involucrin and Laryngeal-Neoplasms

MIB-1 is an antibody which attaches to the Ki67 antigen expressed by proliferating cells. MIB-1 immunoreactivity may be used to quantify the proliferative component of a tumour. Involucrin is a protein expressed by mature keratinocytes and may be used as a marker of differentiation. The present paper studies the expression of these two markers in a group of patients with squamous carcinoma of the larynx. Tumour cell kinetics were studied in 49 patients with squamous cell carcinoma of the larynx using antibodies to "Ki67' and involucrin. The median potential follow-up for the group was 8.1 years with a minimum follow-up of 5 years. The median MIB-1 index was 32%. The median involucrin index was 56%. Fifteen patients had no or only slight involucrin staining whereas 34 stained intensely for this protein. Involucrin expression was found to be associated with histological grade with those patients expressing involucrin tending to have well differentiated tumours and those not expressing this parameter tending to have poorly differentiated tumours (P = 0.045). There were no other associations between host and tumour factors and the various biological parameters. Survival analysis demonstrated that patients with an involucrin count above the median value had a better 5-year survival than those below the median (89% and 56% respectively) (P < 0.05). In addition, patients with no (or poor) involucrin expression had an increased risk of developing a recurrence at the primary site (P < 0.05). Involucrin appears to be a promising marker of tumour differentiation and survival in squamous carcinoma of the larynx.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Division; Female; Follow-Up Studies; Humans; Ki-67 Antigen; Laryngeal Neoplasms; Larynx; Male; Middle Aged; Prognosis; Protein Precursors; Staining and Labeling; Survival Analysis; Time Factors

Human papillomaviruses (HPVs) are important human pathogens associated with a range of epithelial neoplasia. The rising incidence of HPV infection and association of HPV with malignancy has led to increased interest in appropriate management of these infections. Development of new therapies for viral warts has been frustrated by the lack of availability of models permissive for viral replication. Here we describe the development of HPV-severe combined immunodeficient mouse model which reproduces mature HPV-infected epithelia. Grafting of anogenital and laryngeal papillomas harbouring either HPV-6 or HPV-11 resulted in the formation of a differentiated neo-epithelium exhibiting the hallmark features of HPV infection including basal hyperplasia, acanthosis and koilocytosis. The reformed warty epithelium contained amplified HPV DNA and expressed capsid protein in the differentiated layers. A striking feature is the production of macroscopic papillomata in an anatomically relevant and accessible site, providing a system of particular relevance for the temporal evaluation of developing lesions and selection of antiviral agents.

Topics: Animals; Capsid; Condylomata Acuminata; Disease Models, Animal; DNA Replication; Epithelium; Gene Expression; Humans; Keratins; Laryngeal Neoplasms; Mice; Mice, SCID; Neoplasm Transplantation; Papilloma; Papillomaviridae; Papillomavirus Infections; Proliferating Cell Nuclear Antigen; Protein Precursors; Skin; Skin Transplantation; Transplantation, Heterologous; Tumor Virus Infections; Virus Replication

We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas.

Topics: Cell Division; Cell Transformation, Neoplastic; Filaggrin Proteins; Humans; Immunoblotting; Intermediate Filament Proteins; Keratins; Laryngeal Neoplasms; Neoplasm Proteins; Papilloma; Papillomaviridae; Protein Precursors; Staining and Labeling; Thymidine; Tumor Virus Infections; Uridine

Involucrin is a major structural subunit of the cross-linked protein envelope that encases keratin in maturing squamous cells. Intracytoplasmic involucrin is identifiable via immunoperoxidase techniques as these cells migrate from the basal layer to the more superficial layers of the stratified epithelium. Normal squamous epithelia and mildly dysplastic epithelia show uniform staining in the suprabasal and superficial layers of the mucosa but show no staining in the basal layer. Moderate to severe dysplasias and invasive carcinomas demonstrate irregular or focal staining in all three layers. Thirty-three microscopic samples from 27 glottic laryngeal biopsy specimens were reviewed. The histochemically abnormal differentiation identified via involucrin staining correlated with accepted histologic criteria for dysplasia. Involucrin staining may provide objective information to assist the pathologist in differentiating degrees of dysplasia in laryngeal biopsy specimens.

Topics: Biopsy; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Laryngeal Diseases; Laryngeal Neoplasms; Larynx; Mucous Membrane; Protein Precursors; Staining and Labeling