, . 181: 347 (1997)

LETTER TO THE EDITOR

POTENTIAL EARLY MARKERS OF CARCINOGENESIS IN THEMUCOSA OF THE HEAD AND NECK USING EXFOLIATIVE CYTOLOGY

The paper by Bongers et al.1 suggests that identifica-tion of keratin (K) 16, keratin 19, and indeed bloodgroup antigens in exfoliated cell samples from normalmucosa may predict second malignant tumours in thehead and neck. Whilst K19 might be considered amarker of premalignancy,2 K16 should not necessarilybe thought so. The latter is a marker of hyperprolifera-tion and can readily be identified in a variety of normalor benign lesions,3 possibly in response to trauma.However, exfoliative cytology is capable of detecting

field changes in the cytomorphology of normal mucosalcells from oral cancer patients, irrespective of alcohol/tobacco use.4 Furthermore, altered keratin profiles havebeen found in clinically and histopathologically normalmucosa (e.g., K8 expression) in biopsies taken from thewound margins following excision of oral tumours.5These findings are suggestive of a field change,5 particu-larly since expression of K8 in stratified squamous oralepithelium is normally only associated with malignantdisease.6 Thus, keratin expression in exfoliative cytologymay well be capable of detecting field cancerization, butthis would appear to be limited to markers present insuprabasal cells only.7We have previously shown that cells from smears of

normal oral mucosa in oral cancer patients can expressK19,8 although follow-up has revealed that such expres-sion was not always apparent in those who did get afurther tumour. In addition, some patients with markedK19 expression within normal mucosal smears did notdevelop further tumours. Bongers’s samples were col-lected between October 1992 and April 1993. Since themajority of second tumours in the head and neck arisewithin 2 years of the index primary,9 it would be helpful

if they could indicate which cases did develop a furthertumour and whether this was associated with either ofthe keratins studied. Furthermore, since keratins pro-vide a means to assess subtle changes in differentiation,future studies should be extended to include otherkeratins that may be associated with malignant change,such as K8, K17, and K18. Are they predictive of secondmalignant tumours?

G. R. OSenior Lecturer/Consultant Oral Surgeon

University of Dundee, Dental SchoolDundee DD1 4HR, U.K.

REFERENCES1. Bongers V, Snow GB, de Vries N, Braakhuis JM. Potential early markers of

carcinogenesis in the mucosa of the head and neck using exfoliativecytology. J Pathol 1996; 178: 284–289.

2. Lindberg K, Rheinwald JG. Suprabasal 40 kd keratin (K19) expression asan immunohistologic marker of premalignancy in oral epithelium. Am JPathol 1989; 134: 89–98.

3. Lane EB, Alexander CM. The use of keratin antibodies in tumour diag-nosis. Semin Cancer Biol 1990; 1: 165–179.

4. Ogden GR, Cowpe JG, Green MW. Detection of field change in oral cancerusing oral exfoliative cytologic study. Cancer 1991; 68: 1611–1615.

5. Ogden GR, Chisholm DM, Hopwood D, Lane EB. Evidence for fieldchange in oral cancer based on cytokeratin expression. Br J Cancer 1993; 67:1324–1330.

6. Morgan PR, Shirlaw PJ, Johnson NW, Leigh IM, Lane EB. Potentialapplications of antikeratin antibodies in oral diagnosis. J Oral Pathol 1987;16: 212–222.

7. Ogden GR, Leigh I, Chisholm DM, Cowpe JG, Lane EB. Exfoliativecytology of normal oral mucosa—assessing basal cell keratin phenotype.Acta Cytol 1996; 40: 933–936.

8. Ogden GR, McQueen S, Chisholm DM, Lane EB. Keratin profiles ofnormal and malignant oral mucosa using exfoliative cytology. J Clin Pathol1993; 46: 352–356.

9. Langdon JD, Harvey PW, Rapidis AD, Patel MF, Johnson NW, Hopps R.Oral cancer: the behaviour and response to treatment of 194 cases. J MaxFac Surg 1977; 5: 221–237.

? 1997 by John Wiley & Sons, Ltd.