Intestinal stem cell marker LGR5 expression during gastric carcinogenesis

AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records database.Each specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5.The intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact test.RESULTS:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa specimens.Comparison of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue<dysplasia,<gastric adenocarcinoma<metastasis;all P<0.001),with the exception of expression level detected in intestinal metaplasia which was higher than that in normal gastric tissues(P<0.001).Moreover,gastric cancer-associated enhanced expression of LGR5 was found to be signifcantly associated with age,tumor differentiation,Lauren type and TNM stage(Ⅰ+ⅡvsⅢ+Ⅳ)(all P<0.05),but not with sex,tumor site,location,size,histology,lymphovascular invasion,depth of invasion,lymph node metastasis or distant metastasis.Patients with LGR5+gastric cancer specimens and without signs of metastasis from the original biopsy experienced more frequent rates of recurrence or metastasis during follow-up than patients with LGR5-specimens(P<0.05).CONCLUSION:Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer,indicating the potential of this receptor as an early diagnostic and prognostic biomarker.

Over-expression of Metastasis-associated in Colon Cancer-1 (MACC1) Associates with Better Prognosis of Gastric Cancer Patients

Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods： The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results： The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa （P0.001）. MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma （P=0.032）. Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 （P=0.057）. Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer （P=0.002）, but P53 expression was not associated with MACC1 expression. Conclusion： MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.

Prognosis of patients with gastric cancer and solitary lymph node metastasis

AIM:To investigate the relationship of solitary lymph node metastasis(SLNM)and age with patient survival in gastric cancer(GC).METHODS:The medical records databases of China’s Beijing Cancer Hospital at the Peking University School of Oncology and Shanghai Tenth People’s Hospital affiliated to Tongji University were searched retrospectively to identify patients with histologically proven GC and SLNM who underwent surgical resection between October 2003 and December 2012.Patients with distant metastasis or gastric stump carcinoma following resection for benign disease were excluded from the analysis.In total,936 patients with GC+SLNM were selected for analysis and the recorded parameters of clinicopathological disease and follow-up(range:13-2925 d)were collected.The Kaplan-Meier method was used to stratify patients by age(≤50 years-old,n=198;50-64 years-old,n=321;≥65 years-old,n=446)and by metastatic lymph node ratio[MLR<0.04(1/25),n=180;0.04-0.06(1/25-1/15),n=687;≥0.06(1/15),n=98]for 5-year survival analysis.The significance of intergroup differences between the survival curves was assessed by a log-rank test. RESULTS:The 5-year survival rate of the entire GC+SLNM patient population was 49.9%.Stratification analysis showed significant differences in survival time(post-operative days)according to age:≤50 yearsold:950.7±79.0 vs 50-64 years-old:1697.8±65.9 vs≥65 years-old:1996.2±57.6,all P<0.05.In addition,younger age(≤50 years-old)correlated significantly with mean survival time(r=0.367,P<0.001).Stratification analysis also indicated an inverse relationship between increasing MLR and shorter survival time:<0.04:52.8%and 0.04-0.06:51.1%vs≥0.06:40.5%,P<0.05.The patients with the shortest survival times and rates were younger and had a high MLR(≥0.06):≤50 years-old:496.4±133.0 and 0.0%vs 50-65 years-old:1180.9±201.8 and 21.4%vs≥65 years-old:1538.4±72.4 and 37.3%,all P<0.05.The same significant trend in shorter survival times and rates for younger patients was seen with the mid-range MLR group(0.04-0.06),but the difference between the two older groups was not significant.No significant differences were found between the age groups of patients with MLR<0.04.Assessment of clinicopathological parameters identified age group,Borrmann type,histological type and tumor depth as the most important predictors of the survival rates and times observed for this study population.CONCLUSION:GC patients below 51 years of age with MLR of SLNM above 0.06 have shorter life expectancy than their older counterparts.

Lymph node metastatic patterns of gastric carcinoma with a combination of adenocarcinoma and neuroendocrine carcinoma components

BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcinoma(AC)components,with each component ranging from 1%to 99%of the tumour,be classified as a distinct entity.We hereby term this adenoneuroendocrine mixed gastric cancer(G-ANEC).Research on lymph node(LN)involvement in GMANEC has focused mainly on metastasis status,with limited studies on metastatic composition.AIM To investigate the LN metastasis patterns of G-ANEC,the clinicopathological features associated with these metastasis patterns,and to explore adjuvant chemotherapy regimens for G-ANEC.METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022.Utilizingχ2 tests in IBM statistical product and service solutions statistics and R software.RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion,tumour invasion depth,Lauren classification,and tumour location(P values:0.008,0.015,0.01,and 0.004,respectively).When the SOX/XELOX regimen was applied for adjuvant chemotherapy,patients with LN metastasis comprising only AC exhibited better overall survival(OS)(94.25±11.07 months vs 54.36±11.36 months)than did those with NEC.When LN metastasis components contained NEC,there was a trend towards improved OS(64±10.77 months vs 54.35±11.36 months)and disease-free survival(71.28±9.92 months vs 66.28±11.93 months)in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen.CONCLUSION We found a significant correlation between the NEC percentage,tumour invasion depth,Lauren classification,and tumour location and LN metastasis patterns in G-ANEC.For G-ANEC,a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs.Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.