Oral squamous cell carcinomas are among the 10 most common cancers and have a 50% lethality rate after 5 years. Despite easy access to the oral cavity for cancer screening, the main limitations to successful treatment are uncertain prognostic criteria for (pre-)malignant lesions. Identifying a functional cellular marker may represent a significant improvement for diagnosis and treatment. Toward this goal, mechanical phenotyping of individual cells is a novel approach to detect cytoskeletal changes, which are diagnostic for malignant change. The compliance of cells from cell lines and primary samples of healthy donors and cancer patients was measured using a microfluidic optical stretcher. Cancer cells showed significantly different mechanical behavior, with a higher mean deformability and increased variance. Cancer cells (n % 30 cells measured from each patient) were on average 3.5 times more compliant than those of healthy donors [D normal = (4.43 F 0.68) 10 À3 Pa À1 ; D cancer = (15.8 F 1.5) 10À3 Pa À1 ; P < 0.01]. The diagnosis results of the patient samples were confirmed by standard histopathology. The generality of these findings was supported by measurements of two normal and four cancer oral epithelial cell lines. Our results indicate that mechanical phenotyping is a sensible, label-free approach for classifying cancer cells to enable broad screening of suspicious lesions in the oral cavity. It could in principle be applied to any cancer to aid conventional diagnostic procedures.
Objective. The aim of this prospective study was to report on the diagnostic accuracy of conventional oral exfoliative cytology taken from white‐spotted, ulcerated or other suspicious oral lesions in our clinic. In addition we checked DNA‐image cytometry as an adjuvant diagnostic tool. Our hypothesis is that DNA‐aneuploidy is a sensitive and specific marker for the early identification of tumor cells in oral brushings. Study design. 251 cytological diagnoses obtained from exfoliative smears of 181 patients from macroscopically suspicious lesions of the oral mucosa and from clinically seemingly benign oral lesions which were exisiced for establishing histological diagnoses were compared with histological and/or clinical follow‐ups of the respective patients. Additionally nuclear DNA‐contents were measured after Feulgen restaining using a TV image analysis system. Results. Sensitivity of our cytological diagnosis on oral smears for the detection of cancer cells was 94.6%, specificity 99.5%, positive predictive value 98.1% and negative predictive value 98.5%. DNA‐aneuploidy was assumed if abnormal DNA‐stemlines or cells with DNA‐content greater 9c were observed. On this basis the prevalence of DNA‐aneuploidy in smears of oral squamous cell carcinomas in situ or invasive carcinomas was 96.4%. Sensitivity of DNA‐aneuploidy in oral smears for the detection of cancer cells was 96.4%, specificity 100%, positive predictive value 100% and negative 99.0%. The combination of both techniques increased the sensivity to 98.2%, specificity to 100%, positive predictive value to 100% and negative to 99.5%. Conclusions. Brush cytology of all visible oral lesions, if they are clinically considered as suspicious for cancer, are an easily practicable, cheap, non‐invasive, painless, safe and accurate screening method for detection of oral precancerous lesions, carcinoma in situ or invasive squamous cell carcinoma in all stages. We conclude that DNA‐image cytometry is a very sensitive, highly specific and objective adjuvant tool for the early identification of neoplastic epithelial cells in oral smears.
Objective: We describe four patients presenting early oral cancers, detected cytologically on non‐invasive brush biopsies including DNA‐image cytometry as an adjunctive method before histology on scalpel biopsies confirmed the evidence of malignancy. Methods: Brush biopsies were performed and smears thereof investigated cytologically. After Feulgen restaining, DNA‐measurements were performed using a DNA‐Image‐Cytometer. Case reports: Oral squamous cell carcinomas were diagnosed cytologically in macroscopically suspicious lesions and malignancy confirmed by DNA‐cytometry. The initially performed scalpel biopsies did neither supply evidence of oral cancer nor of severe dysplasia. After at least one to 15 months the occurrence of cancer was finally proven histologically on a second scalpel biopsy each (three microinvasive and one in situ carcinoma). Conclusion: Non‐invasive brush biopsies are a suitable instrument for early cytologic detection of cancer of the mouth. DNA‐image‐cytometry, as an adjunctive method, can be used to confirm the cytologic diagnosis or suspicion of cancer in patients with doubtful lesions (dysplasias). DNA‐aneuploidy is a marker for (prospective) malignancy in smears of the oral cavity, which may detect malignancy months prior to histology. In future this method could be used as a mass screening tool in dentists practise. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐4/remmerbach.htm.
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