Summary
We have established an enzyme immunoassay for placental protein 4 (PP4), by using avidin-biotin binding reaction, and set its normal range below 10.9 ng/ml (mean + 2σ). Throughout the menstrual cycle, the serum PP4 profile was similar to that of serum progesterone. In the follicular and ovulatory phase, PP4 remained relatively low, with the mean levels of 1.5 ng/ml and 1.8 ng/ml, respectively. In the luteal phase, the mean level was 3.2 ng/ml. In normal pregnancy, serum PP4 levels were low irrespective of gestational age, with a mean level of 3.0 ng/ml. There was only one case in which the serum PP4 level over 10.9 ng/ml. Mean serum PP4 levels and the frequencies of elevated serum PP4 levels were respectively 6.3 ng/ml and 11% in patients with benign ovarian neoplasms, 4.7 ng/ml and 6% in patients with endometriosis, and 5.5 ng/ml and 18% in patients with uterine myomata. The frequency of raised PP4 levels was 48% and the mean value was 13.3 ng/ml in patients with endometrial carcinoma, and the values were 44% and 13.4 ng/ml respectively in patients with cervical carcinoma. In patients with ovarian malignancy, the respective values were 15% and 7.0 ng/ml. The results did not relate to clinical stages of disease (FIGO), while the frequencies of elevated serum PP4 in patients with uterine carcinoma was over 40% in stage I diseases. Compared with other tumor markers such as carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125), PP4 seems to be more promising as a marker of endometrial carcinoma. In patients with recurrent gynecological malignancy, 79% of serum PP4 levels were elevated. In endometrial carcinoma and recurrent gynecological malignancy, stromal destruction might be the cause of elevated serum PP4 levels.
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References
Bayer E, Wilchek M (1974) [20] Insolubilized biotin for the purification of avidin. Method Enzymol 34:265–267
Bohn H (1980) New placental and pregnancy proteins as possible markers in oncology. Klin Wochenschr 58:489–492
Bohn H, Inaba N, Lüben G (1981) New placental proteins and their potential diagnostic significance as tumor markers. Oncodevelop Biol Med 2:141–153
Bohn H, Kraus W, Winckler W (1985) Isolation and characterization of two membrane associated placental proteins. Arch Gynecol 236:225–233
Disaia PJ, Haverback BJ, Dyce BJ, Paul Morrow C (1977) Carcinoembryonic antigen in patients with gynecologic malignancies. Am J Obstet Gynecol 121:159–163
Fahey JL, Terry EW (1978) Ion exchange chromatography and gel filtration. In: Wier DM (ed) Handbook of experimental immunology, Vol. 1, Chap. 8. Blackwell, London
Fukazawa I, Inaba N, Ota Y, Sato N, Shirotake S, Iwasawa H, Sato T, Takamizawa H, Wiklund B (1988) Relationship between serum levels of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) and their immunohistochemical identification in benign and malignant gynecologic diseases. Arch Gynecol Obstet 243:41–50
Grundmann U, Abel K, Bohn H, Löbermann H, Lottspeich F, Küpper H (1988) Characterization of cDNA encoding human placental protein 4 (PP4): homology with the lipocortin family. Proc Natl Acad Sci USA 85:3708–3712
Inaba N, Renk T, Bohn H (1980) Immunohistochemical location of placental proteins (PP8, PP9, PP10, PP11, PP12) in human term placentae. Arch Gynecol 230:109–121
Inaba N, Renk T, Wurster K, Rapp W, Bohn H (1980) Ectopic synthesis of pregnancy-specific β1-glycoptotein (SP1) and placental proteins (PP5, PP10, PP11, PP12) in non-trophoblastic malignant tumors — possible markers in oncology. Klin Wochenschr 58:789–791
Inaba N, Renk T, Weimann E, Bohn H (1981) Immunohistochemical location of proteins related to pregnancy-specific β1-glycoprotein (SP1) and placental proteins (pp5, PP8, PP9, PP10, PP11, PP12) in the afterbirth of cynomolgus monkeys (Macaca fascicularis). Arch Gynecol 230:195–204
Inaba N, Renk T, Daume E, Bohn H (1981) Ectopic production of placenta-“specific” tissue proteins (PP5 and PP11) by malignant breast tumors. Arch Gynecol 231:87–90
Inaba N, Ishige H, Ijichi M, Sato N, Kato T, Sekiya S, Shirotake S, Okawa R, Takamizawa H, Nito A, Renk T, Bohn H (1982) Possible new markers in trophoblastic diseases. Am J Obst Gynecol 43:973–974
Inaba N et al. (1982) Pregnancy and placental proteins as possible new markers in trophoblastic diseases. Oncodevelop Biol Med (Abstract):A7
Inaba N, Ishige H, Ijichi M, Sato N, Okawa R, Sekiya S, Shirotake S, Takamizawa H, Renk T, Bohn H (1982) Immunohistochemical detection of pregnancy-specific protein (SP1) and placenta-specific tissue proteins (PP5, PP10, P11 and PP12) in ovarian adenocarcinomas. Oncodevelop Biol Med 3:379–389
Inaba N, Sato N, Ijichi M, Sekiya S, Takamizawa H, Lüben G, Bohn H (1983) Immunocytochemical location of membrane-associated proteins, MP1 and PP4 in placental tissue, blood cells and tumor tissues. Oncodevelop Biol Med, Abstract Vol, p 9
Inaba N, Sato N, Ijichi M, Fukazawa I, Nito A, Takamizawa H, Lüben G, Bohn H (1984) The immunocytochemical location of two membrane-associated placental tissue proteins in human and cynomolgus monkey placentae. Tumor Biology 5:75–85
Kato H, Torigoe T (1977) Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma. Cancer 40:1621–1628
Kobayashi O, Shirotake S, Takamizawa H (1983) Studies on enzyme immunoassay for human chorionic gonadotropin and its clinical application. Acta Obstet Gynaecol Jpn 35:764–772 (in Japanese)
Nagell JR, Donaldson ES, Wood EG, Sharkey RM, Goldenberg DM (1977) The prognostic significance of carcinoembryonic antigen in the plasma and tumors of patients with endometrial carcinoma. Am J Obstet Gynecol 128:308–313
Nakane PK, Kawaoi A (1974) Peroxidase-labelled antibody. A new method of conjugation. J Histochem Cytochem 22:1084–1092
Ota Y, Inaba N, Shirotake S, Sato N, Kobori T, Nozawa S, Takamizawa H, Bohn H (1988) Clinical application of an enzyme immunoassay for placental protein 4 (PP4). Placental and Endometrial Proteins, VSP, pp 515–518
Shidara Y (1984) Isolation and purification of placental coagulation. Acta Obstet Gynaecol Jpn 36:2583–2592 (in English)
Shirotake S, Inaba N, Ota Y, Fukazawa I, Takamizawa H, Bohn H (1986) Immunochemical measurement of placental tissue protein-4 in serum. Chem Pharm Bull 34:2191–2195
Szabo D, Gocze P, Than G, Bohn H (1988) Radioimmunoassay of placental protein 4 and its application in gynecological tumors. Placental and Endometrial Proteins, VSP, pp 519–522
Terada N, Shirotake S, Maekawa I, Kobori T, Takamizawa H (1984) Study on the new development of highly sensitive E2-EIA used by two specific binding systems and on the clinical application. Acta Obstet Gynaecol Jpn 36:763–770 (in Japanese)
Würz H, Schneider K, Ockenfels E, Crombach G, Bolte A, Bohn H (1988) Radioimmunological determination of two new placental proteins (PP4 and MP2D) in body fluids. Placental and Endometrial Proteins, VSP, pp 523–526
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Ota, Y., Inaba, N., Shirotake, S. et al. Enzyme immunoassay for placental protein 4 (PP4) and its possible diagnostic significance in patients with genital tract cancer. Arch Gynecol Obstet 247, 139–147 (1990). https://doi.org/10.1007/BF02390862
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DOI: https://doi.org/10.1007/BF02390862