Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 Feb;142(2):557–567.

Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein.

P Garin-Chesa 1, I Campbell 1, P E Saigo 1, J L Lewis Jr 1, L J Old 1, W J Rettig 1
PMCID: PMC1886733  PMID: 8434649

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.

Full text

PDF
557

Images in this article

561Figure 1
on p.561
563Figure 2
on p.563
564Figure 3
on p.564

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bast R. C., Jr, Feeney M., Lazarus H., Nadler L. M., Colvin R. B., Knapp R. C. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981 Nov;68(5):1331–1337. doi: 10.1172/JCI110380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bast R. C., Jr, Klug T. L., St John E., Jenison E., Niloff J. M., Lazarus H., Berkowitz R. S., Leavitt T., Griffiths C. T., Parker L. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med. 1983 Oct 13;309(15):883–887. doi: 10.1056/NEJM198310133091503. [DOI] [PubMed] [Google Scholar]
  3. Bhattacharya M., Chatterjee S. K., Barlow J. J., Fuji H. Monoclonal antibodies recognizing tumor-associated antigen of human ovarian mucinous cystadenocarcinomas. Cancer Res. 1982 May;42(5):1650–1654. [PubMed] [Google Scholar]
  4. Boerman O. C., van Niekerk C. C., Makkink K., Hanselaar T. G., Kenemans P., Poels L. G. Comparative immunohistochemical study of four monoclonal antibodies directed against ovarian carcinoma-associated antigens. Int J Gynecol Pathol. 1991;10(1):15–25. doi: 10.1097/00004347-199101000-00002. [DOI] [PubMed] [Google Scholar]
  5. Campbell I. G., Jones T. A., Foulkes W. D., Trowsdale J. Folate-binding protein is a marker for ovarian cancer. Cancer Res. 1991 Oct 1;51(19):5329–5338. [PubMed] [Google Scholar]
  6. Chesa P. G., Rettig W. J., Melamed M. R. Expression of cytokeratins in normal and neoplastic colonic epithelial cells. Implications for cellular differentiation and carcinogenesis. Am J Surg Pathol. 1986 Dec;10(12):829–835. doi: 10.1097/00000478-198612000-00001. [DOI] [PubMed] [Google Scholar]
  7. Coney L. R., Tomassetti A., Carayannopoulos L., Frasca V., Kamen B. A., Colnaghi M. I., Zurawski V. R., Jr Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein. Cancer Res. 1991 Nov 15;51(22):6125–6132. [PubMed] [Google Scholar]
  8. Elwood P. C. Molecular cloning and characterization of the human folate-binding protein cDNA from placenta and malignant tissue culture (KB) cells. J Biol Chem. 1989 Sep 5;264(25):14893–14901. [PubMed] [Google Scholar]
  9. Garin-Chesa P., Melamed M. R., Rettig W. J. Immunohistochemical analysis of human neuronectin expression in normal, reactive, and neoplastic tissues. J Histochem Cytochem. 1989 Dec;37(12):1767–1776. doi: 10.1177/37.12.2685107. [DOI] [PubMed] [Google Scholar]
  10. Garin-Chesa P., Old L. J., Rettig W. J. Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7235–7239. doi: 10.1073/pnas.87.18.7235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Garin-Chesa P., Rettig W. J. Immunohistochemical analysis of LNT, NeuAc2----3LNT, and Lex carbohydrate antigens in human tumors and normal tissues. Am J Pathol. 1989 Jun;134(6):1315–1327. [PMC free article] [PubMed] [Google Scholar]
  12. Henderson G. B. Folate-binding proteins. Annu Rev Nutr. 1990;10:319–335. doi: 10.1146/annurev.nu.10.070190.001535. [DOI] [PubMed] [Google Scholar]
  13. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  14. Jansen G., Westerhof G. R., Kathmann I., Rademaker B. C., Rijksen G., Schornagel J. H. Identification of a membrane-associated folate-binding protein in human leukemic CCRF-CEM cells with transport-related methotrexate resistance. Cancer Res. 1989 May 1;49(9):2455–2459. [PubMed] [Google Scholar]
  15. Kamen B. A., Capdevila A. Receptor-mediated folate accumulation is regulated by the cellular folate content. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5983–5987. doi: 10.1073/pnas.83.16.5983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kane M. A., Waxman S. Role of folate binding proteins in folate metabolism. Lab Invest. 1989 Jun;60(6):737–746. [PubMed] [Google Scholar]
  17. Kurrasch R. H., Rutherford A. V., Rick M. E., Gallo M. G., Lovelace E. T., Pastan I., Willingham M. C. Characterization of a monoclonal antibody, OVB1, which binds to a unique determinant in human ovarian carcinomas and myeloid cells. J Histochem Cytochem. 1989 Jan;37(1):57–67. doi: 10.1177/37.1.2461982. [DOI] [PubMed] [Google Scholar]
  18. Mattes M. J., Cordon-Cardo C., Lewis J. L., Jr, Old L. J., Lloyd K. O. Cell surface antigens of human ovarian and endometrial carcinoma defined by mouse monoclonal antibodies. Proc Natl Acad Sci U S A. 1984 Jan;81(2):568–572. doi: 10.1073/pnas.81.2.568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miotti S., Canevari S., Ménard S., Mezzanzanica D., Porro G., Pupa S. M., Regazzoni M., Tagliabue E., Colnaghi M. I. Characterization of human ovarian carcinoma-associated antigens defined by novel monoclonal antibodies with tumor-restricted specificity. Int J Cancer. 1987 Mar 15;39(3):297–303. doi: 10.1002/ijc.2910390306. [DOI] [PubMed] [Google Scholar]
  20. Poels L. G., Peters D., van Megen Y., Vooijs G. P., Verheyen R. N., Willemen A., van Niekerk C. C., Jap P. H., Mungyer G., Kenemans P. Monoclonal antibody against human ovarian tumor-associated antigens. J Natl Cancer Inst. 1986 May;76(5):781–791. [PubMed] [Google Scholar]
  21. Rettig W. J., Chesa P. G., Beresford H. R., Feickert H. J., Jennings M. T., Cohen J., Oettgen H. F., Old L. J. Differential expression of cell surface antigens and glial fibrillary acidic protein in human astrocytoma subsets. Cancer Res. 1986 Dec;46(12 Pt 1):6406–6412. [PubMed] [Google Scholar]
  22. Rettig W. J., Cordon-Cardo C., Koulos J. P., Lewis J. L., Jr, Oettgen H. F., Old L. J. Cell surface antigens of human trophoblast and choriocarcinoma defined by monoclonal antibodies. Int J Cancer. 1985 Apr 15;35(4):469–475. doi: 10.1002/ijc.2910350409. [DOI] [PubMed] [Google Scholar]
  23. Rettig W. J., Cordon-Cardo C., Ng J. S., Oettgen H. F., Old L. J., Lloyd K. O. High-molecular-weight glycoproteins of human teratocarcinoma defined by monoclonal antibodies to carbohydrate determinants. Cancer Res. 1985 Feb;45(2):815–821. [PubMed] [Google Scholar]
  24. Rettig W. J., Garin-Chesa P., Beresford H. R., Oettgen H. F., Melamed M. R., Old L. J. Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells. Proc Natl Acad Sci U S A. 1988 May;85(9):3110–3114. doi: 10.1073/pnas.85.9.3110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rettig W. J., Nishimura H., Yenamandra A. K., Seki T., Obata F., Beresford H. R., Old L. J., Silver J. Differential expression of the human Thy-1 gene in rodent-human somatic cell hybrids [corrected]. J Immunol. 1987 Jun 15;138(12):4484–4489. [PubMed] [Google Scholar]
  26. Rettig W. J., Old L. J. Immunogenetics of human cell surface differentiation. Annu Rev Immunol. 1989;7:481–511. doi: 10.1146/annurev.iy.07.040189.002405. [DOI] [PubMed] [Google Scholar]
  27. Rettig W. J., Spengler B. A., Chesa P. G., Old L. J., Biedler J. L. Coordinate changes in neuronal phenotype and surface antigen expression in human neuroblastoma cell variants. Cancer Res. 1987 Mar 1;47(5):1383–1389. [PubMed] [Google Scholar]
  28. Sadasivan E., Rothenberg S. P. The complete amino acid sequence of a human folate binding protein from KB cells determined from the cDNA. J Biol Chem. 1989 Apr 5;264(10):5806–5811. [PubMed] [Google Scholar]
  29. Stein R., Goldenberg D. M., Mattes M. J. Normal tissue reactivity of four anti-tumor monoclonal antibodies of clinical interest. Int J Cancer. 1991 Jan 21;47(2):163–169. doi: 10.1002/ijc.2910470202. [DOI] [PubMed] [Google Scholar]
  30. Tagliabue E., Mènard S., Della Torre G., Barbanti P., Mariani-Costantini R., Porro G., Colnaghi M. I. Generation of monoclonal antibodies reacting with human epithelial ovarian cancer. Cancer Res. 1985 Jan;45(1):379–385. [PubMed] [Google Scholar]
  31. Tsuji Y., Suzuki T., Nishiura H., Takemura T., Isojima S. Identification of two different surface epitopes of human ovarian epithelial carcinomas by monoclonal antibodies. Cancer Res. 1985 May;45(5):2358–2362. [PubMed] [Google Scholar]
  32. Veggian R., Fasolato S., Ménard S., Minucci D., Pizzetti P., Regazzoni M., Tagliabue E., Colnaghi M. I. Immunohistochemical reactivity of a monoclonal antibody prepared against human ovarian carcinoma on normal and pathological female genital tissues. Tumori. 1989 Oct 31;75(5):510–513. doi: 10.1177/030089168907500524. [DOI] [PubMed] [Google Scholar]
  33. Willingham M. C., FitzGerald D. J., Pastan I. Pseudomonas exotoxin coupled to a monoclonal antibody against ovarian cancer inhibits the growth of human ovarian cancer cells in a mouse model. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2474–2478. doi: 10.1073/pnas.84.8.2474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. de Kretser T. A., Thorne H. J., Jacobs D. J., Jose D. G. The sebaceous gland antigen defined by the OM-1 monoclonal antibody is expressed at high density on the surface of ovarian carcinoma cells. Eur J Cancer Clin Oncol. 1985 Sep;21(9):1019–1035. doi: 10.1016/0277-5379(85)90286-x. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES