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
ARTICLE HIGHLIGHTS
Research background

Different histological growth patterns (HGPs) of colorectal carcinoma (CRC) liver metastasis are associated with patients’ prognosis and response to antiangiogenic therapy.

Research motivation

Through studying the relationship between the different HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer, we aimed to evaluate whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis

Research objective

To understand the biology of the primary CRCs in association with different HGPs of liver metastasis, and to identify histological and biology markers in the primary tumor that could predict the HGPs of liver metastasis.

Research 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 from each group were randomly selected for WES analysis.

Research 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).

Research conclusion

The primary CRCs with an expanding growth pattern have a better overall survival that those with an infiltrating growth pattern. Expanding CRCs tend to develop desmoplastic liver metastasis, whereas infiltrating cancers tend to develop replacement liver metastasis. Combined HGP, TBS, and CDR of primary CRC could be used to predict the HGPs of liver metastasis. Up to 40% of primary CRCs with an expanding growth pattern show PIK3CA gene mutations in contrast to 0% of primary CRCs with an invasive growth pattern.

Research perspectives

Multicenter collaborative studies with a larger number of patients and prospective studies to assess the predictive value of the clinicopathological features of primary CRC on the HGPs of its liver metastasis could help to further validate our results. These genomic differences between the two groups of primary CRC, if validated in a larger cohort of case, have the potential to become not only clinically applicable diagnostic and prognostic biomarkers but also therapeutic targets of genomic engineering.