BCL2 AND P53 PROTEIN EXPRESSION IN METASTATIC CARCINOMA OF UNKNOWN PRIMARY ORIGIN - BIOLOGICAL AND CLINICAL IMPLICATIONS - A HELLENIC COOPERATIVE ONCOLOGY GROUP-STUDY

We have previously shown that metastatic carcinomas of unknown primary site overexpress several tumour markers as well as the products of th e oncogenes c-myc, ras and c-erbB2. We analysed the tissue expression of the protein products of the apoptosis modulation genes p53 and bcl- 2 in 47 CUP cases. Formalin-fixed, paraffin embedded tumour specimens were stained with commercially available antibodies to p53 (DO7) and b cl-2 after antigen retrieval by the microwave method Staining was eval uated by intensity (1+ to 3+), percentage of positive cells (1-100%), and the 'intensity times percentage' product defined as the immunoreac tivity index with values ranging from 0 to 300. Immunoreactivity index values higher than 150 were considered to characterize protein overex pression. Expression of p53 was identified in 70.2 % of armours while 53% of them showed a high immunoreactivity index. Bcl-2 expression was detected in 65% of tumours and overexpressed in 40%. Overexpression o f both proteins was detected in 20% of tumours. The detection of eithe r protein was not associated with any of the major clinicopathological variables studied. Nevertheless, a trend towards a mole favourable re sponse to platin based chemotherapy was seen in the cases that showed a strong expression of both proteins, when analysed by immunoreactivit y index and percentage of positive cells. We conclude that CUP overexp ress at a high percentage the p53 and the bcl-2 proteins. The observed weak association of strong expression of these proteins with response to platin-based chemotherapy deserves further evaluation in the CUP s etting.