Involucrin is a recently recognized structural component of mature squamous epithelial cells. We examined involucrin expression using an immunoperoxidase technique in normal skin and in a variety of epidermal hyperplasias and neoplasms to determine whether distinctive staining patterns existed within these lesions. Four patterns of reactivity were observed: diffuse intracellular staining typical of keratinocytes of the upper third of normal epidermis and epidermal hyperplasias and benign neoplasms; staining at cell borders, seen principally in benign epidermal neoplasms; patchy staining characteristic of squamous cell carcinoma in situ; and absence of staining in benign and neoplastic basaloid epithelium. Invasive nests of squamous cell carcinomas were negative for involucrin reactivity, whereas pseudoinvasive tongues of epithelium at the bases of keratoacanthomas were focally positive. These results suggest that immunoperoxidase staining for involucrin may be useful in distinguishing certain benign from malignant epidermal neoplasms as well as in understanding the altered maturation and kinetics of proliferative processes afflicting keratinocytes.

A study was undertaken to determine whether immunoperoxidase stains for keratin and involucrin, the latter a protein present in cells of stratified squamous epithelium that have differentiated beyond the basal stage, distinguish any differences in squamous cells present in the adenoacanthoma from those in the adenosquamous carcinoma of the uterine corpus. Forty-eight tumors were studied, of which 33 were adenoacanthomas and 15 adenosquamous carcinomas. The patients with adenoacanthomas were slightly younger (mean 61.5 vs. 64.5 years) and had tumors that were generally better differentiated than the adenosquamous carcinomas. The squamous epithelium in every tumor, regardless of histologic type, stained positively for keratin. There were no obvious differences in staining when tumors were stratified for histologic type, grade, or location within the tumor. The glandular portion of both tumor types stained irregularly, but nonetheless positively, for keratin in 71% of the cases. Involucrin was detected in 57% of adenoacanthomas and 87% of adenosquamous carcinomas. The deeper or more central portion of the squamous morules stained only if the more superficial or peripheral areas were positive. The extent of the involucrin staining was less in the adenosquamous carcinomas than in the adenoacanthomas. The glandular component of the tumors did not stain for involucrin. It is concluded that no qualitative differences in the staining reactions with respect to keratin and involucrin distinguish the adenoacanthomas from the adenoaquamous carcinoma. These findings support the argument that the adenoacanthoma and adenosquamous carcinoma represent a spectrum of squamous differentiation in a single tumor type.

Involucrin, a protein subunit of keratinocyte cross-linked envelopes, is a distinctive marker for suprabasal differentiation in stratified squamous epithelium. Immunoperoxidase staining for involucrin was used to evaluate paraffin sections of tissue obtained by colposcopically directed biopsies of infectious, metaplastic, and dysplastic lesions of the cervix and vagina. Areas of normal squamous epithelium, papillary and flat condyloma acuminatum, and mature and immature squamous metaplasia showed positive staining in 99 per cent of samples lacking significant inflammation and in 60 per cent of those with moderate or severe inflammation. In contrast, only 19 per cent of the squamous cell dysplasias, even those without much inflammation, showed positive staining, and no area with moderate or severe inflammation showed positive staining. These findings indicate that expression of involucrin is modulated by cellular pathologic features and microenvironment. We suggest that immunoperoxidase staining for involucrin may be useful in distinguishing mild dysplasia from immature metaplasia and flat condyloma in some biopsy specimens in which routine histologic examination yields an indeterminate diagnosis.

Forty-two cervical biopsies with cervical intraepithelial neoplasia were compared with respect to the expression of human papillomavirus (HPV) structural proteins and the expression of the cellular structural protein involucrin, a marker of suprabasal squamous differentiation. HPV structural protein and involucrin expression displayed an inverse correlation with the severity of dysplasia. Both of these proteins were detected in 11 of 28 cases (39%) of mild and moderate dysplasia, but in only two of 14 (14%) cases of severe dysplasia. This difference was statistically significant (p less than 0.001). The presence of HPV was also associated with expression of involucrin in the full thickness of the epithelium, including the basal layer, and an altered staining pattern in the more superficial cells, particularly the koilocytotic cells. These findings support the hypothesis that squamous differentiation is required for the expression of viral structural proteins and that HPV infection begins in the basal epithelium. The study also demonstrates the utility of involucrin staining in differentiating virus-induced cytologic atypia from true neoplasia.