Rapid and prognostically valid quantification of immunohistochemical reactions by immunohistometry of the most positive tumour focus. A prospective follow-up study on breast cancer using antibodies against MIB-1, PCNA, ER, and PR

Biesterfeld, Stefan; Klüppel, Dominik; Koch, R.; Schneider, Susanne A.; G, Steinhagen; Mihalcea, Ana Maria; Schröder, Willibald

doi:10.1002/(sici)1096-9896(199805)185:1<25::aid-path40>3.0.co;2-r

Cited by 26 publications

(12 citation statements)

References 35 publications

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“…The significance of the proliferative activity of fibroblasts forming and not forming FF on lymph node metastasis (LNM) and distant-organ metastasis (DOM) in IDC patients was assessed by comparing it with well-known histological parameters, tumor cell proliferative activity, and tumor angiogenesis, which are significant prognostic factors for breast cancer patients (5)(6)(7). The present study demonstrated that the proliferative activity of the fibroblasts forming FF is an independent parameter predicting LNM and DOM by IDCs with FF and that it was also an important prognostic parameter for IDCs without FF.…”

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confidence: 99%

Highly Proliferative Fibroblasts Forming Fibrotic Focus Govern Metastasis of Invasive Ductal Carcinoma of the Breast

et al. 2001

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We have already reported that invasive ductal carcinomas (IDCs) with fibrotic focus (FF) have more aggressive characteristics than those without FF. FF is composed of a mixture of fibroblasts and various amounts of collagen fibers, suggesting that highly proliferative fibroblasts forming FF increase the malignant potential of IDCs with FF. The purpose of this study was to examine whether there is a difference of proliferative activity of fibroblasts forming and not forming FF, which plays an important role in the tumor progression of IDCs. Two hundred three consecutive cases of IDC of the breast surgically treated at the National Cancer Center Hospital East formed the basis for this study. The proliferative activity of the fibroblasts forming the FF was immunohistochemically evaluated by using mouse MIB-1 monoclonal antibody against Ki-67 antigen. We have already reported that invasive ductal carcinomas (IDCs) with fibrotic focus (FF) have more aggressive characteristics than IDCs without FF (1) and that the former are associated with significantly poorer survival course in short-and long-term survival periods than the latter (2, 3). We also found that IDCs with FF exhibit significantly greater tumor angiogenesis and higher tumor cell proliferative activity and that the presence of FF is an independent prognostic parameter for IDC patients (4). These findings indicate that the presence of FF in IDCs is a very important histological parameter for predicting the outcome of patients with IDC of the breast. FF is composed of a mixture of fibroblasts and various amounts of collagen fibers, and they occupy almost the entire center of the IDC. In routine examination, mitotic figures of fibroblasts forming FF as well as those of the tumor cells are seen in some areas within FF. This suggests that highly proliferative fibroblasts make up FF and heighten the malignant potential of IDCs having FF.The purposes of this study were to determine whether there are biological characteristic differences between fibroblasts forming and not forming FF by evaluating their proliferative activity and also whether their proliferative activity plays a important role in tumor progression of IDC. The significance of the proliferative activity of fibroblasts forming and not forming FF on lymph node metastasis (LNM) and distant-organ metastasis (DOM) in IDC patients was assessed by comparing it with well-known histological parameters, tumor cell

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confidence: 99%

Highly Proliferative Fibroblasts Forming Fibrotic Focus Govern Metastasis of Invasive Ductal Carcinoma of the Breast

et al. 2001

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“…Thereafter, a consensus group consisting of five persons (three pathologists and two technicians), all with considerable experience of IHC, assessed all the slides at a multiheaded microscope without previous knowledge of the results of the other 22 pathologists. The entire slides were assessed, except in cases with variations in receptor staining owing either to tumor heterogeneity or to staining properties where hot-spots were assessed (18). The consensus assessment is used hereafter as the reference result and, furthermore, it was used for exclusion of cases not representative of breast cancer, see below.…”

Section: Methodsmentioning

confidence: 99%

Estrogen and Progesterone Receptor Assay in Paraffin-Embedded Breast Cancer

Chebil¹,

Bendahl²,

Fernö³

2003

Acta Oncologica

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“…Diaminobenzidine (DAB) was used as a chromogen. For immunohistometry, a TV image analysis system, CM-2 (Hund, Wetzlar, Germany), which has been explained in detail previously [4], was used. Measurements were performed using a 20× objective magnification (numerical aperture 0.40), investigating the tumor representatively in a meandering way and sampling both peripheral and central tumor areas.…”

Section: Mib-1 Analysismentioning

confidence: 99%

“…The immunohistochemical analysis of the MIB-1 or proliferating cell nuclear antigen (PCNA) expression revealed prognostic validity in different tumor entities [10,11,12,20,24,26,29,41,42], including carcinoma of the breast [1,4,38]. As recently reviewed, also the analysis of the silver-stainable nucleolar organizer regions (AgNORs) has been frequently found to be prognostically useful [35].…”

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confidence: 99%

Improvement of breast cancer prognostication using cell kinetic-based silver-stainable nucleolar organizer region quantification of the MIB-1 positive tumor cell compartment

Biesterfeld¹,

Farokhzad²,

Klüppel³

et al. 2001

Virchows Arch

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Recently, it was stated that the proliferative activity (P) of a cell population could be indirectly calculated by multiplying the MIB-1 immunopositivity and silver-stainable nucleolar organizer region (AgNOR) features extracted exclusively in MIB-1 positive (pos.) nuclei: P=MIB-1 x AgNOR(MIB-1pos.). To study the prognostic significance of this hypothesis, MIB- immunohistochemistry and AgNOR staining were applied on a series of 89 cases of breast cancer with an 8-year follow-up period. The mean MIB-1 immunopositivity (MIB-1mean) was evaluated immunohistometrically on paraffin sections using a TV image analysis system CM-2 (Hund, Wetzlar, Germany). Later, a combined MIB-1/AgNOR staining was applied and evaluated using a TV image analysis system AMBA (IBSB, Berlin, Germany). The AgNOR features of 150 randomly chosen tumor nuclei were investigated, irrespective of their MIB-1 status (AgNOR count, AgNOR area). Later, a second measurement was performed on 100 MIB-1 positive tumor nuclei exclusively (AgNOR countMIB-1pos., AgNOR areaMIB-1pos.). AgNOR count and AgNOR countMIB-1pos. showed a different data distribution [2.7+/-0.7 (mean+/-SD) vs 3.9+/-1.1; r=0.315, P=0.014]. Similar results were obtained for AgNOR area and AgNOR areaMIB-1pos. (5.1+/-2.1 microm2 vs 7.5+/-2.4 microm2; r=0.501, P<0.001). Kaplan-Meier survival curves revealed significant differences for MIB-1mean (P=0.0018) and AgNOR areaMIB-1pos. (P=0.0340). In Cox models, both parameters provided independent prognostic information. Using their combination, the P, three groups of patients with statistically different survival could be separated (P=0.0014). Thus, the combination of MIB-1-immunopositivity and AgNOR measurements in MIB-1 positive nuclei appears to be more useful in breast cancer prognosis than the exclusive application of one of the two methods. By this combined application, probably effects of tumor biology are represented more precisely.

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Rapid and prognostically valid quantification of immunohistochemical reactions by immunohistometry of the most positive tumour focus. A prospective follow-up study on breast cancer using antibodies against MIB-1, PCNA, ER, and PR

Cited by 26 publications

References 35 publications

Highly Proliferative Fibroblasts Forming Fibrotic Focus Govern Metastasis of Invasive Ductal Carcinoma of the Breast

Highly Proliferative Fibroblasts Forming Fibrotic Focus Govern Metastasis of Invasive Ductal Carcinoma of the Breast

Estrogen and Progesterone Receptor Assay in Paraffin-Embedded Breast Cancer

Improvement of breast cancer prognostication using cell kinetic-based silver-stainable nucleolar organizer region quantification of the MIB-1 positive tumor cell compartment

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