Cases Of Primary Gastric Cancer Research Articles

Racial/ethnic disparities in gastric cancer: A 15-year population-based analysis.

Disparities in gastric cancer incidence and mortality have been reported among ethnic/racial groups. While gastric cancer is not common in the U.S., it is among the top 10 causes of cancer-related death among Hispanics living in Puerto Rico (PRH). This study compared gastric cancer incidence rates during a 15-year period (2002-2006, 2007-2011, and 2012-2016) between PRH and racial/ethnic groups in the mainland U.S., including Non-Hispanic Whites (NHW), Non-Hispanics Blacks (NHB), Hispanics (USH), and Non-Hispanic Asian or Pacific Islanders (NHAPI). Primary gastric cancer cases (ICD-O-3 codes C16.0 to C16.9) from the Puerto Rico Central Cancer Registry and SEER diagnosed from January 1, 2002 to December 31, 2016 were included in the analysis. The Joinpoint Regression Program and standardized rate ratios were used to estimate Annual Percent Changes (APC) and differences in gastric cancer incidence among racial/ethnic groups, respectively. Our analysis included 83,369 gastric cancer cases (PRH n=4202; NHW n=43,164; NHB n=10,414; NHAPI n=11,548; USH n=14,041). USH had the highest number of cases among individuals <50 years, whereas NHW and PRH had the highest percentage among individuals ≥50 years. PRH and USH were the only groups with increasing APCs among individuals <50 years. Gastric cancer continues to be a common cancer among PRH, despite the overall decrease in incidence among other racial/ethnic groups. Studies evaluating the gastric cancer risk factors among high-risk groups are necessary to establish health policy and modify gastric cancer screening algorithms among Hispanics.

Association of Genetic Polymorphisms in TNFRSF11 with the Progression of Genetic Susceptibility to Gastric Cancer.

Objective To investigate the relationship between polymorphism of TNFRSF11 gene rs9533156 and rs2277438 and susceptibility to gastric cancer. Methods A case-control study was conducted to select 577 cases of primary gastric cancer and 678 cases of normal control. We extracted whole blood genomic DNA and amplified the target gene fragment by PCR. The genotyping and allele were tested through the snapshot method. Results In this case-control study, we observed that there was a difference in the genotype distribution of TNFRSF11 gene rs9533156 between the case group and the control group. The frequency distribution of TC heterozygous mutation in the case group was higher than that in the control group. The smoking rate in the case group (34.49%) was higher than that in the control group (27.29%), and the difference in frequency distribution between the two groups was statistically significant (P=0.006). Our findings suggest that TNFRSF11 rs9533156 is associated with susceptibility to GC, which is more evident among elderly patients (>62 years), nonsmokers, and patients who do not consume alcohol. The analysis of the relationship between the TNFSF11 gene rs9533156 site variant and clinical factors of gastric cancer showed that, compared with the tumor size <2 cm group, patients with tumor size ≥2 cm and whom carrying rs9533156 site mutations had a higher frequency distribution, and the difference was statistically significant (P=0.022). Compared with the nonhyperglycemic group, the frequency distribution of patients with rs9533156 site mutations in the diabetes group was higher, and the difference was statistically significant (P < 0.001). Conclusion This study shows that there is a correlation between smoking and the occurrence of gastric cancer. Based on our research, the functional SNP TNFRSF11 TC genotype may be an indicator of individual susceptibility to GC. The mutation at rs9533156 may be related to the size of gastric cancer. The mutation rate of rs9533156 of TNFSF11 gene is higher in diabetic gastric cancer patients.

Association of Genetic Polymorphisms in FOXA1 with the Progression of Genetic Susceptibility to Gastric Cancer.

Objective To investigate the relationship between polymorphism of FOXA1 gene rs12894364 and rs7144658 and susceptibility to gastric cancer. Methods A case-control study was conducted to select 577 cases of primary gastric cancer and 678 cases of normal control. We extracted whole blood genomic DNA and amplified the target gene fragment by PCR. The genotyping and allele was tested through a snapshot method. Results There was no significant difference in the frequency distribution of genotype between the case group and control group (P > 0.05). Stratified analyses showed the SNPs were not correlated with the susceptibility of GC according to different age, gender, cigarette smoking, and alcohol drinking status. Conclusion There is no significant correlation between the polymorphisms of FOXA1 gene rs12894364 and rs7144658 and the risk of gastric cancer.

Mide Karsinomlarında ETS ile İlişkili Genin Doku Ekspresyonu

INTRODUCTION: The ETS-related gene (ERG) encodes a member of the erythroblast transformation-specific (ETS) transcription factor family that has been implicated in both tumor invasion and neovascularization. In this retrospective study, we have aimed to investigate the clinical significance of ERG tissue expressions in gastric cancer. METHODS: We examined the expression of ERG protein by immunohistochemical staining in tissue specimens harvested from 172 primary gastric cancer cases. RESULTS: ERG was expressed in normal vascular endothelium. ERG staining was defined as positive in 9.9 % (17 /172) of gastric cancer cases. According to clinicopathological characteristics, statistically significant differences were not observed between ERG expression and tumor invasion, lymph node and distant metastases, increased tumor stage, histological lymphatic and neural invasion. There were no significant differences in age, gender, or histopathological grading as for ERG expression. DISCUSSION AND CONCLUSION: ERT expression in gastric cancers is not correlated with histological prognostic indicators.

A case of primary gastric cancer composed of both AFP-producing gastric cancer with neuroendocrine carcinoma

A case of primary gastric cancer composed of both AFP-producing gastric cancer with neuroendocrine carcinoma

Methylation of SLFN11 promotes gastric cancer growth and increases gastric cancer cell resistance to cisplatin.

Background and Aim: Human SLFN11 gene encodes a protein with structural similarity to RNA helicases, which was reported to sensitize cancer cells to DNA-damaging agents. This study explored the epigenetic regulation and mechanism of SLFN11 in human gastric cancer.Methods: Eight human gastric cancer cell lines and 201 cases of primary gastric cancer were analyzed. Methylation specific PCR, flow cytometry, xenograft mouse model and siRNA technique were employed.Results: SLFN11 was methylated in 29.9% (60/201) of primary gastric cancer. The expression of SLFN11 was regulated by promoter region methylation. Methylation of SLFN11 was significantly associated with tumor size (p < 0.05). SLFN11 suppressed gastric cancer growth both in vitro and in vivo and enhanced the ability of cisplatin to induce S-phrase arrest and apoptosis in gastric cancer cells.Conclusions: SLFN11 is frequently methylated in human gastric cancer, and its expression is regulated by promoter region methylation. Our results demonstrate that SLFN11 is a tumor suppressor in human gastric cancer, and methylation of SLFN11 may serve as a cisplatin resistant marker in human gastric cancer.

Correction: NLRP6 targeting suppresses gastric tumorigenesis via P14ARF-Mdm2-P53-dependent cellular senescence.

[This corrects the article DOI: 10.18632/oncotarget.22876.].

A Case of Primary Gastric Cancer with Synchronous Primary Colon Cancer Detected by Systematic Inspection of the Gastrointestinal Tract Using Preoperative Abdominal Ultrasound

1年ほど前からの食欲低下と，体重減少，1か月前からの固形物摂取後の嘔吐，全身倦怠感を主訴として，当院内科を受診した60代男性で，上部内視鏡検査に加えて，腹部超音波検査による消化管の系統的走査により，胃角部の胃癌に加えて，横行結腸の腫瘍を術前に検出した症例を経験した。著明な貧血を認め同日入院となった。入院時上部消化管内視鏡検査にて胃癌が疑われ術前検査にて腹部超音波検査が施行された。消化管を系統的走査したところ胃角部に癌と思われる限局性の壁肥厚像を，横行結腸にも異常壁肥厚像を認め横行結腸癌を疑った。後日，下部消化管内視鏡検査にて横行結腸に2型病変を認めた。胃・大腸の重複癌であった。腹腔鏡下にて切除術が施行され，病理所見は胃角部低分化腺癌および横行結腸中分化型管状腺癌であった。腹部超音波検査において消化管を系統的に走査することで病変の見落としを防ぐことが出来た。また消化管の系統的走査は，1つの病変に目を奪われることなく他病変にも目を配ることができ検査精度の向上につながると考えられる。

LRP6 targeting suppresses gastric tumorigenesis via P14ARF-Mdm2-P53-dependent cellular senescence.

NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo. Activation of the P14ARF-P53 pathway played a crucial role in the observed cellular senescence. We further demonstrated that ectopic overexpression of NLRP6 combined with inactivation of NF-κB(p65) and Mdm2 activates P14ARF-P53 to promote the senescence of gastric cancer cells. These findings indicate that NLRP6 functions as a negative regulator of gastric cancer and offer a potential new option for preventing gastric cancer.

Stage IV gastric cancer successfully treated by multidisciplinary therapy including chemotherapy, immunotherapy, and surgery: a case report

BackgroundThe prognosis of stage IV gastric cancer (GC) still remains unfavorable. Multidisciplinary approaches should therefore be considered to improve the survival of patients with stage IV GC. We report here a case of primary GC with potentially unresectable metastasis, successfully treated by a multidisciplinary approach including chemotherapy, immunotherapy, and surgery.Case presentationA 74-year-old man presented with multiple left neck masses. Abdominal computed tomography showed a thickened gastric wall and multiple lymphadenopathies including left supraclavicular lymph node. Gastroenterological endoscopy revealed tumor lesions in the gastric cardia. Tumor biopsy indicated a pathological diagnosis of poorly differentiated adenocarcinoma. Open left cervical lymph node biopsy showed histological features identical with the gastric tumor, indicating left clavicle lymph node metastasis of GC. After 2 years of chemo-immunotherapy with S-1/CDDP, paclitaxel, and cytokine-activated killer cells, lesions other than the stomach lesion had regressed to undetectable on imaging studies. The patient then underwent laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction followed by adjuvant chemo-immunotherapy with paclitaxel and S-1 for 1 year, and immunotherapy with tumor lysate-pulsed dendritic cell-activated killer cells for 5 years. The patient remained well after 5 years and 6 months of follow-up, with no signs of recurrence.ConclusionTherapeutic combinations including immunotherapy may thus allow surgery to be performed in patients previously considered unsuitable for surgical intervention, potentially leading to a clinical cure, as in the current case.

The clinicopathological features and prognostic factors of gastric squamous cell carcinoma

Primary gastric squamous cell carcinoma (SCC) is an exceedingly rare disease. We increased the understanding of gastric SCC and evaluated prognostic factors of gastric SCC.In this large-population cohort study, we retrospectively collected 163 primary gastric SCC and 66,209 primary gastric adenocarcinoma cases from the surveillance, epidemiology, and end results program (SEER) database from 1988 to 2012. The Chi-squared test demonstrated the distributed differences. Cox proportional hazards regression model was used to evaluate the prognostic factors.Gastric SCC accounted for 0.2% of all the primary gastric cancer cases. The mean age of patients with gastric SCC was 69.6 years old, and the man-to-woman ratio was 2.3:1. The proportion of black was higher in gastric SCC than gastric adenocarcinoma (P < 0.001). Almost half of the gastric SCCs were diagnosed in stage IV and more than half were poorly differentiated. In gastric SCC, the median survival was 8.0 months and the 5-year overall survival (OS) was 32.7%; in gastric adenocarcinoma the median survival rate was 19.0 months and the 5-year OS was 35.4%. The multivariate analysis showed that number of primary lesions, tumor location, grade, and stage were independent prognostic factors in gastric SCC. The tumor stage was the most important prognostic factor.Primary gastric SCC is exceedingly rare. Compared with gastric adenocarcinoma, gastric SCC was more frequent in black patients and was usually diagnosed when it was poorly differentiated and at a later stage. On the whole, gastric SCC has a poorer outcome. Disease stage is likely a key determinant in survival.

Distinctive interrelation of p53 with SCO2, COX, and TIGAR in human gastric cancer

Purposep53, widely known as a tumor-suppressing gene, has recently been reported to regulate glucose metabolism in human cancers through the synthesis of cytochrome c oxidase 2 (SCO2), cytochrome c oxidase complex (COX), and TP53-induced glycolysis and apoptosis regulator (TIGAR). In this study, we investigated the interrelations of the aforementioned proteins, particularly in human gastric cancer, with cancer progression, other clinicopathological parameters, and patient outcomes. Materials and MethodsOne hundred and ten cases of primary gastric cancer occurring from June 2006 to June 2009 were investigated and classified into two groups according to the intensity of immunohistochemical staining for p53, SCO2, COX, and TIGAR. The clinicopathological data were organized and analyzed based on electronic medical records. ResultsIn accordance with previous reports, the expression of p53 showed an inverse correlation with the expression of TIGAR (p=0.032) in gastric cancer cells. However, the expression of SCO2 and COX were not shown to be associated with the regulatory role of p53, unlike TIGAR expression. Nevertheless, a significantly high recurrence rate was found in a patient group with high COX expression (p=0.012). ConclusionsThis study demonstrated that a high p53 expression could be associated with the promotion of glycolysis in gastric cancer via the modulation of TIGAR expression. In addition, a high COX expression appeared to be interrelated with poor prognosis of gastric cancer. However, further studies regarding the underlying molecular interactions are required to provide more evidence to propose a novel mechanism that explains our findings in gastric cancer.

New tumour antigen PLAC1/CP1, a potentially useful prognostic marker and immunotherapy target for gastric adenocarcinoma

AimTo evaluate protein expression and clinical significance of PLAC1/CP1 antigen in primary gastric adenocarcinoma.MethodsProtein expression of PLAC1/CP1 was analysed by tissue chip and immunohistochemistry in surgical specimens obtained from 119...

Clinical significance of hmgb1 expression in human gastric cancer.

High mobility group box 1 (HMGB1) has been proved to be implicated in a variety of cell physiological and pathological behaviors including immune response, inflammation and cancer. Accumulating evidence suggests that HMGB1 plays a critical role in the development and progression of multiple malignancies. However, the clinical significance and prognosis of HMGB1 expression in some cancers remain controversial. The present study aimed to investigate whether overexpression of HMGB1 is an independent prognostic factor in patients with gastric cancer. The correlation of HMGB1 expression with clinicopathologic characteristics and prognosis was assessed by immunohistochemical assay through tissue microarray procedure in 50 primary gastric cancer cases. Our results indicated that the positive expression of HMGB1 was significantly increased in the nucleus of gastric cancer tissues compared with the adjacent non-cancerous tissues (ANCT) (64.0&#x0025; vs 44.0&#x0025;, P=0.025), but was not linked to the clinicopathologic features, including the TNM stage (P=0.533) and metastatic lymph node (P=0.771), in patients with gastric cancer. Kapalan-Meier and log-rank analysis demonstrated that overexpression of HMGB1 did not exert significant impact on the overall survival of patients with gastric cancer (P=0.805). Furthermore, Cox regression analysis showed that high HMGB1 protein expression did not represent an independent risk factor for patients with gastric cancer (P=0.677). Taken together, our findings suggest that high expression of HMGB1 is not correlated with the clinicopathologic characteristics of gastric cancer, and cannot serve as an independent prognostic biomarker for patients with gastric cancer.

942 Epigenetic Silencing of DACH1 Induces the Invasion and Migration of Gastric Cancer by Activating TGF-β Signaling

Gastric cancer (GC) is the fourth most common malignancy in males and the fifth most common malignancy in females worldwide and a leading cause of cancer death. Loss of DACH1 expression was found in breast, prostate, endometrial cancer, hepatocellular carcinoma and colorectal cancer. To analyze the regulation and the function of DACH1 in GC, 8 gastric cancer cell lines, 8 cases of normal mucosa and 98 cases of primary GC were employed in this study. Loss of DACH1 expression is correlated with promoter region hypermethylation and re-expression of DACH1 was induced by 5-Aza-2'-deoxyazacytidine treatment in GC cell lines. DACH1 is frequently methylated in primary GC and methylation of DACH1 is associated with reduction of DACH1 expression (p<0.01). These results suggest that DACH1 expression was regulated by promoter region hypermethylation in GC. DACH1 methylation was associated with late tumor stage (p<0.01) and lymph node metastasis (p<0.05). Re-expression of DACH1 suppressed SBE4 luciferase reporter activity and inhibited TGF-β signaling by reducing the level of phosphorylated Smad2. DACH1 inhibited epithelialmesenchymal transition (EMT) and metastasis of GC by inhibition of TGF-β signaling. The tumor size is smaller in DACH1 re-expressed BGC823 cell xenograft than in control group (p<0.01). Restoration of DACH1 expression induced G2/M phase arrest and sensitized GC cells to docetaxel. In conclusion, DACH1 is frequently methylated in human GC and methylation of DACH1 may serve as detective and prognostic markers in GC. DACH1 serve as a tumor suppresser both in vitro and in vivo, suppressed GC metastasis by inhibiting TGFβ signaling. Silencing of DACH1 expression may cause resistance of GC cells to docetaxel.

Loss of has-miR-337-3p expression is associated with lymph node metastasis of human gastric cancer

BackgroundMetastasis is the major cause of cancer-related death in patients with gastric cancer, and aberrant expression of various microRNAs (miRNAs) is associated with cancer metastasis.MethodsProfiling of differentially expressed miRNAs was performed in three cases of primary gastric cancer and the corresponding metastatic lymph node tissues. Then, the five most altered miRNAs were further verified in 16 paired samples. Two of these five miRNAs were further assessed for their effects on the regulation of gastric cancer cell growth and invasion.ResultsThe miRNA profile data showed 151 upregulated miRNAs (≥ 1.5-fold) and 285 downregulated miRNAs (≤ 0.67-fold) in the metastatic tissues compared to the primary gastric cancer tissues. Among these five miRNAs (i.e., hsa-miR-508-5p, hsa-miR-30c, hsa-miR-337-3p, hsa-miR-483-5p, and hsa-miR-134), expression of hsa-miR-337-3p and hsa-miR-134 was significantly downregulated in these 16 lymph node metastatic tissues compared to their primary tumor tissues (P<0.05) and in nine gastric cancer cell lines compared to the nonmalignant GES cell line. Furthermore, induction of hsa-miR-134 or hsa-miR-337-3p expression did not dramatically affect gastric cancer cell proliferation, but transfection of the hsa-miR-337-3p mimic did reduce gastric cancer cell invasion capacity.ConclusionsThese findings indicate that hsa-miR-337-3p plays a role in the reduction of gastric cancer cell invasion capacity, and further studies on the mechanism of hsa-miR-337-3p in gastric cancer metastasis are warranted.

PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression

Background:The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown.Methods:To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer.Results:Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046).Conclusion:The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.

Abstract LB-132: Frequent inactivation of the p53/Mieap/BNIP3 mitochondrial quality control pathway in gastric cancer.

Abstract Recently, we discovered a novel mechanism for mitochondrial quality control (MQC), in which Mieap, a p53-inducible protein, controls MQC by repairing or eliminating unhealthy mitochondria via MALM (Mieap-induced Accumulation of Lysosome-like organelles within Mitochondria) or MIV (Mieap-Induced Vacuole) generation, respectively (1, 2). We also reported that two mitochondrial outer membrane proteins, BNIP3 and NIX, are essential mediators of the MALM (2, 3). To examine the role of Mieap-regulated MQC pathway in tumorigenesis, we analyzed the status of p53, Mieap, BNIP3, and NIX in 50 cases of primary gastric cancer. Of the 50 patients, Mieap and BNIP3 promoter methylation was observed in 2 (4%) and 29 (58%) patients, respectively. A p53 mutation was detected in 2 (10%) of the 20 patients with either Mieap or BNIP3 promoter methylation whereas it was found in 3 (15.8%) of the 19 patients with neither Mieap nor BNIP3 promoter methylation, implying that the p53/Mieap/BNIP3 MQC pathway is inactivated in at least 70% of gastric cancer cases. In a colorectal cancer cell line, hypoxia induced MALM. Knockdown of p53, Mieap, or BNIP3 in the cell line severely inhibited hypoxia-induced MALM, leading to the accumulation of unhealthy mitochondria and increased mitochondrial reactive oxygen species (mtROS) generation. Furthermore, the mtROS dramatically enhanced cancer migration and invasion in hypoxic conditions. These results suggest that the p53/Mieap/BNIP3 MQC pathway plays a tumor-suppressive role in gastric cancer. 1. Miyamoto Y et al. PLoS ONE 6: e16054, 2011 2. Kitamura N et al. PLoS ONE 6: e16060, 2011 3. Nakamura Y et al. PLoS ONE 7: e30767, 2012 Citation Format: Hitoya Sano, Hiroki Kamino, Yasuyuki Nakamura, Masaki Yoshida, Ryuya Murai, Yuri Saito, Manabu Futamura, Kazuhiro Yoshida, Hirofumi Arakawa. Frequent inactivation of the p53/Mieap/BNIP3 mitochondrial quality control pathway in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-132. doi:10.1158/1538-7445.AM2013-LB-132

Assessment of vascular invasion in gastric cancer: A comparative study

To evaluate and compare detection of lymphatic and blood vessel invasion (LVI and BVI) by hematoxylin-eosin (HE) and immunohistochemistry (IHC) in gastric cancer specimens, and to correlate with lymph node status. IHC using D2-40 (a lymphatic endothelial marker) and CD34 (a pan-endothelial marker) was performed to study LVI and BVI in surgical specimens from a consecutive series of 95 primary gastric cancer cases. The results of the IHC study were compared with the detection by HE using McNemar test and kappa index. The morphologic features of the tumors and the presence of LVI and BVI were related to the presence of lymph node metastasis. A χ(2) test was performed to obtain associations between LVI and BVI and other prognostic factors for gastric cancer. The detection rate of LVI was considerably higher than that of BVI. The IHC study identified eight false-positive cases and 13 false-negative cases for LVI, and 24 false-positive cases and 10 false-negative cases for BVI. The average Kappa value determined was moderate for LVI (κ = 0.50) and low for BVI (κ = 0.20). Both LVI and BVI were statistically associated with the presence of lymph node metastasis (HE: P = 0.001, P = 0.013, and IHC: P = 0.001, P = 0.019). The morphologic features associated with LVI were location of the tumor in the distal third of the stomach (P = 0.039), Borrmann's macroscopic type (P = 0.001), organ invasion (P = 0.03) and the depth of tumor invasion (P = 0.001). The presence of BVI was related only to the depth of tumor invasion (P = 0.003). The immunohistochemical identification of lymphatic and blood vessels is useful for increasing the accuracy of the diagnosis of vessel invasion and for predicting lymph node metastasis.

Evaluation of the combined expression of chemokine SDF-1α and its receptor CXCR4 as a prognostic marker for gastric cancer

Chemokine stromal cell-derived factor (SDF)-1α and its receptor CXC chemokine receptor 4 (CXCR4) have been shown to impact cancer progression. Accumulating evidence suggests that CXCR4 and SDF-1α expression is useful for evaluating the risk of gastric cancer progression. Thus, combined analysis of SDF-1α and CXCR4 should have high prognostic potential as a molecular marker for gastric cancer. We investigated the expression of SDF-1α and CXCR4 using immunohistochemistry in relation to prognosis, clinicopathological features and clinical outcomes in 221 cases of primary gastric cancer. Patients were categorized into three groups according to CXCR4 and SDF-1α expression: high CXCR4/high SDF-1α, low CXCR4/low SDF-1α, and high CXCR4/low SDF-1α - low CXCR4/high SDF-1α. No significant differences were noted in age, gender, histology, tumor location, lymphovascular invasion or proportion of tumor size >5 cm among the three groups. However, high CXCR4/high SDF-1α expression in tumor cells was significantly associated with depth of invasion of the tumor, lymph node involvement, and higher tumor stage compared to tumors with low CXCR4/low SDF-1α expression or high CXCR4/low SDF-1α - low CXCR4/high SDF-1α expression. Furthermore, patients with high CXCR4/high SDF-1α expression had the worst patient prognosis, whereas patients who had low CXCR4/low SDF-1α expression showed the most favorable prognosis. In conclusion, CXCR4 and SDF-1α are useful prognostic factors in gastric cancer, and the combination of high CXCR4 protein expression with high SDF-1α expression suggests a dismal prognosis.