Prognostic significance of tumour infiltration growth pattern in patients with advanced gastric cancer

AimsThe prognostic significance of infiltration growth pattern (INF) in patients with gastric cancer (GC) remains controversial. In the present study, we evaluated the impact of INF pattern on the prognosis of patients with advanced GC.MethodsA total of 1455 patients with advanced GC who underwent curative gastrectomy in our institution were retrospectively analysed. All patients were histopathologically classified as INFa/b and INFc pattern according to the Japanese Classification of Gastric Cancer. The prognostic difference between two patterns was compared and clinicopathological features were analysed.ResultsThe prognosis of the patients with INFc pattern was poorer than that of those with INFa/b pattern (5-year disease-free survival, INFa/b: 48.4% vs INFc: 33.5%, p < 0.001), even when they were stratified according to lymph node metastasis and the tumour, node, metastases stage. In addition, the subgroup analysis indicated that INFc pattern was significantly associated with poorer prognosis of T2–T3 stage patients (T2, INFa/b: 72.7% vs INFc: 55.4%; T3, INFa/b: 47.4% vs INFc: 33.5%; p<0.001). However, a similar result was not observed among T4a stage patients (INFa/b: 26.8% vs INFc: 24.8%, p>0.05). The prognosis of T2 stage patients with INFc pattern was similar to that of T3 stage patients with INFa/b pattern (p>0.05). Also, there was no significantly prognostic difference between T3 stage patients with INFc pattern and T4a stage patients (p>0.05). The multivariate analysis indicated that INF pattern was an independent prognostic factor for patients with advanced GC (HR 1.259, 95%CI 1.089 to 1.454).ConclusionIn view of its prognostic significance, histopathological evaluation of INF pattern in surgically resected specimens should be recommended in patients with advanced GC.

Download Full-text

Prognostic significance of ADAM17 expression in patients with gastric cancer who underwent curative gastrectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.60 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 60-60

Author(s):

Ahmet Bilici ◽

Dincer Aydin ◽

Dilek Yavuzer ◽

Hatice Odabas ◽

Ozlem Ercelep ◽

...

Keyword(s):

Gastric Cancer ◽

Multivariate Analysis ◽

Molecular Marker ◽

Cancer Progression ◽

Prognostic Significance ◽

Disease Free Survival ◽

Prognostic Indicator ◽

Curative Gastrectomy ◽

Prognostic Importance ◽

Gastric Cancer Patients

60 Background: Tumor invasion and metastasis are complex processes, involving regulation at the molecular level of adhesive molecules, proteolitic enzymes, and cell growth and angiogenesis factors. A Disintegrin and Metalloproteinase (ADAM)17 has been indicated to be indispensable regulator of celular event from proliferation to migration.Although prognostic importance of ADAM17 expression has been investigated in several tumors, its clinical utility as a useful prognostic molecular marker remains unclearin gastric cancer.In the present study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after surgery. Methods: Prognostic significance of ADAM17 expression was analyzed by immunohistochemically in 158 patients with gastric cancer and the relationship between its expression and clinicopathological factors was also evaluated. Results: High expression of ADAM17 was detected in 81 patients(51%),while low expression was found in 77 cases (49%). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression(p=0.032). The median disease-free survival (DFS) time for patients with high ADAM17 expressed tumors were worse than those of patients with low ADAM17 expressed tumor (16.6 vs. 44.2 months, p=0.004).In addition, patients with low ADAM17 expression had a higher median overall survival (OS)interval than those of high ADAM17 expressed patients (49.6 vs. 26.9 months, p=0.019). Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to known important clinicopathological prognostic indicator for DFS. But its' prognostic importance could not be proved by multivariate analysis for OS. Conclusions: The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively,it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection.

Download Full-text

Prognostic significance of splenectomy during completion total gastrectomy in patients with remnant gastric cancer: propensity score matching analysis

Korean Journal of Clinical Oncology ◽

10.14216/kjco.21015 ◽

2021 ◽

Vol 17 (2) ◽

pp. 96-103

Author(s):

Seung Hyun Back ◽

Sung Eun Oh ◽

Ji Yeong An ◽

Min-Gew Choi ◽

Tae Sung Sohn ◽

...

Keyword(s):

Gastric Cancer ◽

Propensity Score ◽

Propensity Score Matching ◽

Total Gastrectomy ◽

Prognostic Significance ◽

Disease Free Survival ◽

Significant Prognostic Factor ◽

Remnant Gastric Cancer ◽

Significant Difference ◽

The Impact

Purpose: Splenectomy for patients with remnant gastric cancer has been controversial. The purpose of this study is to identify the impact of splenectomy in the treatment of remnant gastric cancer.Methods: We retrospectively analyzed 285 patients with remnant gastric cancer who underwent completion total gastrectomy with or without splenectomy in Samsung Medical Center, between September 1996 and December 2017. We used a 1:1 propensity score matching method for the analysis. The matching factors were age, sex, and pathologic stage. After the matching process, we compared the 5-year overall survival (OS) and the disease-free survival (DFS) between patients with and without splenectomy during completion total gastrectomy.Results: The median duration of follow-up was 58.0 months (range, 0–132 months). After propensity score matching, there were no statistically significant differences between the splenectomy group (n = 77) and no splenectomy group (n = 77) in terms of clinicopathological features. The 5-year OS rate between the no splenectomy and splenectomy group were not significantly different. There was no significant difference between 5-year DFS of the matched groups. Multivariate analysis revealed that splenectomy is not a significant prognostic factor in terms of 5-year OS (no splenectomy vs. splenectomy; 61.5% vs. 60.2%, P = 0.884) or DFS (74.9% vs. 69.8%, P = 0.880).Conclusion: Splenectomy has no impact on the OS and DFS in patients with remnant gastric cancer. Splenectomy during completion total gastrectomy may not be necessary.

Download Full-text

RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients

Medical Sciences ◽

10.3390/medsci10010004 ◽

2021 ◽

Vol 10 (1) ◽

pp. 4

Author(s):

Marina Alessandra Pereira ◽

Marcus Fernando Kodama Pertille Ramos ◽

Andre Roncon Dias ◽

Leonardo Cardili ◽

Renan Ribeiro e Ribeiro ◽

...

Keyword(s):

Gastric Cancer ◽

Inflammatory Infiltrate ◽

Prognostic Significance ◽

Disease Free Survival ◽

Venous Invasion ◽

Molecular Classification ◽

Clinicopathological Characteristics ◽

Curative Gastrectomy ◽

Poorly Differentiated ◽

Prediction Of Prognosis

Background: Recently, markers related to molecular classification were suggested as promising therapeutic targets for treatment and prediction of prognosis in gastric cancer (GC), including c-MET, RhoA, and Claudin-18 (CLDN18). This study aimed to investigate their expression in GC and its correlation with clinicopathological characteristics and survival. Methods: We retrospectively evaluated GC patients who underwent curative gastrectomy. c-MET, RhoA, and CLDN18 were analyzed through immunohistochemistry (IHC), and groups for analysis were determined according to the median values obtained for each marker. Results: Among the 349 GC evaluated, 180 (51.6%), 59 (16.9%), and 61 (17.5%) patients were completely negative for c-MET, RhoA, and CLDN18, respectively. Total gastrectomy, D1 lymphadenectomy, poorly differentiated histology, and greater inflammatory infiltrate were more frequent in the c-MET-negative group. Diffuse type, greater inflammatory infiltrate, and advanced pT and pTNM stage were associated with low-RhoA GC. The venous invasion was more frequent in the low-CLDN18 group. Furthermore, c-MET was positively correlated with RhoA and negatively with CLDN18. HER2 expression was associated with c-MET-positive and high-CLDN18 GC; and loss of E-cadherin expression in c-MET-negative and low-RhoA GC. c-MET-negative and Low-RhoA were significantly associated with worse disease-free survival. Conclusions: c-MET, RhoA, and CLD18 expression occurred frequently in GC. RhoA GC had distinct clinicopathological characteristics related to prognosis. c-MET and RhoA were associated with survival but were not independent predictors of prognosis.

Download Full-text

The Impact of Nerve Involvement on the Prognosis of Gastric Cancer Patients with Curative Gastrectomy: An International Multicenter Analysis

Disease Markers ◽

10.1155/2021/8870562 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Kun Yang ◽

Yu-Qing Dan ◽

Yoon Young Choi ◽

Zong-Guang Zhou ◽

Woo Jin Hyung ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Significance ◽

High Volume ◽

Tumor Location ◽

Lymphatic Invasion ◽

Stage Iii ◽

Curative Gastrectomy ◽

Additional Information ◽

Gastric Cancer Patients ◽

The Impact

Background. Several studies have been conducted to investigate the association between the presence of perineural invasion (PNI) and overall survival (OS) of gastric cancer (GC) patients who underwent curative resection, but no consensus has been reached. This study is aimed at determining the prognostic significance of PNI in gastric cancer. Study Design. The data of 2969 patients with gastric cancer and who had undergone curative gastrectomy from 2006 to 2010 in two high-volume hospitals of China and Korea were retrospectively analyzed. PNI positivity was identified when carcinoma cells were found to infiltrate into the perineurium or neural fascicles. The relationships between PNI and other clinicopathological factors were evaluated, and survival analyses were performed. Results. The presence of PNI was detected in 1055 of the 2969 patients (35.5%). Nationality, age, tumor location, size of tumor, differentiation of the tumor, pT stage, pN stage, lymphatic invasion, and vascular invasion had been associated with PNI positivity. The mean survival time of patients with and without PNI was 62.5 months and 87.3 months, respectively ( P < 0.001 ). However, the presence of PNI was not an independent prognostic factor for gastric cancer, except for patients in stage III ( P = 0.037 , hazard ratio: 1.21, 95% confidence interval: 1.01-1.44). Conclusion. PNI occurs frequently in patients with gastric cancer, and the incidence of PNI increases with the staging of the tumor. The presence of PNI can provide additional information in predicting the survival outcome for those with stage III tumors.

Download Full-text

Evaluation of the prognostic value of CBXs in gastric cancer patients

Scientific Reports ◽

10.1038/s41598-021-91649-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mengya He ◽

Limin Yue ◽

Haiyan Wang ◽

Feiyan Yu ◽

Mingyang Yu ◽

...

Keyword(s):

Gastric Cancer ◽

Target Genes ◽

Prognostic Significance ◽

Disease Free Survival ◽

Genetic Alterations ◽

Genetic Mutation ◽

The Cancer Genome Atlas ◽

Normal Tissues ◽

Interactive Analysis ◽

Gastric Cancer Patients

AbstractChromobox (CBX) proteins were suggested to exert epigenetic regulatory and transcriptionally repressing effects on target genes and might play key roles in the carcinogenesis of a variety of carcinomas. Nevertheless, the functions and prognostic significance of CBXs in gastric cancer (GC) remain unclear. The current study investigated the roles of CBXs in the prognosis of GC using the Oncomine, The Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, The Cancer Genome Atlas (TCGA), and cBioPortal databases. CBX1/2/3/4/5 were significantly upregulated in GC tissues compared with normal tissues, and CBX7 was downregulated. Multivariate analysis showed that high mRNA expression levels of CBX3/8 were independent prognostic factors for prolonged OS in GC patients. In addition, the genetic mutation rate of CBXs was 37% in GC patients, and genetic alterations in CBXs showed no association with OS or disease-free survival (DFS) in GC patients. These results indicated that CBX3/8 can be prognostic biomarkers for the survival of GC patients.

Download Full-text

Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmab026 ◽

2021 ◽

Vol 53 (5) ◽

pp. 547-557

Author(s):

Ya’nan Yang ◽

Chenchen Wang ◽

Congqi Dai ◽

Xinyang Liu ◽

Wenhua Li ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

Disease Free Survival ◽

Positive Association ◽

Her2 Positive ◽

Kaplan Meier ◽

Met Amplification ◽

Amplification Rate ◽

Cox Proportional Hazard Regression

Abstract The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan–Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.

Download Full-text

Dysregulation of ECRG4 is associated with malignant properties and of prognostic importance in human gastric cancer

Cancer Biomarkers ◽

10.3233/cbm-210334 ◽

2021 ◽

pp. 1-12

Author(s):

Yanjie You ◽

Shengjuan Hu

Keyword(s):

Gastric Cancer ◽

Prognostic Significance ◽

Statistical Analyses ◽

Human Gastric Cancer ◽

Advanced Tumor Stage ◽

Protein Levels ◽

Cancer Pathogenesis ◽

Advanced Tumor ◽

Cancer Tissues ◽

The Impact

BACKGROUND: We have previously characterized esophageal carcinoma-related gene 4 (ECRG4) as a novel tumor suppressor gene, which is frequently inactivated in nasopharyngeal carcinoma and breast cancer. Nevertheless, the expression status and prognostic significance of ECRG4 maintain elusive in human gastric cancer. Herein, we examined ECRG4 expression profile in gastric cancer and assessed its association with clinicopathological characteristics and patient survival. METHODS: Online data mining, real-time RT-PCR and immunohistochemistry were employed to determined ECRG4 expression at transcriptional and protein levels in tumors vs. noncancerous tissues. Statistical analyses including the Kaplan-Meier survival analysis and the Cox hazard model were utilized to detect the impact on clinical outcome. Moreover, ECRG4 expression was silenced in gastric cancer SGC7901 cells, and cell proliferation, colony formation and invasion assays were carried out. RESULTS: ECRG4 mRNA and protein levels were obviously downregulated in cancer tissues than noncancerous tissues. Statistical analyses demonstrated that low ECRG4 expression was found in 34.5% (58/168) of primary gastric cancer tissues, which was associated with higher histological grade (P= 0.018), lymph node metastasis (P= 0.011), invasive depth (P= 0.020), advanced tumor stage (P= 0.002) and poor overall survival (P< 0.001). Multivariate analysis showed ECRG4 expression is an independent prognostic predictor (P< 0.001). Silencing ECRG4 expression promoted gastric cancer cell growth and invasion. Western blot analysis revealed the anti-metastatic functions of ECRG4 by downregulating of E-cadherin and α-Catenin, as well as upregulating N-cadherin and Vimentin. CONCLUSIONS: Our observations reveal that ECRG4 expression is involved in gastric cancer pathogenesis and progression, and may serve as a candidate prognostic biomarker for this disease.

Download Full-text

Impact of Total Lymph Node Count on Staging and Survival After Gastrectomy for Gastric Cancer: Data From a Large US-Population Database

Journal of Clinical Oncology ◽

10.1200/jco.2005.14.621 ◽

2005 ◽

Vol 23 (28) ◽

pp. 7114-7124 ◽

Cited By ~ 306

Author(s):

David D. Smith ◽

Rebecca R. Schwarz ◽

Roderich E. Schwarz

Keyword(s):

Gastric Cancer ◽

Linear Trend ◽

Stage Migration ◽

Population Database ◽

Curative Gastrectomy ◽

Data Set ◽

Lymph Node Count ◽

Cancer Data ◽

Survival Difference ◽

The Impact

Background Prognosis of potentially curable (M0), completely resected gastric cancer is primarily determined by pathologic T and N staging criteria. The optimal regional dissection extent during gastrectomy for gastric adenocarcinoma continues to be debated. Methods A gastric cancer data set was created through structured queries to the Surveillance, Epidemiology, and End Results database (1973 to 1999). Relationships between the number of lymph nodes (LNs) examined and survival were analyzed for the stage subgroups T1/2N0, T1/2N1, T3N0, and T3N1. Results In every stage subgroup, overall survival was highly dependent on the number of LNs examined. Multivariate prognostic variables in the T1/2N0M0 subgroup were number of LNs examined, age (for both, P < .0001), race (P = .0004), sex (P = .0006), and tumor size (P = .02). A linear trend for superior survival based on more LNs examined could be confirmed for all four stage subgroups. Baseline model–predicted 5-year survival with only one LN examined was 56% (T1/2N0), 35% (T1/2N1), 29% (T3N0), or 13% (T3N1). For every 10 extra LNs dissected, survival improved by 7.6% (T1/2N0), 5.7% (T1/2N1), 11% (T3N0), or 7% (T3N1). A cut-point analysis yielded the greatest survival difference at 10 LNs examined but continued to detect significantly superior survival differences for cut points at up to 40 LNs, always in favor of more LNs examined. Conclusion Although the impact of stage migration versus improved regional disease control cannot be separated on basis of the available information, the data provide support in favor of extended lymphadenectomy during potentially curative gastrectomy for gastric cancer.

Download Full-text

The Incidence of Postoperative Complications after Gastrectomy Increases in Proportion to the Amount of Preoperative Visceral Fat

Journal of Oncology ◽

10.1155/2019/8404383 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Kazuyuki Okada ◽

Tatsuto Nishigori ◽

Kazutaka Obama ◽

Shigeru Tsunoda ◽

Koya Hida ◽

...

Keyword(s):

Gastric Cancer ◽

Postoperative Complications ◽

Visceral Fat ◽

Visceral Obesity ◽

Continuous Variable ◽

University Hospital ◽

Curative Gastrectomy ◽

Visceral Fat Area ◽

The Impact ◽

The Relationship

Background. Visceral obesity is a risk factor for complications after gastrectomy in patients with gastric cancer. However, it is unclear whether postoperative complications decrease with preoperative reduction of visceral fat without the achievement of a nonobese state. This is because previous studies have performed categorical comparisons of obesity and nonobesity. The current study was performed to estimate the impact of the preoperative visceral fat area (VFA) as a continuous variable on postoperative complications after gastrectomy. Methods. Consecutive patients with gastric cancer who underwent curative gastrectomy between June 2006 and August 2017 at the Kyoto University Hospital were included in this retrospective study. The VFA at the level of the umbilicus was measured using preoperative computed tomography. The relationship between postoperative complications and VFA was investigated with univariate and multivariate analyses. Results. total of 566 patients were included in the study. Their mean VFA was 110 ± 58 cm2, and postoperative complications occurred in 121 patients (21.4%). The larger the VFA (<50, 50–99, 100–149, and ≥150 cm2), the higher the incidence of postoperative complications (11%, 14%, 21%, and 38%, respectively, P<0.001). Multivariate logistic regression analyses showed that the VFA was associated with postoperative complications (odds ratio: 1.009, 95% confidence interval (CI): 1.004–1.013, P<0.001), with an incidence of postoperative complications that was 9% (95% CI: 4%–12%) higher for every 10 cm2 increase in the VFA. Conclusion. The incidence of postoperative complications after gastrectomy increases in proportion to an increase in the preoperative VFA.

Download Full-text