Expression of Keratin Proteins in Deeply Invasive Basal and Squamous Cell Carcinoma: An Immunohistochemical Study

Abstract

The expression of certain classes of keratin is associated with cell maturation and differentiation. During cell transformation and tumor development, the cell specificity of intermediate filament, keratin, is largely conserved. Taking advantage of this, we utilized monoclonal antikeratin immunohistochemical techniques to examine basal and squamous cell carcinomas as they became deeply invasive. Dyskeratotic keratinocytes and keratin pearls in squamous cell carcinomas (SCCs) stain with antikeratin antisera to larger keratins (65-67 Kd). At the deep tumor margins, SCCs no longer express larger keratins but retain expression of 50, 58 Kd, which are markers of keratinocytes derived from stratified squamous epithelial cells. This selective loss of expression of keratin polypeptide markers of differentiation in SCC is associated with progressively more aggressive biologic behavior as the tumor invades deeper structures such as muscle and bone. Recurrent basal cell carcinoma (BCC) which was of the nodular type when first excised, shows features of morphea-like BCC and of aggressive growth patterns at the deep invasive margin. At these deep margins, some tumors express markers of keratinization (65-67 Kd). While tumor cells retain the specificity of the intermediate filament, keratin, the individual cells express products of differentiation as measured by keratin expression independently of their cytologic atypia. At the deeper invasive margin of the tumor, the neoplastic cells synthesize keratin proteins in an unpredictable fashion.

Absence of differentiation-related expression of keratin 10 in earlystages of vulvar squamous carcinoma

“…In the epidermis, keratins 1 and 10 * To whom offprint requests should be sent are expressed only in the suprabasal layers of the epidermis and their expression increases with epidermal maturation. In the terminally differentiated keratinocytes of the stratum corneum (SC), keratins 1 and 10 are modified posttranslationally [4, 251. Consequently, cytokeratins 1 and 10 are regarded as markers of orthokeratinization [14, 27, 291. Keratinizing areas expressing these two keratins were demonstrated in various well-differentiated squamous cell carcinomas (SCC) originating from the epidermis [II, 37, 18, 21,261 or from various internal stratified epithelia [2, 10, 1 I].…”

Current Histologic Preparation Methods for Mohs Micrographic Surgery

“…LABORATORY METHODS used to process the frozen sections of Mohs micrographic surgery have evolved by automating the process and by applying immunohistochemical (IHC) techniques 1–5 . While previous surveys obtained information on the cryostat used and its reliability, 6 and about the use of xylene substitutes in processing frozen sections, 7 staining methods currently used were not available.…”

Innovative 19-Minute Rapid Cytokeratin Immunostaining of Nonmelanoma Skin Cancer in Mohs Micrographic Surgery

“…It uses the same methodology reported on previously for melanoma‐associated antigen recognized by T cells, which was applied to the study of melanocytes in patients with chronically sundamaged skin 14 . The AE1/AE3 cocktail of anti‐CK antibodies was chosen because of its broad recognition of acidic and basic CKs, reportedly a constituent of BCCs and SCCs 12,13,15 . AE1 detects high‐molecular‐weight CK10, 14, 15, and 16 and low‐molecular‐weight CK19.…”

“…Well‐differentiated SCCs stain with the higher‐molecular‐weight CKs between 62 and 67 kDa, yet the more poorly differentiated tumors may express only the lower‐molecular‐weight keratins, such as 45 and 46 kDa. These may not label with individual CK antibodies, but the AE1/AE3 “cocktail” will stain most SCCs, regardless of how deeply invasive they are, and BCCs, regardless of the degree of squamous differentiation 15 . Thus, the mixture of AE1/AE3 antibodies is ideally suited for detecting small fragments of SCC and BCC at surgical margins by immunohistochemistry.…”

“…14 The AE1/AE3 cocktail of anti-CK antibodies was chosen because of its broad recognition of acidic and basic CKs, reportedly a constituent of BCCs and SCCs. 12,13,15 AE1 detects high-molecular-weight CK10, 14, 15, and 16 and low-molecular-weight CK19. The AE3 clone, on the other hand, detects CK 1, 2, 3, 4, 5, and 6 and low-molecular-weight CK 7 and 8.…”