Biopsies routinely performed for the histopathological diagnosis of oral epithelial lesions before treatment were screened for chromosomal imbalances by comparative genomic hybridization. Comparative genomic hybridization was performed on 12 oral premalignant lesions (OPLs; dysplasias and carcinomas in situ) and 14 oral squamous cell carcinomas (OSCCs). Eight biopsies displayed areas of different histopathological appearance , so that OPLs and OSCCs from the same patient were analyzed. To avoid contamination with nonneoplastic cells , defined cell populations were isolated by micromanipulation with a glass needle. Before comparative genomic hybridization analysis , universal DNA amplification was performed using the DOP-polymerase chain reaction protocol. In the 14 OSCCs examined , the average number of chromosomal imbalances was significantly higher than in the 12 OPLs (mean ؎ SEM: 11.9 ؎ 1.9 versus 3.2 ؎ 1.2; P ‫؍‬ 0.003). The DNA copy number changes identified in more than one OPL were gains on 8q ( Oral and oropharyngeal squamous cell carcinoma is the sixth most frequently occurring cancer worldwide, with approximately 400,000 new cases diagnosed each year.1 A high incidence of second primary lesions, both malignant and premalignant, was observed in patients with oral squamous cell carcinoma (OSCC), leading to the concept of field cancerization.2 This phenomenon is partly attributed to the fact that the entire oral mucosa is exposed to exogenous cancer-promoting substances such as alcohol and tobacco. Some OSCCs are preceded by oral premalignant lesions (OPLs), which include dysplasias and carcinomas in situ (CIS) of the oral mucosa. However, 64% of OPLs do not progress to malignancy. 3In most studies on the genetic alterations in cancer of the upper aerodigestive tract, OSCCs are included in the more heterogeneous group of squamous cell carcinomas (SCCs) of the head and neck (HNSCCs). In HNSCCs, losses of genomic material were identified on 3p, 5q, 7q, 8p, 9p, 11q, 13q, 17p, and 18q by chromosome banding Supported by the Deutsche Krebshilfe (grants 10-1124-Li1 and 10-0976-Re1).

Chronic alcohol consumption is a major risk factor for oral and pharyngeal cancer. Besides other mechanisms a toxic effect of ethanol and/or its metabolite acetaldehyde on the oral mucosa and resulting increased cell regeneration seem to play an important role in tumor promotion. In the present study the effect of chronic ethanol consumption on the morphology of the oral mucosa of 40 male wistar rats that had been fed nutritionally adequate liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates for 6 months was investigated. Morphometric analysis showed that in the ethanol rats the size of the basal cell nuclei of the oral mucosa from the floor of the mouth, the edge of the tongue and the base of the tongue were significantly enlarged (p < 0.001). The size of the basal cell layer in these rats was increased, and the stratification of the cells was altered. The percentage of cells in the S-phase of the cell cycle was significantly higher in the ethanol-fed rats (p < 0.01). Mean epithelial thickness of the mucosa from the floor of the mouth was significantly reduced in the ethanol rats (p < 0.01). In conclusion, the reported findings indicate, that chronic ethanol consumption causes oral mucosal atrophy associated with hyper-regeneration, which may result in an enhanced susceptibility of the mucosal epithelium toward chemical carcinogens.

The distribution of selective cytokeratin polypeptides, vimentin, and glial fibrillary protein (GFP) in 5 human cystadenolymphomas of the parotid gland was compared with normal human parotid (n = 5) and submandibular (n = 4) glands using a panel of monoclonal antibodies against diverse and selective cytokeratin polypeptides, vimentin and glial fibrillary protein (GFP). A biotinstreptavidin method was used on cryostat sections. The immunocytochemical finding of identical cytokeratin polypeptides Nos. 7, 8, 18 and 19 and basal cells selectively labeled by the monoclonal antibody KS 8.58, in both the epithelial part of the cystadenolymphomas and in the duct epithelium of the parotid gland, confirms the hypothesis that the epithelial compartment of cystadenolymphomas is derived from the duct system. The triple expression of cytokeratin, vimentin and GFP in myoepithelial cells of the parotid gland is discussed.

Chronic ethanol consumption in rats resulted in a striking fat accumulation in the acinar cells of the parotid gland demonstrated by light microscopy. In addition, a significant decrease in parotid wet weight (p greater than 0.02) and in protein content of the gland (p greater than 0.02) was observed following alcohol feeding. Wet weight, protein content, and morphology of the submaxillar gland were not affected by ethanol feeding. Alcohol metabolism, similar to that found in the pancreas, via a cytosolic alcohol dehydrogenase could be demonstrated in both the parotid and the submaxillar gland. However, the activity of this enzyme was not affected by chronic ethanol ingestion. Subsequently, chronic ethanol consumption significantly decreased salivary flow rate stimulated by pilocarpine hydrochloride (p greater than 0.02), salivary alpha-amylase activity (p greater than 0.02), and salivary sodium concentration (p greater than 0.01), whereas potassium concentration of the saliva was increased (p greater than 0.05). In contrast salivary total protein concentration was not affected by alcohol ingestion. The changes of salivary electrolyte composition observed after chronic ethanol feeding could be due to an altered aldosterone metabolism or to a change in aldosterone receptors of the parotid gland caused by ethanol administration. The reduced salivary flow could play a role in the pathogenesis of oropharyngeal cancer in the alcoholic.

BACKGROUND:Sometimes, cytological lung cancer diagnosis is challenging because equivocal diagnoses are common. To enhance diagnostic accuracy, fluorescent in situ hybridization (FISH), DNA‐image cytometry, and quantitative promoter hypermethylation analysis have been proposed as adjuncts.METHODS:Bronchial washings and/or brushings or transbronchial fine‐needle aspiration biopsies were prospectively collected from patients who were clinically suspected of having lung carcinoma. After routine cytological diagnosis, 70 consecutive specimens, each cytologically diagnosed as negative, equivocal, or positive for cancer cells, were investigated with adjuvant methods. Suspicious areas on the smears were restained with the LAVysion multicolor FISH probe set (Abbott Molecular, Des Plaines, Illinois) or according to the Feulgen Staining Method for DNA‐image cytometry analysis. DNA was extracted from residual liquid material, and frequencies of aberrant methylation of APC, p16INK4A, and RASSF1A gene promoters were determined with quantitative methylation‐specific polymerase chain reaction (QMSP) after bisulfite conversion. Clinical and histological follow‐up according to a reference standard, defined in advance, were available for 198 of 210 patients.RESULTS:In the whole cohort, cytology, FISH, DNA‐image cytometry, and QMSP achieved sensitivities of 83.7%, 78%, 79%, and 49.6%, respectively (specificities of 69.8%, 98.2%, 98.2%, and 98.4%, respectively). Subsequent to cytologically equivocal diagnoses, FISH, DNA‐image cytometry, and QMSP definitely identified malignancy in 79%, 83%, and 49%, respectively. With QMSP, 4 of 22 cancer patients with cytologically negative diagnoses were correctly identified.CONCLUSIONS:Thus, adjuvant FISH or DNA‐image cytometry in cytologically equivocal diagnoses improves diagnostic accuracy at comparable rates. Adjuvant QMSP in cytologically negative cases with persistent suspicion of lung cancer would enhance sensitivity. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.