Expression of matrix proteins in uterine cervical neoplasia using immunohistochemistry

Neoplastic cells of various tumors are capable of modifying extracellular matrix, and can reduce basement membrane components and express matrix proteins and mRNA. Findings in cervical cancer cells have been consistent concerning their ability to reduce basement membrane, but there is a lack of consensus concerning the expression of matrix proteins in the neoplastic cells. We have investigated the expression of matrix proteins in the subepithelial basement membrane, in blood vessels and in the epithelial cells using immunohistochemistry.

A total of 49 cases, including normal cervix, Cervical Intraepithelial Neoplastia (CIN) grades, I, II and III, and invasive squamous cell carcinoma, were stained for fibronectin (FN), laminin (LN) and collagen IV (C IV) and analyzed by immunohistochemistry. Subepithelial and peritumoral basement membrane staining for C IV was scored as 0, 1, 2 or 3 (0, absent; 1, weak and discontinuous; 2, weak or discontinuous; 3, strong and diffuse). Vascular basement membrane staining by all three markers was interpreted as positive or negative. Staining of normal epithelium, CIN lesions and invasive carcinoma cells was evaluated with all three markers.

Subepithelial basement membrane staining was graded as score = 3 in all normal cervices, in contrast to 9/10, 2/10, 1/10 and 0/9 cases of CIN I, CIN, II, CIN III and invasive carcinoma, respectively. Remaining cases showed variable degrees of basement membrane loss. In 6/10 CIN III cases and 8/9 carcinomas, staining was absent (score = 0). Blood vessels stained positive for FN, LN and C IV in all cases studied. Epithelial cells were LN-positive in only one case of CIN II and FN-positive in only two cases of CIN III. Conversely, 3/9 carcinomas were LN-positive, 6/9 were FN-positive and 2/9 were C IV-positive, including two cases positive for all three markers. Staining pattern was cytoplasmic, mainly in the periphery to tumor islands.

Invasive squamous cell carcinomas of the cervix are capable of expressing matrix proteins that are usually absent in normal squamous cervical cells or preinvasive lesions. Secretion or degradation of these proteins could facilitate tumor invasion of stroma and vessels. In addition, basement membrane dissolution becomes pronounced in CIN II-III lesions, being complete in most invasive carcinomas, probably reflecting the ability of pre-invasive neoplastic cells to degrade basement membrane components with metalloproteases.