Poor agreement in recognition of abnormal mitoses: requirement for standardized and robust definitions

Barry, Maurice; Sinha, Sanjay; Leader, M.; Kay, Elaine W.

doi:10.1046/j.1365-2559.2001.01034.x

Cited by 23 publications

(12 citation statements)

References 19 publications

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“…45 Concerns of interobserver variability and reproducibility of nuclear grading have been answered in earlier publications by utilizing well-defined criteria, 24,28 which were used in our study.…”

Section: Discussionmentioning

confidence: 99%

A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma

et al. 2012

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Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant pleural mesothelioma in which only staging is prognostic for survival. In this study of epithelioid diffuse malignant pleural mesothelioma, we investigate the prognostic utility of nuclear features. The slides of 232 epithelioid diffuse malignant pleural mesothelioma patients (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed for the following seven nuclear features: nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, and atypical mitoses. MIB-1 immunohistochemistry was performed using tissue microarray, and MIB-1 labeling index was recorded as the percentage of positive tumor cells. Median overall survival of all patients was 16 months and correlated with nuclear atypia (P<0.001), chromatin pattern (P=0.031), prominence of nucleoli (P<0.001), mitotic count (P<0.001), and atypical mitoses (P<0.001) by univariate analysis. Multivariate analysis revealed nuclear atypia (P=0.012) and mitotic count (P<0.001) as independent prognostic factors, and these two factors were utilized to create a three-tier nuclear grade score. The resulting nuclear grade stratified patients into three distinct prognostic groups: grade I (n=107, median overall survival = 28 months), grade II (n=91, 14 months), and grade III (n=34, 5 months). Not only was nuclear grade an independent predictor of overall survival (P<0.001), but it was also a stronger discriminator of survival than all currently available factors. Furthermore, nuclear grade was associated with time to recurrence (P=0.004) in patients who underwent complete surgical resection (n=159). MIB-1 labeling index correlated with mitotic count (P<0.001) and nuclear atypia (P=0.037) and stratified overall survival (P<0.001) and time to recurrence (P=0.048), confirming the prognostic value of the nuclear grade. Nuclear grading in epithelioid mesothelioma provides a simple, practical, and cost-effective prognostic tool that better stratifies clinical outcome and time to recurrence than currently available clinicopathologic factors.

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Section: Discussionmentioning

confidence: 99%

A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma

et al. 2012

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“…35 Therefore, standardized and robust definitions, which we have rigorously applied in this study, are necessary if prognostic significance is accorded to the findings of those factors. Another important factor is careful review of all tumor slides at an intermediate magnification (×100) to identify the areas with highest nuclear grade.…”

Section: Discussionmentioning

confidence: 99%

A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma

et al. 2012

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The IASLC/ATS/ERS has recently proposed a new lung adenocarcinoma classification. We investigated whether nuclear features can stratify prognostic subsets. Slides of 485 stage I lung adenocarcinoma patients were reviewed. We evaluated nuclear diameter, nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, prominence of nucleoli, intranuclear inclusions, mitotic count/10 high-power fields (HPF) or 2.4 mm2, and atypical mitoses. Tumors were classified into histologic subtypes according to the IASLC/ATS/ERS classification and grouped by architectural grade into low (adenocarcinoma in situ, minimally invasive adenocarcinoma or lepidic predominant), intermediate (papillary or acinar), and high (micropapillary or solid). Log-rank tests and Cox regression models evaluated the ability of clinicopathologic factors to predict recurrence-free probability. In univariate analyses, nuclear diameter (p=0.007), nuclear atypia (p=0.006), mitotic count (p<0.001), and atypical mitoses (p<0.001) were significant predictors of recurrence. The recurrence-free probability of patients with high mitotic count (≥5/10HPF: n=175) was the lowest (5-year recurrence-free probability=73%), followed by intermediate (2–4/10HPF: n=106, 80%), and low (0–1/10HPF: n=204, 91%, p<0.001). Combined architectural/mitotic grading system stratified patient outcomes (p<0.001): low grade (low architectural grade with any mitotic count and intermediate architectural grade with low mitotic count: n=201, 5-year recurrence-free probability=92%), intermediate grade (intermediate architectural grade with intermediate-high mitotic counts: n=206, 78%), and high grade (high architectural grade with any mitotic count: n=78, 68%). The advantage of adding mitotic count to architectural grade is in stratifying patients with intermediate architectural grade into two prognostically distinct categories (p=0.001). After adjusting for clinicopathologic factors including sex, stage, pleural/lymphovascular invasion, and necrosis, mitotic count was not an independent predictor of recurrence (p=0.178). However, patients with the high architectural/mitotic grade remained at significantly increased risk of recurrence (high vs. low: p=0.005) after adjusting for clinical factors. We proposed this combined architectural/mitotic grade for lung adenocarcinoma as a practical method that can be applied in routine practice.

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“…It is notable that many pathological parameters are becoming more and more standardized, however, there are no internationally accepted guidelines or criteria for a standardized and robust assessment of MI, yet (13). Indeed, although there are mitotic figures which most pathologists will agree on, there is undoubtedly a grey zone in the differentiation to apoptotic bodies or even tissue artifacts in which it depends on the single pathologist whether he or she interprets a given finding as mitotic figure or not (13). This likely explains why other interobserver studies on MI also show a poor inter-observer agreement in soft tissue tumors (14), brain tumors (15), prostate cancer (16), and breast cancer (17).…”

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confidence: 99%

What is better/reliable, mitosis counting or Ki67/MIB1 staining?

Kriegsmann¹,

Warth²

2016

Transl. Lung Cancer Res.

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Poor agreement in recognition of abnormal mitoses: requirement for standardized and robust definitions

Abstract: Agreement is poor among practising histopathologists in the recognition of abnormal mitoses. A standardized and robust definition is needed if diagnostic and prognostic significance is accorded to the finding of an abnormal mitosis in the context of neoplasia.

Cited by 23 publications

References 19 publications

A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma

A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma

A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma

What is better/reliable, mitosis counting or Ki67/MIB1 staining?

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