involucrin and Carcinoma--Basal-Cell

Zfp191 represses differentiation and keeps various cells in the stem/progenitor stage. Here, we report that a Zfp191 homolog protein, ZNF396, is expressed in basal cell carcinoma (BCC) and possibly represses the expression of a Notch system effector molecule, Hes1 (hairy and enhancer of split-1), and prevents BCC cells from undergoing Notch-mediated squamous cell differentiation. ZNF396 immunoreactivity was found in the nucleus of 35 of 38 cutaneous BCC and 4 of 74 squamous cell carcinoma tissue specimens. In non-tumorous epidermal tissues, ZNF396 immunoreactivity was restricted in basal cells. siRNA-mediated silencing of ZNF396 induced the expression of Notch2, Hes1, and involucrin in cultured BCC cells. Finally, we found that siRNA-mediated silencing of ZNF396 gene inhibited the proliferation of TE354.T basal cell carcinoma cells. ZNF396 might repress Notch-Hes1 signaling axis and prevent tumor cells from undergoing squamous differentiation in BCC.

Topics: Basic Helix-Loop-Helix Transcription Factors; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Down-Regulation; HEK293 Cells; Homeodomain Proteins; Humans; Protein Precursors; Receptor, Notch2; RNA Interference; RNA, Small Interfering; Skin Neoplasms; Transcription Factor HES-1; Transcription Factors

We investigated protein expression and in situ activity of transglutaminases (TGs) in normal skin and various epidermal neoplasms. In normal skin, TG1 protein expression and TG activity were found at keratinocyte cell membranes in upper epidermis and granular layer, respectively. In seborrhoeic keratosis, TG1 protein was expressed evenly throughout tumors, while TG activity increased in gradient fashion from lower tumor area to cornified layer. In squamous cell carcinoma, TG1 protein was expressed at inner side of cell membranes, whereas TG activity was found in cytoplasm predominantly at horn pearls. In basal cell carcinoma, weak TG activity was found in cytoplasm of all tumor cells without the presence of TG1 protein. Immunoblotting and in situ activity assays using specific substrate peptides confirmed that TG2, but not TG1, contributed to the TG activity. These results suggested that different expression and activation of TGs may contribute to characteristics of the skin tumors.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Keratosis, Seborrheic; Protein Precursors; Skin; Skin Neoplasms; Transglutaminases

Trichoblastoma and nodular basal cell carcinoma are generally held to be distinctive epithelial neoplasms with some overlapping features. We investigated 30 trichoblastomas in which the basaloid cells expressed cytokeratins (CK) CK5/6, CK14, CK17, CK19, and, in a few cells, vimentin. The cells of the periphery of small and large cysts showed the same profile. Cells lining the lumen of small cysts expressed CK14, CK17, and involucrin, and those in larger cysts showed a positivity for CK1, CK4, CK10, CK14, CK17, and involucrin. The remaining tested antibodies (CK7, CK8, CK13, CK18, CK20, alpha-smooth-muscle actin) were negative in all cases. The cells of the stroma expressed vimentin and in 22 cases, the CD34 antigen. Seventeen nodular basal cell carcinomas showed exactly the same staining pattern. Furthermore, there are striking immunohistochemical similarities between the neoplastic basaloid cells of both neoplasms and the cells of the hair germ. Therefore, trichoblastoma and nodular basal cell carcinoma cannot be distinguished by their pattern of cytokeratin expression in paraffin sections. The virtually identical cytokeratin pattern seen in trichoblastoma, basal cell carcinoma, and the developing fetal hair follicle is compelling evidence for common differentiation pathway.

Topics: Actins; Adult; Aged; Aged, 80 and over; Antigens, CD34; Carcinoma, Basal Cell; Cell Differentiation; Cysts; Epithelium; Female; Fetus; Gene Expression Regulation, Neoplastic; Hair Follicle; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Melanocytes; Middle Aged; Neoplasms, Basal Cell; Paraffin Embedding; Protein Precursors; Skin Neoplasms; Vimentin

Whether the peripheral ameloblastoma (PA) and intraoral basal cell carcinoma (BCC) are two different clinical entities or essentially the same lesion still remains unresolved. The immunophenotypes of neoplastic cells of peripheral and intraosseous ameloblastomas, ameloblastic carcinomas, and BCCs were studied using a panel of monoclonal/polyclonal antibodies and lectins. The major cytokeratins (CKs) of neoplastic cells of ameloblastomas were CKs 5 and 14, whereas co-expression of CKs 8, 18, and 19 was observed in the cells of the stellate reticulum-like areas. Metaplastic squamous and keratinizing cells found in follicular and acanthomatous variants of ameloblastomas expressed CKs 1 and 10, involucrin, and binding sites for the lectins Ulex europeaus agglutinin I and Helix pomatia agglutinin. beta 2-Microglobulin was uniformly negative in all cases of ameloblastomas and ameloblastic carcinomas studied. Cutaneous BCCs also demonstrated similar reactive patterns with the above-mentioned antigens. The most striking feature is the presence of a peritumorous band-like peanut agglutinin staining found in both BCCs and PAs but not in intraosseous ameloblastomas. This unique peanut agglutinin staining pattern of PA may be diagnostically useful for its histopathologic distinction from an intraosseous ameloblastoma that has infiltrated the soft tissue. The neoplastic cells of ameloblastomas express markers of less-differentiated epithelial cells. Despite differences in epithelial origins, PAs are tumors analogous to cutaneous BCCs.

Topics: Adolescent; Adult; Aged; Ameloblastoma; Antigens, Differentiation; beta 2-Microglobulin; Bone Neoplasms; Carcinoma, Basal Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lectins; Male; Middle Aged; Protein Precursors; Receptors, Mitogen; Skin Neoplasms; Soft Tissue Neoplasms

Cutaneous lymphadenoma is a recently described tumor with a distinctive histological picture associating a basaloid epithelial proliferation and intraepithelial lymphocytes; it seems to represent a benign adnexal neoplasm of uncertain histogenesis. We documented 2 additional examples of cutaneous lymphadenoma with typical histological features; the contiguity of some tumor lobules with preexisting follicular structures was noted. In 1 case, a cutaneous osteoma was present below the tumor. On immunostainings, S-100 protein revealed numerous dendritic intraepithelial and stromal cells. The basaloid proliferation was positive for broad-spectrum keratin antibodies, but negative for KL1 antibody. In addition, several areas were positive for involucrin within tumor lobules. Our findings are consistent with a pilosebaceous origin of cutaneous lymphadenoma.

Topics: Adult; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Lymphoma; Male; Middle Aged; Protein Precursors; Skin Neoplasms

The distribution of several markers of keratinocyte differentiation was studied in normal epidermis, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs) using the immunoperoxidase technique on frozen sections of punch biopsy specimens. As markers a panel of chain-specific monoclonal antibodies (MoAbs) directed against cytokeratin (CK) 4, 8, 10, 13, 18 and 19, a polyclonal antiserum against involucrin, as well as a MoAb against the epidermal growth factor (EGF) receptor were used. In 15 out of 19 BCCs tested, expression of CK 8 was seen. Only a few individual cells in a limited number of BCCs showed positive staining for CK 4, 18, or 19. No expression of CK 10 was seen except for some foci of cell keratinization. Involucrin was not found in BCCs except for some squamous horn cysts. In all BCC cells expression of EGF receptor was found. In the suprabasal layers of normal epidermis from SCC patients, positive staining for CK 10 was seen. A few individual cells in a limited number of SCCs showed positive staining for CK 4, 8, or 18. Involucrin was expressed in the center of SCCs and in the upper layers of normal epidermis. Expression of EGF receptor was found in all SCC cells. These results demonstrate differences in cellular origin and differentiation between BCC and SCC.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermal Cells; Epidermis; ErbB Receptors; Humans; Immunoenzyme Techniques; Keratins; Protein Precursors; Skin Neoplasms

Involucrin has been recognized recently as a marker of terminal differentiation of squamous epithelial cells and also as a useful marker for keratinization; its expression in epithelial tumors of oral and pharyngeal mucosa and skin was examined. Involucrin in normal oral mucosa and skin was restricted to the granular and upper spinous layers and was absent in the basal layer. Hyperkeratosis was characterized by strong positive staining for involucrum in spinous and granular cell layers. A similar pattern was noted in seborrheic keratosis and verruca vulgaris. Condyloma acuminatum specimens revealed slight staining, whereas Paget cells were negative. Calcifying epitheliomas of Malherbe were usually unreactive. Papillomas exhibited the regular distribution of involucrin, as found in normal squamous epithelium. Basal cell carcinomas were generally negative, whereas squamous cell carcinomas showed an irregular distribution of involucrin. Immunohistochemical staining for involucrin may be useful for identification of keratinizing cells in epithelial tumor foci, just as is the use of monoclonal antibody to keratin KL1.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Papilloma; Pharyngeal Neoplasms; Protein Precursors; Skin Diseases; Skin Neoplasms; Staining and Labeling

Involucrin is a precursor of cross-linked protein of human stratum corneum, and its appearance in the upper layers of the epidermis is a function of the normal differentiation of the keratinocyte. Cases of basal cell and squamous cell carcinoma were evaluated for the presence of involucrin using immunoperoxidase techniques on paraffin sections. Basal cell carcinomas were negative for involucrin with staining restricted to squamous horn cysts, while squamous cell carcinomas stained strongly, particularly in large keratinized cells. Cases of squamous cell carcinoma in situ (Bowen's disease) revealed increased staining for involucrin with staining of dyskeratotic cells at all levels in the epithelium. Abnormal patterns of staining were also noted in non-neoplastic epidermis adjacent to carcinomas. Immunohistochemical staining for involucrin identifying abnormal or premature keratinization is a sensitive marker for dyskeratosis in squamous epithelia and may have applications in the histopathologic evaluation of skin specimens.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermis; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Protein Precursors; Skin Neoplasms