Angiogenic desmoplastic histopathological growth pattern as a prognostic marker of good outcome in patients with colorectal liver metastases

The purpose of this study was to characterise growth patterns, proteolysis, and angiogenesis in colorectal liver metastases from chemonaive patients with multiple liver metastases. Twenty-four patients were included in the study, resected for a median of 2.6 metastases. The growth pattern distribution was 25.8% desmoplastic, 33.9% pushing, and 21% replacement. In 20 patients, identical growth patterns were detected in all metastases, but in 8 of these patients, a second growth pattern was also present in one or two of the metastases. In the remaining 4 patients, no general growth pattern was observed, although none of the liver metastases included more than two growth patterns. Overall, a mixed growth pattern was demonstrated in 19.3% of the liver metastases. Compared to metastases with pushing, those with desmoplastic growth pattern had a significantly up-regulated expression of urokinase-type plasminogen activator receptor (P=0.0008). Angiogenesis was most pronounced in metastases with a pushing growth pattern in comparison to those with desmoplastic (P=0.0007) and replacement growth pattern (P=0.021). Although a minor fraction of the patients harboured metastases with different growth patterns, we observed a tendency toward growth pattern uniformity in the liver metastases arising in the same patient. The result suggests that the growth pattern of liver metastases is not a random phenomenon.

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Histopathological Growth Pattern of Colorectal Liver Metastases Impacts Local Recurrence Risk and the Adequate Width of Surgical Margin

HPB ◽

10.1016/j.hpb.2021.08.078 ◽

2021 ◽

Vol 23 ◽

pp. S709-S710

Author(s):

B. Branciforte ◽

L. Viganò ◽

V. Laurenti ◽

G. Costa ◽

F. Procopio ◽

...

Keyword(s):

Local Recurrence ◽

Liver Metastases ◽

Growth Pattern ◽

Colorectal Liver Metastases ◽

Surgical Margin ◽

Recurrence Risk

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The desmoplastic growth pattern predicts improved survival after resection of colorectal liver metastases

HPB ◽

10.1016/j.hpb.2018.06.118 ◽

2018 ◽

Vol 20 ◽

pp. S225

Author(s):

P.M.H. Nierop ◽

B. Galjart ◽

E.P. van der Stok ◽

R.R.J. Coebergh van den Braak ◽

S. Daelemans ◽

...

Keyword(s):

Liver Metastases ◽

Growth Pattern ◽

Colorectal Liver Metastases

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Radiomics Diagnosed Histopathological Growth Pattern in Prediction of Response and 1-year Progression Free Survival for Colorectal Liver Metastases Patients Treated with Bevacizumab Containing Chemotherapy

European Journal of Radiology ◽

10.1016/j.ejrad.2021.109863 ◽

2021 ◽

pp. 109863

Author(s):

Shengcai Wei ◽

Yuqi Han ◽

Hanjiang Zeng ◽

Shuai Ye ◽

Jin Cheng ◽

...

Keyword(s):

Liver Metastases ◽

Growth Pattern ◽

Colorectal Liver Metastases ◽

Progression Free Survival ◽

Prediction Of Response ◽

Free Survival

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Moy.01HOXB9: an emerging novel prognostic marker and potential target for gene-therapy in colorectal liver metastases

British Journal of Surgery ◽

10.1093/bjs/znab310 ◽

2021 ◽

Vol 108 (Supplement_7) ◽

Author(s):

Eirini Martinou ◽

Carla Moller-Levet ◽

Angeliki Angelidi ◽

Izhar Bagwan ◽

Nariman Karanjia

Keyword(s):

Gene Therapy ◽

Liver Resection ◽

Cell Growth ◽

Liver Metastases ◽

Prognostic Marker ◽

Colorectal Liver Metastases ◽

Experimental Studies ◽

Patient Cohort ◽

Potential Target

Abstract Aims Homeobox (HOX) proteins are emerging as promising biomarkers and targets for gene-therapy in cancer; however, their role in colorectal liver metastases (CRLM) is unknown. This study aims to investigate the role of HOXB9 as prognostic marker and potential therapeutic target in CRLM. Methods Two patient-cohorts were included: a) Patients with colorectal cancer (CRC) from the National Cancer Institute, Tissue Cancer Genome Atlas (TCGA) database (n = 614) and b) Institutional patient cohort who underwent liver resection for CRLM (n = 110) between 2007-2014. Primary outcome was 10-year overall survival (OS). COX regression and Kaplan-Meier survival analyses were performed including HOXB9 expression, demographics, clinicopathological and treatment-related variables. HOXB9 gene expression was modulated to assess its impact on CRC cell growth in vitro. Therefore, we conducted experimental studies using plasmid-vector and siRNA-interference to overexpress and knockdown HOXB9 respectively. Results Univariable TCGA analysis showed that HOXB9 did not predispose to poor OS (HR = 1, 95%CI:0.92-1.1, p = 0.620). On the contrary, univariable analysis in the CRLM patient cohort showed that high HOXB9 levels, right sided CRC, CRLM number≥4, CRLM diameter≥5cm, and intrahepatic recurrence were associated with significantly increased risk for worse OS. On multivariable models, only high HOXB9 expression (HR = 3.82, 95%CI:1.59-9.2, p = 0.003) and intrahepatic recurrence (HR = 4.28, 95%CI:1.88-9.72, p = 0.001) retained significance as independent prognostic factors after liver resection. Experimental studies showed that HOXB9 overexpression increased cell proliferation (p < 0.001) whereas HOXB9 inhibition markedly supressed CRC cell growth (p < 0.001) in vitro. Conclusions HOXB9 demonstrates oncogenic properties and may serve as novel prognostic marker and potential target for gene-directed therapy in CRC/CRLM.

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Abstract B21: Macrophages and T cell infiltration in colorectal liver metastases according to growth pattern

10.1158/1538-7445.tim2013-b21 ◽

2013 ◽

Author(s):

Rikke L. Eefsen ◽

Gert G. Eynden ◽

Warner Alpizar-Alpizar ◽

Gunilla Høyer-Hansen ◽

Ib Jarle Christensen ◽

...

Keyword(s):

T Cell ◽

Liver Metastases ◽

Growth Pattern ◽

Colorectal Liver Metastases ◽

Cell Infiltration ◽

T Cell Infiltration

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Histological growth pattern as a potential marker of oligometastatic disease in patients operated for colorectal liver metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15093 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15093-e15093

Author(s):

Ali Bohlok ◽

Robin Dezes ◽

Valerio Lucidi ◽

Fikri Bouazza ◽

Desislava Germanova ◽

...

Keyword(s):

Liver Metastases ◽

Growth Pattern ◽

Prognostic Value ◽

Colorectal Liver Metastases ◽

Surrogate Marker ◽

Oncological Outcome ◽

International Consensus ◽

Dominant Phenotype ◽

Potential Marker ◽

Surgical Data

e15093 Background: The identification of oligometastatic profile in patients with resectable colorectal liver metastases (CRLM) would represent a major progress to improve selection for surgery. Currently, in the absence of biomarkers, the most reliable method to identify oligometastatic (OLM) and non-oligometastatic (NOLM) tumors relies on the oncological outcome after metastases-targeted surgery. The histological growth pattern (HGP) of CRLM, defined as desmoplastic (dHGP) or replacement (rHGP), has recently been shown to have prognostic value. We analyzed HGP in a series of patients operated for CRLM, characterized as OLM in case of prolonged postoperative recurrence-free survival (RFS) or NOLM in case of rapid postoperative relapse. Methods: In 357 patients operated for CRLM, we identified OLM patients as those with RFS≥5 years (N = 64), and NOLM patients as those with RFS < 1 year (N = 77). Clinicopathologic and surgical parameters were analyzed. In each CRLM, HGP was assessed in archival H&E stained tissue sections, according to international consensus guidelines. Proportions of rHGP and dHGP were determined in each metastasis. In case of multiple metastases, the mean HGP was calculated in each patient. Patients were categorized as pure (> 95% rHGP or dHGP) or dominant phenotypes (> 50% rHGP or dHGP, of the entire tumor-liver interface). Results: Preoperative characteristics of primary tumor and CRLM, and surgical data were identical in OLM and NOLM groups. In a first set of analyses, HGP was determined in 39 OLM and 52 NOLM patients. Pure dHGP was observed in 54.3% of OLM and 17.3% of NOLM patients (p = 0.001). Pure rHGP was similarly distributed among OLM and NOLM groups. Sixty-nine% of the OLM patients displayed a dHGP-dominant phenotype, whereas 57.7% of the NOLM patients presented with a rHGP-dominant phenotype (p = 0.02). Conclusions: These results confirm the potential prognostic value of HGP in patients operated for CRLM. dHGP, associated with angiogenesis and inflammation, could represent a (surrogate) marker for oligometastatic progression, whereas rHGP appears strongly associated with rapid postoperative relapse.

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