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

Abstract

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 ...

Potentiation of the malignant phenotype of the undifferentiated ARO thyroid cell line by insertion of thebcl-2 gene

“…In a survey of 134 tumors, Bcl-2 appeared to be particularly down-regulated in undifferentiated forms (Pollina et al, 1996). In the latter tumors, the proportion of apoptotic cells appeared to be inversely related with Bcl-2 expression and directly related to p53 over-expression (Basolo et al, 1997). This finding is in agreement with what has been observed in immortalized mammary epithelial cell lines (Lu et al, 1996) and suggests that in thyroid cells Bcl-2 may also counteract the apoptotic process.…”

Detection of human parvovirus B19 in papillary thyroid carcinoma

“…However, morphologically, necrosis is not a feature in PTC. On the contrary, PTC often shows high proliferative activity (Saiz et al, 2002) and very low apoptotic index (Basolo et al, 1997). Therefore, whether there is another explanation for the high frequency of B19 in PTC is in question.…”

Histopathological Evaluation of Apoptosis in Cancer

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