Objective analysis of cancer stem cell marker expression using immunohistochemistry

Miller, Tim; McCoy, Melanie J.; Hemmings, Chris; Bulsara, Max; Iacopetta, Barry; Platell, Cameron

doi:10.1016/j.pathol.2016.09.063

Cited by 10 publications

(12 citation statements)

References 14 publications

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“…One of the difficulties of research on stem cell markers is that the evaluation method varies widely for different studies and the results obtained can be inconsistent. 11 We used 5% as a cut-off level for LGR5 based on a previous study on colorectal cancer using the same antibody. 13 In order to ensure maximum credibility of the results, we used pathological sections which included not only the invasive front but also the normal colon tissue whenever possible, so that the normal part can be used as an internal control.…”

Section: Discussionmentioning

confidence: 99%

LGR5 expression predicts peritoneal recurrence after curative resection of primary colon cancer

et al. 2019

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BACKGROUND: The aim of this study was to clarify whether a cancer stem cell marker could be an indicator of post-operative peritoneal recurrence of colon cancer. METHODS: Expression of four putative markers (CD133, CD44 variant 6, aldehyde dehydrogenase-1 and leucine-rich repeating G-protein-coupled receptor-5 (LGR5)) was evaluated immunohistochemically in primary tumour samples from 292 patients who underwent curative resection for non-metastasised pT4 colon cancer at the University of Tokyo Hospital between 1997 and 2015. RESULTS: Peritoneal recurrence was significantly higher in LGR5-negative cases (5-year cumulative incidence: 27.5% vs. 14.4%, p = 0.037). Multivariable analysis confirmed that negative LGR5 expression was an independent risk factor for peritoneal recurrence (hazard ratio (HR) 2.79, p = 0.005) in addition to poor differentiation, positive lymph node metastasis, preoperative carcinoembryonic antigen > 5 ng/mL and anastomotic leakage. The addition of LGR5 significantly improved the predictive value of the multivariable model (net reclassification improvement: 0.186, p = 0.028: integrated discrimination improvement: 0.047, p = 0.008). CONCLUSIONS: Negative LGR5 expression was a significant predictor of peritoneal recurrence in patients with pT4 colon cancer. Therefore, LGR5 might be a promising biomarker to identify patients at high risk of post-operative peritoneal metastasis.

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Section: Discussionmentioning

confidence: 99%

LGR5 expression predicts peritoneal recurrence after curative resection of primary colon cancer

et al. 2019

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“…Multiple pathologists should score a set of cases to investigate how well the new scoring method is reproducible. Digital imaging analysis showed good results in liver fibrosis [ 25 ], in assessing digital ulcers in patients with systemic sclerosis [ 1 ], and in analysis of cancer stem cell marker expression [ 20 ]. This type of tissue analysis might be a good alternative for scoring of MoM periprosthetic tissue.…”

Section: Discussionmentioning

confidence: 99%

Current Pathologic Scoring Systems for Metal-on-metal THA Revisions are not Reproducible

Smeekes

Cleven

Wal

et al. 2017

Clinical Orthopaedics &Amp; Related Research

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BackgroundThe aseptic lymphocyte vasculitis-associated lesion (ALVAL) score and the modified Oxford ALVAL score are frequently used scoring methods to evaluate the morphologic features of periprosthetic tissues around metal-on-metal (MoM) hip implants. Except for the initial studies of these two morphology scoring methods, to our knowledge, no other studies have reported on intraclass correlation coefficient (ICC) values for interobserver reliability of these scoring methods.Questions/purposesAre the ALVAL and Oxford ALVAL scores reproducible?MethodsThe periprosthetic tissue of 37 revisions of 36 patients with failed MoM THAs were independently scored by three experienced pathologists using ALVAL and Oxford ALVAL scoring methods. All patients were included who underwent revision surgery in our hospital until January 2013, with a large-head MoM prosthesis and also met the criteria: blood serum cobalt levels, available MRI scan, and intraarticular cobalt levels. The population included 26 patients with pseudotumors diagnosed by two radiologists using the method described by Matthies et al. The ALVAL describes morphologic features of the synovial lining, tissue organization, and inflammatory cell infiltrate in periprosthetic tissues. The Oxford-ALVAL score uses a semiquantitative measure of the immune response which should be easier to score.ResultsThe ALVAL score showed an ICC of 0.38 (95% CI, 0.18–0.58) (fair) for the sum score and this improved up to 0.50 (95% CI, 0.31–0.68) (moderate) using the modified Oxford ALVAL score. The individual parameters of the ALVAL score showed an ICC for the scoring of inflammatory infiltrate of 0.37 (95% CI, 0.17–0.57), an ICC of 0.32 (95% CI, 0.12–0.53) for the scoring of tissue organization, and an ICC of 0.14 (95% CI, −0.04 to 0.34) for synovial lining.ConclusionsScoring morphologic features of MoM tissue is not reproducible using the ALVAL score or the Oxford ALVAL score. This may reflect heterogeneous morphologic features in tumor tissue and between different tumor tissue samples that cannot be reliably quantified by pathologists using the parameters of these two scoring methods. An alternative, simplified scoring system should be developed to improve the interrater agreement.Level of EvidenceLevel III, diagnostic study.Electronic supplementary materialThe online version of this article (doi:10.1007/s11999-017-5432-4) contains supplementary material, which is available to authorized users.

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“…Sections were scanned on a high-resolution scanner (Aperio Scanscope XT; Leica Biosystems, North Ryde, New South Wales, Australia) and manually annotated to ensure the tissue analysed matched the histology type to which samples had been assigned. Image analysis software was then used to quantify marker expression as previously described (Aperio Imagescope version 11) ( 35 , 36 ). Expression of PD-L1 by immune and tumour cells was included in the analysis.…”

Section: Methodsmentioning

confidence: 99%

Expression of PD‑L1 and SOX2 during rectal tumourigenesis: Potential mechanisms for immune escape and tumour cell invasion

et al. 2018

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Immunoediting is defined as a process whereby tumour cells develop the capacity to escape immune cell recognition. Accumulating evidence suggests that cancer stem-like cells (CSCs) have an enhanced capacity to interact with the immune system. The expression of CSCs and immune cell-associated markers has been demonstrated to change with disease progression from premalignant lesions to invasive cancer. The present study investigated the expression of putative CSC and immune cell-associated markers in different stages of progression from dysplasia to invasive malignancy in rectal lesions. Immunohistochemistry was performed for the CSC markers Lgr5 and SOX2 and the immune-associated markers CD8, Foxp3 and PD-L1 in 79 cases of endoscopically-excised rectal lesions, ranging from low grade adenoma (LG) to invasive adenocarcinoma (AdCa). CD8 and Foxp3 expression significantly increased with advances in disease progression [AdCa vs. LG: Odds ratio (OR) 4.33; 95% confidence interval (CI), 1.16–16.3; P=0.03 and OR, 40.5; 95% CI, 6.57–249.6; P<0.0001, respectively]. An increase in programmed death-ligand 1 (PD-L1) expression was also observed with disease progression (OR, 24.0; 95% CI, 4.23–136.2; P=0.0003). The expression of sex determining region Y-box 2 (SOX2) did not correlate with disease progression, although an elevated expression was observed in areas with high grade dysplasia. Increased PD-L1 expression may be a mechanism by which tumour cells evade immune recognition, facilitating tumour cell invasion in rectal cancer. The expression of SOX2 in areas with high grade dysplasia may indicate the de-differentiation of tumour cells, or the activation of migration pathways for invasion.

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Objective analysis of cancer stem cell marker expression using immunohistochemistry

Cited by 10 publications

References 14 publications

LGR5 expression predicts peritoneal recurrence after curative resection of primary colon cancer

LGR5 expression predicts peritoneal recurrence after curative resection of primary colon cancer

Current Pathologic Scoring Systems for Metal-on-metal THA Revisions are not Reproducible

Expression of PD‑L1 and SOX2 during rectal tumourigenesis: Potential mechanisms for immune escape and tumour cell invasion

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