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KRAS Mutation Predicted More Mirometastases and Closer Resection Margins in Patients with Colorectal Cancer Liver Metastases

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The presence of micrometastases is a source of recurrence after surgical resection of colorectal liver metastases (CRLM). The KRAS mutation is common in colorectal cancer, however the correlation between KRAS status and micrometastases has not been thoroughly clarified.

Methods

We enrolled a cohort of 251 consecutive CRLM patients who received complete liver surgery with known KRAS mutation status, and collected clinicopathological information, including micrometastases, margin status, preoperative chemotherapy, and liver recurrence-free survival (LRFS) and overall survival (OS) rates.

Results

KRAS-mutant (mutKRAS) patients had a higher incidence (60.3 vs. 40.8%; p = 0.002) and higher number of micrometastases [2.0 (range 0–38.0) vs. 0 (range 0–15.0); p < 0.001] than KRAS wild-type (wtKRAS) patients. The micrometastases in the mutKRAS group were more distant than those in the wtKRAS group [0.7 (range 0.1–9.0) vs. 0.6 (range 0.2–5.0) mm; p = 0.018). The mutKRAS group had more involved margin resections (21.5 vs. 9.2%; p = 0.07) and narrower margin widths [2.0 (range 0–40.0) vs. 4.3 (0–50.0) mm; p = 0.002] than the wtKRAS group. In addition, preoperative chemotherapy was associated with a lower rate of micrometastases in mutKRAS CRLM tumors (p < 0.05). mutKRAS status, positive margins, and micrometastases were all related to worse LRFS and OS (p < 0.05); however, micrometastases were not significantly correlated with OS in the multivariate analysis (p = 0.106).

Conclusions

mutKRAS patients had more micrometastases, increased R1 resections, and narrower margins. The presence of micrometastases may have led to the narrow margin width observed in these cases.

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Funding

This study was supported by the Natural Science Foundation of Shanghai (17ZR1406500, 18ZR1408000), Shanghai Hospital Development Center Emerging Advanced Technology Joint Research Project (HDC12014105), and Shanghai Key Developing Disciplines (2015ZB0201).

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Author notes

  1. Qiongyan Zhang and Junjie Peng contributed equally to this paper and share first authorship.

Authors and Affiliations

  1. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

    Qiongyan Zhang MD, Min Ye MD, Weiwei Weng PhD, MD, Cong Tan MD, Shujuan Ni PhD, MD, Dan Huang PhD, MD, Weiqi Sheng PhD, MD & Lei Wang PhD, MD

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Qiongyan Zhang MD, Junjie Peng PhD, MD, Min Ye MD, Weiwei Weng PhD, MD, Cong Tan MD, Shujuan Ni PhD, MD, Dan Huang PhD, MD, Weiqi Sheng PhD, MD & Lei Wang PhD, MD

  3. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

    Qiongyan Zhang MD

  4. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

    Junjie Peng PhD, MD

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  1. Qiongyan Zhang MD
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Contributions

QZ analyzed the data and wrote the original draft of the manuscript. JP provided suggestions for data interpretation. MY and WW collected the follow-up patient information. CT provided methodology suggestions. DH and SN reviewed the pathological features. WS designed the study, critically revised the article, obtained funding, and is responsible for the study. LW designed the study, analyzed the data, obtained funding, and is responsible for the study.

Corresponding authors

Correspondence to Weiqi Sheng PhD, MD or Lei Wang PhD, MD.

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Disclosure

Qiongyan Zhang, Junjie Peng, Min Ye, Weiwei Weng, Cong Tan, Shujuan Ni, Dan Huang, Weiqi Sheng, and Lei Wang declare they have no conflicts of interest.

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Zhang, Q., Peng, J., Ye, M. et al. KRAS Mutation Predicted More Mirometastases and Closer Resection Margins in Patients with Colorectal Cancer Liver Metastases. Ann Surg Oncol 27, 1164–1173 (2020). https://doi.org/10.1245/s10434-019-08065-5

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  • DOI: https://doi.org/10.1245/s10434-019-08065-5

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