© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 21, 1882-1887,
November 3, 1999
© 1999 Oxford University Press
REPORTS |
Laminin-5 as a Marker of Invasiveness in Cervical Lesions
Affiliations of authors: B. Skyldberg, Division of Cellular and Molecular Tumor Pathology, Department of Oncology and Pathology, Karolinska Institute, and Division of Biomedical Laboratory Technology, Department of Immunology, Microbiology, Pathology and Infectious Diseases, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden; E. Eriksson, U. Aspenblad, G. Auer, Division of Cellular and Molecular Tumor Pathology, Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institute and Hospital; S. Salo, Biocenter Oulu and Department of Biochemistry, University of Oulu, Finland; B. Moberger, Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institute and Hospital; K. Tryggvason, Biocenter Oulu and Department of Biochemistry, University of Oulu, Finland, and Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute.
Correspondence to: Barbro Skyldberg, Ph.D., Cancer Center Karolinska, R8:04, Karolinska Hospital, S-171 76 Stockholm, Sweden (e-mail: Barbro.Skyldberg{at}cck.ki.se).
BACKGROUND: Treatment decisions for cervical cancer, a common disease worldwide, depend
on demonstrating whether or not tumor invasion of the surrounding tissue has occurred. Invasion
can be difficult to assess by standard histopathologic methods, especially when limited amounts of
tissue are available. Several studies of a variety of cancers have reported increased expression of
laminin-5—an important attachment protein for epithelial cells—in invasive
carcinomas. This study was designed to investigate whether the presence of laminin-5 is related to
the invasive capacity of cervical lesions. METHODS: We used immunohistochemical methods to
stain archival, paraffin-embedded sections of cervical lesions with a polyclonal antibody
specifically targeting the 
2 chain of human laminin-5 protein. The study sample included 23
lesions of mild and moderate dysplasia (cervical intraepithelial neoplasia [CIN] 1 and
2, respectively), 32 lesions of severe dysplasia or carcinoma in situ (CIN 3), 15 lesions of
microinvasive cancer, and 20 lesions of frankly invasive cancer. Cellular proliferative activity was
also investigated by the use of monoclonal MIB-1 (directed against the antigen Ki-67) and
anticyclin A antibodies. RESULTS: Invasiveness of cervical lesions was positively associated with
immunohistochemical staining of the 2 chain of laminin-5 (two-sided P =
.001). All CIN 1 and CIN 2 lesions—except one CIN 2 lesion later shown to be invasive
cancer—and 21 CIN 3 lesions tested negative for the 2 chain of laminin-5. Eleven
CIN 3 lesions and all invasive cancers tested positive for this protein. One lymph node metastasis
and a pleural metastasis from one of the patients with invasive cancer showed strong
immunohistochemical positivity. Proliferative activity increased with advancement of the lesion
but was not confined to cells positive for the 2 chain of laminin-5. CONCLUSIONS: These
data suggest that antibodies directed against the 2 chain of laminin-5 can identify cervical
lesions with invasive capacity and thus may be useful as a sensitive marker of early invasion.
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