De novo programmed cell death in oral cancer.

Division of Laboratory Medicine, Regional Cancer Centre, Thiruvananthapuram, Kerala State, India.
Histopathology (Impact Factor: 3.45). 04/1999; 34(3):241-9.
Source: PubMed


The importance of programmed cell death or apoptosis in the maintenance of tissue homoeostasis and the pathogenesis of oral cancer was analysed in relation to apoptosis regulatory proteins, tissue proliferation and tumour histology.
The extent of apoptosis was defined by morphological criteria and the TUNEL (terminal deoxy nucleotidyl transferase-mediated dUTP biotin nick end labelling) assay. p53, bax, bcl-2 and cyclin D1 expression was evaluated by immunocytochemistry. The presence of mutant p53 was analysed using a mutant p53-specific ELISA. An inverse correlation was observed between TUNEL reactivity and histology of the lesion (r = -0.555, P = 0.0001). There was also correlation between TUNEL reactivity and immunoreactivity of apoptosis regulatory proteins. p53 (r = 0.641, P = 0.00023), bcl-2 (r = -0.642, P = 0.00014) and bax (r = 0.651, P = 0.00002). The presence of mutant p53 protein showed an inverse correlation to the extent of apoptosis (r = - 0.301, P = 0.00063). Significant correlation was evident between the bax/bcl-2 ratio and TUNEL (r = 0.652, P = 0.00001) as well as between cyclin D1 and TUNEL reactivity (r = 0.577, P = 0.00001).
Results from this study suggest that apoptosis decreases as histological abnormality increases. Apoptotic regulatory proteins are also altered in a histologically dependent manner. Deregulated proliferation occurs simultaneously with decreased apoptosis during tumour progression in the oral mucosa.

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    • "The bcl-2 protein, an anti-apoptotic marker and its over-expression has been reported in several tumors including breast, thyroid, lung and skin carcinomas.[32] In oral carcinomas, over expression of bcl-2 from 7% to 60% has been reported from developed countries[33–36] while Ravi et al.[37] and Kannan et al.[38] reported 100% and 23% bcl-2 expression respectively, in oral cancers from Southern India. It has been suggested that apoptosis is a barrier against cancer. "
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    ABSTRACT: Premalignant/potentially malignant-oral lesions and conditions such as oral submucous fibrosis are known to transform into oral cancer. The malignant transformation is often associated with changes at the genetic level that in turn is reflected by the altered expression of proteins related to cell cycle, proliferation, and apoptosis. To evaluate the expression of p53, Ki67 (MIB), bcl2, and bax in oral submucous fibrosis and oral squamous cell carcinoma. To assess the immunohistochemical expression of p53, Ki67 (MIB), bcl2, and bax in 50 cases of oral submucous fibrosis (OSF) and ten each of normal and oral squamous cell carcinoma (OSCC). The labeling indices (LI) of OSF and OSCC were comparable for p53 and Ki67.The p53 LI ranged from 7.9 to 71.9 in OSF and 65.2 to 85.9 in OSCC, and for Ki67 it ranged from 4.39 to 43.23, 18.35 to 42.33, respectively. The p53, Ki67, and bax profiles of OSF and OSCC were altered compared to the normal and these markers could be used as surrogate markers of malignant transformation in OSF.
    Journal of Oral and Maxillofacial Pathology 05/2011; 15(2):148-53. DOI:10.4103/0973-029X.84478
  • SURI C ·
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    ABSTRACT: The bcl-2 proto-oncogene was first discovered in B-cell lymphomas and is the prototype of cell death regulatory genes. It's gene product, the bcl-2 protein, directly or indirectly inhibits the release of cytochrome C, thus preventing the activation of caspases and hence, inhibiting apoptosis. This leads to cellular immortalization, contributing to formation of the tumour and facilitating the permanent acquisition of mutations. Studies show increased expression of the bcl-2 protein in about 50% of human cancers. Keeping this in view, our study was undertaken to evaluate the expression, to quantify and to determine the intensity and the pattern of bcl-2 in various histological grades of Oral Squamous Cell Carcinoma. Method:The present study investigated the immunohistochemical expression of bcl-2 in 38 cases, of which 32 were histologically diagnosed as Oral Squamous Cell Carcinomas and 5 normal lymph nodes along with 1 normal oral mucosa were included as controls. Each specimen was sectioned at 3 micron thickness, immunostained with the bcl-2 antibody and viewed under a light microscope. Results:All the 38 cases showed bcl-2 immunopositivity. The number of bcl-2 positive cells was more in poorly differentiated SCC than in well differentiated SCC. The intensity of bcl-2 expression was more in moderately differentiated SCC, while in poorly differentiated SCC, an equal number of cases showed light and dark intensity. When the distribution pattern of bcl-2 expression was assessed, the tumour islands devoid of central keratinization showed bcl-2 expression in all the tumour cells. Summary and conclusion:In OSCCs, the number of cells expressing bcl-2 increased from well differentiated to poorly differentiated, showing an inverse relationship with the degree of differentiation. Further correlative studies using markers for other members of the bcl-2 family are necessary to elucidate the specific molecular defects critical to the biology of this tumour, which will have an impact on it's diagnosis and treatment.
    Journal of Clinical and Diagnostic Research 12/2009; 3(6). · 0.23 Impact Factor
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    ABSTRACT: The Bcl-2 family of proteins regulates a late step in the apoptosis pathway. Bcl-2 protein is believed to be involved in imparting resistance to programmed cell death or apoptosis induced by chemotherapeutic agents and radiation. The anti-apoptotic function of the Bcl-2 protein appears to be modulated by its ability to heterodimerize with other members of the gene family, predominantly Bax, a protein favouring induction of apoptosis. Susceptibility to undergoing apoptosis may, therefore, be dependent on the ratio between Bcl-2 and Bax. Both Bax and Bcl-2 are regulated by the tumour-suppressor protein p53. The present study therefore aims to study the significance of the Bcl-2:Bax ratio, p53 expression and apoptosis in paediatric acute lymphoblastic leukaemia (ALL). Expression of Bax, Bcl-2 and p53 was determined by immunocytochemistry, and apoptosis was evaluated by an enzymatic end-labelling technique using biotin-dUTP and further confirmed by annexin binding. The presence of mutant p53 was determined using a mutant-p53-specific enzyme-linked immunosorbent assay (ELISA). A total of 32 cases and 20 controls were evaluated. Bcl-2 was found to be expressed in 22/32 of the ALL cases. Pretreatment (spontaneous) apoptosis was observed in 23/32 cases. The mean pretreatment apoptotic index was 11.34 +/- 2.04% with a median value of 7.5%. There was a positive correlation between apoptosis and Bax expression (r = 0.5044; P = 0.0038). There was good correlation between the immunoreactivity of p53 and detection of mutant p53 by ELISA (r = 0.4605; P = 0.0079). The apoptosis index showed a negative borderline correlation to the expression of Bcl-2 protein (r = -0.3181; P = 0.076). There was an inverse correlation between extent of apoptosis and the presence of mutant p53 protein (r = -0.4732; P = 0.006). p53 protein expression also showed a correlation with both Bcl-2 (r = 0.4647; P = 0.007) and Bax (r = 0.4128; P = 0.018). The Bcl-2/Bax ratio, however, showed no significant correlation with apoptosis (r = -0.3131; P = 0.08) or with p53 expression. No significant association was evident between clinical and laboratory parameters with the Bcl-2/Bax protein expression except lymphadenopathy (r = 0.5774; P = 0.03). However, Bax expression showed a borderline correlation with the immediate tumour response to chemotherapy (r = -0.338; P = 0.0628). These patients are being followed-up to look for any association between clinical outcome, Bcl-2/Bax ratio and apoptosis.
    Journal of Cancer Research and Clinical Oncology 02/2000; 126(1):62-7. DOI:10.1007/s004320050010 · 3.08 Impact Factor
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