| Purpose:To better understand the gene mutational status and heterogeneity between primary and metastatic CRC(mCRC)using a sensitive sequencing method.Methods:The mutational status of EGFR,KRAS,NRAS,PIK3CA,ERBB2,BRAF,KIT and PDGFRAwas analyzed in 65patients,with 147 samples of primary and paired live or lung metastatic CRC,using Next-Generation Sequencing(NGS),quantitative RT-PCR(qPCR)and Sanger sequencing.Results:Fifteen cases(15/22,68.2%)of lung mCRC and thirteen cases(13/20,65%)of liver mCRC harboured the samemutation profiles of KRAS,NRAS or BRAFas in the primary lesions.To all detected genes,11 cases(11/22,50%)of lungmCRC and 11 cases(11/20,55%)of liver mCRC showed different mutational genes in the prima-ry tumours.KRASand RAFmutations were more frequent in lung metastatic lesions than in primary tumors(P=0.004 and 0.003,respectively).The gene mutations in KRAS,NRAS,BRAFand PIK3CAin the lung metastatic sites were more frequent than those in the liver metastatic sites(86.7%vs.44%,respectively,P<0.001).Some new mutations were not covered in the qPCR ranges but were detected by NGS.Conclusion:The study demonstrated that the discordance of gene mutational status between paired primary and metastatictumours is rather high when detected by NGS.Evaluating the mutational status of both the primary and metastatic tumoursshould be considered in clinical mutation testing.Purpose:To investigate the association between clinical pathological factors and lymph node metastases in T1 stage rectal carcinoma.Methods:We retrospectively reviewed the consecutive T1 rectal carcinoma pa-tients who had undergone radical colectomy with lymph node dissection in a sin-gle institution.The histopathological factorsincluding sex,age,tumor diameter,condition of muscularis mucosae,depth of invasion,gross type,adenomatous background,type of adenomatous component,tumor differentiation,histological subtype,PDC,TB,LVI,VI,PNI,tumor necrosis and tumor glandular pattern at the submucosal invasive front were reviewed.The correlation between these fac-tors and lymph node metastasis,tumor recurrence and survival were analyzed.Some molecular biomarkers were also discussed.Results:A total of 251 consecutive patients with T1 rectal carcinoma were in-cluded in this study.Lymph node metastasis occurred in 11.2%of patients.The 3,5 and 10 years overall survival were 98.6%,96.8%and 94.9%,respectively,for all patients.The 3,5 and 10 years overall survival of patients with or without lymph node metastasis were 100%,95.6%and 90.9%or99%,96.9%and 95.4%,respectively.There was no statistical difference between the two group in overall survival.Univariate analysis showed that each of the following histopathological factors had a significant influence on lymph node metastasis,which are patients'age(P=0.05);adenomatous background(P<0.01),tumor differentiation(P<0.01),cribriform structure(P=0.03),PDC(P=0.02),tumor budding(P=0.01),lymphvascular invasion(P<0.01),submucosa venous invasion(P<0.01),glandular patternat the submucosal invasive front(P=0.04)and decreasedGADD45B in expression(P=0.04).Multivariate analysis showed that age(P=0.02),no adenomatous background(P<0.01),tumor differentiation(P=0.04),submucosa venous invasion(P=0.02)and decreasedGADD45B in expression(P=0.04)were significantly associated with lymph node metastasis.We also found that open-type glandular pattern is also correlated with gross plat-type(P=0.03);no adenoma background(P=0.03),complete disruption of the muscularis mucosa(P=0.05),high grade tumor budding(P<0.001)andtumor necrosis(P<0.001).Conclusion:In the present study,we not only verified the effectiveness of those classical pathological factors,but proposed the cribriform structure,open-type glandular pattern at the submucosal invasive front and decreased in GADD45B expression in predicting lymph node metastasis in T1 stage rectal carcinoma. |
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