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Anticancer Res. 1998 May-Jun;18(3B):1907-14.

Bcl2 and p53 protein expression in metastatic carcinoma of unknown primary origin: biological and clinical implications. A Hellenic Co-operative Oncology Group study.

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  • 1Department of Medicine, Medical School, Ioannina University, Greece.


We have previously shown that metastatic carcinomas of unknown primary site overexpress several tumor markers as well as the products of the oncogenes c-myc, ras and c-erbB2. We analyzed the tissue expression of the protein products of the apoptosis modulation genes p53 and bcl-2 in 47 CUP cases. Formalin-fixed, paraffin embedded tumor specimens were stained with commercially available antibodies to p53 (DO7) and bcl-2 after antigen retrieval by the microwave method. Staining was evaluated by intensity (1+ to 3+), percentage of positive cells (1-100%), and the 'intensity times percentage' product defined as the immunoreactivity index with values ranging from 0 to 300. Immunoreactivity index values higher than 150 were considered to characterize protein over-expression. Expression of p53 was identified in 70.2% of tumors while 53% of them showed a high immunoreactivity index. Bcl-2 expression was detected in 65% of tumors and overexpressed in 40%. Overexpression of both proteins was detected in 20% of tumors. The detection of either protein was not associated with any of the major clinicopathological variables studied. Nevertheless, a trend towards a more favourable response to platin based chemotherapy was seen in the cases that showed a strong expression of both proteins, when analysed by immunoreactivity index and percentage of positive cells. We conclude that CUP overexpress at a high percentage the p53 and the bcl2 proteins. The observed weak association of strong expression of these proteins with response to platin-based chemotherapy deserves further evaluation in the CUP setting.

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