PC-cell derived growth factor (PCDGF/GP88): A novel circulating biomarker in breast cancer (BC) patients

Abstract

551 Background: The identification of a measurable biomarker that is also a therapeutic target of malignant transformation or malignant progression of breast carcinoma (BC) is needed. PCDGF/GP88, an 88 kDa glycoprotein autocrine growth factor is expressed in human BC tumors in a positive correlation with their tumorigenicity. In estrogen receptor positive (ER+) cells, PCDGF/GP88 expression is low and is stimulated by estradiol whereas in ER negative cells, it is constitutively overexpressed. In ER+ cells, PCDGF/GP88 mediates estrogen mitogenic activity and its overexpression renders cells estrogen-independent and tamoxifen-resistant. Inhibition of PCDGF/GP88 expression by antisense transfection leads to inhibition of breast tumor incidence and growth in nude mice. PCDGF/GP88 is expressed in 80% of human invasive ductal carcinomas and correlates with expression of markers of poor prognosis whereas normal tissues and benign breast lesions are negative. Methods: A blood sampling study was conducted to determine the serum level of PCDGF/GP88 in healthy volunteers (HV) and BC pts. Approximately 10 ml of blood was drawn every three months and processed to obtain serum. PCDGF/GP88 serum concentration was determined in triplicate by quantitative enzyme immunoassay using human PCDGF/GP88 as standard. One hundred twenty three subjects were accrued: 16 HV and 107 BC pts. BC Patient characteristics: race, Caucasian- 51, African American-51, Asian-5; median age, 52.5 (range 29–84); stage I - 24, II - 29, III - 13, IV - 41. Results: Circulating PCDGF/GP88 was measurable in the serum. Mean level of PCDGF was 33.6 ng/ml (range 23.8–42.8) in HV and 47.4 ng/ml (range 19.9–158.4) in BC pts, (p- value= 0.004). Conclusions: PCDGF/GP88 is measurable in the sera of HV and BC pts. Comparison between the two groups of subjects indicates that PCDGF/GP88 level is significantly higher in the sera of BC pts. Future studies will examine the correlation of PCDGF/GP88 level with BC prognostic factors such as stage, tumor size, lymph node involvement, tumor grade and presence of ER and HER-2neu. We will also attempt to correlate the serum level of PCDGF/GP88 with median survival of BC pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration A&G A&G