Monoclonal antibodies against recombinant parts of the Ki‐67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave‐processed formalin‐fixed paraffin sections

Cattoretti, Giorgio; Becker, M. H. G.; Key, Göran; Duchrow, M.; Schlüter, Carsten; Galle, J.; Gerdes, Johannes

doi:10.1002/path.1711680404

Cited by 1,377 publications

(720 citation statements)

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“…In the present study, we report the percentage of apoptotic cells in different histotypes of thyroid tumours. In the same tumours, we also evaluate the proliferative activity by using the MIB-1 antibody generated against recombinant parts of the Ki-67 antigen, which is present in GI, S, G2 and M phases (Cattoretti et al, 1992). The apoptotic fraction was 0.2 in well-differentiated papillary thyroid carcinomas as well as in poorly differentiated carcinomas, 0.6 in medullary carcinoma and 1.4 in undifferentiated tumours.…”

Section: Discussionmentioning

confidence: 99%

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Apoptosis and proliferation in thyroid carcinoma: correlation with bcl-2 and p53 protein expression

Basolo

Pollina²,

Fontanini³

et al. 1997

Br J Cancer

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Summary The aim of this study was to determine the apoptotic cell death in 92 thyroid carcinomas of different histotypes (42 papillary, PTC; 12 poorly differentiated, PDC; 21 undifferentiated, UC; and 17 medullary, MC) by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL). Apoptotic index (Al, evaluated as a percentage of TUNEL-positive cells of neoplastic cells) was calculated in each tumour. The Al was very low in all subtypes of thyroid carcinoma, ranging from a median value of 0.2 in PTC to 1.4 in UC. The proliferative activity was determined by immunohistochemistry using monoclonal antibody, MIB-1. The percentage of proliferating cells was significantly different among the histotypes, increasing with tumour aggressiveness (from the mean value of 3.1 for PTC to 5.6 for PDC and 51.8 for UC). In addition, the ratio between proliferative activity and apoptosis was significantly higher in UC than in the other histotypes. The expression of bcl-2 and p53 protein (important in the modulation of cell death) was correlated (bcl-2, inverse correlation, r2 = 0.1, P= 0.04; p53, direct correlation, r2= 0.11, P= 0.02) with apoptotic index in PTC.Keywords: apoptosis p53; bcl-2; thyroid cancer Cell numbers are regulated by a balance between proliferation, growth arrest and programmed cell death (apoptosis, PCD). Until recently, the majority of the studies on oncogenesis have focused on the regulation of cell proliferation. The finding that alterations of negative growth control, including growth arrest and PCD, play a key role in the development of human cancer has been demonstrated by the explosion of reports in this field (Barr and Tomei, 1994; Canman and Kastan, 1995;Katsikis and Leben, 1995;Salomon and Diaz-Cano, 1995; Stauton and Gaffeney, 1995). PCD is an active cellular process involved in a variety of physiological events in which rapid elimination of unwanted cells must occur. Its importance in the turnover of self-renewing tissues, morphogenesis, embryonic development, maturation of cells of the immune system, as well as in the development of cancer and other pathologies, is increasingly being recognized (Chandler et al, 1994; Cotman and Anderson, 1995;Isner et al, 1995;Osborne, 1995). Apoptotic cells can be identified both by nuclear morphology and by techniques that detect fragmentated DNA. The latter methodology could be applied for the in situ visualization of apoptosis by specific labelling of DNA fragmentation. By using Gavrieli's method (Gavrieli et al, 1992), apoptosis can be detected at singlecell level in formalin-fixed, paraffin-embedded tissue sections, thereby allowing the study of retrospective cases.In the present study, we analysed apoptosis in thyroid carcinoma, focusing on its association with the proliferation rate of the tumours themselves. In addition, since apoptosis can be regulated by the p53 tumour-suppressor gene and by bcl-2, we analysed the p53 and bcl-2 expression on the tumour. WHO (Hedinger, 1988) and subsequent updating (Sakamoto et ...

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Section: Discussionmentioning

confidence: 99%

“…Briefly, dewaxed sections were treated with 0.3% hydrogen peroxidase in methanol for 30 min to block the endogenous peroxidase. In order to unmask the p53 and Ki-67 epitopes, we microwaved the sections in 10 mm citrate buffer, pH 6.0 (Cattoretti et al, 1992 …”

Section: Immunohistochemistrymentioning

confidence: 99%

Apoptosis and proliferation in thyroid carcinoma: correlation with bcl-2 and p53 protein expression

Basolo

Pollina²,

Fontanini³

et al. 1997

Br J Cancer

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“…(In immunoblotting it recognizes the major human cyclin E-encoded proteins as three bands including a doublet at around 50 kDa and a single band at 42 kDa.) MIB-1 mouse monoclonal antibody against the Ki-67 antigen (Cattoretti et al, 1992) (The Binding Site); polyclonal rabbit anti p53 antiserum (CM1) from Novo Castra. All secondary reagents were from Dako UK.…”

Section: Antibodiesmentioning

confidence: 99%

Lack of cyclin E immunoreactivity in non-malignant breast and association with proliferation in breast cancer

Scott

Walker²

1997

Br J Cancer

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Summary Cyclin E is a G, cyclin that is essential for the transition from G, to S phase in the cell cycle. Alterations to cyclin E expression or regulation could be important in tumorigenesis. Previous immunohistochemical and immunoblotting studies have investigated the expression of cyclin E in breast carcinomas. In this study, cyclin E has been investigated in a range of non-malignant and malignant breasj using immunohistochemistry. Normal and benign tissue from pre-and post-menopausal women (39 cases), non-involved tissue from cancercontaining breasts (47 cases), ductal carcinoma in situ (22 cases) and invasive breast carcinomas (109 cases) have been examined. There was no reactivity in any of the non-malignant breast. Only one ductal carcinoma in situ contained more than 5% reactive cells. A total of 28% of invasive carcinomas had > 5% of reactive cells (range 0-88% positive cells, mean 12.59%, median 1.0%). A significant association was found with poorer differentiation (P < 0.001), high MIBl index (P < 0.001), lack of oestrogen receptor (0.05 > P > 0.025) and the presence of p53 protein (0.05 > P > 0.025). Virtually all cases with cyclin E and p53 were poorly differentiated. The presence of cyclin E is therefore only found in breast malignancies and is associated with more aggressive features, including high proliferation.Keywords: breast cancer; normal breast; cyclin E; immunohistochemistry The cell cycle is the ordered set of processes by which one cell grows and divides into two daughter cells (Murray and Hunt, 1993). This process is the basis for the continuity of life and underlies the complexity of growth, renewal and repair active in all multicellular organisms. Over the last two decades, our knowledge of the complex machinery which regulates the cell cycle has dramatically increased; in particular, the links between oncogenesis and the cell cycle components.Transition through the different phases of the cell cycle is achieved by the formation and inhibition of enzymatically active protein complexes composed of cyclins and their regulatory subunits, the cyclin-dependent kinases (CDKs) (Hunter and Pines, 1994). Among the GI cyclins, cyclin E appears to be essential for the G1/S transition as inhibition of the function of cyclin E and its related cyclin-dependent kinase, cdk2, prevents mammalian cells from entering S phase (Pagano et al, 1993;Tsai et al, 1993;Ohtsubo et al, 1995). The cyclin E protein level peaks in late GI (Dulic et al, 1992;Koff et al, 1992), which correlates with the phosphorylation of pRb, the product of the retinoblastoma tumour suppressor gene. pRb plays a critical role in the cell cycle as its phosphorylation leads to the liberation of certain bound transcription factors essential for DNA synthesis (Nevins, 1992;La Thangue, 1994). The importance of cyclin E in the cell cycle suggests that it is a potential target in tumorigenesis.In the search for newer markers which can provide information about breast cancer behaviour, attention has recently focused on the role of cyclin E. P...

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“…The MIB-1 labeling index was used to assess the tumor proliferation and invasiveness (8). RCAS1 (receptor-binding cancer antigen expressed on SiSO cells), a membrane molecule expressed on human cancer cells, was isolated from 22-1-1.…”

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confidence: 99%

Immunohistochemical Analysis of RCAS1 in Human Pituitary Adenomas

et al. 2001

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Monoclonal antibodies against recombinant parts of the Ki‐67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave‐processed formalin‐fixed paraffin sections

Cited by 1,377 publications

References 7 publications

Apoptosis and proliferation in thyroid carcinoma: correlation with bcl-2 and p53 protein expression

Apoptosis and proliferation in thyroid carcinoma: correlation with bcl-2 and p53 protein expression

Lack of cyclin E immunoreactivity in non-malignant breast and association with proliferation in breast cancer

Immunohistochemical Analysis of RCAS1 in Human Pituitary Adenomas

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