Comparison of the Manual, Semiautomatic, and Automatic Selection and Leveling of Hot Spots in Whole Slide Images for Ki-67 Quantification in Meningiomas

Background. This paper presents the study concerning hot-spot selection in the assessment of whole slide images of tissue sections collected from meningioma patients. The samples were immunohistochemically stained to determine the Ki-67/MIB-1 proliferation index used for prognosis and treatment planning.Objective. The observer performance was examined by comparing results of the proposed method of automatic hot-spot selection in whole slide images, results of traditional scoring under a microscope, and results of a pathologist’s manual hot-spot selection.Methods. The results of scoring the Ki-67 index using optical scoring under a microscope, software for Ki-67 index quantification based on hot spots selected by two pathologists (resp., once and three times), and the same software but on hot spots selected by proposed automatic methods were compared using Kendall’s tau-b statistics.Results. Results show intra- and interobserver agreement. The agreement between Ki-67 scoring with manual and automatic hot-spot selection is high, while agreement between Ki-67 index scoring results in whole slide images and traditional microscopic examination is lower.Conclusions. The agreement observed for the three scoring methods shows that automation of area selection is an effective tool in supporting physicians and in increasing the reliability of Ki-67 scoring in meningioma.

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Comparison of Manual and Digital Assessment of KI-67 in Neuroendocrine Tumors

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.274 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S125-S125

Author(s):

B S Raju ◽

M Quinton ◽

L Hassell

Keyword(s):

Image Analysis ◽

Neuroendocrine Tumors ◽

Digital Image ◽

Digital Image Analysis ◽

Hot Spot ◽

World Health ◽

Proliferation Index ◽

Digital Analysis ◽

Ki 67 ◽

Digital Assessment

Abstract Introduction/Objective Proliferative activity is an essential prognostic and treatment indicator for neuroendocrine tumors (NET). Ki-67 proliferation index, if reported by unaided microscopic estimation on hot-spot locations could lead to variability and inconsistencies. This study aims to compare the Ki-67 assessment of NETs by visual estimation versus automated digital image analysis (Roche iCoreo/Virtuoso). Methods 212 patients with Ki-67-graded GI NETs (117 G1; 61 G2; 34 G3) from 2010 to 2019 were reassessed using digital image analysis quantification of hot spot areas of at least 500 cells (average 800 cells). Revised tumor grades were assigned according to the European Neuroendocrine Tumor Society guidelines and the 2010 World Health Organization classification and compared to initially reported grade. Results We found 75% concordance for G1, with 22% of cases upgraded to G2 and 3% of cases upgraded to G3. For G2, there was 70.5% agreement, with 13.1% of cases downgraded to G1 and 16.4% upgraded to G3. For G3, there was 100% agreement, (kappa=0.64, overall). Retrospective review of discordant G3 cases revealed cases with known metastasis, small fragments of tissue, or polyps. Scanning and scoring required approximately 10 minutes per case. Conclusion Our data shows the time/effort difference of visually estimating versus automated digital analysis may lead to significant classification errors in these tumors. Although digital analysis has limitations, including tumor heterogeneity, misidentification of tumor cells, and poor immunostaining which could require manual counting by a pathologist, this rigor should be reinforced and explicitly stated to increase accuracy and reproducibility of grading.

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Predictors of invasive breast cancer or DCIS recurrence in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) ductal carcinoma in situ (DCIS) patients with and without associated invasive carcinoma (IC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e11523 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e11523-e11523 ◽

Cited By ~ 1

Author(s):

J. Picarsic ◽

A. Brufsky ◽

A. Onisko ◽

M. Chivukula

Keyword(s):

Estrogen Receptor ◽

Biological Markers ◽

Hormone Receptors ◽

Invasive Carcinoma ◽

Ductal Carcinoma ◽

Response To Therapy ◽

Proliferation Index ◽

Low Grade ◽

Ki 67 ◽

Mib 1

e11523 Background: DCIS is a heterogeneous pre-invasive carcinoma with a spectrum of clinical behavior. Patients with ER+ IC have better outcomes compared to ER- patients. FOXA1 and GATA 3 family of transcription factors have been shown to be associated with hormone receptors (ER and PR) and other variables of good prognosis with better overall and relapse-free survival rate. The specific aim of this study is to analyze the expression of these novel biological markers: FOXA1, GATA-3, with recognized markers: MIB-1(Ki-67) and HER2 /neu in DCIS patients with/without associated IC. Methods: Sixty-nine (69) cases of DCIS [(fifty two (52) cases in ER+; seventeen (17) in ER-] were retrieved from our Pathology database. The expressions of the biological markers are analyzed by using a panel of immunohistochemical stains. FOXA1, GATA 3, ER, PR are nuclear stains, a cumulative “H score” is derived based on proportionality (PS) and intensity scores (IS). A proliferation index (PI) is calculated for MIB-1 (Ki67) nuclear stain (low <10%, moderate 11–25%, high 26–50%, very high>50%). Her2/neu is scored as per guidelines for HercepTest (0, or 1+ =negative, 2+ =weakly positive, 3+ =strongly positive). Results: DCIS is categorized into low grade (LG) (nuclear grade 1 and 2), high grade (HG) (grade 3). In the HGDCIS (n=48), four (4) cases had IC after a mean of 7.75 years; three cases of recurrent DCIS after a mean 6 years. No recurrent IC or DCIS is seen in the LGDCIS (n=21) group. The results are shown in the Table . Conclusions: (1) Decreased expression of GATA 3 is observed in HGDCIS ER- group may be a contributor to higher recurrence observed in this group (14%) versus (0%) in ER+ group. (2) A strong expression of FOXA, GATA3, low Ki-67 index, absent Her 2 expression are characteristically seen in our ER+ DCIS group, as previously described in IC. 3. Comparing the response to therapy and outcome in the ER+ and ER- groups is on going. [Table: see text] No significant financial relationships to disclose.

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Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count in pulmonary carcinoids

Virchows Archiv ◽

10.1007/s00428-013-1408-2 ◽

2013 ◽

Vol 462 (5) ◽

pp. 507-513 ◽

Cited By ~ 39

Author(s):

Arne Warth ◽

◽

Ludger Fink ◽

Annette Fisseler-Eckhoff ◽

Danny Jonigk ◽

...

Keyword(s):

Interobserver Agreement ◽

Mitotic Count ◽

Proliferation Index ◽

Ki 67 ◽

Pulmonary Carcinoids

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Ki-67 (clone MIB-1) proliferation index in recurrent glial neoplasms: no prognostic significance

Surgical Neurology ◽

10.1016/s0090-3019(97)00312-1 ◽

1998 ◽

Vol 50 (6) ◽

pp. 579-585 ◽

Cited By ~ 15

Author(s):

N.Scott Litofsky ◽

T.-Christian H. Mix ◽

Stephen P. Baker ◽

Lawrence D. Recht ◽

Thomas W. Smith

Keyword(s):

Prognostic Significance ◽

Proliferation Index ◽

Ki 67 ◽

Mib 1

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Classification Model to Estimate MIB-1 (Ki 67) Proliferation Index in NSCLC Patients Evaluated With 18F-FDG-PET/CT

Anticancer Research ◽

10.21873/anticanres.14318 ◽

2020 ◽

Vol 40 (6) ◽

pp. 3355-3360

Author(s):

BARBARA PALUMBO ◽

ROSANNA CAPOZZI ◽

FRANCESCO BIANCONI ◽

MARIO LUCA FRAVOLINI ◽

SILVIA CASCIANELLI ◽

...

Keyword(s):

Fdg Pet ◽

Classification Model ◽

Proliferation Index ◽

Ki 67 ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct ◽

Nsclc Patients ◽

Mib 1

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Correlation of 11C-Methionine Combined Positron Emission and Computed Tomography and Ki-67 Proliferation Index in Pretreatment Assessment of Cerebral Gliomas

Radiology - Practice ◽

10.52560/2713-0118-2021-4-34-48 ◽

2021 ◽

pp. 34-48

Author(s):

T. Yu. Skvortsova ◽

Zh. I. Savintceva ◽

D. V. Zakhs ◽

A. F. Gurchin ◽

A. I. Kholyavin ◽

...

Keyword(s):

Computed Tomography ◽

Proliferative Activity ◽

Hot Spot ◽

Proliferation Index ◽

Low Grade ◽

Normal Brain ◽

Ki 67 ◽

Positron Emission ◽

Pet Ct ◽

Cerebral Gliomas

The purpose of the study was to explore the correlation between 11С-methionine (Met) uptake measured by combined positron emission and computed tomography (PET/CT) in newly diagnosed cerebral gliomas and tumor proliferative activity as measured by Ki-67 labeling index (Ki-67 LI).The results of PET/CT with 11С-methionine (PET-Met) of 236 adult patients with pretreated glial brain tumors were included in retrospective analysis. The final diagnosis of glioma according to WHO classification of CNS tumors (2007) was based on both histology and immunohistochemistry using Ki-67 antibodies. On PET-Met tumor-to normal brain uptake ratio (TBR) was calculated by dividing maximum Met uptake in the tumor (hot spot 10 mm in diameter) to activity concentration in the contralateral cortex. The Spearmen rank correlation test was used to analyze the relationships between TBR and Ki-67 LI.PET-Met analysis showed that TBR increases with an increase in the aggressiveness of the glial tumor. The differences of TBR values between gliomas grade II vs III and grade III vs IV were significant (p < 0,001). Among grades II-III gliomas Met uptake was significantly higher in oligodendroglial and mixed gliomas than in astrocytomas (p < 0,001), but the differences did not depend on Ki-67 LI.Correlation analysis demonstrated significant correlation between Ki-67 LI and TBR values (r = 0,49, p < 0,05, Spearman rank test). With analyzing glioma subgroups TBR values correlated with Ki-67 LI in diffuse astrocytomas (r = 0,52, p < 0,05), oligodendrogliomas (r = 0,40, p < 0,05), oligoastrocytomas (r = 0,47, p < 0,05) and in high-grade gliomas (r = 0,45, p < 0,05) but not in low-grade gliomas. Comparison between TBR value and Ki-67 LI in each glioma showed a lack of coincidence in 22 % of cases (high Met uptake but low Ki-67 LI and vice versa). The main reasons for such discrepancies were tumor molecular biology or incorrect biopsy target.Met uptake in diffuse gliomas correlates with proliferative activity which justifies the use of PET-Met for glioma grading. In case of mismatch between two biomarkers one should rely on the indicator that implies a higher aggressiveness of the glioma.

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