A Comparative Study Of Clinicopathological Features And Prognosis Of Gastrointestinal Signet Ring Cell Carcinoma And Mucinous Adenocarcinoma

Background and purpose:Signet ring cell carcinoma(SRC)is a rare and distinct entity of adenocarcinoma with unique biological behavior and pathomorphological characteristics,of which gastrointestinal tract and pancreas are the most common place.The incidence of mucinous adenocarcinoma(MA)in gastrointestinal cancer is relatively low,primary MA of colon and rectum is more common.Mucinous gastric carcinoma(MGC)and Signet ring cell gastric carcinoma(SRGC)have a lot of same characteristics.They belong to gastric mucin-producing adenocarcinoma,which is rare histological type of gastric cancer.Compared with the common non-mucinous gastric adenocarcinoma,both of them are characterized by high malignancy,rapid progress,lower radical resection rate and insensitivity to radiotherapy and chemotherapy.The early manifestations are not easy to detect with lack of unified diagnosis,treatment standards and prognostic markers.Based on the data of SEER database,this study analyzed the patients with primary SRC and MA of gastrointestinal tract who had been diagnosed from 2000 to2014.It analyzed the change of the overall incidence trend of SRC and MA of gastrointestinal tract,clarified the clinical distribution and prognosis of different primary sites,and revealed the prognostic factors.In this study,222 patients with gastric mucin-producing adenocarcinoma in the First Affiliated Hospital of Nanchang University and the Second Affiliated Hospital of Nanchang University from July 2011to October 2016 were followed up.The correlation between the three-year survival time and recurrence-free survival(RFS)with CEA,Fib,Alb,pAlb and FPR was analyzed.Methods:We extracted the clinicopathological data of 24613 patients with gastroenteropancreatic SRC and 51632 gastrointestinal MA who were reported to SEER project from January 2000 to December 2014.SEER*Stat software,version8.3.4 was used to evaluate the trend of survival time and prognosis.Multivariate Cox risk model was used to evaluate the predictors related to the prognosis.The multivariate variables included diagnosis time,primary site,tumor stage,differentiation degree,gender,age and race.222 patients with gastric mucin-producing adenocarcinoma in the First Affiliated Hospital of Nanchang University and the Second Affiliated Hospital of Nanchang University from July 2011 to October 2016 were enrolled.The X-tile software 3.6.1was used to calculate the optimal cut-off values of FPR,pAlb,Alb,Fib.Pearson?~2test and Mann-Whitney U or Kruskal Wallis test were used to analyze the correlation between basic clinicopathological characteristics,inflammation and nutrition related indexes with survival prognosis.Kaplan-Meier curve and log rank test were used for survival analysis.Cox proportional risk regression model was used to analyze independent prognostic factors of disease.P<0.05 was considered to indicate a statistically significant difference.Result:1.Analysis of clinicopathological characteristics and prognostic factors of gastroenteropancreatic SRC based on SEER databasePeople diagnosed with appendix SRC were significantly younger(mean age,58years)than people diagnosed with SRC located in any of the other site(P<0.01 for all comparisons).The decrease in the incidence of gastroenteropancreatic SRC in the period of 2000 to 2014 appeared across all stages,grades and all site apart from appendix(rise 2.9-times)and esophagus(remained stable).Among grade groups,incidence decreased the most in Grade II gastroenteropancreatic SRC,from 0.129 per100000 persons in 2000 to 0.042 per 100000 persons in 2014(P<0.001).SRC in the appendix(26.1 months)had the best median OS among site groups,while SRC in the pancreas(3.4 months)had the worst median OS.Patients with localized gastroenteropancreatic SRC showed better median OS(55.6 months)in comparison with regional gastroenteropancreatic SRC(19.4 months)and distant gastroenteropancreatic SRC(5.6 months).The improvement in survival over the same time intervals was more pronounced in the subgroup with localized and regional signet ring cell carcinoma.Age,race,gender,stage,and site were all found to have significant correlation with survival.SRC in the pancreas had the worst OS(HR,3.06;95%CI,2.69-3.49).2.Analysis of clinicopathological characteristics and prognostic factors of gastrointestinal MA based on SEER databaseThe mean ages at diagnosis of patients with appendiceal MA was significantly younger than that of patients with the disease in other sites(59.2).26,058(50.5%)were women,and 25,574(49.5%)were men.Distant metastasis in patients with colorectal MA was less common than in those with MA in other locations.The decrease in the incidence of gastrointestinal mucinous MA from 2000 to 2014occurred across all stages,grades and sites apart from the appendix(1.7 times increase).Among stage groups,the incidence decreased the most in localized gastrointestinal mucinous MA from 1.688 per 100,000 persons in 2000 to 0.736 per100,000 persons in 2014.Among the different grade groups,the incidence of Grade II gastrointestinal mucinous MA decreased dramatically from 1.343 per 100,000persons in 2000 to 0.556 per 100,000 persons in 2014.The median OS for all patients was 54.8 months.The best and worst median OS were observed in the appendix(86.6 months)and stomach(10.6 months).Patients with localized gastrointestinal MA showed better survival than individuals with regional or distant disease for 120 months vs.71.9 months vs.13.9 months,respectively.Age,stage and site were all found to have significant correlations with survival.The patients who were diagnosed during 2010-2014 and during 2005-2009had an 8%(HR,0.92,95%CI,0.83-0.91)and 7%(HR,0.89,95%CI,and 0.91-0.96)decreased risk of death,respectively,compared with patients who were diagnosed between 2000 and 2004.3.Analysis of clinicopathological characteristics and prognostic factors of gastric mucin-producing adenocarcinoma based on Chinese dataAccording to the X-tile software,the optimal cut-off value of Fib,Alb,CEA,pAlb and FPR for predicting the total survival time are 3mg/mL,38.6g/L,3.6ng/mL,211.6mg/L and 14.3.Increased Fib and FPR,decreased Alb have correlations with age(more than 60 years)and tumor site(located in the upper 1/3 of the stomach).Increased Fib,FPR and decreased pAlb were positively correlated with tumor size(over 5cm),invasion depth,lymph node metastasis and tumor stage(P<0.05).Univariate analysis showed that pathological type,age,tumor size,invasion depth,lymph node metastasis,tumor stage,chemotherapy and serological indexes(Fib,Alb,CEA,pAlb and FPR)have significant correlations with survival(P<0.05).Multivariate analysis showed that pathological type(HR=2.325,P<0.001),tumor stage,CEA(HR=1.962,P=0.001),FPR(HR=2.313,P<0.001)still significantly affected the prognosis(P<0.05).4.Comparison of clinicopathological features and survival analysis of SRGC and MGC based on Chinese dataThere was no significant difference between SRGC and MGC in tumor location,invasion depth,clinical stage,chemotherapy,Fib,Alb,CEA,pAlb,FPR(P>0.05),but there was significant difference in differentiation degree,tumor size,lymph node metastasis and recurrence(P<0.05).The median survival time of MGC was 36 months,SRGC was 32 months,and the difference was statistically significant(?~2=4.261,P<0.05).The median RFS of MGC was 32 months,and SRGC was 27 months,the difference was statistically significant(?~2=8.165,P<0.05).The median survival time of lymph node metastasis(N1-N3)MGC was 36 months,N1-N3 SRGC was 16 months,and the difference was statistically significant(?~2=9.011,P<0.05).The mean RFS of N1-N3 MGC was 36months,N1-N3 SRGC was 20 months,and the difference was statistically significant(?~2=12.870,P<0.05).Univariate COX analysis of N1-N3 SRGC and MGC showed that pathological type,tumor stage,chemotherapy,Fib,Alb,CEA,pAlb and FPR were significant correlations with survival(P<0.05).Multivariate COX analysis showed that pathological type,CEA and FPR were independent prognostic factors(P<0.05).Univariate COX analysis of recurrence in N1-N3 SRGC and MGC showed that pathological type,differentiation degree,tumor stage,chemotherapy,Fib,Alb,CEA,pAlb and FPR were the factors affecting recurrence(P<0.05).Multivariate analysis showed that pathological type,tumor stage and FPR were independent factors influencing recurrence(P<0.05).Conclusion:1.The result showed a slow decline from 2000 to 2014 except for appendix and esophagus.There was significant difference in median survival time in different tumor location.Age,race,gender,stage,and site were all found to have significant correlation with survival.2.Except for appendix,the incidence rate of MA in other sites of gastrointestinal tract decreased.The median survival time of MA patients was higher than before,especially the prognosis of MA patients with distant metastasis improved more significantly.Multivariate Cox regression analysis showed that age,differentiation degree,the stage of SEER and the primary site were the independent prognostic factors of the death risk of gastrointestinal MA.3.Based on the analysis of the Chinese data of gastric mucin-producing adenocarcinoma,we found that the incidence of male is more than that of female,SRGC is more than MGC,most of them are low differentiation and have metastasis and infiltration.Pathological type,tumor stage,CEA and FPR affected the prognosis significantly The increased FPR indicated a significant increase in the risk of postoperative recurrence and a decrease in survival time in patients with gastric mucin-producing adenocarcinoma.The increased FPR is consistent with the TNM stage and adverse prognosis.4.There are significant differences between SRGC and MGC in clinicopathological characteristics,tumor biological behavior,overall survival prognosis and recurrence risk.The subgroup analysis of patients with lymph node metastasis(N1-N3)showed that pathological type,CEA and FPR were independent factors of prognosis,while pathological type,tumor stage and FPR were independent factors of recurrence.