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Clinicopathological and mutational differences between tumors with multiple metastases and single lung metastasis in colorectal cancer.

Abstract：

:Cancer metastasis, particularly multiple metastatic cancer, is a significant event that affects patient prognosis. However, single metastasis can be treated by partial resection, although the clinicopathological and molecular profile of single lung metastasis has not been thoroughly elucidated. The present study examined tumor heterogeneity by comparing the mutation status between primary colorectal cancer (CRC) and corresponding metastatic lesions to identify prognostic factors associated with single lung metastasis and multiple metastases. The present study enrolled 31 cases of CRC; 20 cases with multiple metastases and 11 cases with single lung metastasis. Clinicopathologically, all cases with multiple metastases were tubular adenocarcinoma, and 3/11 cases with single metastasis were mucinous adenocarcinoma originating from the left side, the remaining 8 cases were tubular adenocarcinoma from the left side. CRC cases with multiple metastases exhibited more frequent vascular invasion, but not lymphatic invasion, than those with single lung metastasis. Furthermore, CRC with multiple metastases was associated with strong tumor budding (P=0.04). Patients with CRC with multiple metastases had lower recurrence-free survival rates compared with those with single lung metastasis (P=0.02). However, there was no significant difference between these two groups in terms of overall survival rates. A next-generation sequencing cancer hotspot panel was used to analyze a heterochronous multiple metastases case, including brain metastasis. Sanger sequencing, immunohistochemistry and microsatellite instability were examined for all 31 cases to reveal the molecular features. KRAS and TP53 mutation signatures were largely preserved throughout the metastatic events. TP53/APC mutations and overexpression of p53 appeared to be associated with the presence of lymphovascular invasion and strong tumor budding, respectively, although these differences were not statistically significant. Early relapses in patients with CRC could be a sign for eventual multiple metastases, although these may not affect the overall survival of patients with CRC. Considerable mutational changes were seemingly rare during metastatic events in patients with CRC.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Yanai Y,Hayashi T,Akazawa Y,Yatagai N,Tsuyama S,Yao T,Saito T

doi

10.3892/ol.2020.11627

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

541-550

issue

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-11627

journal_volume

pub_type

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Clinicopathological and mutational differences between tumors with multiple metastases and single lung metastasis in colorectal cancer.