Examination of oral cancer tissue for the presence of the proteins ICP 4, ICP 5, ICP 6, ICP 8, and gB of herpes simplex virus type 1.

Although patients with oral cancer have increased levels of antibody to herpes simplex virus type 1, the origin of the antigenic stimulation remains unknown. We have therefore looked for proteins of herpes simplex in oral squamous cell carcinomas by staining frozen sections with monoclonal antibodies to the proteins ICP 4, ICP 5, ICP 6, ICP 8, and gB. No staining was seen of the tumor cells of any of 11 oral cancer cases or of the epithelium of 29 other oral lesions, which included cases of leukoplakia, lichen planus, and aphthous ulcers. Frequent staining of mast cells was seen in the connective tissue associated with oral cancer when ascitic fluid was used as the source of monoclonal antibody, but such staining was not seen when the precipitated IgG fraction was used.

Feulgen microspectrophotometry of oral cancer and leukoplakia.

Feulgen microspectrophotometry was performed using the two wavelength method on 33 lesions and showed that five of ten carcinomas and 12 of 16 leukoplakias had diploid cell lines. This correlates well with similar findings in cervical cancer and dysplasia suggesting that changes in nuclear deoxyribonucleic acid content occur quite early in the evolution of cancer.

Significance of DNA content in oral carcinoma.

Standard cytophotometric measurement of DNA in normal, leukoplakic and cancerous oral and oropharyngeal tissues with a Leitz Weitzler Aristophot Cytophotometer showed both 1% and 5% significance in different grades of malignancy and 5% as regards sites of malignancy. The differences were marked in different grades of malignancy and specially with progression of the lesion. Cytophotometry can be useful to diagnose the stages of carcinoma.

Dyskeratosis in human and experimental oral precancer and cancer. An immunohistochemical and ultrastructural study in men, mice and rats.

Dyskeratotic cells were examined with light and electron microscopy in human oral leukoplakias and carcinomas and in chemically-induced oral premalignant and malignant lesions of mice and rats. Specific antisera against small and large keratins were used to analyse the distribution of keratin polypeptides. In normal oral mucosa, basal cells did not react with antibodies against large keratins in contrast to the suprabasal cells which did react. Small keratins were found in all epithelial cell layers. In human and experimental premalignant and malignant lesions, intensely labelled dyskeratotic cells were seen, which contained small and large keratins regardless of their position in the epithelium. At the ultrastructural level, these cells showed dense aggregates of tonofilaments. Dyskeratotic cells were often seen in advanced stages of degeneration of phagocytosis of these cells by macrophages and giant cells was frequent. The disturbance of the keratinization process in oral precancer and cancer is easily visualized using keratin antisera. Keratin analysis can give new insights in epithelial maturation and may be helpful for the classification of oral leukoplakia.

DNA content in reactive hyperplasia, precancerosis, and carcinomas of the oral cavity. A cytophotometric study.

Cytophotometry has been used to study DNA content in oral epithelial cells of Feulgen-stained specimens from a total of 43 patients: 3 with erythema exudativum multiforme (EEM), 5 with pemphigus, 3 with stomatitis aphtosa, 5 with lichen ruber planus, 8 with leukoplakia, and 19 with carcinomas. In contrast to reactive hyperplasia (EEM, pemphigus, stomatitis aphthosa) leukoplakia has histograms closest to those of carcinoma, with a high percentage of cells in the polyploid regions. This emphasizes the significance of cytophotometry for diagnosis of preneoplastic and neoplastic lesions of the oral cavity.

Ha-ras oncogene product in human oral squamous cell carcinoma.

The expression of Ha-ras oncogene product (Ha-ras p21) in the biopsy or operation materials derived from 70 oral squamous cell carcinomas, 10 oral leukoplakias and 10 normal oral mucosae was examined immunohistochemically using anti-Ha-ras p21 antibody. Ha-ras p21 was detected in 43 (61%) of 70 carcinomas, 3 (30%) of 10 oral leukoplaskias and 3 (30%) of 10 normal oral mucosae. Patients with Ha-ras p21-positive carcinomas had a significantly worse prognosis than those with Ha-ras p21-negative carcinomas. These observations strongly suggest that the expression of Ha-ras p21 is a common event in oral squamous cell carcinomas, and that Ha-ras p21 serves as a tissue tumor marker for determining the prognosis of patients with oral squamous cell carcinomas.

[Cytoplasmic receptors of steroid sex hormones in malignant tumors amd precancerous processes of the human oral mucosa]. / Tsitoplazmaticheskie retseptory polovykh steroidnykh gormonov v zlokachestvennykh opukholiakh i predopukholevykh protsessakh slizistoi obolochki polosti rta cheloveka.

The ability of receptor cytoplasmic proteins to bind estrogens and androgens was studied in 25 biopsies obtained from cases of squamous-cell carcinoma and leukoplakia of oral cavity mucosa. Androgen receptors were more frequently identified in cancer than in leukoplakia whereas the estrogen receptor situation was reverse.

Distribution of fibronectin and laminin in oral leukoplakia and carcinoma.

We determined the distribution of 2 components of the extracellular matrix, fibronectin and laminin, in normal, premalignant, and malignant oral mucosa. Both indirect immunofluorescence and avidin-biotin complex immunoperoxidase techniques were used with antisera to each glycoprotein. Fibronectin was consistently present in the basement membrane and connective tissue of normal, leukoplakic and malignant oral mucosa regardless of anatomic site. A continuous laminin-reactive basement membrane structure separated tumor parenchyma from the associated stroma except in areas of invasion in which no laminin staining was evident.

Circulating immune complexes detected by binding of radiolabelled protein A in patients with oral cancer and oral premalignant lesions.

Circulating immune complexes were determined in 48 patients with oral squamous cell cancer, 17 patients with oral keratosis and 49 controls, using a rapid sensitive assay using a Staphylococcus aureus immunoadsorbent. Concentrations of immune complexes were significantly higher in patients with oral cancer and in patients with oral keratosis than in controls, but the levels in those with oral cancer were not significantly different from those in keratosis. Immune complexes might be responsible for the cell-mediated immune defect in patients with cancer in the head and neck.

Microspectrophotometric determination of DNA in oral lesions.

The DNA content of the epithelial basal cells of oral lesions was determined by Feulgen microspectrophotometry. The DNA histograms of the radicular cysts showed a definite peak in the diploid range and a slight deviation to the right. The keratocysts also showed a well-defined modal peak in the diploid range; however, another cell population defined a peak in the tetraploid range. In leukoplakias of the oral cavity, two different profiles of DNA distribution were found. Where both the clinical and microscopic traits defined a nondysplastic lesion, the histogram showed a diploid peak and a percentage of cells in diploid-tetraploid range. For the more active lesion, a shift of the mode towards higher values was evident. The microspectrophotometric studies of oral epidermoid carcinomas showed a broad distribution towards the right and ill-defined modal values.

[S phase fraction and immunohistologic demonstration of the epithelial marker MAM-6 in orofacial tumors]. / S-Phasenfraktion und immunhistologischer Nachweis des Epithelmarkers MAM-6 in orofazialen Tumoren.

Tissue samples of 9 leukoplakias, 19 oral squamous cell carcinomas, 9 basaliomas and 6 specimens of normal oral mucosa were labeled with 3H-thymidine using an in vitro technique; the size of the S-phase fraction was determined histoautoradiographically. Whereas leukoplakias (with or without dysplasia) showed an homogeneous growth pattern, carcinomas and basaliomas demonstrated significantly higher proliferative activity in the tumor periphery. In the basaliomas the pallisade cells showed significantly higher indices than the polygonal cells. The proliferative potential of the oral squamous cell carcinomas is high compared to other neoplasias and depends on the grade and type of growth. The epithelial marker MAM-6 detected immunohistologically on the same tissue, showed a stronger expression in oral carcinomas than in leukoplakias. A direct relationship between the intensity of antigen expression and the proliferative behaviour (size of the S-phase fraction) was not detectable.

Oral hairy leukoplakia.

Oral hairy leukoplakia was first described in homosexual men infected with the human immunodeficiency virus. It is thought to be caused by infection with both the Epstein-Barr virus and human papillomavirus. We report 59 cases of oral hairy leukoplakia. The disease was diagnosed in patients in all risk groups and was categorized in all classes of the Walter Reed classification without significant differences in prevalence. Epstein-Barr virus could be demonstrated in all tissue samples examined; human papillomavirus was found in only a few specimens. In our series oral hairy leukoplakia had a chronic course, although temporary spontaneous healing occurred in some cases. Its appearance was a poor prognostic sign because acquired immunodeficiency syndrome developed in a significant proportion of patients within a few months of onset.

Comparison of cytokeratin, filaggrin and involucrin profiles in oral leukoplakias and squamous carcinomas.

As the distribution pattern of cytokeratin (CK), filaggrin and involucrin has recently been suggested to discriminate between benign and malignant epithelial growths, biopsies of healthy oral mucosa, leukoplakias without and with dysplasia and squamous cell carcinomas were examined immunohistochemically using a panel of 4 monoclonal antibodies (AB) against different cytokeratin polypeptides (34 beta E12, KL1 and Pkk1) and filaggrin as well as a polyclonal AB to involucrin. Major and statistically significant differences were observed in the profiles of CKs (except Pkk1), filaggrin and involucrin between leukoplakias without and with epithelial dysplasia. However, the alteration in the expression of CKs, filaggrin and involucrin proved to be not a constant feature in leukoplakias with dysplasia as a considerable portion (20-25%) of them revealed the profiles of CKs, filaggrin and involucrin similar to those of benign leukoplakias, and vice versa. Immunostaining of these antigens did not define the diagnosis of dysplasia in leukoplakias more precisely than grading in conventional histology can do so far. However, immunohistochemical sensitivity in detecting a broad range of variation in the abnormal maturation patterns of keratinocytes in leukoplakias with dysplasia can be used to divide these lesions into subgroups to elucidate their prognosis in follow-up studies.

Histochemical studies of lectin binding patterns in keratinized lesions, including malignancy.

Histochemical detection of lectin binding was carried out using the HRP-conjugated lectin method in hyperkeratinized lesions including leukoplakia, carcinoma in situ, Paget's disease, keratoacanthoma, and condyloma acuminatum. The lectins used for demonstrating sugar residues were: Con A (hexose), PNA and RCA-1 (Gal), DBA and SBA (GalNAc), UEA -1 (Fuc), and WGA (GlcNAc). Lectin binding in normal squamous epithelium showed regional distribution patterns of keratinized, spinous and basal layer types. Histochemical localization of lectin binding was generally at the cellular surface and in the intercellular substance and sometimes in the cytoplasm of normal epithelial cells. Dysplastic cells or carcinoma cell, in contrast, displayed a loss of cellular surface and intercellular staining. Paget's cells were devoid of lectin staining. In keratoacanthoma and condyloma specimens, spinous cells, which were PAS-positive, showed an intense PA/Con A-HRP staining and moderate binding by other lectins, which was somewhat decreased when compared with that in the surrounding intact epithelium. The cytochemical distribution of epithelial lectin binding might be indicative of the expression of normal stratification and keratinocytic differentiation , and the disappearance of this typical epithelial pattern may suggest severe dysplasia and malignancy.