Tissue microarray and digital image analysis: a methodological study with special reference to the microenvironment in Hodgkin lymphoma

Glimelius, Ingrid; Qvarnström, Fredrik; Simonsson, Martin; Ekwall, Anders; Smedby, Karin E.; Molin, Daniël; Amini, Rose‐Marie

doi:10.1111/j.1365-2559.2012.04185.x

Cited by 9 publications

(12 citation statements)

References 20 publications

(22 reference statements)

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“…According to this setting, the CD30 values, measured by digital image analysis represented the neoplastic cell burden within the individual sections. This approach is in line with the limited amount of image analysis approaches which examined Hodgkin’s lymphomas on a slide-based digital platform [19,20,24]. As next, CAIX-related immunopositivity could be determined and individual H-scores were generated using an almost identical setup.…”

Section: Discussionmentioning

confidence: 81%

Quantitative Analysis of Carbonic Anhydrase IX Uncovers Hypoxia-Related Functional Differences in Classical Hodgkin Lymphoma Subtypes

Matolay

Beke

Gyurkovics

et al. 2019

IJMS

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Upregulation of carbonic anhydrase IX (CAIX) was found to be associated with unfavorable prognosis and resistance to treatment in a broad spectrum of malignancies, recently also in classical Hodgkin’s lymphoma (cHL). As demonstrated, variable CAIX expression in a significant number of cHL cases was associated with poor treatment response. The current study focused on the quantification CAIX immunopositivity and its relative expression compared to the total CD30+ neoplastic pool using digital image analysis. One hundred and one lymph node samples featuring cHL histology were analyzed for both CD30 and CAIX by immunohistochemistry. Whole histological slides were scanned and immunopositivity was determined as the histoscore (H-score) using the DensitoQuant software module (3DHistech Kft., Budapest, Hungary). CAIX positivity was observed in the HRS-cells of 56/101 cases (55.44%) and frequently observed in the proximity of necrotic foci. CAIX H-scores were highly variable (range: 2.16–90.36, mean 18.7 ± 18.8). Individual CAIX values were independent of the much higher CD30 values (range 3.46–151.3, mean 52.37 ± 30.74). The CAIX/CD30 index proved to be the highest in the aggressive lymphocyte-depleted (LD) subtype (CAIX/CD30: 0.876). The CAIX expression and the CAIX/CD30 relative index can be precisely determined by image analysis, and values reflect the extent of a tumor mass undergoing hypoxic-stress-related adaptation in the most aggressive forms of cHL.

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Section: Discussionmentioning

confidence: 81%

Quantitative Analysis of Carbonic Anhydrase IX Uncovers Hypoxia-Related Functional Differences in Classical Hodgkin Lymphoma Subtypes

Matolay

Beke

Gyurkovics

et al. 2019

IJMS

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“…This method has been validated when investigating markers expressed by tumour cells, 18,19 as well as surrounding cells in the tumour stroma. 14 Because some evidence exists that cells expressing IDO can suppress T-cell responses and promote tolerance, 20,21 we were interested in the combined study of IDO+ and FOXP3 cells infiltration. For the morphometric analysis, we manually differentiated epithelial IDO+ cells from dendritic IDO+ cells.…”

Section: Discussionmentioning

confidence: 99%

“…Our histopathology department has developed a computer-aided analysis of whole slide digital image derived from tissue microarray (TMA). 14 This new analysis overcomes the considerable challenges of classic methods due to tumour heterogeneity, the extreme difficulty of reproducing semi-quantitative analysis results, and the time-consuming nature of analysing whole-tissue samples. The second aim of this study was to compare IDO+ infiltration in the tissues with plasma IDO concentration, evaluated with serum kynurenine (Kyn) level and the Kyn/Trp ratio.…”

Section: Introductionmentioning

confidence: 99%

Immunological environment in colorectal cancer: a computer-aided morphometric study of whole slide digital images derived from tissue microarray

et al. 2018

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Cancer research has moved from investigating tumour cells to including analysis of the tumour microenvironment as well. The aim of this study was to assess the cellular infiltrate of colorectal cancer (CRC) using computer-aided analysis of whole slide digital image derived from tissue microarray (TMA). TMA slides from 31 CRC patients were immunostained for forkhead box protein 3 (FOXP3) and immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) at four sites: centre (C) and invasive front (F) of the tumour, proximal non-metastatic draining lymph node (N-), tumour-draining lymph node with metastasis (N+) and healthy mucosa at 10 cm from the cancer (M). We analysed the proportion of IDO+ tissue areas in the lamina propria or in the non-epithelial area of the lymph node and in epithelial cells in each site. The normal mucosa of patients operated on for benign disease was also analysed. The proportion (%) of FOXP3+ tissue area in C, F, N-, N+ and M were 2.3 ± 1.8, 2.6 ± 2.9, 6.0 ± 2.9, 14.2 ± 5.8 and 1.2 ± 0.8 (p < 0.001). The proportion (%) of IDO+ tissue area in the lamina propria of C, F, N-, N+ and M were 1.6 ± 3.1, 1.1 ± 1.3, 3.4 ± 2.5, 9.1 ± 8.5 and 6.7 ± 5.4 (p < 0.001). IDO+ tissue area in the lamina propria was not significantly different between healthy mucosa of patients with cancer than without (1.8 ± 3 vs 1.1 ± 0.95). The proportion of IDO positive tissue area in the epithelium was significantly higher in healthy mucosa of patients with cancer than without (5.4 ± 13.8 vs 2.1 ± 2.4). The FOXP3+ tissue area was increased in healthy mucosa of CRC patients in comparison with healthy mucosa of patients with colorectal resection for disease other than cancer: 1.20 ± 1.81 versus 0.81 ± 0.51 (p < 0.05). The proportion of IDO+ tissue area in lymph node (N-) was correlated with the proportion of FOXP3+ tissue area in tumour area (r = 0.44, p < 0.01). TMA technique permits simultaneous analysis of FOXP3+ and IDO+ cells at different sites including tumour, draining non-metastatic lymph node, metastatic lymph node and normal mucosa.

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“…View Crossmark data Citing articles: 2 View citing articles differences in the metabolism of the two agents: zoledronic acid retains in the skeleton for years while denosumab does not incorporate in bone [8,12,16].…”

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confidence: 99%

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confidence: 99%

Core needle biopsies for the diagnosis of diffuse large B-cell lymphoma – a great concern for research

et al. 2016

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View related articlesView Crossmark data Citing articles: 2 View citing articles differences in the metabolism of the two agents: zoledronic acid retains in the skeleton for years while denosumab does not incorporate in bone [8,12,16].Recently, a study on 1822 patients with bone metastases from multiple myeloma, breast cancer or prostate cancer compared zoledronic acid administered every three months to the standard monthly dosing. The less frequent dosing was shown to be non-inferior as the risk of SREs was similar during the three-monthly and monthly dosing of zoledronic acid. ONJ developed twice as often during the monthly as the three-monthly dosing [17]. Comprehensive data on the less intensive dosing of denosumab is lacking. REDUCE is a large phase III study currently recruiting prostate and breast cancer patients with bone metastases which randomizes patients to monthly or three-monthly dosing of denosumab.The risk of medication associated ONJ during bone-targeted therapies seems higher in clinical practice as compared to that reported in randomized trials. Our single institution case series found an 11.4% frequency of ONJ among prostate cancer patients. Only one third of the ONJ cases showed marked improvement whereas the rest caused chronic disability. ONJ is a common and often chronic complication of denosumab and zoledronic acid and more effective preventative measures are warranted. Disclosure statementLeena Vehmanen and Tapio Utriainen: scientific congress costs and lecture fees from pharmaceutical companies. Carl Blomqvist, Risto Kontio and Juho Suojanen: participation in an Amgen study project.

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Tissue microarray and digital image analysis: a methodological study with special reference to the microenvironment in Hodgkin lymphoma

Abstract: Because a high correlation was observed between TMA and WS, TMA can be utilized when evaluating cells in the tumour microenvironment. DIA appears to provide a reliable measurement method, provided that manual control of the tumour slides is conducted.

Cited by 9 publications

References 20 publications

Quantitative Analysis of Carbonic Anhydrase IX Uncovers Hypoxia-Related Functional Differences in Classical Hodgkin Lymphoma Subtypes

Quantitative Analysis of Carbonic Anhydrase IX Uncovers Hypoxia-Related Functional Differences in Classical Hodgkin Lymphoma Subtypes

Immunological environment in colorectal cancer: a computer-aided morphometric study of whole slide digital images derived from tissue microarray

Core needle biopsies for the diagnosis of diffuse large B-cell lymphoma – a great concern for research

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