Early Stage Gastric Carcinoma Research Articles

Surface electric field enhanced biosensor based on symmetrical U-tapered HCF structure for gastric carcinoma biomarker trace detection

In this article, a novel U-tapered hollow-core fiber (HCF) surface plasmon resonance (SPR) biosensor coated with PtS2 for early-stage gastric carcinoma (GC) diagnosis was demonstrated. The article proposed the first investigation to detect Interleukin-10 (IL10) and Interleukin-1β (IL1β) which were associated with the risk of developing gastric carcinoma, using optical fiber SPR technology. Herein, the sensitivity of sensor was effectively improved through a combination of tapered and U-shaped structures. Additionally, to further enhance the detection capability, two-dimensional material PtS2 was utilized to increase the surface electric field intensity of the sensor. Simultaneously, optimization of structural parameters such as taper ratio, bending diameters, and Au film thickness was conducted. Ultimately, the designed sensor achieved a remarkable sensitivity of 13210 nm/RIU within the refractive index (RI) range of 1.33–1.37. The sensor demonstrated exceptional performance, achieving sensitivities of 3.64 nm/(ng/ml) and 7.46 nm/(ng/ml) for the detection of IL10 and IL1β biomarkers, respectively, along with limit of detection (LOD) of 2.74 pg/ml and 1.33 pg/ml, and successfully detecting the presence of these biomarkers in the serum of gastric cancer patients. Overall, the proposed sensor exhibits significant potential in early gastric cancer detection and advances the application of optical fiber SPR sensors in trace biodetection.

Feasibility and Efficacy of Sentinel Lymph Node Mapping in Gastric Cancer.

Lymph node metastasis is a critical prognostic factor for patients with gastric carcinoma (GC). Sentinel lymph node (SLN) mapping has the potential to identify the initial site of draining lymph node metastasis and reduce the extent of surgical lymphadenectomy. This study aimed to evaluate the diagnostic accuracy of SLN mapping in GC. The study enrolled 129 GC patients undergoing total or partial gastrectomy with D2 lymphadenectomy and indocyanine green fluorescence-guided SLN mapping. The primary outcomes were the negative predictive value (NPV) and sensitivity of SLN mapping. The secondary outcomes were clinicopathologic factors associated with SLN mapping accuracy and successful SLN mapping. The SLN detection rate in this study was 86.8 %. The study had an overall NPV of 83.1 % and an overall sensitivity of 65.8 %. The NPV was found to be significantly higher in the patients with no lymphovascular invasion (LVI) than in those with LVI (96.0 % vs 59.3 %; p < 0.001) and in the patients whose pathologic T (pT) stage lower than 3 than in those whose T stage was 3 or higher (92.0 % vs 66.7 %; p = 0.009). The sensitivity of SLN mapping was 50 % in the patients with no LVI and 33 % in the patients with a pT stage lower than 3. The study results showed that for patients with early-stage GC with no LVI, negative SLN findings may represent a potential additive predictor indicating the absence of regional LN metastasis. However, given the low sensitivity rates noted, further research is needed to identify specific patient populations that may benefit from SLN mapping in GC.

Lung ultrasound score evaluation of the effect of pressure-controlled ventilation volume-guaranteed on patients undergoing laparoscopic-assisted radical gastrectomy.

Laparoscopic-assisted radical gastrectomy (LARG) is the standard treatment for early-stage gastric carcinoma (GC). However, the negative impact of this procedure on respiratory function requires the optimized intraoperative management of patients in terms of ventilation. To investigate the influence of pressure-controlled ventilation volume-guaranteed (PCV-VG) and volume-controlled ventilation (VCV) on blood gas analysis and pulmonary ventilation in patients undergoing LARG for GC based on the lung ultrasound score (LUS). The study included 103 patients with GC undergoing LARG from May 2020 to May 2023, with 52 cases undergoing PCV-VG (research group) and 51 cases undergoing VCV (control group). LUS were recorded at the time of entering the operating room (T0), 20 minutes after anesthesia with endotracheal intubation (T1), 30 minutes after artificial pneumoperitoneum (PP) establishment (T2), and 15 minutes after endotracheal tube removal (T5). For blood gas analysis, arterial partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) were observed. Peak airway pressure (Ppeak), plateau pressure (Pplat), mean airway pressure (Pmean), and dynamic pulmonary compliance (Cdyn) were recorded at T1 and T2, 1 hour after PP establishment (T3), and at the end of the operation (T4). Postoperative pulmonary complications (PPCs) were recorded. Pre- and postoperative serum interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Compared with those at T0, the whole, anterior, lateral, posterior, upper, lower, left, and right lung LUS of the research group were significantly reduced at T1, T2, and T5; in the control group, the LUS of the whole and partial lung regions (posterior, lower, and right lung) decreased significantly at T2, while at T5, the LUS of the whole and some regions (lateral, lower, and left lung) increased significantly. In comparison with the control group, the whole and regional LUS of the research group were reduced at T1, T2, and T5, with an increase in PaO2, decrease in PaCO2, reduction in Ppeak at T1 to T4, increase in Pmean and Cdyn, and decrease in Pplat at T4, all significant. The research group showed a significantly lower incidence of PPCs than the control group within 3 days postoperatively. Postoperative IL-1β, IL-6, and TNF-α significantly increased in both groups, with even higher levels in the control group. LUS can indicate intraoperative non-uniformity and postural changes in pulmonary ventilation under PCV-VG and VCV. Under the lung protective ventilation strategy, the PCV-VG mode more significantly improved intraoperative lung ventilation in patients undergoing LARG for GC and reduced lung injury-related cytokine production, thereby alleviating lung injury.

Update on diagnosis and treatment of early signet-ring cell gastric carcinoma: A literature review.

Gastric signet-ring cell gastric carcinoma (GSRC) is an unfavorable subtype of gastric cancer (GC) that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC. However, GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC. Therefore, the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients. In recent years, technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients. Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection (ESD), indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation. This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.

Prevalence of Regional Lymph Node Metastasis of Mucosal Gastric Signet Ring Cell Carcinoma: Analysis of the Collaborative Stage Data Survey of the Korean Central Cancer Registry

Introduction: Patients with very early-stage gastric signet ring cell carcinoma (SRC) are eligible for minimally invasive treatment, like endoscopic submucosal dissection. However, population-based data on regional lymph node metastasis (LNM) and distant metastasis of gastric SRC are lacking. This study aimed to identify the prevalence of LNM and distant metastasis in mucosal cancer (T1a) of gastric SRC. Methods: The Collaborative Stage Data Survey was performed by the Korean Center of Cancer Registry between 2010 and 2015 to establish collaborative stage data of the stomach, colon, rectum, rectosigmoid junction, and breast. From the survey data, information on patients with gastric SRC was extracted for analysis. Variables including age, sex, diagnosis date, primary site, tumor size, histology, American Joint Committee on Cancer staging system scores, and Surveillance, Epidemiology, and End Results summary stage were analyzed. Results: A total of 1,335 (65.7%) patients had mucosal gastric SRC, and 1,189 (89.1%) patients had surgery and 134 (10%) had endoscopic treatment. Of them, 1,283 (96.1%) patients did not have regional LNM, and 52 (3.9%) patients had regional LNM and 6 (0.4%) had distant metastasis. The hazard ratios of LNM and distant metastasis were 14.98 (95% CI: 4.18–53.2) and 10.09 (95% CI: 2.30–44.17). Conclusions: Reginal LNM and distant metastasis occur very less in mucosal gastric SRC, but they are associated with an increased risk of cancer-related death. Even in early stage, surgery should be considered as a standard treatment of mucosal gastric SRC.

Long-Term Oncological Outcomes of Reduced Three-Port Laparoscopic Gastrectomy for Early-Stage Gastric Carcinoma: a Retrospective Large-Scale Multi-Institutional Study.

PurposeWith advances in surgical techniques, reduced-port laparoscopic surgery is increasingly being performed for the treatment of gastric carcinoma. Many studies have reported satisfactory short-term outcomes after reduced 3-port laparoscopic gastrectomy (LG). The aim of this study was to investigate the long-term oncological outcomes of 3-port LG in patients with gastric carcinoma.Materials and MethodsWe reviewed the medical records of 1,117 patients who underwent LG for gastric carcinoma in three major institutions between 2012 and 2015. The data showed that 460 patients underwent 3-port LG without assistance, and 657 underwent conventional 5-port LG. We compared the overall and disease-free survival rates between the 2 groups.ResultsThere were 642 male and 475 female patients with a mean age of 56.1 years. Among them, 1,028 (92.0%) underwent distal gastrectomy and 89 (8.0%) underwent total gastrectomy. In the final pathologic examination, 1,027 patients (91.9%) were stage I, 73 (6.5%) were stage II, and 17 (1.5%) were stage III, and there were no significant difference in the pathologic stage between groups. The 3- and 5-port LG groups showed no significant differences in the 5-year overall survival (94.3% vs. 96.7%, P=0.138) or disease-free survival (94.3% vs. 95.9%, P=0.231). Stratified analyses according to pT and pN stages also showed no significant differences in overall or disease-free survival between the two groups.ConclusionsLong-term survival after 3- and 5-port LG was comparable in patients with early-stage gastric carcinoma. The 3-port technique requiring limited surgical assistance may be an appropriate surgical option for this patient population.

1435P Survival of T1a of gastric signet ring cell carcinoma for guidance of safe endoscopic treatment: Analysis of Collaborative Stage Data of Korean Central Cancer Registry

Early-stage gastric signet ring cell carcinoma (SRC) is a candidate of endoscopic treatment. However, there were few population-based data on lymph node metastasis and distant metastasis of gastric SRC. The aim of this study was to identify the risk of lymph node metastasis and distant metastasis in mucosal cancer, very early-stage, suitable for endoscopic treatment. Collaborative Stage Data Survey was performed by the Korean Center of Cancer Registry to establish Collaborative Stage Data (CSD) of stomach, colon, rectum, rectosigmoid junction, and breast between 2010 and 2015. In our study, from CSD, patients with gastric SRC were extracted for analysis. Variables included age, sex, diagnosis date, primary site, tumor size, histology, American Joint Committee on Cancer (AJCC) staging system, and Surveillance, Epidemiology, and End Results (SEER) summary stage. These variables were analyzed. Between 2010 and 2015, 1,335 (65.7%) patients had T1a of gastric SRC. Of them, 1,283 patients (96.1%) had no regional lymph node metastasis (LNM), but 52 (3.9%) had regional LNM. In T1a gastric SRC, 6 (0.4%) patients had distant metastasis. Estimated survival time were higher in negative distant metastasis than positive distant metastasis (8.90 vs 4.66, P<0.0001). T1a gastric SRC have lymph node and distant metastasis, which are associated with shorter survival time. These findings suggest that before endoscopic treatment, vigorous examination to find lymph node metastasis and distant metastasis should be necessary for safe endoscopic treatment.

Unusual growth of an Epstein-Barr virus-associated differentiated early-stage gastric carcinoma: A case report

Epstein-Barr virus (EBV) infection is involved in a subset of gastric carcinoma (GC) cases, and is associated with distinct clinicopathological features. The present study reports a unique case of EBV-associated early-stage GC compared with the other cases experienced in our hospital. A 72-year-old male receiving treatment for cerebral infarction underwent an esophagogastroduodenoscopy (EGD) for suspicion of gastrointestinal bleeding. EGD revealed a type 0-I protruding lesion in the lesser curvature of the upper gastric corpus. Biopsy indicated well-differentiated adenocarcinoma. As the tumor diameter was >3 cm and the thickness of the tumor suggested submucosal invasion, laparoscopic gastrectomy was performed. Histological assessment revealed polypoid growth of an intramucosal, differentiated, tubular or papillary adenocarcinoma, with dense infiltration of lymphocytes. The carcinoma crypts were found to be EBV-positive on in situ hybridization. A review of the clinicopathological features of 25 EBV-associated GCs from 20 patients treated in our hospital between 2005 and 2014 was performed. All of these tumors, except that in the current case, appeared as shallow, depressed or ulcerative lesions. Thus, the current case appears to represent an unusual growth of EBV-positive GC.

Incidence, Survival, and Predictors of Lymph Node Involvement in Early-Stage Gastric Signet Ring Cell Carcinoma in the US

IntroductionThe incidence, survival, and propensity for nodal metastasis in early-stage gastric signet ring cell carcinoma have not been defined in the United States. These data are critical determinants for treatment allocation. MethodsCases of gastric signet ring cell carcinoma were extracted from the national SEER database for the years 2004–2013. Age-standardized incidence was derived. Survival was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of nodal metastasis. Exclusion criteria included neoadjuvant radiotherapy and lack of histologic or nodal data. ResultsA total of 10,624 cases were initially identified. The analysis cohort included 506 cases with early T-stage N0M0 disease following exclusions. The incidence was 0.094 per 100,000 person-years. The 5-year survival rate was 82.8%. Tumor stage (p < 0.001) and size (p < 0.001) were independent predictors of nodal metastasis. The incidence of nodal involvement for T1a tumors <2 cm was 5.4% (p < 0.004). ConclusionThe incidence of potentially resectable signet ring gastric carcinoma has not changed significantly over the past decade. While presenting with predominantly high-grade histology, early T-stage disease has a high survival rate. Small T1a tumors have low rates of nodal metastasis, suggesting that an endoscopic resection could be considered in this subset.

Lgr5High/DCLK1High phenotype is more common in early stage and intestinal subtypes of gastric carcinomas.

Gastric carcinoma is the third most common malignancy and is one of the main causes of cancer deaths worldwide. Cancer stem cells (CSCs) are a subpopulation of tumour cells capable of self-renewal and differentiation, likely responsible for the initiation, recurrence, metastasis and chemo/radio-resistance. This study was conducted to evaluate the expression patterns and clinicopathologic significance of putative CSC markers, Lgr5 and DCLK1, in gastric carcinoma. The expression levels of Lgr5 and DCLK1 were examined in a well-defined series of gastric carcinoma tissues, including 75 (80%) from intestinal and 19 (20%) from diffuse subtypes, using tissue microarray (TMA). In addition, the correlation of the expression of these markers with clinicopathological factors was explored. Higher expressions of Lgr5 and DCLK1 were mainly detected in intestinal subtypes of gastric carcinomas compared to diffuse subtypes (P= 0.005 and P= 0.050, respectively). We also found a higher expression of Lgr5 and DCLK1 more frequently in well-differentiated gastric carcinoma cases (P< 0.001 and P= 0.007). The combined analysis demonstrated that the co-expression of Lgr5 and DCLK1 (Lgr5High/DCLK1High) was more common in intestinal subtypes (P= 0.025) and well-differentiated gastric carcinoma samples (P< 0.001). Interestingly, there was a significant correlation between Lgr5High/DCLK1High phenotype and early-stage gastric carcinoma specimens (P= 0.045). Our findings indicated that the Lgr5High/DCLK1High expression pattern may be considered as a signature phenotype for intestinal subtypes of gastric carcinoma.

1013 - Incidence, Survival, and Predictors of Lymph Node Metastasis in Early Stage Gastric Signet Ring Cell Carcinomas in the United States

1013 - Incidence, Survival, and Predictors of Lymph Node Metastasis in Early Stage Gastric Signet Ring Cell Carcinomas in the United States

High expression of miR-16 and miR-451 predicating better prognosis in patients with gastric cancer.

To investigate the expression pattern of miR-16 and miR-451 and evaluate their prognostic value in 180 GC patients undergoing surgery. In our previous study, a panel of five circulating miRNAs (miR-16, miR-25, miR-92a, miR-451 and miR-486-5p) can be used as a potential biomarker for detecting of early-stage gastric carcinoma (GC). Tissue microarrays were constructed from 180 patients with GC after surgery. MiR-16 and miR-451 expression was detected by miRNA-locked nucleic acid in situ hybridization, and their relationship with clinicopathological parameters and overall survival was analyzed. MiR-16 expression was decreased in 30.6% (55/180) of GC, increased in 54.4% (98/180) and unchanged in 15.0% (27/180), compared with paracancerous normal tissue (P<0.001). MiR-451 expression was decreased in 17.8% (32/180), increased in 62.8% (113/180) and unchanged in 19.4% (35/180) of GC, compared with paracancerous normal tissue (P<0.001).Univariate analysis indicated that low miR-16 and miR-451 expression, tumor stage, tumor status, node status and tumor size were significant negative prognostic predictors for overall survival in patients with GC (P<0.001, P<0.001, P=0.002, P<0.001 and P=0.001, respectively). Multivariate regression analysis demonstrated that stage [hazard ratio (HR) 1.80; 95% confidence interval (CI) 1.0-3.26; P=0.05], low expression of miR-16 (HR 2.26; 95% CI 1.51-3.40; P<0.001) and miR-451 (HR 2.01; 95% CI 1.36-2.96; P<0.001) predicted shorter OS, while tumor status (HR 1.59; 95% CI 0.73-3.48 P=0.242), lymph node metastasis (HR 1.41; 95% CI 0.71-2.82; P=0.326) and tumor size (HR 1.53; 95% CI 0.92-2.55; P=0.099) were not. Moreover, patients with both miR-16 and miR-451 high expression have better OS than those with two miRNAs unchanged or low expression in GC tissues. Patients with both miR-16 and miR-451 high have better OS than patients with single miR-451 high expression. High expression of miR-16 and miR-451 was associated with longer OS in GC patients. Especially patients with miR-16 and miR-451 double high expression will predict better OS. MiR-16 and miR-451 may be used as novel makers to evaluate prognosis and provide a new treatment target in GC.

Gastric Medullary Carcinoma: A Rare Case Report.

A case of 64-year-old female patient with early stage gastric medullary carcinoma has been presented, along with a review of the literature.

Tedavisiz üç yıllık takiplerinde belirgin progresyon göstermeyen taşlı yüzük hücreli mide kanseri olgusu

Mide kanseri, dünyada mortaliteye neden olan en sık ikinci kanserdir. Taşlı yüzük hücreli mide kanserinin genel olarak kötü prognoza sahip olduğu bildirilmektedir. Bu vaka sunumunda 3 yıllık takibe rağmen çok hızlı progresyon göstermeyen taşlı yüzük hücreli mide kanseri sunulmuştur. Hastanın cerrahi tedaviyi kabul etmemesi nedeniyle üç yıl süreyle takip edilmesi mümkün olmuştur. Bu olguda radyolojik ve endoskopik incelemelerde üç yıllık takibe reğmen yayılım veya tümör çapında belirgin artış saptanmamıştır.

Comparison of disease‐specific survival in the United States and Korea after resection for early‐stage node‐negative gastric carcinoma

Disease-specific survival (DSS) for GC patients differs in Eastern and Western countries. The aim is to compare outcomes of US and Korean patients following resection of early-stage, node-negative gastric carcinoma (GC). All patients (1995-2005) with T1N0 gastric carcinoma, excluding gastroesophageal tumors, were evaluated. DSS was compared by adjusting for prognostic variables from an internationally validated GC nomogram. The cohort included 598 Korean patients and 159 US patients. Age and BMI were significantly higher in US patients. Distal tumor location was more frequent in Korea (60% vs. 52%) and proximal location in the US (19% vs. 5%, P < 0.0001). Five-year DSS did not differ significantly between Korea and the US. After multivariate analysis, DSS of Korean patients persisted, with no significant differences when compared to US patients (HR = 1.2, 95% CI: 0.3-5.2, P = 0.83). Despite widespread speculations that GC differs in the East and West, when we compare similarly staged, node-negative GC patients, survival did not differ significantly between Korea and the US. This suggests that GC is a heterogeneous disease and when similar subtypes of gastric cancer are compared, these differences disappear. This study suggests more similarities than previously hypothesized between US and Korean GC patients.

Proximal gastric cancer: advances of laparoscopic surgery

Although the overall incidence of gastric cancer is decreasing, gastric cancer still remains the fourth most common cancer worldwide. The decrease in the incidence rate varies considerably depending on the geographical area. For example, gastric cancer is continuously the most common cancer type in Asian countries such as Japan, Korea, and China, with a slow and slight drop in the prevalence of the disease in these countries. There has been a greater decrease in the incidence curve over the last few decades in the USA and northwest Europe, but the prevalence of proximal and gastroesophageal junction cancer in these areas is increasing. Therefore, there is interest in how to manage patients with upper-third stomach cancer to improve oncological and quality-of-life (QOL) outcomes not only in the Eastern but also in the Western world. The Aihara et al. [1] report in the September issue of Surgical Endoscopy provides useful information for the laparoscopic surgical treatment of patients with proximal gastric cancer. The authors describe a technique of laparoscopy-assisted proximal gastrectomy (LAPG) and gastric tube reconstruction using a miniloop retractor (MLR). The feasibility and safety of this technique was evaluated in 44 patients with early-stage upper gastric carcinoma. Five surgical ports were inserted into the abdomen and the stomach was lifted to the abdominal wall side with a MLR. Reconstruction with a gastric tube (20 cm long, 3 cm wide) using a circular stapler was performed through a small incision, through which the specimen was removed. The mean operating time was 202 min. There were no serious complications no deaths, and no conversions to open surgery. The authors concluded that this technique of LAPG and gastric tube reconstruction using MLR is feasible and safe for the treatment of proximal early gastric cancer. The data provided by Aihara et al. [1] support the safety of their technique, which is technically more complicated than laparoscopy-assisted distal gastrectomy (LADG). The incidence of early gastric cancer (EGC) in Japan and Korea is high and approximately 50% of cases are diagnosed at this early stage through established nationwide endoscopic screening. These high EGC rates have led to the development and validation of minimally invasive approaches, including endoscopic submucosal dissection (ESD) and laparoscopic surgery in these countries. Criteria for clinical decision-making on ESD, laparoscopic gastrectomy, or open surgery have been defined by Japanese scientific associations. There is now an explosion in laparoscopic surgery for the treatment of gastric cancer in Asian countries and also an increase in the use of this minimally invasive approach in some specialized centers in the West [2]. Based on strong evidence of the superiority of laparoscopic versus open surgery with respect to quality of life for colorectal cancer patients [3] and accumulating evidence, although still incomplete, for early gastric cancer patients [4–6], the technique of laparoscopic gastrectomy has evolved rapidly. Now, the evolution includes totally intracorporeal laparoscopic distal, proximal, or total gastrectomy with standardized extended D2 lymphadenectomy, and indications for its use have been expanded to include patients with advanced resectable stage II and stage III disease [2]. Survival benefits of D2 surgery [7] are now being confirmed by the long-term 15 year survival results of a Dutch trial [8]. This assessment of D2 surgery gains in open surgery makes this standardized lymphadenectomy an C. Batsis (&) Department of Surgery, School of Medicine, University of Ioannina, 451 10 Ioannina, TK, Greece e-mail: chbatsis@hotmail.com

Telomere shortening occurs early during gastrocarcinogenesis

When telomeres are shortened to a critical length, they will initiate chromosomal instability (CIN) and may finally cause tumorigenesis. The purpose of the present study was to evaluate the shortened telomere as a potential biomarker for tumorigenesis in gastric carcinoma. The telomeres in matched cancer and adjacent noncancer mucosa samples from 86 gastric carcinoma patients were measured by real-time polymerase chain reaction (PCR). According to the International Union Against Cancer (UICC), tumor stages were classified into four groups: stage I (n = 23), stage II (n = 20), stage III (n = 23), and stage IV (n = 20). Telomere length decreased with aging in both adjacent noncancer mucosa and cancer tissue (r = -0.261 (P = 0.008) and r = -0.27 (P = 0.012), respectively). The telomere length of UICC stage I tumors was significantly shorter than the average telomere length in adjacent noncancer mucosa (P = 0.023). Telomere length increased gradually with increasing UICC stage (P = 0.032). The telomere length of UICC stage IV tumors was significantly longer, when compared to that in noncancer mucosa (P = 0.019) and stage I tumors (P = 0.002). In summary, telomere length undergoes shortening in early stage gastric carcinoma and lengthening in advanced gastric carcinoma. Additionally, telomere shortening may initiate the tumorigenesis of gastric carcinoma.

Differential Expression of Metallothionein in Gastrointestinal Stromal Tumors and Gastric Carcinomas

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that account for about 2% of gastric tumors. Metallothioneins (MTs) are multifunctional proteins associated with carcinogenesis and known to be coded by 10 functional MT genes. This study evaluated MT mRNA and protein expression in GISTs and compared the expression levels with gastric carcinomas. An immunohistochemical study of MT protein expression was performed in 15 GISTs (specifically located in the stomach) and 38 early stage gastric carcinomas. The percentage of cells stained and intensity of staining were determined. MT-2A mRNA expression was investigated in 6 GISTs and 6 early stage gastric carcinoma patients. All GISTs displayed positive nuclear immunostaining, with most GISTs having predominantly mildly stained nuclei (93.3%). On the other hand, 37 out of 38 gastric carcinoma cases were positively stained for nuclear MT with 24 cases (63.2%) exhibiting predominantly mild nuclear staining, 7 cases (18.4%) moderate nuclear staining, and 6 cases (15.8%) strong nuclear staining. Nuclear MT expression was found to be significantly lower in GIST samples when compared with gastric carcinoma tissues based on the percentage stained and immunoreactive score. We then established that the MT-2A gene transcript was the most abundant MT isoform in MKN28 gastric cancer cells and analyzed its expression in GIST and gastric carcinoma tissues. We found that GISTs had significantly lower MT-2A mRNA levels than gastric carcinoma tissues. Lower MT-2A gene expression and nuclear MT protein expression in GISTs when compared with gastric carcinomas may reflect their different underlying biology and divergent histogenesis.

Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer

BackgroundAberrant regulation of glycogen synthase kinase-3β (GSK-3β) has been implicated in several human cancers; however, it has not been reported in the gastric cancer tissues to date. The present study was performed to determine the expression status of active form of GSK-3β phosphorylated at Tyr216 (pGSK-3β) and its relationship with other tumor-associated proteins in human gastric cancers.MethodsImmunohistochemistry was performed on tissue array slides containing 281 human gastric carcinoma specimens. In addition, gastric cancer cells were cultured and treated with a GSK-3β inhibitor lithium chloride (LiCl) for immunoblot analysis.ResultsWe found that pGSK-3β was expressed in 129 (46%) of 281 cases examined, and was higher in the early-stages of pathologic tumor-node-metastasis (P < 0.001). The expression of pGSK-3β inversely correlated with lymphatic invasion (P < 0.001) and lymph node metastasis (P < 0.001) and correlated with a longer patient survival (P < 0.001). In addition, pGSK-3β expression positively correlated with that of p16, p21, p27, p53, APC, PTEN, MGMT, SMAD4, or KAI1 (P < 0.05), but not with that of cyclin D1. This was confirmed by immunoblot analysis using SNU-668 gastric cancer cells treated with LiCl.ConclusionsGSK-3β activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis. Thus, these findings suggest that GSK-3β activation is a useful prognostic marker for the early-stage gastric cancer.

Microsatellite instability with promoter methylation and silencing of hMLH1 can regionally occur during progression of gastric carcinoma

Microsatellite instability (MSI) is known to result from inactivation of mismatch repair genes largely by promoter methylation. However, the methylation usually accumulates time-dependently. To know whether MSI can be acquired later in tumorigenesis, we examined intratumoral heterogeneity of MSI and promoter methylation of hMLH1 after immunohistochemical screening for heterogeneous expression of hMLH1 in 55 cases of gastric carcinomas. We demonstrated for the first time that MSI-H can develop from MSI-L or the absence of MSI due to time-dependent accumulation of DNA methylation during progression of early-stage gastric carcinomas. The resultant replication errors may play a role in enhancing invasive activity.