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).


CONCLUSIONS
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.
Schneider
J
J
Unidad de Investigación, Hospital de Cruces, Universidad del Pais Vasco, Spain.
Romero
H
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D005557:Formaldehyde; D015870:Gene Expression; D006652:Histological Techniques; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D010232:Paraffin; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000906:Antibodies; D005557:Formaldehyde; D010232:Paraffin