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Epithelial distribution of filaggrin, a histidine-rich protein related to squamous terminal differentiation, was investigated in 87 cervical biopsies using an avidin-biotin-peroxidase technique with a monoclonal anti-human filaggrin antibody (AKH1). Normal squamous cervical epithelium exhibited a positive homogeneous immunoperoxidase stain in the upper parabasal, intermediate and superficial cell layers. Similar findings were obtained in cervical condylomas, although full-thickness staining was observed in 35.7% of the cases (P < 0.001). Filaggrin expression in CIN was inversely related to the severity of the lesion (P < 0.001). An irregular staining pattern was present in most high-grade CIN. Filaggrin expression was closely connected to the degree of tumour differentiation (P < 0.05) in squamous cell carcinomas of the cervix. Abnormal filaggrin stainings identified a premalignant/malignant cervical squamous lesion with a positive predictive value of 92.3%. Non-squamous epithelia showed lack of filaggrin expression. Filaggrin may therefore be considered a marker of squamous differentiation in both the normal and pathological human uterine cervix.

We used immunoperoxidase methods employing antibodies against involucrin and filaggrin, both markers of squamous terminal differentiation, to study squamous metaplastic transformation in the human endocervix. Expression of involucrin and filaggrin was restricted to squamous metaplastic cells whereas columnar epithelial cells were constantly negative. Immature squamous metaplastic epithelium also showed a positive immunostaining. In mature squamous metaplasia a suprabasal homogeneous staining pattern similar to that found in the exocervical epithelium was detected, although with full-thickness filaggrin immunoreactivity in 45% of cases (P less than 0.05). These results support the hypothesis of an epithelial origin of reserve subcolumnar cells, and suggest that precocious squamous differentiation seems to take place in metaplastic cells of the human endocervix.

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