The expression of cytokeratins (CKs) in normal cervical ephitelium, low grade squamous intraepithelial lesions (SIL), high grade SILs and squamous cell carcinoma (SCC) were analyzed using four different monoclonal antikeratin antibodies. In normal cervical epithelium, CK 18 showed strong immunoreactivity in basal and parabasal layers. CK 19 and 14 were expressed only in the basal layer while CK 13 was found selectively in the spinal cells. As the lesions progressed from low grade SIL to high grade SIL, immunoreactivity of CK 18, 19 and 14 in the basal cell compartment increased while the expression of CK 13 decreased. In SCC, well-differentiated tumors showed decreased immunoreactivity for CK 18, 19 and 14 with CK 13 showing a strong and focal (localized) immunoreactivity. Undifferentiated carcinomas totally lacked CK 13 reactivity. Our findings therefore suggest that expression of CK 18, 19 and 14 may be directly related to tumor grade and CK 13 may be a marker of differentiation in cervical lesions.
The expression of involucrin, a cytoplasmic protein synthesized during squamous maturation, was assessed by immunocytochemistry in different grades of cervical lesions. In normal/benign cervical epithelium and low-grade squamous intraepithelial lesions [SILS or cervical intraepithelial neoplasia (CIN)-1] involucrin showed intense and homogenous cytoplasmic expression in the spinal layers of 75 and 57% of samples, respectively. The basal cell layers showed no expression of involucrin. In high-grade SILs (CIN-2/3) 40% of the samples showed diffuse and focal cytoplasmic expression of involucrin in the differentiated basaloid cells. In the squamous cell carcinomas (SCCs) analyzed, well-differentiated tumors showed intense focal expression in 61 % of the cases, moderately differentiated SCCs showed intense expression in 33% of the cases, while poorly differentiated SCCs (PDSCC) showed only a mild focal expression in 7% of cases. With increasing severity of the lesions, patchy expression of involucrin with a mixture of reactive and nonreactive cells predominated. Patterns of immunocytochemical staining for involucrin in cervical lesions of different grades, from low-grade to high-grade SILs, and invasive carcinoma may be of critical importance, if loss of involucrin expression is used as a criterion for neoplastic transformation in cervical epithelium. Our findings suggest that involucrin may be a sensitive marker in identifying the differentiation status of the lesion while the absence of involucrin in PDSCC may be helpful in differential diagnosis.
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