Human ovarian carcinomas: correlation of malignancy and survival with the expression of epidermal growth factor receptors (EGF-R) and EGF-like factors (EGF-F)
Tóm tắt
We have studied the concentration of epidermal growth factor receptors (EGF-R) in 115 different malignant ovarian tumors (101 ovarian carcinomas) and EGF-like factors (EGF-F) in tissue extracts of 63 different ovarian carcinomas and 20 non-malignant tissues. 36% of ovarian carcinomas are EGF-R positive. The calculated mean EGF-F level of 4.2 ± 1.5 ng mg−1 (range: 0–15 ne mg−1) in ovarian carcinomas is significantly enhanced compared to 1.5 ± 0.7 ng mg−1 (range: 0–4 ng mg−1) of non-malignant tissue extracts. The correlation between EGF-R positive as well as negative ovarian carcinomas and the results of a primary chemotherapy of advanced ovarian carcinomas (n = 92) revealed a significantly higher remission rate of EGF-R positive tumors (66%) compared to EGF-R negative cases (23%). 84% of tumors with progressive disease were EGF-R negative. The mean EGF-F levels were calculated for prognostic subgroups of ovarian carcinomas. Increased EGF-F levels are significantly associated with progressive disease compared to all patients or the remission group. 15/16 cases with EGF-F levels > 5 ng mg−1 showed progressive disease. The overall survival time of patients with tumor tissue EGF-F levels > 3.5 ng mg−1 was worse than that of patients with low EGF-F levels. Multivariate analysis showed that the EGF-F level was, after gracling, the second most important factor for predicting overall survival.
Tài liệu tham khảo
Keski-Oja J, Leof E, Lyons R, Coffey R, Moses H: Transforming growth factors and control of neoplastic cell growth.J cell Biochem 33, 95 (1987).
Derynck R: Transforming growth factor: structure and biological activities.J cell Biochem 32, 293 (1986).
Bringman T, Lindquist P, Derynck R: Different transforming growth factor species are derived from a glycosylated and palmitoylated transmembrane precursor.Cell 48, 429 (1987).
Singletary S, Baker F, Spitzer G, Tucker S, Tomasovic B, Brock W, Ajani J, Kelly A: Biological effect of epidermal growth factor on thein vitro growth of human tumors.Cancer Res 47, 403 (1987).
Frolik C, Wakefield L, Smith D, Sporn M: Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney cells.J biol Chem 259, 10995 (1984).
Bauknecht T: Die klinische Bedeutung membranständiger Rezeptoren beim Ovarialkarzinom.Onkologie 7 (Suppl), 54 (1984).
Bauknecht T, Rau B, Meerpohl H, Pfleiderer A: The prognostic value of the presence of EGF receptors in ovarian carcinomas.Tumor Diagnost Ther 51, 62 (1984).
Bauknecht T, Runge M, Schwall M, Pfleiderer A: Occurrence of epidermal growth factor receptors (EGF-R) in human adnexal tumors and their prognostic value in advanced ovarian carcinomas.Gynec Oncol 29, 147 (1988).
Harris A, Sainsbury R, Needham G, Veale D, Neal D, Kerr N, Farndorn J, Sherbet G, Hall R: Epidermal growth factor receptor in human breast, bladder and lung cancer — correlations with biological behaviour.J cell Biochem 10C (Suppl), L292 (1986).
Sainsbury J, Farndon J, Needham G, Malcolm A, Harris A: Epidermal growth factor receptor status as predictor of early recurrence of and death from breast cancer.Lancet 1, 1398 (1987).
Bauknecht T, Kiechle M, Bauer G, Siebers J: Characterization of growth factors in human ovarian carcinomas.Cancer Res 46, 2614 (1986).
Derynck R, Goeddel D, Ullrich A, Guttermann J, Williams R, Bringman T: Synthesis of messenger RNAs for transforming growth factors and β and the epidermal growth factor receptor by human tumors.Cancer Res 47, 707 (1987).
Meerpohl H: Prognosefaktoren des Ovarialkarzinoms.Onkologie 8, 296 (1985).
Pfleiderer A:Maligne Tumoren der Ovarien. Stuttgart, Enke (1986).
Scatchard G: The attractions of proteins for small molecules and ions.Ann NY Acad Sci 51, 660 (1949).
Cox D: Regression models and life tables.J R Stat Soc B 34, 187 (1972).
Carpenter G: Receptors for epidermal growth factor and other polypeptide mitogens.Ann Rev Biochem 56, 881 (1987).
Wittmaack F, Schwörer D, Wintzer O, Bauknecht T, Pfleiderer A: The immunohistochemical expression of epidermal growth factor receptors in various gynecological tumors.J Cancer Res clin Oncol 114 (Suppl), 115 (1988).
Schreiber A, Winkler M, Derynck R: Transforming growth factor: a more potent angiogenic mediator than epidermal growth factor.Science 232, 1250 (1986).
Neal D, Marsh C, Bennett Met al: Epidermal growth factor receptors in human bladder cancer: comparison of invasive and superficial tumours.Lancet 1, 366 (1985).
Veale D, Marsh C, Ashcroft T, Harris A: Epidermal growth factor receptors in non-small cell lung cancer.Br J Cancer 52, 441 (1985).
Larsen A: Tumorigenicity and drug resistance.Cancer J 8, 362 (1987).