Pregnancy-specific b-1-glycoprotein (SP1)

Sources/Clones
Axcel/Accurate, Biodesign (BD4D8), Biogenesis (polyclonal), Biogenex (4E4, polyclonal), Chemicon (polyclonal), Dako (polyclonal), Fitzgerald (M32236), Research Diagnostics (BB4E4) and Zymed (polyclonal).

Fixation/Preparation
The antigen is fixation resistant and immunoreactivity may be improved with proteolytic digestion or HIER.

Background
Pregnancy specific b-1-glycoprotein (SP1), together with human chorionic gonadotropin (hCG) and placental alkaline phosphatase (PLAP), are three major proteins produced by the trophoblast of the human placenta. Immunohistochemical studies suggest that SP1 and hCG are also present in the human amnion. Recent molecular cloning studies indicate that the human SP1s form a group of closely related placental proteins that, together with the carcinoembryonic antigen family members, comprise a subfamily within the immunoglobulin superfamily. The main source of SP1 is the syncytiotrophoblast but it has been demonstrated that amniotic as well as chorionic membranes express low levels of SP1 genes, although only certain subpopulations of SP1 transcripts were expressed, with differences in species expression between amnion, chorion and trophoblasts (Plouzek et al, 1993).

Applications
The immunohistochemical applications of SP1 have been mainly in the study of placental elements and their corresponding tumors. Differing levels of expression of hCG, human placental lactogen (hPL) and SP1 were observed in the fetomaternal tissues throughout pregnancy. hCG was strongly localized in the cytoplasm of the syncytiotrophoblast in the 12-day blastocysts, remaining strong until 8-10 weeks before decreasing and becoming almost negative at term. hCG showed variable staining in the implantation site. hPL and SP1 appeared later than hCG in the syncytiotrophoblast, increasingly rapidly by week 8 and remaining strong until term (Sabet et al, 1989). Immunolocalization studies of SP1 in syncytiotrophoblasts suggest a secretory pathway including synthesis in the endoplasmic reticulum, processing by the Golgi and exocytic release into maternal blood in the intervillous space (Schlafke et al, 1992).
The presence of SP1, vimentin, cytokeratin and PLAP, particularly the first three antigens, has been used to identify intermediate trophoblasts in the placental site nodule (Shibata & Rutgers, 1994).

Comments
SP1 is not specific to placental cells. It is expressed in a variety of non-placental tumors. In an immunoelectron microscopic study of colonic carcinomas, SP1 and carcinoembryonic antigen were found in all seven tumors studied, none of the tumors showing morphologic evidence of choriocarcinoma. PLAP and hCG were found in two tumors (Haynes et al, 1985). In urothelial tumors, immunoreactive SP1 were observed in five of 47 high-grade tumors. HCG and hPL were found in nine and seven cases respectively. These findings suggested that morphologic and functional trophoblastic differentiation evolved from transitional cell carcinoma (Campo et al, 1989). Earlier studies suggested that SP1 expression was a poor prognostic factor in breast carcinoma but this has not been substantiated (Wright et al, 1987). SP1 has been employed in the panel for the distinction of mesothelioma from adenocarcinoma, being positive in almost 60% of adenocarcinomas. However, SP1 is also expressed in mesotheliomas, albeit in lower frequency (6%) (Pfaltz et al, 1987).

References
•Campo E, Algaba F, Palacin A et al 1989. Placental proteins in highgrade urothelial neoplasms. An immunohistochemical study of human chorionic gonadotropin, human placental lactogen, and pregnancy-specific beta 1-glycoprotein. Cancer; 63: 2497-2504.

•Haynes WD, Shertock KL, Skinner JM, Whitehead R 1985. The ultrastructural immunohistochemistry of oncofetal antigens in large bowel carcinomas. Virchows Archives A Pathology Anatomy and Histopathology; 405: 263-275.

•Pfaltz M, Odermatt B, Christen B, Ruttner JR 1987. Immunohistochemistry in the diagnosis of malignant mesothelioma. Virchows Archives A Pathology Anatomy and Histopathology; 411: 387-393.

•Plouzek CA, Leslie KK, Stephens JK, Chou JY 1993. Differential gene expression in the amnion, chorion, and trophoblast of the human placenta. Placenta; 14: 277-285.

•Sabet LM, Daya D, Stead R et al 1989. Significance and value of immunohistochemical localization of pregnancy specific proteins in feto-maternal tissue throughout pregnancy. Modern Pathology; 2: 227-232.

•Schlafke S, Lantz KC, King BF, Enders AC 1992. Ultrastructural localization of pregnancy-specific beta 1-glycoprotein (SP1) and cathepsin B in villi of early placenta of the macaque. Placenta; 13: 417-428.

•Shibata PK, Rutgers JL 1994. The placental site nodule: an immunohistochemical study. Human Pathology; 25: 1295-1301.

•Wright C, Angus B, Napier J et al 1987. Prognostic factors in breast cancer: immunohistochemical staining for SP1 and NCRC 11 related to survival, tumour epidermal growth factor receptor and oestrogen receptor status. Journal of Pathology; 153: 325-331.

Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.