Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2019; 25(26): 3408-3425
Published online Jul 14, 2019. doi: 10.3748/wjg.v25.i26.3408
Histologic features and genomic alterations of primary colorectal adenocarcinoma predict growth patterns of liver metastasis
Jing-Bo Wu, Ali Lopez Sarmiento, Pierre-Olivier Fiset, Anthula Lazaris, Peter Metrakos, Stephanie Petrillo, Zu-Hua Gao
Jing-Bo Wu, Department of Pathology, The Fifth People’s Hospital, Fudan University, Shanghai 200240, China
Ali Lopez Sarmiento, Pierre-Olivier Fiset, Zu-Hua Gao, Department of Pathology, McGill University and the Research Institute of McGill University Health Center, Montreal H4A 3J1, Quebec, Canada
Anthula Lazaris, Peter Metrakos, Stephanie Petrillo, Cancer Research Program, The Research Institute of McGill University Health Center, Montreal H4A 3J1, Quebec, Canada
Author contributions: All authors helped to perform the research; Wu JB performed the research and wrote the paper; Sarmiento AL contributed to paper writing and data analysis; Fiset PO provided experimental advice; Lazaris A and Petrillo S contributed to the analysis of clinical data; Metrakos P contributed to the project design; Gao ZH designed the project and edited the manuscript.
Supported by the Human Resources Development Program for the Outstanding Talents in The Fifth People’s Hospital of Shanghai, Fudan University, No. 2017WYRCJY09; and the Key Medical Speciality of The Fifth People’s Hospital of Shanghai, Fudan University, No. 2017WY202K08.
Institutional review board statement: This study was reviewed and approved by McGill University Health Center Research Ethics Board, No. 11-066-SDR.
Informed consent statement: All patients in our study provided informed consent.
Conflict-of-interest statement: All authors declare no conflict of interest related to the article.
Data sharing statement: No additional data are available.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zu-Hua Gao, FRCPC, MD, PhD, Professor, Department of Pathology, McGill University and the Research Institute of McGill University Health Center, Room E04.1820, 1001 Decarie Boulevard, Montreal H4A 3J1, Quebec, Canada. zu-hua.gao@mcgill.ca
Telephone: +1-514-9341934
Received: March 18, 2019
Peer-review started: March 19, 2019
First decision: May 9, 2019
Revised: June 5, 2019
Accepted: June 7, 2019
Article in press: June 8, 2019
Published online: July 14, 2019
Abstract
BACKGROUND

Different histological growth patterns (HGPs) of colorectal carcinoma (CRC) liver metastasis are associated with patients’ prognosis and response to antiangiogenic therapy. However, the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established.

AIM

To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis.

METHODS

A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups: A (15 cases with desmoplastic liver metastasis) and B (14 cases with replacement liver metastasis). Clinical information was obtained from patients’ charts. Mismatch repair proteins, BRAFV600E, and PD-L1 were evaluated by immunohistochemistry. Five cases were selected randomly from each group for whole exome sequencing (WES) analysis.

RESULTS

In the primary tumor, expanding growth pattern, low tumor budding score (TBS), and Crohn’s disease-like response (CDR) were associated with desmoplastic liver metastasis and better overall survival, whereas infiltrating growth pattern alone of primary carcinoma could predict the replacement liver metastasis and worse overall survival (P < 0.05). On WES analysis, primary carcinoma with desmoplastic liver metastasis showed mutations in APC (4/5); TP53 (3/5); KRAS, PIK3CA, and FAT4 (2/5); BRCA-1, BRCA2, BRAF, and DNAH5 (1/5), whereas primary carcinoma with replacement liver metastasis showed mutations in APC and TP53 (3/5); KRAS, FAT4, DNH5, SMAD, ERBB2, ERBB3, LRP1, and SDK1 (1/5).

CONCLUSION

The HGPs, TBS, and CDR of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis, response to therapy, and patients’ prognosis.

Keywords: Colorectal carcinoma, Liver metastasis, Histologic growth pattern, Clinicopathological characteristics, Whole exome sequencing

Core tip: Different histological growth patterns (HGPs) of colorectal carcinoma (CRC) liver metastasis are associated with patients’ prognosis and response to antiangiogenic therapy. The aim of our study was to assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis. We found that the HGPs, tumor budding score, and Crohn’s disease-like response of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis, response to therapy, and patients’ prognosis.