Comparison of the methods for measuring the Ki-67 labeling index in adrenocortical carcinoma: manual versus digital image analysis

Yamazaki, Yuto; Nakamura, Yasuhiro; Shibahara, Yukiko; Konosu-Fukaya, Sachiko; Sato, Naomi; Kubota-Nakayama, Fumie; Osuga, Yutaka; Baba, Satoshi; Midorikawa, Sanae; Morimoto, Ryo; Satoh, Fumitoshi; Sasano, Hironobu

doi:10.1016/j.humpath.2015.10.017

Cited by 30 publications

(18 citation statements)

References 21 publications

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“…In all cohorts in this multicentre study, the high agreement of distinction between low, intermediate, and high density of cells was confirmed. Many new automatic methods were described and a concordance with manual methods was shown [ 24 – 27 ]. Our study also confirmed this concordance.…”

Section: Discussionmentioning

confidence: 99%

Elevated Foxp3/CD8 Ratio in Lung Adenocarcinoma Metastatic Lymph Nodes Resected by Transcervical Extended Mediastinal Lymphadenectomy

Domagała‐Kulawik

Kwiecień

Pankowski

et al. 2017

BioMed Research International

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A balance between tumor invasion and immune defence system is widely investigated. Objective. The aim of this study was to evaluate lymphocyte phenotype in lymph nodes (LNs) of patients with lung cancer in relation to the presence of metastases. Methods. We investigated 364 LNs resected by transcervical extended mediastinal lymphadenectomy (TEMLA) of 49 patients with squamous cell carcinoma (SCC) or adenocarcinoma (AD) with (A) and without metastases (B). Expression of CD4, CD8, CD25, CTLA-4, and Foxp3 was assessed by immunohistochemical staining. Results. We observed a strong nuclear staining for Foxp3 in lymphocytes and cancer cells and strong membranous/cytoplasmatic reaction for CD4 and CD8, but low for CD25 and CTLA-4. There were significantly higher proportions of CD8+ cells in AD (B) versus AD (A) LNs (80% versus 52.5%, p < 0.05). The Foxp3/CD8 ratio was higher in AD (A) versus AD (B) LNs (0.4 versus 0.25, p < 0.05). No significant differences in the cell markers expression in SCC LNs were found. Conclusion. Significant differences in lymphocyte phenotype in AD may indicate an exceptional biology of this type of lung cancer. TEMLA resected LNs may serve as valuable samples for evaluation of immune status in lung cancer patients.

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Section: Discussionmentioning

confidence: 99%

Elevated Foxp3/CD8 Ratio in Lung Adenocarcinoma Metastatic Lymph Nodes Resected by Transcervical Extended Mediastinal Lymphadenectomy

Domagała‐Kulawik

Kwiecień

Pankowski

et al. 2017

BioMed Research International

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“…Overall, the Ki67 index was superior to mitotic count (irrespective of method of estimation) in the prognostic stratification of adrenocortical carcinomas for overall survival . A study comparing methods for measuring Ki67 proliferation indices in 18 adrenocortical carcinomas by seven pathologists using microscopes (manual analysis) and digital image analysis and by selecting ‘hotspots’ and ‘average’ indices found that digital image analysis significantly correlated with manual analysis in hotspots but not in the average fields . The hotspots had significantly and consistently higher Ki67 indices than the average areas by both methods .…”

Section: Proliferative Activitymentioning

confidence: 99%

“…A study comparing methods for measuring Ki67 proliferation indices in 18 adrenocortical carcinomas by seven pathologists using microscopes (manual analysis) and digital image analysis and by selecting ‘hotspots’ and ‘average’ indices found that digital image analysis significantly correlated with manual analysis in hotspots but not in the average fields . The hotspots had significantly and consistently higher Ki67 indices than the average areas by both methods . Patients with carcinomas with Ki67 indices <10% had significantly better outcomes than those with Ki67 indices >10% by manual analysis in hotspots.…”

Section: Proliferative Activitymentioning

confidence: 99%

“…Patients with carcinomas with Ki67 indices <10% had significantly better outcomes than those with Ki67 indices >10% by manual analysis in hotspots. Overall, the Ki67 index in hotspots measured by manual analysis best reflected the clinical and pathological features of the tumours . The authors suggested that digital image analysis needs improvement, including correction of its overestimation of the value by counting of non‐tumour cells and nuclear segmentation in areas of high cell density .…”

Section: Proliferative Activitymentioning

confidence: 99%

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Challenges in surgical pathology of adrenocortical tumours

Erickson

2017

Histopathology

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Adrenocortical carcinomas are rare tumours that can be diagnostically challenging. Numerous multiparametric scoring systems and diagnostic algorithms have been proposed to differentiate adrenocortical adenoma from adrenocortical carcinoma. Adrenocortical neoplasms must also be differentiated from other primary adrenal tumours, such as phaeochromocytoma and unusual primary adrenal tumours, as well as metastases to the adrenal gland. Myxoid, oncocytic and sarcomatoid variants of adrenocortical tumours must be recognized so that they are not confused with other tumours. The diagnostic criteria for oncocytic adrenocortical carcinoma are different from those for conventional adrenocortical carcinomas. Adrenocortical neoplasms in children are particularly challenging to diagnose, as histological features of malignancy in adrenocortical neoplasms in adults may not be associated with aggressive disease in the tumours of children. Recent histological and immunohistochemical studies and more comprehensive and integrated genomic characterizations continue to advance our understanding of the tumorigenesis of these aggressive neoplasms, and may provide additional diagnostic and prognostic utility and guide the development of therapeutic targets.

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“…The Ki-67 labeling index (LI) was determined according to the counting method de ned by WHO in 2017 [25], using the HALO image analysis software (Indica Laboratories, Corrales, New Mexico, USA) with the CytoNuclear IHC v1.6 algorithm module. We performed imaging analysis, according to a previously reported study using this digital data to obtain the Ki-67 LI [26]. We analyzed nuclear immunoreactivity according to the gradients of brown color (3,3-diaminobenzidine [DAB]) spectrum intensity.…”

Section: Evaluation Of Ki-67 Labeling Indexmentioning

confidence: 99%

O 6-Methylguanine DNA Methyltransferase and Glucose Transporter 2 in Foregut and Hindgut Gastrointestinal Neuroendocrine Neoplasms

Watanabe

Yamazaki

Fujishima

et al. 2020

Preprint

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Background: Streptozocin (STZ) is used for treating both pancreatic (PanNET) and gastrointestinal (GI-NET) neuroendocrine tumors but its therapeutic efficacy is relatively low in GI-NETs. Therefore, it has become pivotal to select GI-NET patients who could benefit from STZ treatment. STZ is transported via the glucose transporter 2 (GLUT2) into the cells and the loss of O6-methylguanine DNA methyltransferase (MGMT) also increases its therapeutic efficacy. Therefore, GLUT2 high and MGMT low status could be the surrogate markers of STZ. Methods: In this study, we examined the MGMT and GLUT2 status in gastrointestinal neuroendocrine neoplasm (NEN). We studied 84 NEN cases: 33 foregut and 37 hindgut GI-NETs and 14 gastrointestinal neuroendocrine carcinomas (GI-NECs). Results: In GI-NETs, MGMT scores of ≥2 and ≥3 were 77% (54/70) and 56% (39/70), respectively, and GLUT2 scores of ≥4 and ≥6 were 30% (21/70) and 4.3% (3/70), respectively. Methylation-specific polymerase chain reaction revealed that MGMT promoter methylation was detected only in 2/14 GI-NECs but in none of GI-NETs. GLUT2 (GLUT2 score) and MGMT immunoreactivity (MGMT and H-scores) were both significantly correlated with Ki-67 labeling index (GLUT2 score: P = 0.0045, ρ = -0.4570; MGMT score: P = 0.0064, ρ = -0.4399; H-score: P = 0.0110, ρ = -0.4135) and MGMT immunoreactivity were both significantly correlated with GLUT2 immunoreactivity (MGMT score: P = 0.0198; H-score, P = 0.0004, ρ = 0.5483) in hindgut NETs, but not in foregut NETs. However, discrepancies from the above correlation between GLUT2 and MGMT immunoreactivity were detected in several GI-NET cases which could be potential candidates for STZ therapy. Conclusion: The evaluation of MGMT and GLUT2 status could provide an important information in planning STZ therapy in GI-NET patients.

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Comparison of the methods for measuring the Ki-67 labeling index in adrenocortical carcinoma: manual versus digital image analysis

Cited by 30 publications

References 21 publications

Elevated Foxp3/CD8 Ratio in Lung Adenocarcinoma Metastatic Lymph Nodes Resected by Transcervical Extended Mediastinal Lymphadenectomy

Elevated Foxp3/CD8 Ratio in Lung Adenocarcinoma Metastatic Lymph Nodes Resected by Transcervical Extended Mediastinal Lymphadenectomy

Challenges in surgical pathology of adrenocortical tumours

O 6-Methylguanine DNA Methyltransferase and Glucose Transporter 2 in Foregut and Hindgut Gastrointestinal Neuroendocrine Neoplasms

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