involucrin and Nasopharyngeal-Neoplasms

Abnormal expression of Notch1 protein was often found in many kinds of primary tumors, but its correlation with nasopharyngeal carcinoma (NPC) is still unclear. This study was designed to investigate the expression of Notch1 and its downstream proteins P21(WAF1) and Involucrin in NPC, and analyze their correlations with the differentiation of NPC cells.. The expression of Notch1, P21(WAF1), and Involucrin in 101 specimens of NPC and 20 specimens of chronic inflammatory nasopharyngeal mucosa were detected by SP immunohistochemistry.. The positive rates of Notch1, P21(WAF1), and Involucrin were 100%, 90.0%, and 100% in chronic inflammatory nasopharyngeal mucosa, and were 77.2%, 89.1%, and 80.1% in NPC, respectively. The expression of Notch1, P21(WAF1), and Involucrin were significantly suppressed along with descending differentiation of NPC (P=0.000, P=0.026, and P=0.000). The positive rates of Notch1, P21(WAF1), and Involucrin were significantly higher in keratinizing squamous cell carcinoma (KSCC) than in differentiated nonkeratinizing carcinoma (DNKC) and undifferentiated carcinoma (UDC) (P<0.05), and were significantly higher in DNKC than in UDC (P<0.05). The expression of Notch1 in NPC was positively correlated with the expression of P21(WAF1) (r=0.306, P=0.002) and Involucrin (r=0.325, P=0.001). No significant correlation was found between the expression of P21(WAF1) and Involucin.. The expression of Notch1, P21(WAF1), and Involucrin are closely correlated to the differentiation of NPC cells.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Cell Differentiation; Cyclin-Dependent Kinase Inhibitor p21; Epithelium; Female; Humans; Male; Middle Aged; Nasopharyngeal Neoplasms; Nasopharyngitis; Protein Precursors; Receptor, Notch1

The effect of expression of the Epstein-Barr-virus (EBV) latent membrane protein (LMP1) derived from B-lymphocytes (B) and nasopharyngeal carcinoma (NPC) (C) on the in vitro growth and differentiation of a human keratinocyte line, Rhek-1, was analyzed in clonal growth and in in vitro differentiation assays. In contrast to the polygonal parental cells, the B-LMP1-expressing sublines were spindle-shaped while the C-LMP1-expressing cells were pleomorphic. Both B- and C-LMP1-expressing sublines showed increased proliferation as evidenced by: (1) higher colony-forming efficiency (CFE) and larger colony size at reduced serum levels; (2) an increased number of epithelial cell layers formed in the air-liquid-interface culture system and (3) increased expression of proliferative cell nuclear antigen (PCNA). At low serum concentration, the C-LMP1-expressing sublines formed larger colonies than those expressing B-LMP1. In the air-liquid-interface culture system, both B- and C-LMP1-expressing lines showed reduced epithelial differentiation resulting in reduced stratification and reduced involucrin expression similar to those of the cancer cell line, Siha. The results of the present study indicate that the expression of LMP1 in human keratinocytes is associated with morphological transformation and predisposes these cells to a more neoplastic phenotype. The structural difference between the 2 genes responsible for the functional differences and transforming ability will be pinpointed in further experiments.

Topics: Antigens, Viral; B-Lymphocytes; Carcinoma; Cell Differentiation; Cell Division; Epithelium; Herpesvirus 4, Human; Humans; Nasopharyngeal Neoplasms; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Protein Precursors; Transfection; Viral Matrix Proteins

Forty nasopharyngeal carcinomas (NPC) were studied by immunohistochemistry using an antibody to involucrin and the following three keratin antibodies: (1) an antibody to low molecular weight keratin reactive with nonsquamous epithelium, (2) a high molecular weight keratin antibody reactive with suprabasal squamous epithelium, and (3) a keratin antibody reactive with full thickness stratified epithelium. In its pattern of reactivity, the last antibody overlaps the low and high molecular weight keratin antibodies and is used as a broad spectrum keratin antibody. By World Health Organization (WHO) classification, the cases in this article included eight keratinizing squamous cell carcinomas, eight nonkeratinizing carcinomas, 20 undifferentiated carcinomas, and four adenocarcinomas. The antibody to broad spectrum keratin had an overall sensitivity of 87.5% and was positive in all eight keratinizing squamous cell carcinomas, seven nonkeratinizing carcinomas (87.5%), 18 undifferentiated carcinomas (90%), and two adenocarcinomas (50%). Low molecular weight keratin antibody stained one additional NPC, which was negative when broad spectrum keratin antibody was used. Involucrin and high molecular weight keratin antibodies demonstrated near parallel staining in all histologic classes; there was marked localization to areas of squamous differentiation. While involucrin is a marker for foci of greater squamous differentiation, broad spectrum keratin antibody may aid in the diagnosis of all histologic subtypes of NPC.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antibody Specificity; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Protein Precursors