| Objective:Esophageal spindle cell squamous cell carcinoma is a rare subtype of esophageal squamous cell carcinoma(ESCC)that has unequal amounts of sarcomatoid spindle cell components.Because of the low incidence of esophageal spindle cell squamous cell carcinoma,most of the existing studies are case reports.The pathological characteristics and prognosis of esophageal spindle cell squamous cell carcinoma are still unclear.Our study aims to discuss the clinicopathological features,molecular pathological features and prognosis of esophageal spindle cell squamous cell carcinoma.Methods:A total of 56 esophageal spindle cell squamous cell carcinoma patients who underwent radical esophagectomy without neoadjuvant therapy between May 2010 and August 2018 were included in this retrospective study.The paraffin blocks were collected and the pathological slides were reviewed.The clinicopathological parameters including age,gender,smoking,alcohol consumption,location,tumor morphology,tumor differentiation,tumor size,tumor pedicle,tumor thickness,T,N,angiolymphatic invasion,perineural invasion,heterologous components,the proportion of spindle cell components,necrosis,metachronous distant metastasis and metachronous lymph node metastasis were collected,whereas 129 esophageal basaloid squamous cell carcinoma(BSCC)cases between January 2010 and December 2016 and 549 poor differentiated ESCC cases between January 2010 and December 2013 were selected for comparative analysis.The survival data of patients was followed-up.In addition,the immunohistochemistry(IHC)expression of AE1/AE3,p40,Vimentin,p53,INI1,BRG1 in esophageal spindle cell squamous cell carcinoma was analyzed.The DNA of 12 cases were extracted by microdissection of common/basaloid squamous cell carcinoma components and spindle cell components respectively,and the whole-exome sequencing was carried out to analyze the molecular clonal relationship of esophageal spindle cell squamous cell carcinoma.Results:Esophageal spindle cell squamous cell carcinoma mainly occurred in males with a history of smoking or alcohol consumption,and was mostly located in the middle and lower esophagus.The endoluminal growth pattern(66.1%)was more common,the percentage of T1(53.6%)was higher,and the incidence of angiolymphatic invasion(10.7%)was lower than those in esophageal BSCC and poor differentiated ESCC patients.The carcinoma components was common squamous cell carcinoma components in 35(62.5%)cases and included BSCC components in 21(37.5%)cases,the common squamous cell carcinoma components,BSCC components and spindle cell components were coexisted in 14 cases.The proportion of spindle cell components in the tumor was 10%-90%,and the median value was 60%.The lymph node metastasis rate was 44.6%,and the proportion of common/basaloid squamous cell carcinoma in lymph node metastatic components was higher in esophageal spindle cell squamous cell carcinoma cases.The rate of metachronous distant metastasis was 17.9%in esophageal spindle cell squamous cell carcinoma and the rate of metachronous distant metastasis was 20.0%in T1 esophageal spindle cell squamous cell carcinoma.Survival analysis showed that the 5-year overall survival rate of esophageal spindle cell squamous cell carcinoma was 63.4%.Moreover,the 5-year overall survival rate of Tla was 75.0%,the 5-year overall survival rate of T1b was 80.8%.Univariate Cox analysis showed that tumor location,T,N and the proportion of spindle cell components(<60%)were significantly correlated with overall survival(OS).T,N were significantly correlated with disease-free survival(DFS).Multivariate Cox analysis showed that tumor location,T,N,proportion of spindle cell components(<60%)were independent prognostic factors of OS.T was an independent prognostic factor of DFS.In 56 esophageal spindle cell squamous cell carcinoma cases,for common/basaloid squamous cell carcinoma components,the positive rate of Vimentin was 32.1%(18/56),for spindle cell components,the positive rate of AE1/AE3 was 46.4%(26/56),the positive rate of p40 was 33.9%(19/56).The concordance expression rate of p53 between common/basaloid squamous cell carcinoma components and spindle cell components was 100%,the p53 protein mutation expression rate was 73.2%(41/56),the p53 missense mutant expression rate was 39.3%(22/56),and the p53 nonsense mutant expression rate was 33.9%(19/56).The expression of INI1 and BRG1 of the common/basaloid squamous cell carcinoma components and the spindle cell components were positive in all cases,the positive rate of INI1 and BRG1 IHC expression were 100%(56/56).The AE1/AE3 expression was significantly correlated with tumor morphology.The p40 expression was significantly correlated with the presence or absence of BSCC components of the tumor.The p53 protein mutation expression patients had poorer OS.The expression of AE1/AE3,p40 and Vimentin were not significantly correlated with the prognosis.A total of 12 cases were selected for whole-exome sequencing analysis,but two cases were not included in the analysis due to DNA quality problems.Among the 10 cases of whole-exome sequencing,5 cases were BSCC components and spindle cell components,5 cases were common squamous cell carcinoma components and spindle cell components.The result showed that the common/basaloid squamous cell carcinoma components and spindle cell components might have the same clonal origin.For the lymph node metastasis case,the result showed that the lymph node metastatic BSCC components and the BSCC components and spindle cell components of the primary tumor might have the same clonal origin.Conclusions:1.In esophageal spindle cell squamous cell carcinoma,the endoluminal growth pattern was common,the percentage of T1 was high,the incidence of angiolymphatic invasion was low and the prognosis was good.2.The rate of metachronous distant metastasis was high in T1 esophageal spindle cell squamous cell carcinoma.3.In esophageal spindle cell squamous cell carcinoma,tumor location,T,N,the proportion of spindle cell components(<60%)were the independent prognostic factors of OS.T was the independent prognostic factor of DFS.4.The common/basaloid squamous cell carcinoma components and spindle cell components might have the same clonal origin in esophageal spindle cell squamous cell carcinoma.5.The OS of esophageal spindle cell squamous cell carcinoma patients with p53 protein mutation expression was shorter and the prognosis was poor.Objective:Esophageal squamous cell carcinoma(ESCC)is the main histological type of esophageal carcinoma in China.Despite great progress in surgery and other treatments,the prognosis of ESCC patients is still very poor.HER2 has strong therapeutic implications in certain cancers,such as breast cancer and gastric cancer.However,literature on the frequency of HER2 expression in ESCC is scarce.In the present study,HER2 protein expression,HER2 gene amplification and the relationship between HER2 status and clinicopathological characteristics were evaluated in a large cohort of Chinese ESCC patients.Methods:A total of 862 consecutive patients who received radical esophagectomy without neoadjuvant therapy between January 2014 and October 2015 were included in this retrospective study.The paraffin blocks were collected and the pathological slides were reviewed.The clinicopathological parameters including age,gender,tumor location,tumor differentiation,angiolymphatic invasion,perineural invasion,T,N,TNM were collected.HER2 expression was analyzed by immunohistochemistry(IHC),and its correlation with clinicopathological parameters was assessed.In addition,65 cases from the 862-case cohort,and another 104 ESCC cases between January 2008 and May 2009 were selected to construct the tissue chip.Dual-color in situ hybridization(DISH)was performed on the tissue chip to assess HER2 gene amplification and the relationship with clinicopathological parameters.Results:We found HER2 overexpression(3+)status in 1.5%(13/862)of cases and HER2 equivocal(2+)status in 6.0%(52/862)of cases.HER2 expression was significantly associated with gender.HER2 equivocal(2+)expression was more likely to occur in females(P=0.029).Regarding the 169 cases of the tissue chip analyzed by DISH,which included 65 cases from the 862-case cohort(13 HER2 overexpression(3+)cases,52 HER2 equivocal(2+)cases)and another 104 ESCC cases between January 2008 and May 2009(1 HER2 overexpression(3+)case,3 HER2 equivocal(2+)cases and 100 HER2 negative(1+/0)cases).The results showed 14(of 14,100%)HER2 overexpression(3+)cases,10(of 55,18.2%)HER2 equivocal(2+)cases,and 0(of 100,0%)HER2 negative(1+/0)cases showed HER2 gene amplification.HER2 gene amplification was not significantly associated with clinicopathological characteristics such as age,gender,tumor differentiation,T,N,M and TNM(P>0.05).Combined the results of IHC and DISH,we found 2.7%(23/862)of cases had HER2 positive expression(IHC 3+//IHC 2+ and ISH+),32.9%(284/862)of cases had HER2 low expression(IHC 2+/IHC 1+and ISH-or IHC 1+and ISH not detected).A high concordance rate of 100%was observed between IHC and DISH.Conclusions:1.HER2 overexpression(3+)rate was 1.5%in Chinese ESCC patients based on IHC.2.All of HER2 overexpression(3+)cases showed HER2 gene amplification.3.The 18.2%of HER2 equivocal(2+)cases showed HER2 gene amplification.4.Combined the results of IHC and DISH,HER2 positive expression rate was 2.7%,HER2 low expression rate was 32.9%.5.The concordance rate of HER2 IHC and DISH was 100%.These results provided valuable theoretical support for the future treatment of ESCC and a potential research direction for other sites of squamous cell carcinoma. |
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