Δημοσίευση

Genotype - phenotype associations in colorectal adenocarcinomas and their matched metastases.

ΤίτλοςGenotype - phenotype associations in colorectal adenocarcinomas and their matched metastases.
Publication TypeJournal Article
Year of Publication2020
AuthorsChatzopoulos, K., Kotoula V., Koliou G-A., Giannoulatou E., Papadopoulou K., Karavasilis V., Pazarli E., Pervana S., Kafiri G., Tsoulfas G., Chrisafi S., Sgouramali H., Papakostas P., Pectasides D., Hytiroglou P., Pentheroudakis G., & Fountzilas G.
JournalHum Pathol
Date Published2020 Nov 05
ISSN1532-8392
Abstract

Although primary colorectal carcinomas (CRC) frequently share genetic alterations with their metastases, morphologic surrogates reflecting the genotype contexture of metastases remain largely unknown. We investigated phenotype/genotype associations in paired primary and metastatic colorectal adenocarcinomas from 75 patients. Thirty-three (44%) metastatic lesions were synchronous and 42 (56%) were metachronous. Tumor budding, micronecrosis and tumor infiltrating lymphocyte density (TILs) were compared with matched NGS genotypes. Micronecrosis in the primary were significantly associated with nodal status (p=0.0054) and with micronecrosis in metastatic sites (p=0.0216), particularly in metachronous metastases (p=0.0033). With a 57-gene panel, one or more mutations were identified in 64 (85.3%) cases. In metastases, high (brisk) TILs were associated with overall mutational burden (p=0.0058) and with mutations in EGF (p=0.0325), RAS genes (p=0.0043) and MMR genes (p=0.0069), while high-level micronecrosis correlated with mutations in APC (p=0.0004) and MSH6 (p=0.0385). Genomic alterations were shared in 90.1% of primary/metastatic pairs, but clonality of the same mutation was shared in only 57.1% of paired lesions. Compared to synchronous, metachronous metastases had more private clonal alterations (p=0.0291); in this group, clonal alterations coincided with brisk TILs (p=0.0334) and high micronecrosis (p=0.0133). High TILs in metastatic lesions were predictive of favorable overall survival (log-rank p=0.044). The observed phenotype/genotype associations favor the clonal evolution model in CRC metastases that seems accompanied by intense host immune response. If the role of micronecrosis and brisk TILs in metachronous metastases is validated in larger studies, these histologic parameters will be worth adding in the armamentarium for the evaluation of metastatic CRC.

DOI10.1016/j.humpath.2020.10.009
Alternate JournalHum Pathol
PubMed ID33161028

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