Laminin-5 as a marker of invasiveness in cervical lesions

Background: Treatment decisions for cervical cancer, a common disease world wide, depend on demonstrating whether or not tumor invasion of the surround ing tissue has occurred. Invasion can be difficult to assess by standard hi stopathologic methods, especially when limited amounts of tissue are availa ble. Several studies of a variety of cancers have reported increased expres sion of laminin-5-an important attachment protein for epithelial cells-in i nvasive carcinomas. This study was designed to investigate whether the pres ence of laminin-5 is related to the invasive capacity of cervical lesions. Methods: We used immunohistochemical methods to stain archival, paraffin-em bedded sections of cervical lesions with a polyclonal antibody specifically targeting the gamma 2 chain of human laminin-5 protein. The study sample i ncluded 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 lesio ns of frankly invasive cancer. Cellular proliferative activity was also inv estigated by the use of monoclonal MIB-1 (directed against the antigen Ki-6 7) and anticyclin A antibodies. Results: Invasiveness of cervical lesions w as positively associated with immunohistochemical staining of the gamma 2 c hain 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 tes ted negative for the gamma 2 chain of laminin-5. Eleven CIN 3 lesions and a ll invasive cancers tested positive for this protein. One lymph node metast asis and a pleural metastasis from one of the patients with invasive cancer showed strong immunohistochemical positivity. Proliferative activity incre ased with advancement of the lesion but was not confined to cells positive for the gamma 2 chain of laminin-5. Conclusions: These data suggest that an tibodies directed against the gamma 2 chain of laminin-5 can identify cervi cal lesions with invasive capacity and thus may be useful as a sensitive ma rker of early invasion.