Clinicopathological Parameters Related To Metastasis And Prognosis Of T1b Esophageal Squamous Cell Carcinoma

Background and objective:The risk of metastasis and recurrence of T1b esophageal squamous cell carcinoma(ESCC)couldn t be ignored.Studies in multiple cancers have shown that the presence and quantitative grading of lymph-vascular invasion is significantly associated with tumor metastasis and poor prognosis in patients.Tumor budding,desmoplastic reaction,and tumor infiltration patterns also plays an important role in tumor metastasis and poor prognosis.According to HE slices,the diagnosis of lymph-vascular invasion and tumor budding were subjective.Studies have shown that immunohistochemical staining combined with elastic tissue staining contribute to the identification of lymph-vascular invasion.Immunohistochemical staining can also improve the recognition of tumor budding,but there is no relevant research report in T1b ESCC.This study was to analyze the correlation between these factors and metastasis and prognosis of T1b ESCC.Methods:A total of 158 cases of T1b ESCC radical resection with complete pathological and clinical data from February 1990 to January 2004 of the Chinese Academy of Medical Sciences Cancer Hospital were collected.All the archived sections of the patients were reviewed for selecting all of paraffin tissue blocks with invasive carcinoma.Hematoxylin and eosin(HE)staining,elastic tissue+AE1/AE3 double staining,CD31+AE1/AE3 and D2-40+AE1/AE3 double immunohistochemical staining are performed for the recognizing lymph-vascular invasion,tumor budding,desmoplastic reaction(DR)and tumor infiltration patterns(INF).Tumor thickness,submucosal invasive depth and maximum diameter of the largest infiltrating lesion were measured,and other relevant clinical and pathological data of the patient,including patient age,gender,the degree of differentiation,tumor location,gross classification,lymph node metastasis(LNM)and follow-up data were collected.The relationship between clinical pathological parameters and metastasis and prognosis of patient was analyzed.Results:In 158 patients,the positive rate of venous invasionby elastic tissue+AE1/AE3 double staining(E-VI)was 69%(109/158),which is higher than 3.8%(6/158)by HE staining(HE-VI).CD31+AE1/AE3 double immunohistochemical staining showed a positive rate of vascular invasion(CD31-VI)of 25.3%(40/158),which is significantly higher than the positive rate of HE-VI(3.8%)(P=0.001).D2-40+AE1/AE3 double immunohistochemical staining showed that the positive rate of lymphatic invasion(D2-40-LI)was 49.4%(78/158),which was significantly higher than the positive rate of lymphatic invasion(HE-LI)by HE staining(22.8%,36/158).D2-40-LI adjacent to cancer,D2-40-LI>4 was significantly associated with simultaneous LNM(P<0.05),multivariate logistic regression analysis of D2-40-LI>4 is an independent predictor of simultaneous LNM(OR=2.319,95%CI=1.471-3.655,P=0.001).CD31-VI and D2-40-LI were predictors of metachronous distant metastasis(DM)in patients(P<0.05).Multivariate COX regression analysis showed that D2-40-LI and tumor differentiation were independent predictors with metachronous DM of patients(P<0.01).Univariate COX regression analysis showed that E-VI,CD31-VI,D2-40-LI,tumor sites were poor prognostic factors for patients with recurrence-free survival(RFS)and overall survival(OS)(P<0.01),multivariate COX regression analysis showed E-VI(HR=2.524,95%CI=1.224-5.202,P=0.012),CD31-VI(HR=2.235,95%CI=1.291-3.869,P-0.004),D2-40-LI(HR=1.785,95%CI=1.035-2.985,P=0.037)and tumor located in the upper thoracic region(HR=2.474,95%CI=1.372-4.462,P=0.003)were independent prognostic factor for RFS.E-VI(HR=2.681,95%CI=1.179-6.096,P=0.019),LNM(HR=1.960,95%CI=1.082-3.551,P=0.026)tumor located in the upper thoracic region(HR=2.626,95%CI=1.382-4.991,P=0.003)were independent poor prognostic factor for OS.There were 151 cases(95.6%)of tumor budding(TB)positive by AE1/AE3 immunohistochemical staining.After standardization,the maximum value of TB(0.785mm2)was 60,and the average value was 11.TB≥15/0.785mm2 was significantly associated with simultaneous LNM of T1b ESCC patients(P=0.001).Multivariate logistic regression analysis showed that TB≥15 was an independent predictor of simultaneous LNM(OR=4.017,95%CI=1.812-8.904,P<0.001).Patients with TB>15 had a higher risk of recurrence than patients with TB<15,and patients with TB>15 had a lower overall survival than those with TB<15,but the difference was not statistically significant(P=0.053,0.061).In 158 patients,there were 39 cases(24.7%)of mature stroma,and 16 cases(10.1%)of moderate mature stroma,and 103 cases(65.2%)of immature stroma.There was no significant correlation between DR and simultaneous LNM,metachronous DM,RFS and OS(P>0.05).There were 119 cases(75.3%)of INFa/b in 158 patients,and 39 cases(24.7%)of INFc.There was no significant correlation between INF and simultaneous LNM,metachronous DM,RFS and OS.(P>0.05).Tumor thickness≥3000μm,submucosal infiltration depth≥2000μm,maximum diameter of maximal infiltration≥2cm were not correlated with simultaneous LNM,metachronous DM,RFS and OS(P>0.05).Conclusion:1.Elastic tissue staining and immunohistochemical staining can significantly improve the detection rate of ESCC lymph-vascular invasion in T1b ESCC.It is recommended to routinely perform elastic tissue staining and CD31,D2-40 immunohistochemical staining.2.The location and number of lymph-vascular invasion should be noted at the same time.The D2-40-LI adjacent to cancer and D2-40-LI>4 were significantly associated with simultaneous LNM.D2-40-LI>4 is an important predictor of simultaneous LNM.3.D2-40-LI is an independent predictor of metachronous DM in patients.4.E-VI,CD31-VI,D2-40-LI,tumor located in the upper thoracic region were independent poor prognostic factor for RFS.E-VI,LNM,and tumor located in the upper thoracic region were independent poor prognostic factors for OS.5.TB>15/0.785mm2 identified based on AE1/AE3 immunohistochemical staining was significantly associated with simultaneous LNM of T1b ESCC.These findings are conducive to the accurate diagnosis of the metastasis and prognosis of T1b ESCC,and guide accurate treatment in the future.Objective:To analyze the clinicopathological features and immunohistochemical expression of esophageal basaloid squamous cell carcinoma(BSCC)in T1b stage.Methods:All cases diagnosed as T1b stage BSCC from January 1990 to October 2018 in the Department of Pathology of the Cancer Hospital of Chinese Academy of Medical Sciences were collected.HE slices were reviewed and the clinicopathological features were collected,including age,gender,lympho-vascular invasion and the status of lymph node metastasis.The patients were followed up.The clinicopathological features,metastasis and prognosis of BSCC patients were analyzed and compared with the cases of T1b stage conventional squamous cell carcinoma(SCC)in our previous study group.Immunohistochemical staining of AE1/AE3,CK14,CK5/6,CK34(3E12,Vimentin,CD117,MYB,CD56,Syn,CgA,Calponin,SMA,P40,P53,Ki-67 was performed.The expression characteristics of each antibody in BSCC and its significance in diagnosis and differential diagnosis were analyzed.Results:Of the 102 patients with T1b esophageal BSCC,87 were male and 15 were female.The proportion of male patients was significantly higher than that of females.There were 60 patients aged 60 years old and 42 patients aged<60 years old.Compared with conventional SCC,BSCC is more likely to occur in older male patients.The vascular invasion rate(17.8%)and lymph node metastasis rate(22.5%)were slightly lower in patients with BSCC than in patients with conventional SCC,but the difference was not statistically significant(P=0.386,0.555).Of the 102 patients with T1b esophageal BSCC,4 were lost to follow-up.The follow-up time of 98 patients with T1b BSCC was 3-185 months.The average follow-up time was 49.17 months.The 5-year overall survival rate and 10-year overall survival rate were respectively.74%and 65.1%,respectively.The 5-year recurrence-free survival rate and 10-year recurrence-free survival rate were 66.3%and 60.5%,respectively.Thirty-one patients(31.6%)relapsed between 3 and 150 months,with a median recurrence time of 15 months.Distant metastasis(DM)occurred in 19 patients(19.4%)from march to 42 months,with the median DM time of 24 months.Survival analysis showed that no recurrence survival(RFS),total survival(OS)of BSCC patients were not significantly different from that of normal SCC patients(P=0.286,0.719).However,patients with distant metastases in BSCC had significantly lower survival than patients with normal SCC(P<0.001).The immunohistochemical staining of BSCC showed that the P40 positive rate was 95.8%,the medium-strong positive rate was 84.2%.Cytokeratin AE1/AE3,CK14,CK34 E12,and ck5/6 can present negative expression.Neuroendocrine markers were weakly-moderately positive.The positive rate of CD56 expression was 32.6%,Syn was 13.7%,CgA was 8.5%.The positive rate of myogenic marker Calponin was 10.6%,the positive rate of SMA was 12.7%,and the positive rate of CD117 was 60%.The MYB protein was positive for cytoplasm in BSCC,the positive rate was 32.6%,and there was no strongly diffuse expression of nuclear.However,the biopsy tissue of esophageal adenoid cystic carcinoma as a control was strongly diffuse positive for nuclear.The expression of P53 was diffusely strongly positive(43.2%),weakly positive(18.9%),and completely negative(37.9%).The ki-67 proliferation index of BSCC was high,77.9%for>50%and 22.1%for<50%.Conclusion:T1b esophageal BSCC occurs in elderly male patients.The prognosis is not significantly different from that of conventional SCC patients,but the distance metastasis free survival of patients was significantly lower than that of conventional SCC patients.BSCC could express myoepithelial markers and neuroendocrine markers.The positive rate of CD117 in BSCC is high.When the tumor appears as sieve-like structure and it is difficult to distinguish from adenoid cystic carcinoma,the strong diffuse expression of MYB protein in adenoid cystic carcinoma may contribute to its differential diagnosis.