| Objective: The clinicopathological and immunohistochemical characteristics of patients with pulmonary sarcomatoid carcinoma(PSC)were analyzed in the first part to clarify the prognosis factors of PSC.The progression free survival(PFS)was also analyzed so as to discover the predictive factors of post-operative PFS.In the second part,high-throughput sequencing technique was performed in 7 patients to analyze gene mutations and to identify key genes and potential therapeutic targets related to the occurrence and development of PSC.Methods: This study retrospective analyzed 48 patients with PSC who were hospitalized in Tianjin Medical University General Hospital from January 2010 to December 2017.The clinical and histopathological characteristics were analyzed as well as the data of treatment and prognosis.SPSS 18.0 statistical software was used for statistical analysis.Kaplan-Meier method was conducted for survival curves and log-rank test for the significant difference of survival time.Cox proportional hazard model was used for multivariate analysis.All tests were performed bilaterally with statistical difference at P < 0.05.The second part of this study collected the pathological specimens of 7 patients with PSC who were hospitalized in Tianjin Medical University General Hospital from January 2014 to December 2015.The DNA of tumor tissue was extracted and then sequenced to screen the hotspot mutation genes that may be related to cancer.Results: The results showed that most of the patients were male,age?60 years and smoker.The tumor size usually more than 5cm.Pleural invasion and lymph node metastasis were common.Most patients were advanced stage and the most common histological subtype was pleomorphic carcinoma.Vimentin,CK,CK7 and EMA usually positive.The median overall survival(OS)was 15.0 months and the median survival time(MST)was 10 months(95% CI 8.169-11.831).Univariate analysis showed that non-smoking history(p = 0.034),tumor length ?5 cm(p = 0.007),and TNM I-II stage(p < 0.001)were predictors of long MST.Cox analysis showed that TNM stage(HR 3.902,95%CI 1.802-8.449,p=0.001)was an independent risk factor that significantly affected the OS of all patients.In surgical patients,Cox analysis showed that lymph node metastasis(HR 4.107,95% CI 1.575-10.713,P = 0.004)and TNM staging(HR 4.459,95% CI 1.857-10.709,P = 0.001)were risk factors of PFS.In pleomorphic carcinoma,Cox analysis showed that lymph node metastasis(HR 4.364,95% CI 1.647-11.559,P = 0.003)was a negative prognostic factor and adverse factors affecting PFS included lymph node metastasis(HR 3.472,95% CI 1.089-11.064,p=0.035)and TNM stage(HR 3.515,95% CI 1.332-9.275,p=0.011).In the second part,the results of gene sequencing showed that there were high frequency somatic gene mutations in PSC.16 non-silent mutations were identified as hotspot mutations that may be related to tumors.In addition,an EML4-ALK fusion gene was identified.Most of these mutations were SNP mutations,then INDEL and gene fusion.Six patients had multiple mutations and only one patient had single mutation.TP53 point mutation was the most common mutation.Other mutations including FAT3,MET,NCOR1,TSHR,APC,HGF,PIK3 CA,EGFR,BRAF,BRIP1 and KMT2 D.Conclusion: PSC patients are mostly elderly,male and smokers with poor prognosis.The tumors are generally large,prone to pleural invasion and lymph node metastasis.Distant metastasis occurs early and the overall survival time is short.The most common subtype is pleomorphic carcinoma.Vimentin,CK,CK7 and EMA usually are highly expressed by immunohistochemical staining.The predictors of survival and PFS include lymph node metastasis and TNM stage.Surgical resection may improve the survival rate.Chemotherapy is not ideal for the treatment of PSC.There are high frequency TP53 gene mutations and a large number of other somatic mutations and rare mutations in PSC.Mutations in PSC are often multiple gene co-mutations. |
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