RHAMM in liver metastases of stage IV colorectal cancer with mismatch-repair proficient status correlates with tumor budding, cytotoxic T-cells and PD-1/PD-L1

Burren, Sandra; Reche, Katharina; Blank, Annika; Galván, José A.; Dawson, Heather; Berger, Martin D.; Zlobec, Inti; Lugli, Alessandro (2021). RHAMM in liver metastases of stage IV colorectal cancer with mismatch-repair proficient status correlates with tumor budding, cytotoxic T-cells and PD-1/PD-L1. Pathology, research and practice, 223, p. 153486. Elsevier 10.1016/j.prp.2021.153486

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Background: During the last decades, the management for metastatic colorectal cancer patients has improved due to novel therapeutic approaches. A mismatch-repair deficient status seems to favour a better response to checkpoint inhibitor therapy, but the question arises whether a specific subgroup of stage IV patients with mismatch-repair (MMR) proficient status should also be considered. RHAMM (Receptor for Hyaluronic Acid Mediated Motility/HAMMR/CD168) is characterized by tumor progression and immunogenicity. Therefore, the aim of this study is to determine whether RHAMM within the CRLM of MMR-proficient patients correlate with a more immunological microenvironment, represented by cytotoxic T-cells, PD-1 and PD-1.

Methods: Two patient cohorts of liver metastases from MMR colorectal cancers were included into the study (n = 81 and 76) using ngTMA® technology and immunohistochemically analyzed for RHAMM, cytotoxic T-cells (CD8+), PD-1/PD-L1, intrametastatic budding (IMB) and perimetastatic budding (PMB).

Results: RHAMM-positive IMB was linked to a higher PD-L1 expression (r = 0.32; p = 0.233 and r = 0.28; p = 0.044) in the center and periphery of the metastasis and RHAMM-positive PMB was associated with a higher expression of PD-1 (r = 0.33; p = 0.0297), and especially PD-L1 (r = 0.604; p < 0.0001 and r = 0.43; p = 0.003) in the center and periphery of the metastasis. IMB and PMB were additionally associated with a higher count of CD8+ T-cells (p < 0.0001; r = 0.58; p < 0.0001; r = 0.53).

Conclusions: The RHAMM status can be assessed in IMB/PMB either in biopsies or in resections of colorectal cancer liver metastases. A positive RHAMM status in IMB and/or PMB may be a potential indicator for a checkpoint inhibitor therapy for stage IV colorectal cancer patients with MMR proficient status.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit

UniBE Contributor:

Burren, Sandra; Blank, Annika; Galván Hernández, José Alberto; Dawson, Heather; Berger, Martin Dave; Zlobec, Inti and Lugli, Alessandro

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0344-0338

Publisher:

Elsevier

Language:

English

Submitter:

José Alberto Galván Hernández

Date Deposited:

22 Jun 2021 15:00

Last Modified:

27 Jun 2021 03:08

Publisher DOI:

10.1016/j.prp.2021.153486

PubMed ID:

34051513

BORIS DOI:

10.48350/156899

URI:

https://boris.unibe.ch/id/eprint/156899

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