Web-based automated tissue microarray system WATMAS analysis of Her2/neu expression and prognostic significance in a monnoinstitutional series of 436 breast cancers

We investigated the prognostic significance of Her2/neu expression using FDA approved Herceptest® and the tissue microarray (TMA) technique. We used our in-house developed WATMAS, and investigated the most appropriate scoring system to be applied to the analysis of multiple replica samples from the same tumors. Methods: WATMAS includes Beecher TMA arrayer, robotized microscope, relational database and internet technology through DHTML, XML, JavaScript and VBScript. WATMAS allowed remote analysis of the TMA slides. 436 breast cancers were analysed; complete follow-up was obtained for 185 patients (120m median f-up). Four 1 mm cores per sample (i.e.: 4 replica) were included in TMA blocks; sections were immunostained with Herceptest®. For each core we evaluated using the FDA approved score, and data were stored in the database through web interface. Scores of the 4 different replica of each case were separately analysed in order to obtain the most clinically representative v! alue. Results: The maximum score (Maxscore) of the 4 replicas pertaining to the single case was selected as the most representative. Maxscores were distributed as follows: 0= 60%, 1= 20%, 2=12% and 3= 8%. High Maxscore was associated with high grade (p=0.03) and with poor overall and relapse free survival in the whole series of cases, and in N1/2 subgroup. Prognostic value was retained after multivariate analysis. Conclusions: Our study is one of the largest published studies of Her2/neu expression in relation to prognosis using TMA and the FDA approved Herceptest®. Our results confirm the value of TMA in the evaluation of prognostic/predictive markers in breast cancer and the need of an appropriately tailored scoring system. Our WATMAS improved reliability and ease in the evaluation of TMA and allowed remote cooperation between researchers