DNA Cytometry Combined with Brush Biopsy, a Significant Advance in the Diagnosis of Oral Cancer PDF Print Email
Wednesday, 29 June 2011 09:01

Oral medicine In a recent article by A Bocking and colleagues from the Institute of Cytopathology, Heinrich-Heine-University, the Department of Cranio-and Maxillofacial Surgery as well as the Department of General Visceral, and Pediatric Surgery, Germany, in the Journal of Oncology, present a review of the use of DNA Cytometry for not only diagnosis, but also prevention, therapy and followup care in patients with oral cancer (A Bocking, et al. Review Article: Role of brush biopsy and DNA cytometry for prevention diagnosis, therapy, and followup care of oral cancer. J of Oncology. 2011:875959. Epub 2010 Dec 20, p 1-7).

Squamous cell carcinoma is associated with a fairly low five year survival rate of approximately forty five percent. While cancer rates have been going up the survival rate has remained essentially unchanged. The authors of the review article suggest that late diagnosis may be one of the reasons for this discrepancy.

In their article they review concepts of prevention, cell sampling, assessment of dysplasia, diagnostic impact, auxiliary cytometry, and the role of brush biopsy in therapy and followup care.

With respect to prevention, the authors suggest that mortality could be improved via the use of techniques that could identify pre-cancerous lesions such as leukoplakia and erythroplakia as there is a 6.8 percent rate of transformation of these conditions into neoplasm. Verrucous leukoplakia and lichen planus are two additional conditions with potential for conversion.

It is suggested that since traditional biopsies has low compliance, the use of exfoliative cytology might be more accepted and pursued by patients, thus increasing the rate of detection of curable cancers identified early in their development.

Cell sampling techniques that are described include the CytoBrush and Orca Brush. The upper layers of squamous epithelium that are acquired via rotation of the brush and delivery to a slide include deeper layers because of migration of cells. As the authors note, “the degree of nuclear abnormality in the surface layers reflects the degree of disturbance of maturation of the whole thickness of the epithelium”

The purpose of cytology is to identify nuclear abnormalities for prediction of the pathology or histological grade of the dysplasia. The WHO classification is divided into: hyperplasia, mild, moderate, and severe dysplasia and carcinoma in situ. But one of the problems of its use is that there is very poor interobserver reproducibility in the histological reading of premalignant lesions. Thus, if there is an interpretation that suggests abnormality, the standard of care is for there to be followup with a standard tissue biopsy.

The authors site numerous studies confirming the diagnostic accuracy of cytology, particularly for pre-malignant dysplasias. And they also point out that the use of DNA image cytometry, also known as AgNOR analysis and multimodal cell analysis has demonstrated significant improvement in the accuracy of oral cytology.

The latter is based on microdensitometric DNA measurements of hundreds of atypical cells in the cytologic specimens. This system is based on the fact that nuclear DNA with aneuploidy may exceed standardized values in cases of dysplasia. The authors indicate that diagnostic sensitivity of cytology for detecting oral cancers increases from 91.3 to 97.8 percent using this technique with specificity increasing from 95.1 to 100 percent. Several supportive studies are cited. The other technique that they report as useful is AgNOR analysis which uses silver-staining of the nucleolar regions. The number and size of these nucleolar areas are dependent on protein synthesis. Very high sensitivity and specificity percentages are reported by at least one cited author.

Exfoliative cytology may find, as the authors note, a role in therapy in the evaluation of post-resection reoccurring lesions. As they note, there is some evidence that the technique may be useful in this regard. However they further note that: “it has to be investigated in a consecutive clinical trial, whether the additional or modified treatment leads to a longer relapse-free period”

It is concluded that DNA cytometry is a technique that could impact the diagnosis and therapy of head and neck squamous cell cancer, particularly as it is combined with DNA assessment techniques.  The technique is non-invasive which makes in attractive to both patient and doctor. As they state “DNA image cytometry could help to find the appropriate treatment option for the patients and thus might improve their prognosis.

Submitted by Jeff Burgess, Editor in Chief