Urinary epidermal growth factor concentrations in various human malignancies

Abstract

Summary We determined the concentrations of immunoreactive epidermal growth factor in the urine (U-irEGF) of 97 adult patients with various malignancies, including carcinomas of the urinary bladder, kidney, stomach, colon, rectum, breast, endometrium, uterine cervix, ovary, vagina, prostate, pancreas and thyroid, liposarcoma and skin melanoma. The relative U-irEGF concentrations (ng m-1 creatinine) were higher (P=0.002) for the whole series of female patients than for healthy controls matched for sex and age. Such difference did not appear for male patients. The only specific group with a statistically supranormal U-irEGF concentration (P=0.0005) comprised women with endometrial carcinoma of the uterus.Epidermal growth factor (EGF) appears to be involved in the regulation of proliferation, differentiation and differentiated functions of a multitude of cell types (Gospodarowicz, 1981;Carpenter & Zendegui, 1986). In certain normal cells in vitro EGF elicits transformation-associated responses (Stoscheck et al., 1986). There is also a considerable body of evidence associating EGF receptor with oncogenesis. The EGF receptor is the product of the c-erbB proto-oncogene, which is closely related to the v-erb B (Downward et al., 1984). The receptor is present in enormous numbers on the cells of many human epidermoid and glial malignancies (Lin et al., 1984;Merlino et al., 1984;Libermann et al., 1984). Many malignant cells produce another EGF receptor agonist, transforming growth factor alpha (TGF-a) Roberts et al., 1980). TGF-cx is excreted in urine by patients with various malignancies (Sherwin et al., 1983), but not by healthy subjects (Twardzik et al., 1985). Uchihashi et al. (1983) and Kurobe et al. (1985) found urinary excretion of EGF to be higher in patients with cancer than in healthy persons. This has not been generally accepted. We have now measured urinary immunoreactive EGF (U-irEGF) levels in patients with a variety of malignancies before and after tumour removal. Materials and methodsSubjects and samples Spot urine samples were collected from 97 patients (49 men and 48 women, aged 28-88 years) with various malignancies before surgical removal (or any other treatment) of the tumour. In addition to those shown in Figure 1, six patients had carcinomas, I of the vagina, 2 of the pancreas, and 3 of the thyroid, and 1 patient had liposarcoma and 1 skin melanoma. The malignancies included both metastasized and in situ tumours. We also measured U-irEGF concentration in 24 patients daily during the first week after removal of the tumour, and in a further 7 patients on the sixth postoperative day. For comparison, urine samples were collected from age-and sex-matched healthy subjects (56 men and 62 women, aged 28-86 years).Assay procedures Human EGF, used both as standard and labelled tracer, and a rabbit antiserum against it (8C-217,3129) were donated by AMGen (Thousand Oaks, California). U-irEGF was measured by a specific homologous radioimmunoassay (Mattila et al., 1985) and creatinine by the kinetic method of Ja...

Urinary laminin fragments as a tumour marker potentially reflecting basement membrane destruction

“…. (Mattila et al, 1988). The results of laminin measurements in all urine samples are represented in Figure 4.…”

“…Many urinary tumour markers have been investigated previously (Kardana et al, 1988;Mattila et al, 1988;Katayama et al, 1991). Fibronectin (FN), major extracellular matrix components with a high molecular mass, is a very popular cell adhesive glycoprotein as well as laminin and collagens (Hynes & Yamada, 1982).…”

Epidermal growth factor receptor-binding growth factors in the urine of patients with cancers of the digestive tract

“…Our results are in keeping with reported raised EGF and TGF-α expression in various malignancies. [5][6][7][8][9][10][11][12][13][14][15] Previously, we demonstrated the existence of EGFR-binding growth factors in the urine of patients with HCC, and up to 65% of patients with HCC had raised levels of TGF-α in urine. [12][13][14] Over-expression of TGF-α has also been reported in human HCC tissue.…”

“…Overexpression or increased production of EGF, TGF-α, and EGFR have been reported in tumor tissues and/or body fluid of patients with various cancers, including cancers of the digestive tract. [5][6][7][8][9][10][11][12][13][14][15] EGFR-binding peptides may play an important role in the development of cancer through an autocrine mechanism, and may also serve as markers for malignant potential, metastasis, and prognosis. 6,7,16 Although there are raised levels of EGFRrelated peptides in cancer patients, the clinical application of these growth factors has rarely been well elucidated.…”

Urinary epidermal growth factor (hEGF) levels in patients with carcinomas of the breast, colon and rectum

“…In a more recent study, Matilla et al (1988) studied 97 adults with carcinomas of the bladder, kidney, stomach, colon, rectum, breast, cervix and endometrium. Significantly elevated urinary hEGF was found only in females with endometrial carcinoma, and the levels did not return to normal after surgery.…”