Serum sErbB1 and epidermal growth factor levels as tumor biomarkers in women with stage III or IV epithelial ovarian cancer

Epithelial ovarian cancer (EOC) has a high mortality rate, which is due pri marily to the fact that early clinical symptoms are vague and nonspecific; hence, this disease often goes undetected and untreated until in its advanc ed stages. Sensitive and reliable methods for detecting earlier stages of E OC are, therefore, urgently needed. Epidermal growth factor (EGF) is a liga nd for EGF receptor (ErbB1); this receptor is the product of the cerbB1 pro to-oncogene, ErbB1 overexpression is common in human ovarian carcinoma-deri ved cell lines and tumors, in which overexpression is thought to play a cri tical role in tumor etiology and progression. Furthermore, ErbB1 overexpres sion is associated with disease recurrence and decreased patient survival. Recently, we have developed an acridinium-linked immunosorbent assay that d etects a similar to 110-kDa soluble analogue of ErbB1, i.e., sErbB1, in ser um samples from healthy men and women (A. T. Baron, et at, J. Immunol. Meth ods, 219: 23-43, 1998), Here, we demonstrate that serum p110 sErbB1 levels are significantly lower in EOC patients with stage III or IV disease prior to (P < 0.0001) and shortly after (P < 0.0001) cytoreductive staging laparo tomy than in healthy women of similar ages, whereas EGF levels are signific antly higher than those of age-matched healthy women only in serum samples collected shortly after tumor debulking surgery (P < 0.0001), We observe th at the preoperative serum sErbB1 concentration range of advanced stage EOC patients barely overlaps with the serum sErbB1 concentration range of healt hy women. In addition, we show that serum sErbB1 and EGF levels changed tem porally for some EOC patients who were surgically debulked of tumor and who provided a second serum sample during the course of combination chemothera py, Finally, we observe a significant positive association between sErbB1 a nd EGF levels only in serum samples of EOC patients collected prior to cyto reductive surgery (correlation coefficient = 0.61968; P = 0.0027), These da ta suggest that epithelial ovarian tumors concomitantly affect serum sErbB1 and EGF levels. In conclusion, these data indicate that serum sErbB1 and E GF (postoperative only) levels are significantly different between EOC pati ents and healthy women and that altered and/or changing serum sErbB1 and EG F levels may provide important diagnostic and/or prognostic information use ful for the management of patients with EOC.