PROGNOSTIC-SIGNIFICANCE OF PLATELET IMMUNORELATED GPIB EXPRESSION IN BREAST-CANCER

PURPOSE Prior reports have indicated that adhesive glycoprotein recept ors expressed by tumor cells enhance their invasive and metastatic pro perties. We have recently isolated and characterized a platelet immuno related GPIb receptor expressed by cultured breast tumor cell lines th at participates in initial adhesive events in the metastatic process. Whether expression of this receptor predicts tumor behavior or clinica l prognosis remains unknown. PATIENTS AND METHODS Forty sequential bre ast tissue specimens were examined for GPIb alpha, GPIb/IX, and alpha( IIb)beta(3) (GPIIb/IIIa) expression by immunohistochemical staining. O f 35 assessable breast specimens, 20 were invasive ductal carcinomas o r lobular invasive carcinomas, six were ductal carcinomas in situ (DCI S), and the remaining nine consisted of nonmalignant pathologies. RESU LTS The expression of an immunorelated GPIb alpha and GPIb/IX complex by invasive mammary carcinoma specimens was highly significant (P < 0. 0001). However there was no correlation between alpha(IIb)beta(3) expr ession and invasive breast cancer. A GPIb alpha or GPIb/IX staining sc ore of less than or equal to 2.0 and > 2.0 correlated highly with the diagnosis DCIS and invasive carcinoma, respectively (P < 0.0039). Inva sive breast carcinoma specimens demonstrated a 120% (P < 0.001) and 14 0% (P < 0.027) increase in GPIb alpha and GPIb/IX staining score in co mparison with DCIS specimens. Expression of GPIb alpha and GPIb/IX cor related significantly with a tumor stage of greater than or equal to I II (P < 0.008), a tumor size of > 3 cm (P < 0.012), involved axillary nodes (P < 0.004), and estrogen receptor negativity (P < 0.008). Final ly, a significant correlation was observed between this receptor's exp ression and the presence of nodal and/or visceral metastases (P < 0.00 35). DISCUSSION These results demonstrate a significant correlation be tween GPIb expression and breast malignancy. The expression of the GPI b receptor appears to represent an unfavorable prognostic factor and a biomarker predictive of aggressive disease.