma (P < 0.05). Expression of IGFBP-2 in gastric carcinoma with lymph node metastasis was higher than that without lymph node metastasis (P < 0.01). IGFBP-2 expression was a positively related to the clinical stage of gastric carcinoma (P < 0.01). There was a positive correlation between IGFBP-2 and Ki-67 (P < 0.05). IGFBP-2 may be involved in carcino-genesis and progression of gastric carcinoma by promoting cell proliferation.

Surgical staging of gastric carcinoma: sources and consequences of error.

Macroscopic 'TNM' staging was performed during 78 consecutive operations for gastric carcinoma and compared with subsequent pathological staging. Surgical assessment was correct for tumour (T) in 60 per cent when depth of invasion was assessed, for nodes (N) in 61 per cent, for liver metastases (M) in 92 per cent but for all aspects in only 21 per cent. Curability (conservatively defined as T1-3, N0-1, M0) was correct in 8 of 18 patients thus assessed at surgery and incurability was pathologically correct in 58 of 60 patients. Despite inaccurate surgical staging, no patient was denied a resection although 10 patients had unduly radical procedures for their stage and 2 had inappropriately conservative procedures for their stage (but without evidence of residual disease). Staging errors did not jeopardize conventional surgical management substantially and use of intra-operative microscopic sampling of nodes would have improved surgical treatment only minimally.

766 POSTER Prominent tumour-infiltrating lymphocites improved disease free survival in early stage gastric carcinoma

766 POSTER Prominent tumour-infiltrating lymphocites improved disease free survival in early stage gastric carcinoma

Expressions of EGFR, PCNA and BCL-2 and their prognosis value in human gastric carcinoma

目的 为了寻找胃癌临床病理特征和预后的可靠分子指标,建立一种能被临床普遍应用的简易方法.方法应用SP免疫组化方法,观察具有完整随访资料55例胃癌中EGFR、PCNA及BCL-2的表达情况.结果 (1)EGFR、PCNA及BCL-2的表达与胃癌分期、浸润深度、生存时间呈显著相关性.病变为进展期、深浸润、低生存率者,其表达高(P＜0.01).(2)胃癌低分化、有淋巴结转移者的EGFR和PCNA表达率高于高分化和无淋巴结转移者(P＜0.05).BCL-2则高分化表达率高,与淋巴结有无转移关系不大(P＞0.05).结论测定EGFR、PCNA及BCL-2基因的表达对临床判断预后有较大的帮助。

Endoscopic Ultrasonography for Gastric Cancer: Does it Influence Treatment?

Introduction: This study was aimed to evaluate the utility and shortcomings of EUS (endoscopic ultrasound) in TNM staging of gastric cancer and its influence on treatment. Methods: The series included 126 gastric cancer patients underwent EUS from July 1997 to June 2003 at National University Hospital, Singapore. 109 patients were included in the final analysis. There were 65 male and 44 female patients with age range 29 to 97 years(mean 63.13). Results: EUS staging for primary: Specimen histology was available for 102/109 patients operated. The accuracy for T1, T2, T3 and T4 was 79%, 73.9%, 85.7% and 72.7% respectively (overall accuracy = 80.4%). EUS staging for Nodes The sensitivity of EUS for detecting nodal disease was 74.2% for N0, 78% for N1, 53.8% for N2 and 50% for N3 respectively. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for N staging by EUS were 82.8%, 74.2%, 85.4%, 70.2%, and 79.8%, respectively . Radical gastrectomy was proposed in 95 patients based on the staging with EUS and CT scan and 87 patients underwent the same (91.6%). Preoperative staging accurately predicted the operative strategy in 89% of the patients. Performing a logistic regression analysis for the correct staging of T stage using EUS and adjusting for tumor location (middle part / distal third / whole stomach versus Proximal/Cardio-esophageal) (p = 0.873), operator (p = 0.546)and subject's sequence (Initial 50 versus last 50 cases)(p = 0.06), there was no significant predictor for accuracy. Conclusion EUS is the most accurate and reliable method for preoperative staging of gastric carcinomas and mandatory if tailored therapeutic approach is planned according to stage. Introduction: This study was aimed to evaluate the utility and shortcomings of EUS (endoscopic ultrasound) in TNM staging of gastric cancer and its influence on treatment. Methods: The series included 126 gastric cancer patients underwent EUS from July 1997 to June 2003 at National University Hospital, Singapore. 109 patients were included in the final analysis. There were 65 male and 44 female patients with age range 29 to 97 years(mean 63.13). Results: EUS staging for primary: Specimen histology was available for 102/109 patients operated. The accuracy for T1, T2, T3 and T4 was 79%, 73.9%, 85.7% and 72.7% respectively (overall accuracy = 80.4%). EUS staging for Nodes The sensitivity of EUS for detecting nodal disease was 74.2% for N0, 78% for N1, 53.8% for N2 and 50% for N3 respectively. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for N staging by EUS were 82.8%, 74.2%, 85.4%, 70.2%, and 79.8%, respectively . Radical gastrectomy was proposed in 95 patients based on the staging with EUS and CT scan and 87 patients underwent the same (91.6%). Preoperative staging accurately predicted the operative strategy in 89% of the patients. Performing a logistic regression analysis for the correct staging of T stage using EUS and adjusting for tumor location (middle part / distal third / whole stomach versus Proximal/Cardio-esophageal) (p = 0.873), operator (p = 0.546)and subject's sequence (Initial 50 versus last 50 cases)(p = 0.06), there was no significant predictor for accuracy. Conclusion EUS is the most accurate and reliable method for preoperative staging of gastric carcinomas and mandatory if tailored therapeutic approach is planned according to stage.

Value of transabdominal ultrasonography in preoperative assessment of gastric carcinoma

To investigate the value of transabdominal ultrasonography (TAUS) in preoperative assessment of TNM stage and tumor angiogenesis for patients with gastric carcinoma. Sixty- four patients with gastric carcinoma preoperatively underwent TAUS, in whom transabdominal color Doppler ultrasonography was used for measuring color Doppler vascularity index (CDVI) of each tumor in 37 cases and microvessel density (MVD) was evaluated by using immunohistochemical staining of surgical specimens with anti- CD34 antibody. The overall accuracy rate was 56.0% for T staging of gastric carcinoma (T (1) 2/3 cases, T (2) 28.6% , T (3) 73.1% , T (4) 50.0% , respectively) by TAUS. The diagnostic accuracy rate was 63.3% for lymph node status of gastric carcinoma. The diagnostic sensitivity and specificity for lymph node metastasis was 37.9% and 100% respectively. The overall accuracy for N staging of gastric carcinoma was 57.1% (N (0) 100% , N (1) 16.7% , N (2) 35.3% , respectively). The diagnostic sensitivity and specificity for determining distant metastases was 58.3% and 100% respectively. The CDVI of gastric carcinoma determined by color Doppler ultrasonography was significantly correlated to vascular invasion (P=0.0418), a linear correlation between CDVI and MVD was determined by logistic regression analysis (r=0.5628, P< 0.01). TAUS can be a routine diagnostic approach for preoperative gastric carcinoma patients.

Correlation between CK18 gene and gastric carcinoma micrometastasis

To explore the biological behavior of gastric carcinoma micrometastasis (MM) with a marker of cytokeratin 18 (CK18) and to evaluate the clinical stage of gastric carcinoma and its prognosis. Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of CK18 mRNA in 298 lymph nodes from 35 patients with gastric carcinoma and 20 lymph nodes from 10 patients with chronic peptic ulcer and gastric perforation diagnosed by pathological examination and surgery. CK18 mRNA expression of peripheral blood from 54 patients with gastric carcinoma and 10 healthy people were also examined. Expression of CK18 mRNA was not found in 10 patients with benign pathological changes. CK18 mRNA expression in gastric carcinoma tissues was strongly positive. In gastric carcinoma patients, pathological examination revealed that 99 of 298 (33.2%) lymph nodes were positive, while RT-PCR showed that 133 of 298 (44.6%) lymph nodes had expression of CK18 mRNA. The difference was significant (P<0.05). Among the 199 negative lymph nodes identified by pathological examinations, 34 (17.1%) displayed positive expression of CK18 mRNA by RT-PCR. The positive expression of CK18 mRNA was associated with lymph node micrometastasis (LMM) of gastric carcinoma. CK18 mRNA was negatively expressed in all 10 healthy cases and positively expressed in 38.9% of 54 blood specimens from gastric carcinoma patients. The positive rate was not correlated with tumor invasion of gastric carcinoma, but was significantly associated with TNM stage, lymph node metastasis (P=0.0290, P<0.05) and tumor differentiation (P=0.2956, P<0.05). RT-PCR with CK18 mRNA as a molecular marker is highly sensitive and specific in detecting LMM of gastric carcinoma. It can benefit the diagnosis of MM and guide studies on biological behavior, clinical phase, and therapy as well as relapse monitoring.

Noncurative Total Gastrectomy and Oesophagogastrectomy in the Treatment of Advanced Gastric Carcinoma in a Country with High Incidence

The role of extensive resectional surgery, including total gastrectomy for the palliation of advanced gastric cancer is controversial. This study shows operative results with complications and mortality occurring after total gastrectomy in patients with advanced stage gastric carcinoma. The study included 83 (48 males and 35 females, median age was 54.6 ± 11.4 years) patients who underwent palliative total gastrectomy or oesophagogastrectomy (distal oesophagectomy in continuity with total gastrectomy).The reason for nonradical treatment was a too locally advanced disease. There was no case of carcinoma without serosal extension. Only five patients were free of histological lymph node metastases. A total of 72 (86.7%) early postoperative complications, including 17 self-limited wound complications, and 21 pulmonary complications were noted. Dehiscence of the oesophagojejunal anastomosis was noted in 7 patients, 3 of whom subsequently died. A total of 8 (9.6%) patients died in the postoperative period. The mean survival period was 12.8 ±0.8 months for all patients. It was 18.16 ± 2.04 months in stage IIIA patients, 13.37 ± 0.79 months in stage IIIB, and 7.51 ± 0.97 months in stage IV patients. Total gastrectomy is a relatively safe procedure even when performing as a palliative procedure, with acceptable mortality and low lethal complication rate, and should be considered an alternative option in palliative treatment of advanced gastric cancer.

Clinicopathological features of gastric carcinoma patients with other primary carcinomas

Multiple primary carcinomas are increasingly being found because of the development of diagnostic techniques and the increasing incidence of early stage carcinoma. The purpose of this study was to determine the prevalence and clinicopathological features of gastric carcinoma patients with other primary carcinomas. There were 65 (incidence 2.6%) gastric carcinoma patients with other primary carcinomas compared with 2,444 patients with gastric carcinoma alone. Associated primary carcinomas were often found in the gastrointestinal (GI) tract, especially in the colon (33.8%). In patients with gastric carcinoma only, poorly differentiated adenocarcinoma was the most common (43.2%), followed by moderately and well-differentiated adenocarcinoma. Similarly, poorly differentiated adenocarcinoma (33.8%) was also the prevalent histological type in gastric carcinoma patients with other primary carcinomas, although its incidence was lower. The stage of gastric carcinoma did not differ between the two groups. The estimated 5-year survival rate was 51.6% for patients with gastric carcinoma alone, and 50.7% for those with other primary carcinomas; the difference was not significant (P=0.82). Gastric carcinoma should be treated aggressively, since the prognosis of gastric carcinoma patients treated for other primary carcinomas is not poorer than that of patients treated for gastric carcinoma alone.

Role of p53, apoptosis, and cell proliferation in early stage Epstein-Barr virus positive and negative gastric carcinomas

Aims: Mechanisms of Epstein-Barr virus (EBV) associated gastric tumour development are incompletely understood. The interrelations between EBV infection, apoptosis, cell proliferation, and the expression of the tumour suppressor gene p53...

ENDOSCOPIC ULTRASOUND STAGING OF GASTRIC MALIGNANCY

Endoscopic ultrasound (EUS) has been well established as a good tool for the staging of gastric malignancy. So far, it is accepted as the most accurate image study for local staging of gastric malignancy. Staging of gastric carcinoma is important for decision‐making in management and prediction of prognosis. With the power of high‐resolution imaging on gastric layering, the overall accuracy rate of T staging by EUS ranges 70–98%. For T2 tumors, however, EUS assessment is less reliable. N staging by EUS for gastric carcinoma is unsatisfactory and its accuracy rate has been reported 55–87%. However, the application of EUS should depend on whether examination will alter the choice of therapeutic methods and whether patients benefit from EUS evaluation. Among the indications, EUS staging is very important for the patients referred for local endoscopic treatment, such as endoscopic mucosal resection, endoscopic submucosal dissection or tumor ablation by argon plasma coagulation (APC) tumor ablation. EUS can provide the depth of invasion of the gastric wall, and also the longitudinal spread of lymphoma in the gastric wall. The overall accuracy rate of depth staging is 80–96%. For the metastatic lymph nodes, accuracy rate of N staging is 72–90%. EUS is also applied to restaging of gastric lymphoma after chemotherapy. Mucosa‐associated lymphoid tissue (MALT) lymphoma is a subset of B‐cell lymphoma with good prognosis and high prevalence of Helicobacter pylori infection. EUS staging of depth invasion of MALT lymphoma can predict the outcome of antimicrobial treatment. Taiwan's experience shows that lesions limited to mucosal and submucosal layers respond better after treatment than lesions with deeper infiltration, no matter if the MALT lymphoma is low‐grade or high‐grade.

Endosonography Versus Helical Computed Tomography for Locoregional Staging of Gastric Cancer

Endosonography (EUS) has been shown to be more accurate than incremental computed tomography (CT) in the local (T) and regional (N) staging of gastric carcinoma; however, EUS has never been compared with helical CT (HCT). The fifth edition of the TNM classification changed the guidelines for N-staging of gastric carcinoma. The accuracy of imaging methods in this new system remains unknown. Staging accuracy of EUS and HCT were compared prospectively with pathological or intraoperative findings in 88 gastric carcinoma patients. Staging was done according to the fourth and fifth editions of the TNM classification. EUS was done with a radial echo endoscope, and HCT with a scanner with two rows of detectors (two-phase contrast-enhanced scanning of a water-filled stomach). The T-staging accuracy of EUS (63 %, CI 52 - 73 %) was superior to the accuracy of HCT (44 %, CI 34 - 55 %; P = 0.021). N-staging accuracy of both methods was similar when the fourth edition of the TNM classification was used (EUS 47 %, CI 34 - 60 %; HCT 52 %, CI 38 - 65 %). However, HCT was more accurate than EUS when the fifth edition of the classification was applied (EUS 30 %, CI 18 - 43 %, HCT 47 %, CI 34 - 60 %; P = 0.044). The accuracy of detection of lymph node metastases was similar for both methods (EUS 67 %, CI 54 - 78 %; HCT 77 %, CI 64 - 86 %). EUS is more accurate than HCT in the T-staging of gastric carcinoma. Both methods are comparable for N-staging, when this is done according to the older, fourth edition of the TNM classification. If the fifth edition is used, EUS is less accurate than HCT.

Laparoscopy alone is superior to peritoneal cytology in staging gastric and esophageal carcinoma.

Laparoscopy identifies metastatic disease in patients with upper gastrointestinal malignancies; however, it has been suggested that cytological examination of peritoneal washings may increase the diagnostic yield. We hypothesize that the addition of cytologic washings to a standardized staging laparoscopy is unnecessary for the identification of intraabdominal metastasis in patients with gastric/esophageal cancer. Forty patients with gastric/esophageal cancer were prospectively evaluated. Patients successfully underwent a diagnostic laparoscopy protocol (with biopsies) during which peritoneal washings were obtained and processed for cytologic analysis. Laparoscopic versus cytologic identification of intraabdominal metastasis were compared. Forty patients successfully completed laparoscopy with collection of peritoneal washings. Laparoscopic examination of the peritoneal cavity upstaged 21 (52.5%) patients. Laparoscopic examination consistently identified a statistically significant higher number of positive patients than cytologic examination of peritoneal washings (p = 0.001) and examination of cytologic washings alone failed to identify 45% of patients with positive findings and laparoscopy. The addition of cytologic examination added no additional stage IV patients to the laparoscopy-negative group. A standardized laparoscopic examination alone is sufficient for the identification of intraabdominal metastatic disease in patients with gastric and esophageal cancer.

Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma

Accumulating evidence has identified a mechanism potentially responsible for the inactivation of tumor suppressor genes, namely transcriptional silencing by aberrant methylation of CpG islands. A previous study has shown the loss of RUNX3 expression, due to aberrant methylation of its CpG island, in gastric cancer cell lines, suggesting that RUNX3 is a target for epigenetic gene silencing in gastric carcinogenesis. However, there are limited data on the methylation status of RUNX3 in the neoplastic and non-neoplastic tissues in various types of human cancers, including gastric cancer. Here, we report that 60% of gastric cancer cell lines and 64% of primary gastric carcinomas (n=75) were methylated at the RUNX3 CpG island. RUNX3 methylation was also detected in hepatocellular carcinomas (73%, n=48), larynx cancers (62%, n=37), lung cancers (46%, n=24), breast cancers (25%, n=25), prostate cancers (23%, n=44), endometrial cancers (12.5%, n=24), colon cancers (4.9%, n=61) and uterine cervical cancers (2.5%, n=40), showing that RUNX3 methylation is not restricted to gastric cancer. Interestingly, the RUNX3 methylation was especially frequent in tumors from tissues of a foregut derivative, that is, the stomach, liver, larynx and lung. Next, the methylation status of RUNX3 in various non-neoplastic tissues was examined, including the premalignant lesions of gastric carcinomas. The RUNX3 methylation was found in 8.1% of chronic gastritis (n=99), 28.1% of intestinal metaplasia (n=32), 27.3% of gastric adenomas (n=77) and 64% of gastric carcinomas (n=75), but not in chronic hepatitis B, normal prostate and colon mucosa, even though in cases of chronic hepatitis, the methylation frequency of its neoplastic tissues was very high. In conclusion, RUNX3 methylation is frequently found in human cancers, including gastric cancer, and is mostly cancer specific, with the exception of the stomach, and thus, might be useful as a potential diagnostic biomarker of cancer.

Expression of seven main Rho family members in gastric carcinoma

Rho GTPases were previously shown to have an important role in cancer development and progression, including cell transformation, proliferation, invasion, metastasis, and angiogenesis. However, there is still little information available on the clinical significance of Rho GTPases expression in human cancer specimens. In the present study, we systemically investigated the mRNA expression levels of seven main members RhoA, RhoB, RhoC, Rac1, Rac2, Rac3, and Cdc42 of Rho family using semi-quantitative reverse transcription-PCR in 53 patients with gastric carcinoma and 7 gastric cancer cell lines. The total and activities of RhoA, Rac1 and Cdc42 in 5 gastric cancer cell lines were also examined. The mean mRNA expression levels of RhoA and Rac1 in gastric cancer tissue specimens were significantly higher than those in the adjacent non-tumorous tissue specimens ( p<0.01). The higher expression of RhoA was significantly correlated with higher TNM stage ( p<0.05) as well as with pooly differentiated histological type ( p<0.05) of gastric carcinoma. The increased expression of Rac1 was related to higher TNM stages of gastric carcinoma ( p<0.05). The expression levels of mRNA, total protein and activities of RhoA and Rac1 in 7 gastric cancer cell lines were all higher than that in gastric mucosal epithelial cell line GES-1. These findings indicate that RhoA and Rac1 may play important roles in the carcinogenesis and progression of gastric carcinoma.