Correlation of P-glycoprotein overexpression and cellular prognostic factors in formalin-fixed, paraffin-embedded tumor samples from breast cancer patients.

BACKGROUND

P-glycoprotein overexpression seems to play a prognostic role independent from its association with multidrug resistance. We have been able to verify this previously on fresh-frozen tumor samples, but up to now P-glycoprotein detection on formalin-fixed, paraffin-embedded material has generally been unsatisfactory.

METHODS

Two distinct groups of previously untreated mammary carcinomas were studied for P-glycoprotein expression by means of immunohistochemistry, using the NCL-p-GLYp polyclonal antibody, carried out on slides from archival, paraffin-embedded material. The first group was composed of 15 tumors expressing at least three out of four factors indicative of a worse prognosis: c-erb-B2, mutant p53, cathepsin-D and PCNA (proliferating cell nuclear antigen). The control group was composed of 16 tumors lacking expression of any of these proteins.

RESULTS

There was a statistically significant difference in survival (Fisher's exact test, p = 0.0036) between both groups. All four patients who died during the follow-up period (mean 55.1 months) belonged to the first group. Three of these patients harbored tumors with the highest level of expression of P-glycoprotein. This association between P-glycoprotein overexpression and prognosis was also statistically significant (Fisher's exact test, p = 0.0059).

CONCLUSION

These results, obtained from a group of mostly operable tumors stratified for cellular risk factors, complement those previously reported by us for locally advanced, inoperable breast cancer only, using fresh-frozen tissue. P-glycoprotein again seems to play a prognostic role, independent of its involvement in multidrug-resistance. The technique used by us yielded useful results on formalin-fixed, paraffin-embedded archival tumor samples. This opens the possibility for larger studies on populations with a closed follow-up.