Abstract
The monoclonal antibody, INS‐2, was raised against rat fibroblasts transformed by open reading frames E6 and E7 of human papillomavirus (HPV) DNA. In immunoperoxidase testing of frozen sections, the INS‐2 antibody was reactive with all squamous cell carcinomas of the uterine cervix and esophagus tested. In contrast, no antibody binding was detected with adenocarcinomas of various origins. Similarly, normal tissues, lymphoid cells and erythrocytes from multiple donors were negative, except that binding localized at basal cells in normal squamous epithelium was observed. Interestingly, strong staining was observed in dysplastic cells of cervical intraepithelial neoplasia and at the growing edge of squamous cell carcinomas. The antigen for the INS‐2 antibody is a non‐sialyl glycoprotein with Mw. 40,000 and appears to be a squamous cell‐specific cell differentiation marker, although it is not related to HPV‐DNA‐derived protein.
Keywords: Tumor marker, Differentiation marker, Cancer‐associated antigen, Squamous cell carcinoma, Cervical cancer
Full Text
The Full Text of this article is available as a PDF (875.2 KB).
REFERENCES
- 1. ) Dürst , M. , Gissmann , L. , Ikenberg , H. and zür Hausen H.A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions . Proc. Natl. Acad. Sci. USA , 80 , 3812 – 3815 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. ) Yoshikawa , H. , Matsukura , T. , Yamamoto , E. , Kawana , T. , Mizuno , M. and Yoshiike , K.Occurrence of human papillomavirus types 16 and 18 DNA in cervical carcinomas from Japan: age of patients and histological type of carcinomas . Jpn. J. Cancer Res , 76 , 667 – 671 ( 1985. ). [PubMed] [Google Scholar]
- 3. ) Kadish , A. , Burk , R. , Kress , Y. , Calderin , S. and Romney , S.Human papillomaviruses of different types in precancerous lesions of the uterine cervix: histologic, immuno‐cytochemical and ultrastructural studies . Hum. Pathol. , 17 , 384 – 392 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Saito , J. , Yutsudo , M. , Inoue , M. , Ueda , G. , Tanizawa , O. and Hakura , A.New human papillomavirus sequences in female genital tumors from Japanese patients . Jpn. J. Cancer Res. , 78 , 1081 – 1087 ( 1987. ). [PubMed] [Google Scholar]
- 5. ) Schwarz , E. , Freese , U. K. , Gissmann , L. , Mayer , W. , Roggenbuck , B. , Stremlau , A. and zür Hausen H.Structure and transcription of human papillomavirus sequences in cervical carcinoma cells . Nature , 314 , 111 – 113 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Yutsudo , M. , Okamoto , Y. and Hakura , A.Functional dissociation of transforming genes of human papillomavirus type 16 . Virology , 166 , 594 – 597 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Seedorf , K. , Oltersdorf , T. , Krammer , G. and Rowekamp , W.Identification of early proteins of human papilloma viruses type 16 (HPV 16) and type 18 (HPV 18) in cervical carcinoma cells . EMBO J. , 6 , 139 – 144 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Oltersdorf , T. , Seedorf , K. , Röwekamp , W. and Gissmann , L.Identification of human papillomavirus type 16E7 protein by monoclonal antibodies . J. Gen. Virol. , 68 , 2933 – 2938 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Schneider‐Gadicke , A. , Kaul , S. , Schwanz , E. , Gausepohl , H. , Frank , R. and Bastert , G.Identification of the human papillomavirus type 18E6 and E6 proteins in nuclear protein fractions from human cervical carcinoma cells grown in nude mouse or in vitro . Cancer Res. , 48 , 2969 – 2974 ( 1988. ). [PubMed] [Google Scholar]
- 10. ) Sato , H. , Watanabe , S. , Furuno , A. and Yoshiike , K.Human papillomavirus type 16E7 protein expressed in Escherichia coli and monkey COS‐1 cells: immunofluorescence detection of the nuclear E7 protein . Virology , 170 , 311 – 315 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Inoue , H. , Yutsudo , M. and Hakura , A.Rat mutant cells showing temperature sensitivity for transformation by wild‐type Moloney murine sarcoma virus . Virology , 125 , 242 – 245 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Freeman , A. E. , Igel , H. J. and Price , P. J.In vitro transformation of rat embryo cells: correlations with the known tumorigenic activities of chemicals in rodents . In Vitro , 11 , 107 – 116 ( 1975. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Mann , R. , Mulligan , R. C. and Baltimore , C.Construction of a retrovirus packaging mutant and its use to produce helper‐free defective retrovirus . Cell , 33 , 153 – 159 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Köhler , G. and Milstein , C.Continuous cultures of fused cells secreting antibody of predefined specificity . Nature , 256 , 495 – 497 ( 1975. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Hsu , S. M. , Raine , L. and Fanger , H.The use of avidinbiotin‐peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures . J. Histochem, Cytochem. , 29 , 577 – 581 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Towbin H.Staehelin T. and Gordon J.Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications . Proc. Natl. Acad. Sci. USA , 76 , 4350 – 4354 ( 1979. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. ) Moll , R. , Franke , W. W. , Schiller , D. L. , Geiger , B. and Krepler , R.The catalog of human cytokeratins: patterns of expression in normal epithelia, tumor and cultured cells . Cell , 31 , 11 – 21 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Moll , R. , Levy , R. , Czeernoblsky , B. , Hohlweg‐Majevt , P. , Dallenback‐Hellweg , G. and Franke , W. W.Cytokeratins of normal epithelia and some neoplasms of the female genital tract . Lab. Invest. , 49 , 599 – 610 ( 1983. ). [PubMed] [Google Scholar]
- 19. ) Gigi‐Leitner , O. , Geiger , B. , Levy , R. and Czernobilsky , B.Cytokeratin expression in squamous metaplasia of the human uterine cervix . Differentiation , 31 , 191 – 205 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Kyoizumi , S. , Akiyama , M. , Kouno , N. , Kobuke , K. , Hakoda , M. , Jones , S. L. and Yamakido , M.Monoclonal antibodies to human squamous cell carcinoma of the lung and their application to tumor diagnosis . Cancer Res. , 45 , 3274 – 3281 ( 1985. ). [PubMed] [Google Scholar]
- 21. ) Prat , M. , Morra , I. , Bussolati , G. and Comoglio , P. M.CAR‐3, a monoclonal antibody‐defined antigen expressed on human carcinomas . Cancer Res. , 45 , 5799 – 5807 ( 1985. ). [PubMed] [Google Scholar]
- 22. ) Koprowska , I. , Zipfel , S. A. , Himes , T. R. and Herlyn , M.Common antigenic sites on exfoliated cells derived from cervical carcinoma and in tumor cells of nonuterine origin as demonstrated by monoclonal antibodies in immunoperoxidase assay . Cancer Res. , 45 , 5964 – 5968 ( 1985. ). [PubMed] [Google Scholar]
- 23. ) Boeheim , K. , Speak , J. A. , Frei , E. and Bernal , S. D.SQM1 antibody defines a surface membrane antigen in squamous carcinoma of the head and neck . Int. J. Cancer , 36 , 137 – 142 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Fernsten , P. D. , Pekny , K. W. , Reisfeld , R. A. and Walker , L. E.Antigena associated with human squamous cell lung carcinoma defined by murine monoclonal antibodies . Cancer Res. , 46 , 2970 – 2977 ( 1986. ). [PubMed] [Google Scholar]
- 25. ) Hanai , N. , Shitara , K. and Yoshida , H.Generation of monoclonal antibodies against human lung squamous cell carcinoma and adenocarcinoma using mice rendered tolerant to normal human lung . Cancer Res. , 46 , 4438 – 4443 ( 1986. ). [PubMed] [Google Scholar]
- 26. ) Kato , H. , Suehiro , Y. , Morioka , H. , Torigoe , T. , Myoga , A. , Sekiguchi , K. and Ikeda , I.Heterogeneous distribution of acidic TA‐4 in cervical squamous cell carcinoma: immunohistochemical demonstration with monoclonal antibodies . Jpn. J. Cancer Res. , 78 , 1246 – 1250 ( 1987. ). [PubMed] [Google Scholar]
- 27. ) Morhenn , V. B. , Schreiber , A. B. , Soriero , O. , McMillan , W. and Allison , A. C.A monoclonal antibody against basal cells of human epidermis . J. Clin. Invest. , 76 , 1978 – 1980 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. ) Kimmel , K. A. and Carey , T. E.Altered expression in squamous carcinoma cells of an orientation restricted epithelial antigen detected by monoclonal antibody A9 . Cancer Res. , 46 , 3614 – 3623 ( 1986. ). [PubMed] [Google Scholar]
- 29. ) Ranken , R. , White , C. F. , Gottfried , T. G. , Yonkovich , S. J. , Blazek , B. E. , Moss , M. S. , Fee , W. E. , Jr. and Liu , Y‐S. V.Reactivity of monoclonal antibody 17.13. with human squamous cell carcinoma and its application to tumor diagnosis . Cancer Res. , 47 , 5684 – 5690 ( 1987. ). [PubMed] [Google Scholar]
- 30. ) Samuel , J. , Neujaim , A. A. , Willans , D. J. , Brzezinska , G. S. , Haines , D. M. and Longenecker , B. M.A novel marker for basal (stem) cells of mammalian stratified squamous epithelia and squamous cell carcinoma . Cancer Res. , 49 , 2465 – 2470 ( 1989. ). [PubMed] [Google Scholar]