Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein. Garin-Chesa, P; Campbell, I; Saigo, PE; Lewis, JL; Old, LJ; Rettig, WJ Am J Pathol
142
557-67
1993
Show Abstract
The LK26 antigen is a cell surface glycoprotein (M(r)35,000 to 40,000) of normal placenta and gestational choriocarcinomas that shows highly restricted distribution in normal tissues, being expressed primarily in a subset of simple epithelia. In this study, immunohistochemical methods were used to examine LK26 expression in 78 ovarian tumors and > 400 tumors of other histological types. Ovarian carcinomas derived from coelomic epithelium showed the most consistent and strongest immunostaining for LK26, with 52 of 56 cases being LK26+. Ovarian tumors of sex cord, germ cell, and stromal origin were generally LK26-. LK26 was not found in normal fetal or adult ovary; however, it was present in the lining epithelia of some benign ovarian cysts. Mesotheliomas, which share a common mesothelial origin with LK26+ ovarian tumors, expressed no or only low levels of LK26. Other epithelial cancers expressed LK26 in subsets of cases and generally showed heterogeneous or weak immunostaining; this group of LK26+ tumors includes endometrial (10 of 11 cases tested), colorectal (six of 27), breast (11 of 53), lung (six of 18), and renal cell (nine of 18) carcinomas. Four of five brain metastases derived from epithelial cancers and three of 21 neuroendocrine carcinomas showed prominent LK26 immunoreactivity. Only rare neuroectodermal tumors (two of 70) and none of the sarcomas (none of 58) or lymphomas tested (none of 21) were LK26+. Tests with cultured cells showed that the LK26 proteins expressed in choriocarcinoma and ovarian cancer cells are biochemically similar, and transfection experiments identified LK26 as an adult-type, high-affinity folate-binding protein. The present study provides the first detailed specificity and sensitivity analysis for folate-binding protein/LK26 in human tumors and defines a role for folate-binding protein/LK26 in immunobiological studies of ovarian cancers and other LK26+ neoplasms. | 8434649
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Cell surface antigens of human trophoblast and choriocarcinoma defined by monoclonal antibodies. Rettig, WJ; Cordon-Cardo, C; Koulos, JP; Lewis, JL; Oettgen, HF; Old, LJ Int J Cancer
35
469-75
1985
Show Abstract
Six distinct cell surface antigens of human trophoblast and choriocarcinoma were defined with MAbs. The distribution of the antigens was determined by MHA assays on 150 tumor cell lines and normal cell cultures and by immunofluorescence tests with a wide range of normal adult and fetal tissues and a tumor panel. Antigen LK26 is expressed on all cultured choriocarcinoma, teratocarcinoma and renal cancer lines but is absent from most cell lines derived from other tumor types and from cultures of normal kidney epithelium and fibroblasts. LK26 expression in normal tissues is restricted to the trophoblast. No other adult or fetal tissue was found to express the antigen, but choriocarcinoma and teratocarcinoma tissues were LK26+. SV19 is expressed on cultured choriocarcinomas and teratocarcinomas and on subsets of breast and colon cancer lines, but not on 120 additional cultures tested. In tissues, SV19 is detected in normal placenta, mammary gland and colon epithelium as well as in tumors of breast, colon and lung. Two antibodies, AbSV63 and AbK8, react with PLAP and AbSV63 also reacts with the intestinal form of the enzyme. AbLK24 defines a heat-stable determinant present on choriocarcinoma and breast cancer cell lines but absent from most other cultured cells. It is expressed on a small range of normal and malignant epithelial tissues, including normal trophoblast, normal breast epithelium and urothelium and tumors derived from these tissues. One antigen, K66, showed a wide distribution on cultured epithelial cells but was not found in any normal or malignant tissue. Finally, S4, a previously described marker of normal and malignant kidney epithelial cells, was also expressed on the choriocarcinoma cell lines. Four of the antigens are glycoproteins that could be immunoprecipitated from radiolabelled extracts of choriocarcinoma cells: LK26 (Mr 35,000), SV19 (Mr 40,000), PLAP (Mr 68,000) and S4 (Mr 160,000). The highly restricted distribution of LK26, SV19, S4, and PLAP in normal tissues and their expression in tumors make these antigens potential diagnostic markers of gestational choriocarcinoma and germ-cell tumors and, possibly, targets for immunotherapy. | 2580800
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