1. Predictive value of immunohistochemistry with p21, bcl-2 and p53 to pre-operative radiotherapy for patients with rectal cancer Zlobec, Inti 1 ; Vuong, Té 2 ; Compton, Carolyn C 3. 1 Pathology, McGill University, Montreal, QC, Canada; 2 Radiation Oncology, McGill University Health Centre, Montreal, QC, Canada; 3 Pathology, McGill University Health Centre, Montreal, QC, Canada

2. Objective: Immunohistochemistry for tumor markers p21, bcl-2 and p53 is evaluated as a means to predict rectal tumor response from biopsies of patients treated on pre-operative HDR brachytherapy protocol Immunohistochemistry is performed on 68 pre-treatment tumor biopsies from patients who have had radiotherapy (response to therapy known). Tumors classified post-operatively by response: complete, partial or no response. Immunohistochemistry scored as percentages for each protein: percent-positive tumor cell staining is obtained (%p21, %bcl-2, %p53) Correlation between tumor response and percent-positive tumor cell staining with p21, bcl-2, p53 and with possible combinations of proteins. Graphical representation of tumor response groups.

3. proteinp21p53bcl-2p21/p53p21/bcl-2bcl-2/p53p21/ bcl-2/p53 p-value  =0.0 5 0.930.650.060.3430.4340.2040.037 Correlation of tumor cell staining from biopsies with response to pre-operative radiotherapy  Bcl-2 expression may be a predictive marker of response in these tumors.  The combined variable p21/bcl-2/p53 appears to be a more important predictive marker in these tumors than the evaluation of either three proteins individually. Logistic regression using SAS Table 1

4. % p21 %bcl-2 %p53 Complete response Unresponsive Partial response  Graphical representation of tumor response groups is achieved by plotting each tumor biopsy using the percentages for p21, bcl-2 and p53 as coordinate axes.  The best-fitting line through the biopsies of each group demonstrates a pronounced difference between them.

5. Summary  The results of this study suggest that p21, bcl-2 and p53 may be used as predictive markers of tumor response to radiotherapy when their expression is evaluated together