Correlation and Heterogeneity of the Immune Microenvironment and Histopathological Growth Patterns in Resectable Colorectal Cancer Liver Metastases

NCT07564908 | Active Not Recruiting

• 1 other identifier: Approval No. 2021, 2024
• Study Type: observational
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Correlation and Heterogeneity of the Immune Microenvironment and Histopathological Growth Patterns in Resectable Colorectal Cancer Liver Metastases

Conditions

Colorectal Neoplasms

Keywords

Colorectal cancer liver metastases; Histopathological growth patterns; Tumor microenvironment

Outcome Measures

Primary Outcomes (4)

• OS(Overall survival)

  OS was defined as the time from the date of the first liver metastasis resection to death due to any cause or loss to follow-up.

  OS is defined as the time from the date of the first liver metastasis resection to death due to any cause or loss to follow-up, assessed up to 100 months.

• RFS (Recurrence-free Survival)

  The definition of recurrence-free survival is the time from the liver surgery to the first imaging evidence showing disease recurrence or death due to any cause, whichever occurs first.

  From the date of liver resection until the first occurrence of a measurable recurrence of the disease, or until death due to any cause (whichever occurs first), the assessment period can be up to 100 months.

• HGPs (Histopathological Growth Patterns)

  The histopathological growth pattern of the tumor-liver interface.

  From the completion of HE staining to the failure of staining or the damage and loss of the slides, the assessment period can be up to 100 months.

• TME (Tumor Microenvironment)

  Multiplex immunohistochemistry (mIHC) staining was performed on FFPE sections of liver metastases using two panels (Panel 1: CD4, CD8A, Foxp3, PD-L1, Panck; Panel 2: CD68, CD163, FAP-α, α-SMA, Panck), encompassing a total of nine immune cell markers. Using QuPath pathology imaging software, tissue sections were divided into the tumor center (defined as regions \>500 μm from the liver-tumor interface) and the invasive tumor front (defined as a 1 mm region extending 500 μm on either side of the liver-tumor interface). Quantitative analysis of immune cell populations was performed in the tumor center, the invasive tumor front, and regions corresponding to different histopathological growth patterns.

  From the completion of mIHC staining to the failure of staining or the damage and loss of the slides, the assessment period can be up to 100 months.

Study Arms (1)

patients with CRLM who underwent R0 resection

According to the 2017 guidelines on histopathological growth patterns of liver metastases, HGPs are primarily classified into three types: the desmoplastic histopathological growth pattern (dHGP), the replacement histopathological growth pattern (rHGP), and the pushing histopathological growth pattern (pHGP). The tumor-liver interface was independently delineated by two pathologists using QuPath software, and distinct HGPs at the tumor-liver interface were identified. Formalin-fixed, paraffin-embedded (FFPE) sections of colorectal cancer liver metastases were stained with hematoxylin and eosin (H\&E).Multiplex immunohistochemistry (mIHC) staining was performed on FFPE sections of liver metastases using two panels (Panel 1: CD4, CD8A, Foxp3, PD-L1, Panck; Panel 2: CD68, CD163, FAP-α, α-SMA, Panck), encompassing a total of nine immune cell markers.

Other: Formalin-fixed, paraffin-embedded (FFPE) sections of colorectal cancer liver metastases were stained with hematoxylin and eosin (H&E) and Multiplex immunohistochemistry (mIHC) staining.

Interventions

Formalin-fixed, paraffin-embedded (FFPE) sections of colorectal cancer liver metastases were stained with hematoxylin and eosin (H&E) and Multiplex immunohistochemistry (mIHC) staining. OTHER

Formalin-fixed, paraffin-embedded (FFPE) sections of colorectal cancer liver metastases were stained with hematoxylin and eosin (H\&E) and Multiplex immunohistochemistry (mIHC) staining.

patients with CRLM who underwent R0 resection

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study enrolled patients with CRLM who underwent R0 resection.

You may qualify if:

• Patients with CRLM who underwent R0 resection
• Histologically or cytologically confirmed CRLM
• Have sufficient liver metastasis tissue specimens available for analysis
• Complete treatment and follow-up records

You may not qualify if:

• Patients did not undergo R0 resection
• Postoperative specimens were unavailable
• Clinical data were incomplete.

Sponsors & Collaborators

• Meng Qiu: lead

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (7)

• Zhang A, Zhang Y, Xu J, Zhu R, Liang T, Guo L. Molecular landscape of colorectal cancer liver metastasis: Tumor microenvironment heterogeneity and driver inference. Crit Rev Oncol Hematol. 2025 Dec;216:104946. doi: 10.1016/j.critrevonc.2025.104946. Epub 2025 Sep 12.

  PMID: 40946880 BACKGROUND

• Liang JY, Xi SY, Shao Q, Yuan YF, Li BK, Zheng Y, Wang DS, Wu XJ, Ding PR, Chen G, Li LR, Wang FH, Wang ZQ, Pan ZZ, Xu RH, Li YH. Histopathological growth patterns correlate with the immunoscore in colorectal cancer liver metastasis patients after hepatectomy. Cancer Immunol Immunother. 2020 Dec;69(12):2623-2634. doi: 10.1007/s00262-020-02632-6. Epub 2020 Jun 29.

  PMID: 32601799 BACKGROUND

• He Y, Han Y, Fan AH, Li D, Wang B, Ji K, Wang X, Zhao X, Lu Y. Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases. J Transl Med. 2022 Oct 4;20(1):454. doi: 10.1186/s12967-022-03667-2.

  PMID: 36195882 BACKGROUND

• Hoppener DJ, Nierop PMH, Hof J, Sideras K, Zhou G, Visser L, Gouw ASH, de Jong KP, Sprengers D, Kwekkeboom J, Vermeulen PB, Grunhagen DJ, Verhoef C. Enrichment of the tumour immune microenvironment in patients with desmoplastic colorectal liver metastasis. Br J Cancer. 2020 Jul;123(2):196-206. doi: 10.1038/s41416-020-0881-z. Epub 2020 May 18.

  PMID: 32418992 BACKGROUND

• Stremitzer S, Vermeulen P, Graver S, Kockx M, Dirix L, Yang D, Zhang W, Stift J, Wrba F, Gruenberger T, Lenz HJ, Scherer SJ. Immune phenotype and histopathological growth pattern in patients with colorectal liver metastases. Br J Cancer. 2020 May;122(10):1518-1524. doi: 10.1038/s41416-020-0812-z. Epub 2020 Mar 24.

  PMID: 32205863 BACKGROUND

• van Dam PJ, van der Stok EP, Teuwen LA, Van den Eynden GG, Illemann M, Frentzas S, Majeed AW, Eefsen RL, Coebergh van den Braak RRJ, Lazaris A, Fernandez MC, Galjart B, Laerum OD, Rayes R, Grunhagen DJ, Van de Paer M, Sucaet Y, Mudhar HS, Schvimer M, Nystrom H, Kockx M, Bird NC, Vidal-Vanaclocha F, Metrakos P, Simoneau E, Verhoef C, Dirix LY, Van Laere S, Gao ZH, Brodt P, Reynolds AR, Vermeulen PB. International consensus guidelines for scoring the histopathological growth patterns of liver metastasis. Br J Cancer. 2017 Nov 7;117(10):1427-1441. doi: 10.1038/bjc.2017.334. Epub 2017 Oct 5.

  PMID: 28982110 BACKGROUND

• Latacz E, Hoppener D, Bohlok A, Leduc S, Tabaries S, Fernandez Moro C, Lugassy C, Nystrom H, Bozoky B, Floris G, Geyer N, Brodt P, Llado L, Van Mileghem L, De Schepper M, Majeed AW, Lazaris A, Dirix P, Zhang Q, Petrillo SK, Vankerckhove S, Joye I, Meyer Y, Gregorieff A, Roig NR, Vidal-Vanaclocha F, Denis L, Oliveira RC, Metrakos P, Grunhagen DJ, Nagtegaal ID, Mollevi DG, Jarnagin WR, D'Angelica MI, Reynolds AR, Doukas M, Desmedt C, Dirix L, Donckier V, Siegel PM, Barnhill R, Gerling M, Verhoef C, Vermeulen PB. Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights. Br J Cancer. 2022 Oct;127(6):988-1013. doi: 10.1038/s41416-022-01859-7. Epub 2022 Jun 1.

  PMID: 35650276 BACKGROUND

Related Links

• Pubmed Official website

Biospecimen

Retention: SAMPLES WITHOUT DNA

Surgical resection samples of liver metastases from patients with colorectal cancer liver metastasis

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Hematoxylin; Eosine Yellowish-(YS); Staining and Labeling

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fluoresceins; Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Xanthenes; Heterocyclic Compounds, 3-Ring; Polycyclic Compounds; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: West China Hospital

Study Record Dates

• First Submitted: April 27, 2026
• First Posted: May 4, 2026
• Study Start: January 1, 2018
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

CN (1)