Multiple marker analysis in breast tumors with long term follow-up using Tissue Microarray: Immunohistochemical evaluation of ER, PgR, MIB1, p27, p63, HMWCK, FITH, Her2/neu and p53.

686 Background: The tissue microarray (TMA) technique allows to assemble multiple tumor samples in the same paraffin block to evaluate multiple markers using immunohistochemistry.,we have constructed TMAs of 293 breast carcinomas with complete follow-up (median 132 mos). Four tumor cores per sample (i.e.: 4 replica) were included in TMA blocks. We evaluated the expression of ER, PgR, Her2/neu (Herceptest), p53, MIB1, Bcl2, p27, p63, HMW cytokeratin (HMWCK), and FITH. The 4 different replica of each case were separately analysed by two pathologists. Her2/neu was evaluated according to FDA score. For all other markers we evaluated cellular compartimentalization, intensity (from 0 to 3) and percentage of reacting cells.,from the original 1172 cores in the TMAs, 78% were evaluable for each marker because of lack of cells or loss of cores during the TMA sections processing. The most relevant prognostic markers were Her2/neu and p53: they retained prognostic value even after adjusting for N status (p<0.01 for OS and DFS). MIB1 was of borderline prognostic significance. ER, PgR, Bcl2, p27, FITH, p63 and HMWCK did not provide prognostic information.,Our results confirm that TMA may be a reliable tool in the evaluation of prognostic/predictive markers, with the advantage of sparing time and tissues. The most reliable prognostic marker was Her2/neu. These data further support that Her2/neu, beside being predictive of therapeutic response to Herceptin, is a reliable prognostic marker. Unexpected negative results for ER,PgR and Bcl2 are more difficult to explain, and further studies on larger TMA are necessary.Loss of p27 or FITH, and the identification of markers of the so-called "basal phenotype" (p63 and HMWCK) of breast carcinomas were not prognostic predictors in our series, in keeping with their known controversial prognostic role No significant financial relationships to disclose.