bromochloroacetic-acid and Leukoplakia

Intraepithelial neoplasia of the upper aerodigestive tract (UADT), including both histologically defined dysplasia and carcinoma in situ (CIS), appears to fall into two broad groups similar to intraepithelial neoplasia of other squamous mucosae, keratinizing and non-keratinizing. Keratinizing dysplasia/CIS is common in the UADT and uncommon in other sites such as the cervix. In general, keratinizing epithelial proliferation results in thick epithelium, usually with prominent superficial keratin expression with a whitish or "leukoplakic" clinical appearance. Although most clinical leukoplakic changes in the UADT mucosa do not represent neoplastic transformation and do not progress to invasive carcinoma, keratinizing dysplasia, defined by nuclear atypism and maturation alterations, has an appreciable progression to invasive carcinoma. Non-keratinizing dysplasia/CIS, common in the cervix, is less common in the UADT mucosa. In general, non-keratinizing epithelial alterations consist of a proliferation of incompletely differentiated cells as measured by a spectrum of maturation markers. These changes result in a thin epithelium which commonly has a red, or clinically "erythroplakic," appearance. Non-keratinizing dysplasias are less common, but are more likely to harbor high grade dysplasia or early invasive carcinoma.

Topics: Animals; Carcinoma, Verrucous; Digestive System Neoplasms; Epithelium; Erythroplasia; Humans; Keratins; Leukoplakia; Precancerous Conditions; Respiratory Tract Neoplasms

Topics: Adult; Cervix Uteri; Cheek; Diagnosis, Differential; Female; Genital Neoplasms, Female; Humans; Keratins; Leukoplakia; Leukoplakia, Oral; Male; Middle Aged; Mouth Mucosa; Vagina

Intermediate filaments are involved in cell migration and intracellular signal transduction pathways. In a variety of organs, the expression of distinct intermediary filaments are further associated with distinct steps of malignant transformation. In this study, we seeked to define the cytokeratin (Ck) expression pattern in oral leukoplakia and oral squamous cell carcinoma (OSCC). One hundred and ninety-two patients with OSCC, 117 patients with oral leukoplakia without dysplasia (OL) and 23 with oral leukoplakia with dysplasia (squamous intraepithelial neoplasia) (OLD) of the oral cavity were investigated for the immunohistochemical expression of Ck 5-6, Ck 8/18, Ck 1 Ck 10, Ck 14, Ck 19 using the tissue microarray technique. Correlations between clinical features and the expression of cytokeratins were evaluated statistically by chi2 tests. The expression of Ck 8/18, Ck 19 and Ck 1 was seen in 3.1% (Ck 8/18), 12.5% (Ck 19), 75.4% (Ck 1) of all leukoplakias, 1.0% (Ck 8/18), 9.4% (Ck 19), 76.8% (Ck 1) in OL, 13.0% (Ck 8/18), 27.3% (Ck 19), 68.4% (Ck 1) in OLD and was significantly associated with the degree of dysplasia (Ck 8/18 p<0.01; Ck 19 p<0.01; Ck 1 p<0.01) and the acquisition of invasive growth properties. The highest frequencies were observed in invasive squamous cell carcinomas. The expression of Ck 8/18 and Ck 19 in transformed oral lesions can be regarded as an early feature in the pathogenesis of invasive OSCC. However, the aberrant expression of Ck 8/18 and Ck 19 in an even higher frequency in invasive carcinomas characterizes the expression of typical glandular cytokeratins as a general progression marker in squamous cell carcinomas. These results can be interpreted as first hints that oral leukoplakias with an expression of Ck 8/18 or 19 independent of dysplasia, should be resected totally since they might indicate an increased progression potential.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Keratins; Leukoplakia; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging

An increasing number of syndromes with palmoplantar keratoderma (PPK) with associated diseases are being identified, representing a wide spectrum of distinct entities. At present only one case report has described the combination of marked anogenital leukokeratosis with diffuse PPK evolving in a collodion baby. We report a patient with a diffuse, nonprogressive PPK in combination with an intermittently pruritic, slowly progressive anogenital leukokeratosis. Hyperkeratosis of the perineal area was most pronounced and extended to the distal portion of the anal mucosa. The opalescent lesion was also visualized at the margin of the major labia. Vulvar structures were not otherwise involved or dystrophic. There were no signs or symptoms of ectodermal dysplasia. Specifically, the nails were normal and showed no signs of pachyonychia congenita. Other differential diagnoses included dyskeratosis congenita and white sponge nevus, which may be associated with anogenital leukokeratosis, but a keratoderma is not associated with these entities. Keratin immunocytochemistry showed marked expression of suprabasal K17 and absence of K6 and K16. Further examination of the initial case described by Itin and Rufli demonstrated the same expression pattern and supports the contention that these two cases represent the same entity.

Topics: Adult; Anal Canal; Female; Genital Neoplasms, Female; Hand Dermatoses; Humans; Immunohistochemistry; Keratins; Keratoderma, Palmoplantar, Diffuse; Leukoplakia; Skin

Leukoplakia is only a descriptive clinical term designating a white patch or plaque of the mucosa and must be complemented by histology. On the other hand, keratosis is an exclusively histological term denoting pathological production and accumulation of keratin on the surface of the laryngeal epithelium. Leukoplakia is usually keratosis, but not always. Keratosis can mask various epithelial changes, from simple hyperplasia to invasive squamous carcinoma and is only the superficially visible manifestation of an underlying pathological process. Keratosis means total replacement of superficial epithelial cells by keratin filaments, and dissolution of the nuclei. When nuclei are retained in keratinized cells, the process is termed parakeratosis. Therefore, keratosis can be classified as a separate entity only when histopathological examination reveals superficial keratotic changes accompanying a normal squamous epithelium. To identify the presence of keratosis in various benign laryngeal entities divided according to severity of epithelial abnormalities, and to determine whether keratosis has any prognostic value, we performed a retrospective analysis on bioptic material on 4,291 tissue specimens over a period of 15 years. Our results suggest that keratosis must be considered as only one sign of the disorder within the complex of other pathological changes and not as a distinct pathological entity. For this very reason, keratinization of the epithelial surface was not included among significant parameters used for the grading of epithelial changes into the particular group according to Kambic-Lenart classification.

Topics: Epithelium; Humans; Hyperplasia; Keratins; Laryngeal Diseases; Laryngeal Mucosa; Laryngeal Neoplasms; Leukoplakia; Prognosis; Retrospective Studies

In a clinical trial the effect of chemoprevention with beta-carotene, vitamin E and C on dysplastic tissue was studied. The study included 24 patients with oral leukoplakia and 24 patients after radical resection of a primary oral cancer. There was a reduction of increased cell kinetic parameters like the S-phase portion or the average number of nuclear-organizer regions (NOR) per cell nucleus, a decrease of the micronuclei portion and a normalization of the cytokeratin gene-expression. The general response was 97.5%. Stopping the alcohol and tobacco abuse the effect of the antioxidative vitamins on redifferentiation of the oral mucosa was more intense than by persistance of the alcohol and tobacco abuse, but a long term prevention seems to be ineffective.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Biopsy; Cell Differentiation; Cohort Studies; Drug Therapy, Combination; Humans; Keratins; Leukoplakia; Mouth Mucosa; Mouth Neoplasms; Nucleolus Organizer Region; S Phase; Time Factors; Vitamin E

Pachyonychia congenita (PC) is a rare autosomal dominant condition characterized by multiple ectodermal abnormalities. Patients with Jadassohn-Lewandowsky Syndrome (MIM #167200; PC-1) have nail defects (onchyogryposis), palmoplantar hyperkeratosis, follicular hyperkeratosis and oral leukokeratosis. Those with the rarer Jackson-Lawler Syndrome (MIM #167210; PC-2) lack oral involvement but have natal teeth and cutaneous cysts. Ultra-structural studies have identified abnormal keratin tonofilaments and linkage to the keratin gene cluster on chromosome 17 has been found in PC families. Keratins are the major structural proteins of the epidermis and associated appendages and the nail, hair follicle, palm, sole and tongue are the main sites of constitutive K6, K16 and K17 expression. Furthermore, mutations in K16 and K17 have recently been identified in some PC patients. Although we did not detect K16 or K17 mutations in PC families from Slovenia, we have found a heterozygous deletion in a K6 isoform (K6a) in the affected members of one family. This 3 bp deletion (AAC) in exon 1 of K6a removes a highly conserved asparagine residue (delta N170) from position 8 of the 1A helical domain (delta N8). This is the first K6a mutation to be described and this heterozygous K6a deletion is sufficient to explain the pathology observed in this PC-1 family.

Topics: Amino Acid Sequence; Base Sequence; DNA; Female; Genes, Dominant; Heterozygote; Humans; Keratins; Keratoderma, Palmoplantar; Leukoplakia; Male; Molecular Sequence Data; Nails, Malformed; Pedigree; Sequence Deletion; Syndrome

Topics: Humans; Keratins; Leukoplakia; Male; Metaplasia; Middle Aged; Urinary Bladder Neoplasms

We have analyzed the expression of the three retinoic acid receptor (RAR) (alpha, beta, gamma) mRNAs and the intermediate filament protein keratin 19 (K19) mRNA in cell lines cultured from oral and epidermal human squamous cell carcinoma (SCC) and from benign, hyperplastic, and hyperkeratotic (leukoplakia) lesions arising in various regions of the oral cavity. Seven of the SCC lines were derived from tumors arising in regions of the oral cavity in which the normal epithelial cells (keratinocytes) express RAR beta transcripts. Seven of the nine SCC lines tested did not exhibit detectable RAR beta mRNA levels, even in response to addition of retinoic acid (RA). The RAR beta gene did not appear to be rearranged or deleted in the five nonexpressing SCC lines examined by Southern analysis. The steady-state RAR gamma mRNA levels were 2- to 4-fold lower in 6 of the 9 SCC lines than in their normal counterparts, whereas the RAR alpha message levels in SCC lines were similar to those of the normal cell strains. The expression of keratin 19 message, which is RA inducible in normal keratinocytes, was also abnormal in many of the SCC cell lines. Some SCC lines, e.g., those derived form tumors of the soft palate epithelium, did not express high levels of K19 message even though normal soft palate keratinocytes expressed high levels of K19 mRNA. Two of the nine SCC lines expressed higher than normal levels of K19 mRNA, and this expression was RA independent. Cells cultured from four oral leukoplakia lesions were also examined and found to express RAR beta mRNA at relatively normal levels, but they expressed RAR gamma message at half the level of epithelial cells cultured from normal tissue. These results show that the correlation between RAR beta gene expression and K19 gene expression that we have observed in the various normal keratinocyte subtypes of the oral cavity (D.L. Crowe et al., manuscript in preparation) is not present in transformed keratinocytes (SCC cells). The lack of apparent RA regulation of the K19 gene in SCC lines may be associated with other aberrations in differentiation which have been identified in SCC cells. Abnormally low expression of the RAR beta receptor may contribute to neoplastic progression in stratified squamous epithelia. It may also determine whether a tumor is responsive to RA as a chemotherapeutic agent.

Topics: Blotting, Southern; Carcinoma, Squamous Cell; Carrier Proteins; DNA; Genomic Library; Humans; Keratinocytes; Keratins; Leukoplakia; Mouth Neoplasms; Receptors, Retinoic Acid; RNA, Messenger; Skin Neoplasms; Transcription, Genetic; Tumor Cells, Cultured

Topics: Conjunctiva; Epithelial Cells; Humans; Keratins; Langerhans Cells; Leukoplakia; Microscopy, Electron

Formalin-fixed, paraffin-embedded biopsies of metaplastic keratinized oral mucosa (fibromas and leukoplakias), oral mucosa with epithelial dysplasia and oral squamous cell carcinomas were stained with two monoclonal anti-keratin antibodies (AE1 and AE2). Intense suprabasal staining was seen with AE1 in metaplastic keratinized epithelium, whereas staining of adjacent normal unkeratinized epithelium generally was restricted to basal cells. In dysplastic epithelium and squamous cell carcinomas, staining with AE1 revealed a highly disturbed anti-keratin staining pattern. AE2 stained metaplastic keratinized epithelium in a suprabasal pattern but adjacent unkeratinized epithelium did not stain. In dysplastic epithelium and squamous cell carcinomas, AE2 staining was variable and sometimes absent. Further studies are indicated to clarify whether changes in anti-keratin staining patterns can be used for diagnostic and prognostic purposes.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Epithelium; Erythroplasia; Fibroma; Humans; Keratins; Leukoplakia; Mouth Mucosa; Mouth Neoplasms; Precancerous Conditions; Staining and Labeling

Topics: Aspirin; Candidiasis; Cheilitis; Denture, Complete; Diagnosis, Oral; Foreign Bodies; Hyperplasia; Keratins; Leukoplakia; Lichen Planus; Palatal Neoplasms; Phenols; Salivary Duct Calculi; Stomatitis; Stomatitis, Aphthous; Stomatitis, Denture

The fine structural morphology of dyskeratotic and dysplastic keratinocytes in human oral epithelium was investigated by light microscopy as well as by transmission and scanning-electron microscopy. On the epithelial-connective tissue border, marked changes are seen in the form of polymorphous microinvasive cytoplasmic processes of basal keratinocytes, structural alterations of the basement membrane and rarefaction of the subepithelial connective tissue. Dyskeratotic keratinocytes with abnormal tonofilament configuration are phagocytized by dermal macrophages and are transported to the lamina propria. Ultrastructural signs of atypia are found in the nucleus, nucleolus, cytoplasmic organelles and mitotic apparatus. Furthermore, multiple alterations of the plasma membrane, decrease in numbers of junctional complexes and acantholytic widened intercellular spaces are observed. Intracytoplasmic lumina are formed by endocytotic invagination of desmosome-studed plasma membrane regions at the cell surface. Despite an inverse relationship between the degree of keratinization and the glycogen content of the epithelium at the subcellular level, large amounts of glycogen are found in some keratinocytes. The epithelial surface is formed by hyper-, para-, or orthokeratosis, or shows individual cell keratinization, alteration of the disintegration process and defective keratin synthesis. The ultrastructural analysis of dysplastic keratinocyte populations reveals some morphological criteria common with invasive squamous cell carcinoma, which may be important in the early diagnosis and prognosis of malignant transformation of epithelial dysplasia.

Topics: Cell Membrane; Cell Transformation, Neoplastic; Epithelial Cells; Epithelium; Glycogen; Humans; Intercellular Junctions; Keratins; Leukoplakia; Macrophages; Mouth Mucosa; Organoids; Phagocytosis

Topics: Biopsy; Glycogen; Humans; Keratins; Leukoplakia; Lichen Planus; Mouth Mucosa; Precancerous Conditions

Topics: Adult; Aged; Biopsy; Cytoplasmic Granules; Epithelium; Female; Gingiva; Glycogen; Histocytochemistry; Humans; Keratins; Leukoplakia; Leukoplakia, Oral; Lichen Planus; Male; Microscopy, Electron; Middle Aged; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Palate; Tongue

Two hundred and ninety-nine oral leukoplakias were examined by exfoliative cytology; 83 of these lesions were biopsied because of clinical or previous histological features. Epithelial atypia was found in 16 of these biopsies, exfoliative cytology detecting epithelial atypia in only 6 of these cases. Thus exfoliative cytology used alone would have led to a false negative diagnosis in 10 out of 16 (62%) of the cases with epithelial atypia verified by histology. In addition, in no instance was exfoliative cytology responsible for the detection of an epithelial atypia that had been overlooked by consideration of clinical or previous histological features. Exfoliative cytology was successful in the detection of atypia only in those cases in which the surface of the lesion was either ulcerated or not keratinized; all keratinized lesions with atypia yielded negative cytology. The results of this study lead to the conclusion that exfoliative cytology is not to be recommended as a routine diagnostic or screening procedure for the detection of possibly pre-malignant features in oral leukoplakias.

Topics: Biopsy; Cytodiagnosis; Denmark; Epithelium; False Negative Reactions; Humans; Keratins; Leukoplakia; Leukoplakia, Oral; Mass Screening; Mouth Neoplasms

Topics: Cell Differentiation; Cell Division; Culture Techniques; Epithelium; Histocytochemistry; Humans; Keratins; Keratosis; Leukoplakia; Leukoplakia, Oral; Lichen Planus; Metaplasia; Mouth Mucosa; Mouth Neoplasms; Organ Culture Techniques

Topics: Cell Membrane; Cell Nucleus; Cheek; Cytoplasmic Granules; Epithelium; Glycogen; Histocytochemistry; Humans; Inflammation; Keratins; Keratosis; Leukoplakia; Leukoplakia, Oral; Lichen Planus; Microscopy, Electron; Mouth Mucosa; Mouth Neoplasms; Smoking

Sixty-two "leukoplakias" from the cheeks of betel-nut chewers in West Malaysia were studied histologically. Ten biopsies were from non-tobacco betel-nut chewers. An amorphous von Kossa positive layer was seen on the keratin surface in 42 specimens. Tobacco did not appear essential for its formation, and it appeared to be significantly associated with parakeratosis. Its possible significance as a cuticle-like layer prolonging contact between carcinogens and the mucosa is discussed.Parakeratosis appeared to be the most common form of cornification seen, and the mitotic activity in parakeratinized leukoplakias appeared to be significantly greater than orthokeratinized leukoplakias.Comparison with studies on other population samples using different quids suggested that severe histological changes were more likely to be seen when tobacoo-containing quids were chewed as compared to non-tobacco-containing quids.An attempt to correlate the histological changes seen with the clinical habit in leukoplakias from chewers using tobacco-containing quids suggested that epithelial atrophy appeared to be significantly related to the duration of the habit but not to the "intensity" of the habit.

Topics: Adult; Aged; Areca; Biopsy; Connective Tissue; Epithelium; Humans; Keratins; Keratosis; Leukoplakia; Leukoplakia, Oral; Middle Aged; Mitosis; Mouth Mucosa; Mouth Neoplasms; Plants, Medicinal

Topics: Adult; Carcinoma, Squamous Cell; Collagen; Conjunctiva; Cornea; Epithelium; Eye Neoplasms; Female; Humans; Keratins; Keratitis; Leukoplakia; Malawi; Male; Retinal Pigments

Topics: Adolescent; Adult; Aged; Female; Humans; Keratins; Leukoplakia; Male; Mouth Diseases; Nails; Skin Diseases

Topics: Adult; Aged; Female; Glycogen; Histocytochemistry; Humans; Inflammation; Keratins; Leukoplakia; Male; Middle Aged; Mouth Mucosa; Staining and Labeling; Vitamin A

Topics: Adult; Female; Gingival Hyperplasia; Glycogen; Humans; Keratins; Keratosis; Leukoplakia; Male; Middle Aged

Topics: Epithelial Cells; Humans; Keratins; Leukoplakia; Microscopy, Electron; Mouth Diseases; Mouth Mucosa

Topics: Adolescent; Child; Humans; Keratins; Leukoplakia; Mouth Mucosa; Mouth Neoplasms; Nevus; Nevus, Pigmented; Pathology; Skin Neoplasms

Topics: Biomedical Research; Electrons; Gingiva; Humans; Keratins; Leukoplakia; Microscopy; Microscopy, Electron; Mouth; Mouth Mucosa; Mucous Membrane; Palate; Pathology

Topics: Biomedical Research; Blood Chemical Analysis; Carotenoids; Cytodiagnosis; Geriatrics; Humans; Keratins; Leukoplakia; Leukoplakia, Oral; Mouth Neoplasms; Pathology; Pharmacology; Sweden; Toxicology; Vitamin A