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Immune phenotype and histopathological growth pattern in patients with colorectal liver metastases.

ABSTRACT:

Background

Patients with desmoplastic (angiogenic) histopathological growth pattern (HGP) colorectal liver metastases (CLM) might derive more benefit from bevacizumab-based chemotherapy than those with replacement (non-angiogenic) HGP. This study investigated the association of HGP with the immune phenotype (IP) and clinical outcome after liver resection.

Methods

CLM of patients treated with perioperative bevacizumab-based chemotherapy and liver resection were investigated. Association of HGP and IP with response, recurrence-free survival (RFS) and overall survival (OS) was investigated.

Results

One hundred and eighteen patients (M/F 66/52, median age 62.3 (31.0-80.4) years, median follow-up 32.2 (5.0-92.7) months) were enrolled. The inflamed IP was associated with the desmoplastic HGP. The desmoplastic HGP was associated with better radiological and histological response compared to the replacement HGP, respectively. The replacement HGP was associated with shorter RFS (8.7 versus 16.3 months, HR 2.60, P = 0.001) and OS (36.6 months versus not reached, HR 2.32, P = 0.027), respectively. The non-inflamed IP was associated with shorter RFS (10.8 versus 16.5 months, HR 1.85, P = 0.029). The HGP but not the IP remained significant in multivariable analysis for RFS.

Conclusions

The desmoplastic HGP is associated with the inflamed IP and HGP may be a potential biomarker for adjuvant treatment that includes targeting the immune contexture.

SUBMITTER: Stremitzer S

PROVIDER: S-EPMC7217855 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn patients with resectable colorectal liver metastases (CRLM), distinct histopathological growth patterns (HGPs) develop at the interface between the tumour and surrounding tissue. The desmoplastic (d) HGP is characterised by angiogenesis and a peripheral fibrotic rim, whereas non-angiogenic HGPs co-opt endogenous sinusoidal hepatic vasculature. Evidence from previous studies has suggested that patients with dHGP in their CRLM have improved prognosis as compared to patients with non-desmoplastic HGPs. However, these studies were relatively small and applied arbitrary cut-off values for the determination of the predominant HGP. We have now investigated the prognostic effect of dHGP in a large cohort of patients with CRLM resected either with or without neoadjuvant chemotherapy.MethodsAll consecutive patients undergoing a first partial hepatectomy for CRLM between 2000 and 2015 at a tertiary referral centre were considered for inclusion. HGPs were assessed in archival H&E stained slides according to recently published international consensus guidelines. The dHGP was defined as desmoplastic growth being present in 100% of the interface between the tumour and surrounding liver.ResultsIn total, HGPs in CRLMs from 732 patients were assessed. In the chemo-naive patient cohort (n = 367), the dHGP was present in 19% (n = 68) and the non-dHGP was present in 81% (n = 299) of patients. This dHGP subgroup was independently associated with good overall survival (OS) (HR: 0.39, p < 0.001) and progression-free survival (PFS) (HR: 0.54, p = 0.001). All patients with any CRLM with a non-dHGP had significantly reduced OS compared to those patients with 100% dHGP, regardless of the proportion of non-dHGP (all p values ≤ 0.001). In the neoadjuvantly treated patient cohort (n = 365), more patients were found to express dHGP (n = 109, 30%) (adjusted odds ratio: 2.71, p < 0.001). On univariable analysis, dHGP was associated with better OS (HR 0.66, p = 0.009) and PFS (HR 0.67, p = 0.002). However, after correction for confounding by means of multivariable analysis no significant association of dHGP with OS (HR 0.92, p = 0.623) or PFS (HR 0.76, p = 0.065) was seen.ConclusionsThe current study demonstrates that the angiogenic dHGP in CRLM resected from chemo-naive patients acts as a strong, positive prognostic marker, unmatched by any other prognosticator. This observation warrants the evaluation of the clinical utility of HGPs in prospective clinical trials.

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