Changes in mitotic rate and cell cycle fractions caused by delayed fixation

Donhuijsen, K; Schmidt, Ulrich; Hirche, H.; Beuningen, D. van; Budach, Volker

doi:10.1016/0046-8177(90)90030-9

Cited by 112 publications

(45 citation statements)

References 20 publications

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“…14,[25][26][27] In conclusion, in times when diagnostic tools permit the identification of ever smaller tumors of the breast, resulting in less cancer tissue for biofunctional and molecular analyses, 'old' morphometric parameters such as mitotic index are regaining importance and must be evaluated with rigorous interobserver quality control procedures. Grade and its components in breast cancer A Volpi et al…”

Section: Discussionmentioning

confidence: 99%

Prognostic relevance of histological grade and its components in node-negative breast cancer patients

Volpi

Bacci

Paradiso³

et al. 2004

Modern Pathology

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Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P ¼ 0.013) as well as overall survival (98, 90 and 86%, P ¼ 0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P ¼ 0.014) and overall survival (97, 87 and 85%, P ¼ 0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.

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Section: Discussionmentioning

confidence: 99%

Prognostic relevance of histological grade and its components in node-negative breast cancer patients

Volpi

Bacci

Paradiso³

et al. 2004

Modern Pathology

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“…Prompt transfer of postmortem specimens into fixative is critical. 149 Delayed fixation can decrease the mitotic index, with up to 40% reduction when fixation is delayed more than 12 hours; 70,82,151 this reduction in mitotic index can alter tumor grade. 356 Likewise, with biopsy specimens, once the tissue is removed from the living body, biochemical alterations include adenosine triphosphate (ATP) depletion and disruption of sodium, potassium, and calcium gradients.…”

Section: Fixationmentioning

confidence: 99%

When Tissue Antigens and Antibodies Get Along

2013

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Once focused mainly on the characterization of neoplasms, immunohistochemistry (IHC) today is used in the investigation of a broad range of disease processes with applications in diagnosis, prognostication, therapeutic decisions to tailor treatment to an individual patient, and investigations into the pathogenesis of disease. This review addresses the technical aspects of immunohistochemistry (and, to a lesser extent, immunocytochemistry) with attention to the antigen-antibody reaction, optimal fixation techniques, tissue processing considerations, antigen retrieval methods, detection systems, selection and use of an autostainer, standardization and validation of IHC tests, preparation of proper tissue and reagent controls, tissue microarrays and other high-throughput systems, quality assurance/quality control measures, interpretation of the IHC reaction, and reporting of results. It is now more important than ever, with these sophisticated applications, to standardize the entire IHC process from tissue collection through interpretation and reporting to minimize variability among laboratories and to facilitate quantification and interlaboratory comparison of IHC results.

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“…Although several methods have been used to determine the tumor proliferative fraction in the research setting, the only practical methods used in the pathology laboratory were Ki-67 and mitotic count (2). Mitotic count was long used by surgical pathologists as diagnostic and prognostic criteria in malignant tumors, but is subjective, has poor reproducibility and is dependent on laboratory techniques (3)(4)(5).…”

Section: Ki-67 As a Proliferative Markermentioning

confidence: 99%

Ki-67 expression in pulmonary tumors

Chirieac

2016

Transl. Lung Cancer Res.

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Changes in mitotic rate and cell cycle fractions caused by delayed fixation

Cited by 112 publications

References 20 publications

Prognostic relevance of histological grade and its components in node-negative breast cancer patients

Prognostic relevance of histological grade and its components in node-negative breast cancer patients

When Tissue Antigens and Antibodies Get Along

Ki-67 expression in pulmonary tumors

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