Bcl‐2 protein expression in carcinomas originating from the follicular epithelium of the thyroid gland

Pilotti, Silvana; Collini, Paola; Rilke, F; Cattoretti, Giorgio; Bo, Romualdo Del

doi:10.1002/path.1711720408

Cited by 122 publications

(78 citation statements)

References 27 publications

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“…In our non-neuroendocrine group, mutually exclusive staining was observed in only two tumours (cases 1 and 10) but was relatively exclusive in three others (cases 8, 12 and 13). These results mirror the inverse relationship between p53 and bcl-2 expression found in breast (Leek et al, 1994;Silvestrini et al, 1994) and thyroid (Pilotti et al, 1994) carcinoma. This may be explained by the down-regulation of bcl-2 expression by p53 via a negative response element on the bcl-2 gene (Miyashita et al, 1994a).…”

Section: Discussionsupporting

confidence: 76%

Cell proliferation, cell loss and expression of bcl-2 and p53 in human pulmonary neoplasms

Kennedy

Lamb²,

King³

et al. 1997

Br J Cancer

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Summary Immunohistochemical staining of bcl-2 and p53 proteins was compared with thymidine labelling index (TLI) and cell loss factor (0) in lung cancer. Neither bcl-2 nor p53 overexpression was associated with high cell loss but strong bcl-2 staining was associated with higher TLI. Concomitant strong p53 and bcl-2 expression, not the usual inverse relationship, plus high cell-loss factor was present in three neuroendocrine carcinomas. Other factors presumably have a role in controlling cell death in these tumours.Keywords: lung carcinoma; neuroendocrine; thymidine labelling index; cell loss factor; bcl-2; p53; apoptosis; immunohistochemistry Apoptosis is a major mechanism of tumour cell loss, itself a major determinant of tumour growth rate, and the protein products of both the p53 and bcl-2 genes have a role in this process. The functions of both these genes and their relationship to other regulatory proteins has been extensively reviewed (Lane, 1993;Piepentol and Vogelstein, 1993;Lu et al, 1996;Yang and Korsmeyer, 1996).In an earlier study (Kerr and Lamb, 1984), we derived data on cell proliferation and cell loss in 17 human lung tumours. Tumour thymidine labelling index (TLI) was measured in vitro and, using recognized methods and formulae (Collins et al, 1956; Steel 1967), a cell loss factor (0) was calculated. Cell loss factor expresses the proportion of cells being lost from a population relative to the number being added to it by mitotic activity. Thus a cell loss factor of 0.90 implies that for every 100 cells being added to a population by mitosis, 90 are lost by whatever means.In this study, we investigate the relationship between the cell proliferation/loss data in these 17 human lung tumours and their expression of the p53 and bcl-2 genes assessed immunohistochemically. MATERIALS AND METHODSThe histological classification of the tumours required revision of the original (Kerr and Lamb, 1984). 'Large-cell carcinoma with stratification' is now classified as poorly differentiated squamous carcinoma. One tumour, thought originally to be a metastatic deposit of large-cell carcinoma, now, with follow-up, fulfils criteria of a primary large-cell neuroendocrine cancer. Thirteen of the cases were typical bronchogenic carcinomas (six squamous, three adenocarcinoma, two small-cell undifferentiated, one largecell neuroendocrine and one large-cell undifferentiated carcinoma). Two were renal cell carcinoma metastases and one a primary clear cell carcinoma.Tumour thymidine labelling index (TLI) was obtained by in vitro incubation of tumour fragments with tritiated thymidine

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Section: Discussionsupporting

confidence: 76%

Cell proliferation, cell loss and expression of bcl-2 and p53 in human pulmonary neoplasms

Kennedy

Lamb²,

King³

et al. 1997

Br J Cancer

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“…The bcl-2 proto-oncogene is shown to confer resistance to apoptotic cell death (Craig, 1995) and is restricted to the long-lived progenitor cells requiring an extended life-span (Hockenbery et al, 1991). We and others (Pollina et al, 1996;Pilotti et al, 1994) have reported recently that in the thyroid, both from fetal and adult tissue, as well as in differentiated carcinomas, the bcl-2 protein is highly expressed. Conversely, the expression of the same protein is significantly reduced in undifferentiated tumours.…”

Section: Discussionmentioning

confidence: 74%

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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“…Several oncogenes or tumor suppressor genes have been shown to contribute to the malignant progression and dedifferentiation of thyroid cancer (31)(32)(33)(34)(35). The expression of bcl-2 has been observed in differentiated and poorly differentiated thyroid carcinoma and to a lesser degree in anaplastic carcinoma (31,32); p53 expression on the other hand is seen more often in poorly differentiated and anaplastic carcinoma compared to differentiated thyroid carcinoma (33)(34)(35). Mutation of the p53 gene has been found in a high percentage of anaplastic carcinomas.…”

Section: Discussionmentioning

confidence: 99%

The Role of Cell Cycle Regulatory Protein, Cyclin D1, in the Progression of Thyroid Cancer

et al. 2000

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Cell cycle progression is facilitated by cyclindependent kinases that are activated by cyclins including cyclin D1 and inactivated by cyclindependent kinase inhibitors (CDKIs) such as p27. Our previous studies have demonstrated decreased p27 expression in both papillary and more aggressive carcinomas of the thyroid compared to thyroid adenoma and almost similar level of cyclin D1 expression between thyroid adenoma and papillary carcinoma. These results indicate that CDKIs may have an important role in the carcinogenesis of the thyroid and that they probably have a limited role in malignant progression of the thyroid cancer. The role of cyclin D1 in malignant progression of thyroid carcinoma has yet to be established. We studied the expression of cyclin D1 by immunohistochemistry in 34 cases of conventional papillary carcinoma (CPC), 10 cases of minimally invasive follicular carcinoma (MIFC), and 32 cases of more aggressive thyroid carcinoma (ATC), which included 11 tall cell variants, one columnar cell variant of papillary carcinoma, seven insular carcinomas, and 13 anaplastic carcinomas. Cyclin D1 staining was classified by staining score as 0, negative; 1؉, less than 25%; 2؉, 25 to 50%; and 3؉, more than 50% tumor cells staining positive. Kruskal-Wallis oneway ANOVA and Wilcoxon Rank Sum/MannWhitney U Test was used to assess the difference in the expression of cyclin D1 between the study groups. Twenty-eight out of the 34 CPCs were cyclin D1 positive, 24 (70%) were 1؉, 3 (9%) were 2؉, and one (3%) were 3؉ positive. Seven of 10 MIFCs were cyclin D1 positive, five (71%) were 1؉, and the remaining two (29%) were 2؉ positive. On the other hand, 28 of 32 ATCs showed cyclin D1 immunostaining. Of these, three (9%) were 1؉, five (13%) were 2؉, and 20 (63%) were 3؉ positive. This study demonstrates a significant overexpression of cyclin D1 in ATC compared CPC (P < .001) and MIFC (P < .005), suggesting that the cyclin D1 expression may play a role in tumor progression and may have prognostic significance in thyroid cancer.

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Bcl‐2 protein expression in carcinomas originating from the follicular epithelium of the thyroid gland

Cited by 122 publications

References 27 publications

Cell proliferation, cell loss and expression of bcl-2 and p53 in human pulmonary neoplasms

Cell proliferation, cell loss and expression of bcl-2 and p53 in human pulmonary neoplasms

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

The Role of Cell Cycle Regulatory Protein, Cyclin D1, in the Progression of Thyroid Cancer

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