Published online Jul 14, 2019. doi: 10.3748/wjg.v25.i26.3408
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
Different histological growth patterns (HGPs) of colorectal carcinoma (CRC) liver metastasis are associated with patients’ prognosis and response to antiangiogenic therapy.
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
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.
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.
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).
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.
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.