Sources/Clones
Accurate (8B6, polyclonal), American Research (polyclonal), Biogenesis (PLAP001, polyclonal), Biogenex (polyclonal), Dako (8B6, 8A9, polyclonal), Novocastra (polyclonal), Sanbio (MIG-P), Sigma (8B6) and Zymed (polyclonal).
Fixation/Preparation
The antigen is resistant to fixation and both polyclonal and monoclonal antibodies are immunoreactive in fixed paraffin-embedded sections. HIER enhances staining.
Background
The alkaline phosphatases (AP) are a heterogenous group of glycoproteins, which are usually confined, to the cell surface (Stolbach et al, 1969). The isoenzymes differ in terms of their biochemical properties, anatomical sites of production and reactivity with different antibodies. APs probably have a role in cellular transport, regulation of metabolism, gene transcription and cellular differentiation. At least three genes encode the human AP isoenzymes, one for tissue-nonspecific AP present in the liver, bone and kidney, one for the synthesis of intestinal AP and one or more genes for the placental isoenzyme (PLAP). The different isoenzymes differ in molecular weight and amino acid composition and have different properties. The tissue-nonspecific and intestinal variants are heat sensitive whereas the PLAP isoenzymes are heat resistant. PLAP occurs only in higher primates and displays a high degree of genetic polymorphism. It is a dimer of 65 kD subunits and is synthesized during the G1 phase of the cell cycle. The enzyme is produced by trophoblasts and is responsible for the hyperphosphatemia observed during pregnancy. Biochemically, immunologically and electrophoretically, PLAP can be separated into three distinct subtypes (Fishman, 1995). The phase 1 isoenzyme corresponds to that produced by 6-8 week trophoblasts, the second is a mixture of the early phase and term placental isoenzymes and the phase 3 corresponds to the 13 weeks-term gestation AP isoenzymes. PLAP-like reactivity has been reported in the serum of about 5% of patients with tumors that included carcinoma of the lung, ovary, breast, colon and endometrium, as well as malignant lymphoma and multiple myeloma. Raised levels of serum PLAP were found in 25% of patients with seminoma. Several isoenzymes of AP have been specifically named. The Regan isoenzyme was named after a patient with lung cancer whose serum had the phase 3-type isoenzyme. It was also found in 4-14% of patients with a variety of neoplasms including testicular germ cell tumors and carcinomas of the breast, ovary, lung, stomach and pancreas as well as in the serum of patients with ulcerative colitis, familial polyposis and cirrhosis of the liver. The Nagao isoenzyme was named after a patient with pleural carcinomatosis and bears some similarities to the phase 3 PLAP. The Nagao AP has been found in the serum and tumor cells of patients with adenocarcinoma of the bile ducts and pancreas. The Kashahara variant was detected in tumor extracts of hepatocellular carcinoma and possesses some of the properties of the placental isoenzyme. Other non-Regan isoenzymes have been described in patients with gastrointestinal cancer, benign gynecological disease and female genital cancer, testicular teratomas and lung tumors.
Applications
Antibodies to PLAP are primarily used as a diagnostic discriminator of germ-cell tumors in the context of separation anaplastic tumors (Appendices 1.5, 1.31). Membrane-based PLAP has been documented immunohistochemically in seminoma, embryonal carcinoma, gonadoblastoma, endodermal sinus tumor and choriocarcinoma (Manivel et al, 1987) and metastatic deposits of seminoma (Koshida et al, 1996). Spermatocytic seminoma and immature teratomas were negative. Epithelial neoplasms of the ovary (Nakopoulou et al, 1995) and intratubular neoplastic germ cells also labeled for PLAP. It has been suggested that PLAP immunostaining may help separate partial and complete hydatidiform moles and choriocarcinoma. Partial moles show weak hCG and strong PLAP, complete moles show strong expression of hCG and weak PLAP, whereas choriocarcinoma displays strong expression of hCG and weak PLAP and human placental lactogen (hPL) (Losch & Kainz, 1996). PLAP has also been observed in cell lines from human bladder cancer and in somatic tumors such as tumors of the female genital tract, intestine, lung and less frequently in breast and renal carcinomas (Wick et al, 1987). Epithelial membrane antigen (EMA) is said to help the distinction of germ cell tumors from these somatic tumors which also express EMA, whereas the former do not.
References
•Fishman WH 1995. The 1993 ISOBM Abbott Award Lecture: isoenzymes, tumor markers and oncodevelopmental biology. Tumour Biology 16: 394-402.
•Koshida K, Uchibayashi T, Yamamoto H, et al 1996. A potential use of a monoclonal antibody to placental alkaline phosphatase (PLAP) to detect lymph node metastases of seminoma. Journal of Urology 155: 337-341.
•Losch A, Kainz C 1996. Immunohistochemistry in the diagnosis of the gestational trophopblastic disease. Acta Obstetrica Gynaecologica Scandinavia 75: 753-756.
•Manivel JC, Jessurun J. Wick MR, Dehner LP 1987. Placental alkaline phosphatase immunoreactivity in testicular germ cell neoplasms. American Journal of Surgical Pathology 11:21-29.
•Nakopoulou L, Stefanaki K, Janinis J, Mastrominas M 1995. Immunohistochemical expression of placental alkaline phosphatase and vimentin in epithelial ovarian neoplasms. Acta Oncologica 34: 511-515.
•Stolbach LL, Krant MJ, Fishman WH 1969. Ectopic production of an alkaline phosphatase isoenzyme in patients with cancer. New England Journal of Medicine 281: 757-762.
•Wick MR, Swanson PE, Manivel JC 1987. Placental-like alkaline phosphatase reactivity in human tumors: an immunohistochemical study of 520 cases. Human Pathology 18: 946-954.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
Accurate (8B6, polyclonal), American Research (polyclonal), Biogenesis (PLAP001, polyclonal), Biogenex (polyclonal), Dako (8B6, 8A9, polyclonal), Novocastra (polyclonal), Sanbio (MIG-P), Sigma (8B6) and Zymed (polyclonal).
Fixation/Preparation
The antigen is resistant to fixation and both polyclonal and monoclonal antibodies are immunoreactive in fixed paraffin-embedded sections. HIER enhances staining.
Background
The alkaline phosphatases (AP) are a heterogenous group of glycoproteins, which are usually confined, to the cell surface (Stolbach et al, 1969). The isoenzymes differ in terms of their biochemical properties, anatomical sites of production and reactivity with different antibodies. APs probably have a role in cellular transport, regulation of metabolism, gene transcription and cellular differentiation. At least three genes encode the human AP isoenzymes, one for tissue-nonspecific AP present in the liver, bone and kidney, one for the synthesis of intestinal AP and one or more genes for the placental isoenzyme (PLAP). The different isoenzymes differ in molecular weight and amino acid composition and have different properties. The tissue-nonspecific and intestinal variants are heat sensitive whereas the PLAP isoenzymes are heat resistant. PLAP occurs only in higher primates and displays a high degree of genetic polymorphism. It is a dimer of 65 kD subunits and is synthesized during the G1 phase of the cell cycle. The enzyme is produced by trophoblasts and is responsible for the hyperphosphatemia observed during pregnancy. Biochemically, immunologically and electrophoretically, PLAP can be separated into three distinct subtypes (Fishman, 1995). The phase 1 isoenzyme corresponds to that produced by 6-8 week trophoblasts, the second is a mixture of the early phase and term placental isoenzymes and the phase 3 corresponds to the 13 weeks-term gestation AP isoenzymes. PLAP-like reactivity has been reported in the serum of about 5% of patients with tumors that included carcinoma of the lung, ovary, breast, colon and endometrium, as well as malignant lymphoma and multiple myeloma. Raised levels of serum PLAP were found in 25% of patients with seminoma. Several isoenzymes of AP have been specifically named. The Regan isoenzyme was named after a patient with lung cancer whose serum had the phase 3-type isoenzyme. It was also found in 4-14% of patients with a variety of neoplasms including testicular germ cell tumors and carcinomas of the breast, ovary, lung, stomach and pancreas as well as in the serum of patients with ulcerative colitis, familial polyposis and cirrhosis of the liver. The Nagao isoenzyme was named after a patient with pleural carcinomatosis and bears some similarities to the phase 3 PLAP. The Nagao AP has been found in the serum and tumor cells of patients with adenocarcinoma of the bile ducts and pancreas. The Kashahara variant was detected in tumor extracts of hepatocellular carcinoma and possesses some of the properties of the placental isoenzyme. Other non-Regan isoenzymes have been described in patients with gastrointestinal cancer, benign gynecological disease and female genital cancer, testicular teratomas and lung tumors.
Applications
Antibodies to PLAP are primarily used as a diagnostic discriminator of germ-cell tumors in the context of separation anaplastic tumors (Appendices 1.5, 1.31). Membrane-based PLAP has been documented immunohistochemically in seminoma, embryonal carcinoma, gonadoblastoma, endodermal sinus tumor and choriocarcinoma (Manivel et al, 1987) and metastatic deposits of seminoma (Koshida et al, 1996). Spermatocytic seminoma and immature teratomas were negative. Epithelial neoplasms of the ovary (Nakopoulou et al, 1995) and intratubular neoplastic germ cells also labeled for PLAP. It has been suggested that PLAP immunostaining may help separate partial and complete hydatidiform moles and choriocarcinoma. Partial moles show weak hCG and strong PLAP, complete moles show strong expression of hCG and weak PLAP, whereas choriocarcinoma displays strong expression of hCG and weak PLAP and human placental lactogen (hPL) (Losch & Kainz, 1996). PLAP has also been observed in cell lines from human bladder cancer and in somatic tumors such as tumors of the female genital tract, intestine, lung and less frequently in breast and renal carcinomas (Wick et al, 1987). Epithelial membrane antigen (EMA) is said to help the distinction of germ cell tumors from these somatic tumors which also express EMA, whereas the former do not.
References
•Fishman WH 1995. The 1993 ISOBM Abbott Award Lecture: isoenzymes, tumor markers and oncodevelopmental biology. Tumour Biology 16: 394-402.
•Koshida K, Uchibayashi T, Yamamoto H, et al 1996. A potential use of a monoclonal antibody to placental alkaline phosphatase (PLAP) to detect lymph node metastases of seminoma. Journal of Urology 155: 337-341.
•Losch A, Kainz C 1996. Immunohistochemistry in the diagnosis of the gestational trophopblastic disease. Acta Obstetrica Gynaecologica Scandinavia 75: 753-756.
•Manivel JC, Jessurun J. Wick MR, Dehner LP 1987. Placental alkaline phosphatase immunoreactivity in testicular germ cell neoplasms. American Journal of Surgical Pathology 11:21-29.
•Nakopoulou L, Stefanaki K, Janinis J, Mastrominas M 1995. Immunohistochemical expression of placental alkaline phosphatase and vimentin in epithelial ovarian neoplasms. Acta Oncologica 34: 511-515.
•Stolbach LL, Krant MJ, Fishman WH 1969. Ectopic production of an alkaline phosphatase isoenzyme in patients with cancer. New England Journal of Medicine 281: 757-762.
•Wick MR, Swanson PE, Manivel JC 1987. Placental-like alkaline phosphatase reactivity in human tumors: an immunohistochemical study of 520 cases. Human Pathology 18: 946-954.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
