Abstract

BackgroundColorectal cancer liver metastases (CRLM) has not been identified as a unified disease entity due to the differences in the severity of metastatic disease and tumor aggressiveness. A screen for specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of DNA ploidy, stroma fraction and nucleotyping of initially resectable liver metastases from patients with CRLM.MethodsOne hundred thirty-nine consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. DNA ploidy, stroma fraction and nucleotyping of liver metastases were evaluated using automated digital imaging systems. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression models.ResultsDNA ploidy was identified as an independent prognostic factor for RFS (HR, 2.082; 95% CI 1.053–4.115; P = 0.035) in the multivariate analysis, while stroma-tumor fraction and nucleotyping were not significant prognostic factors. A significant difference in 3-year RFS was observed among the low-, moderate- and high-risk groups stratified by a novel parameter combined with the tumor burden score (TBS) and DNA ploidy (72.5% vs. 63.2% vs. 37.3%, P = 0.007). The high-risk group who received adjuvant chemotherapy had a significantly better 3-year RFS rate than those without adjuvant chemotherapy (46.7% vs. 24.8%; P = 0.034).ConclusionsOur study showed that DNA ploidy of liver metastases is an independent prognostic factor for patients with initially resectable CRLM after liver resection. The combination of DNA ploidy and TBS may help to stratify patients into different recurrence risk groups and may guide postoperative treatment among the patients.

Highlights

  • Colorectal cancer (CRC) is the third most common cancer worldwide and one of the leading causes of cancerrelated death [1, 2]

  • Patients included in the final analysis satisfied the following inclusion criteria: (1) histologically confirmed colorectal adenocarcinoma, (2) metastases limited to the liver, (3) no preoperative chemotherapy before liver resection, (4) radical resection of both the colorectal primary tumor and liver metastases, (5) at least a 3 month followup period after liver resection, (6) available formalinfixed and paraffin-embedded (FFPE) samples of liver metastases, and (7) sufficient tumor tissue for detection

  • The results showed that the nondiploid DNA ploidy of liver metastases and tumor burden score” (TBS) are negative prognostic factors for patients with initially resectable cancer liver metastases (CRLM) after liver resection, so we combined both of them as a novel parameter in the following study

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Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer worldwide and one of the leading causes of cancerrelated death [1, 2]. Accumulating studies have reported that the “tumor burden score” (TBS) developed based on the tumor size and the number of liver metastases showed better prognostic discriminatory power than the clinical risk score for patients with CRLM [13, 14]. Those scoring systems were only generated based on the gross level of the tumor, and the tumor cell structure level was not considered. The current study aimed to investigate the prognostic value of DNA ploidy, stroma fraction and nucleotyping of initially resectable liver metastases from patients with CRLM

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