Predictive value of immunohistochemistry with p21, bcl-2 and p53 to pre-operative radiotherapy for patients with rectal cancer

Zlobec, Inti1; Vuong, Té2; Compton, Carolyn C3. 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

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 representationof tumor response groups.

protein p21 p53 bcl-2 p21/p53 p21/bcl-2 bcl-2/p53 p21/ bcl-2/p53

p-value =0.05

0.93 0.65 0.06 0.343 0.434 0.204 0.037

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

% 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.

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