Superiority of Tumor Location-Modified Lauren Classification System for Gastric Cancer: A Multi-Institutional Validation Analysis

This study aimed to investigate the expression and cellular function of the centromeric family of proteins (CENPs), especially centromere protein I (CENP-I), in gastric cancer (GC) and identified its clinical significance and cellular functions. CENP-I expression in GC was studied by cDNA microarray, quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC), and using datasets from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. Microarray and bioinformatic analyses identified upregulated CENP-A/E/F/H/I/K/P/W and HJURP in stomach adenocarcinoma (STAD), but not in signet ring cell carcinoma (SRCC). Significantly higher CENP-I mRNA expression was also confirmed in 40 pairs of GC tissues than in paired normal gastric tissues by qRT-PCR ( P<.001). IHC showed that elevated CENP-I expression was associated with higher tumor stage, lymph node invasion, increased HER2-positive rate (36.7% vs 10.0%), and intestinal Lauren classification in 69 GC samples compared to paired paracancerous normal tissues. The survival of the high-CENP-I group members was poor compared with that of the low-CENP-I group ( P = .0011). Cox univariate regression analysis identified tumor size ( P = .008), HER2 status ( P = .027), and CENP-I expression ( P = .049) were independent prognostic factors of GC. The cellular function of CENP-I was studied in MKN45 and MKN28 GC cell lines in vitro. Cell proliferation, migration, and apoptosis were determined using CCK-8, transwell assay, TUNEL assay, and flow cytometry. Our results showed that CENP-I promoted GC cell proliferation, inhibited apoptosis, facilitated cell migration, and induced epithelial–mesenchymal transition (EMT), possibly by activating the AKT pathway. CENP-I expression was correlated with genetic signatures of the proliferative subtype of GC, characterized by intestinal Lauren classification, HER2 amplification, and TP53 mutation. In conclusion, this study revealed an elevated CENP-I expression in GC, which was associated with malignant features and poor prognosis of GC patients, and identified its function in modulating cell proliferation, apoptosis, and migration.

Download Full-text

Is the Urokinase-type Plasminogen Activator System a Reliable Prognostic Factor in Gastric Cancer?

The International Journal of Biological Markers ◽

10.1177/172460080602100305 ◽

2006 ◽

Vol 21 (3) ◽

pp. 162-169 ◽

Cited By ~ 9

Author(s):

T. Luebke ◽

S.E. Baldus ◽

D. Spieker ◽

G. Grass ◽

E. Bollschweiler ◽

...

Keyword(s):

Gastric Cancer ◽

Prospective Study ◽

Univariate Analysis ◽

Prognostic Impact ◽

Lauren Classification ◽

Plasminogen Activator System ◽

Number Of Patients ◽

Laurén Classification ◽

Gastric Cancer Patients ◽

Pai 1

Aim The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohisto-chemically assessed uPA and PAI-1 in patients with gastric cancer. Methods This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. Results Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). Conclusions Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.

Download Full-text

A cohort study and meta-analysis of the evidence for consideration of Lauren subtype when prescribing adjuvant or palliative chemotherapy for gastric cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920930359 ◽

2020 ◽

Vol 12 ◽

pp. 175883592093035 ◽

Cited By ~ 1

Author(s):

Kunning Wang ◽

Enxiao Li ◽

Rita A. Busuttil ◽

Joseph C. Kong ◽

Sharon Pattison ◽

...

Keyword(s):

Gastric Cancer ◽

Systemic Chemotherapy ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Diffuse Gastric Cancer ◽

Lauren Classification ◽

Significant Difference ◽

Laurén Classification ◽

Better Than

Background: The association between the survival or efficacy of chemotherapy and the Lauren subtype of gastric cancer (GC) remains unclear. We aimed to clarify whether patients with different Lauren subtypes have different survival after treatment with systemic chemotherapy: intestinal gastric cancer (IGC) patients survived better than patients with mixed type gastric cancer (MGC) or diffuse gastric cancer (DGC) after treatment with systemic chemotherapy. Patients & methods: Relevant studies for the meta-analysis were identified through searching Pubmed, Embase, Cochrane and Ovid up to March 2020. We also included our own prospectively collected cohort of patients that were followed over a 10-year period. Sub-group and sensitivity analyses were also performed. Results: In our prospective cohort, the overall survival (OS) of IGC patients receiving systemic chemotherapy (chemoIGC) [median OS 5.01 years, interquartile range (IQR) 2.63–6.71] was significantly higher than that of DGC patients receiving the same chemotherapy (chemoDGC) (median OS 1.33 years, IQR 0.78–3.33, p = 0.0001). After adjusting for age, gender and cancer stage, there was a significant difference in OS in patients treated with chemotherapy based on the Lauren classification of GC {hazard ratio (HR) for OS of the IGC versus DGC 0.33, [95% confidence interval (CI), 0.17–0.65; p < 0.001]}. In the IGC patients, the adjusted HR associated with chemotherapy was 0.26 (95% CI, 0.12–0.56; p = 0.001), whereas the association was 0.64 (95% CI, 0.30–1.33; p = 0.23) in the DGC patient group. In our meta-analysis, 33 studies comprising 10,246 patients treated with systemic chemotherapy (chemoIGC n = 4888, chemoDGC n = 5358) met all the selection criteria. While we accounted for much of the heterogeneity in these studies, we found that chemoIGC patients showed significantly improved OS [HR, 0.76 (95% CI, 0.71–0.82); p < 0.00001] when compared with similarly treated chemoDGC patients. Conclusion: Our results support the consideration of Lauren subtype when prescribing systemic chemotherapy for GC, particularly for MGC or DGC, which may not benefit from chemotherapy. Lauren classification should be considered to stratify chemotherapy regimens to GC patients in future clinical trials, with particular relevance to MGC or DGC, which is more difficult to treat with current regimens.

Download Full-text

Analysis of the Incidence and Survival of Gastric Cancer Based on the Lauren Classification: A Large Population-Based Study Using SEER

Frontiers in Oncology ◽

10.3389/fonc.2020.01212 ◽

2020 ◽

Vol 10 ◽

Author(s):

Chao-Tao Tang ◽

Ling Zeng ◽

Jing Yang ◽

Chunyan Zeng ◽

Youxiang Chen

Keyword(s):

Gastric Cancer ◽

Large Population ◽

Population Based ◽

Population Based Study ◽

Lauren Classification ◽

Laurén Classification

Download Full-text

Metastatic lymph node ratio and Lauren classification are independent prognostic markers for survival rates of patients with gastric cancer

Oncology Letters ◽

10.3892/ol.2018.8497 ◽

2018 ◽

Cited By ~ 3

Author(s):

Huan Wang ◽

Xiao‑Ming Xing ◽

Lei‑Na Ma ◽

Lian Liu ◽

Jing Hao ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Ratio ◽

Prognostic Markers ◽

Metastatic Lymph Node ◽

Survival Rates ◽

Lauren Classification ◽

Metastatic Lymph ◽

Node Ratio ◽

Laurén Classification

Download Full-text

Prognostic analysis of the patients with operable gastric cancer and the importance of tolerability of therapy: Study of Anatolian Society of Medical Oncology.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14526 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14526-e14526

Author(s):

Mehmet Kucukoner ◽

Erkan Arpaci ◽

Abdurrahman Isikdogan ◽

Mehmet Bilici ◽

Dogan Uncu ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factors ◽

Univariate Analysis ◽

Tumor Grade ◽

Tumor Stage ◽

Adjuvant Chemoradiotherapy ◽

Lauren Classification ◽

Prognostic Analysis ◽

Medical Centers ◽

Laurén Classification

e14526 Background: The aims of this study were to evaluate the tolerability and toxicity with adjuvant chemoradiotherapy (CRT) and prognostic analysis of patients with operable gastric cancer. Methods: The retrospective analysis included 723 patients with operable gastric cancer, stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. Patients’ age, sex, tumor localization, Lauren classification, grade, stage, type of dissection, toxicity and tolerability status were analyzed. Results: 73.9% of the patients were with stage III- IVM0. 61.0% of the patients were in the intestinal type, 51.1% of the patients were with the distal type of gastric cancer and 61.4% of the patients had undergone D2 dissection. 545 (75.4%) of patients completed the entire of adjuvant CRT. The median follow-up period was 20.8 months. Overall Survival (OS) rates were 80% and 52% while relapse free survival (RFS) rates were 75% and 48%, at 1, 3 years, respectively. In univariate analysis of groups, according to the group under the age of 65 and above (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), toxicity (p=0.062 / p=0.077), tolerability of therapy (p=0.002 / p=0.001) were significantly different in both RFS and OS. In multivariate analysis, three independent prognostic factors were identified on RFS / OS; stage (ods ratio (OR)=3.0, 95% confidence interval (CI):1.8-5.0, / OR=3.2, CI=1.8-5.4), for Lauren classification (OR=1.5, CI=0.9-2.2 / OR=1.5, CI= 1.1-2.2), for tolerability of therapy (OR=2.0, CI=1.0-3.8 / OR=1.9, CI=1.0-3.6). Conclusions: We found a new independent prognostic factor whether or not tolerate adjuvant CRT because of toxicity, except for the known prognostic factors like tumor stage and Lauren classification. We suggest that the treatment of the patients with intolerable to adjuvant CRT, is to change with less toxic adjuvant therapies.

Download Full-text

The estrogenic hormone effect in gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.85 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 85-85

Author(s):

Youjin Jang ◽

Youjae Mok

Keyword(s):

Gastric Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Treatment Effect ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

High Expression ◽

Lauren Classification ◽

Laurén Classification

85 Background: Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. A few of studies have examined the expression of ER in gastric cancer. However, considerable controversy is raised as to the expression level of ER and its prognostic value in gastric cancer. In the present study, the expression profile of ERα, ERβ was determined in gastric cancer cell lines according Lauren classification and evaluate that the treatment effect of selective estrogen receptor modulator. Methods: Using four cell lines established from human gastric carcinomas according Lauren classification, check endogenous ERα, ERβ expression levels with RT-PCR. The SERM treatment effect were detected MTT test. Using immunohistochemical detection, the present study analyzed the clinical relevance of ERα, ERβ expression in tumor cells in 197 patients who underwent curative radical surgery and who were observed on long-term follow-up. Results: Endogenous ERα was high expression not intestinal cancer cell lines but in diffuse cancer cell line. Endogenous ERβ was high expression both type cancer cell line than normal gastrointestinal cell lines. According MTT assay, only raloxifene among SERM was significant treatment effect. In immonohistochemial study of gastric tissue, ERα negative and ERβ positive was associated with good prognosis. Conclusions: ERβ may be partly involved in gastric carcinogenesis and ERβ antagonist might be new therapeutic drug for gastric cancer.

Download Full-text

Expanding the Lauren Classification: A New Gastric Cancer Subtype?

Gastroenterology ◽

10.1053/j.gastro.2013.07.019 ◽

2013 ◽

Vol 145 (3) ◽

pp. 505-508 ◽

Cited By ~ 6

Author(s):

Emily S. Turner ◽

Jerrold R. Turner

Keyword(s):

Gastric Cancer ◽

Lauren Classification ◽

Cancer Subtype ◽

Laurén Classification

Download Full-text

HER2 protein expression correlates with Lauren classification and P53 in gastric cancer patients

10.21203/rs.3.rs-45602/v1 ◽

2020 ◽

Author(s):

Yiming Chu ◽

Hongbo Li ◽

Dan Wu ◽

Qingqu Guo

Keyword(s):

Gastric Cancer ◽

Protein Expression ◽

Cancer Patients ◽

Clinical Significance ◽

P53 Expression ◽

Her2 Protein ◽

Lauren Classification ◽

Laurén Classification ◽

Gastric Cancer Patients ◽

Expression Status

Abstract Background and objective: Human epidermal growth factor receptor 2 (HER2) is a key pathological characteristic in gastric cancer patients. However, the clinical significance of HER2 protein expression in gastric carcinoma remains controversial. The purpose of the study is to analyze the clinicopathological characteristics of HER2 protein expression, Lauren classification and P53 expression and evaluate the clinical significance of the HER2 protein expression. Methods: A total of 176 consecutive patients were recruited prospectively between January 2014 and December 2016 in The Second Affiliated hospital of Zhejiang University School of Medicine. Histological analysis was performed on resected tissue for HER2 protein expression by immunohistochemistry (IHC). The patients with IHC grade 2+ were analyzed by fluorescence in situ hybridization (FISH) to assess the expression status of HER2 protein. Moreover, standardized criteria of HER2 protein expression in gastric cancer was used in this study. Additionally, the expression status of HER2 protein and clinicopathological features were analyzed by Chi-square (c2) test. All statistical analyses were conducted using the SPSS 22.0 statistical software program (IBM Corp., SPSS statistics, Chicago, IL).Results: A total of 176 gastric cancer patients were enrolled in this study. Intratumorally heterogeneity of HER2 protein overexpression was 42 of 176 cases with IHC grade 2+ accompanied with FISH positivity and IHC grade 3+. HER2 protein expression correlated with tumor differentiation (p < 0.001), Lauren classification (p = 0.001), Borrmann type (p = 0.003) and P53 expression (p < 0.001). Overall survival (OS) was not analyzed because the follow-up duration was too short and the high rate of missed interview.Conclusions: The overexpression of HER2 protein was determined in 23.9% of the cases and significantly related to Lauren intestinal subtype and P53 expression.

Download Full-text