Histopathology zyxwvutsrqponmlkji 1995. zyxwvutsrq 27, 169-174 zyxwvutsrq Cytokeratin 20 expression by non-invasive transitional cell carcinomas: potential for distinguishing recurrent from non-recurrent disease P.HARNDEN, A.ALLAM?, A.D.JOYCE*, A.PATEL*, P.SELBY~ t~ J.SOUTHGATE~ zy Departments of Histopathology and *Urology, The General Infirmary and ‘Imperial Cancer Research Fund Cancer Medicine Research Unit, zyxwvutsrqpo St James’s University Hospital, Lee& UK Date of submission 20 September 1994 Accepted for publication 21 March 1995 HARNDEN P.. ALLAM A,. JOYCE A.D.. PATEL A,. SELBY P. zyxwvutsrq & SOUTHGATE J. (1995) Histopathology 27, 169-174 Cytokeratin 20 expression by non-invasive transitional cell carcinomas: potential for distinguishing recurrent from non-recurrent disease Although approximately 50% of patients with non-invasive (T,) papillary transitional cell carcinoma show no recurrence of their disease, current histopathological approaches cannot distinguish this sub-group from those patients in whom the disease will recur. In this 5 year retrospective study, we have shown that cytokeratin 20 (CK20) was expressed in 19 of 2 9 (65.5%) of non-invasive papillary tumours of grades 1 or 2. CK20 expression patterns were predictive of disease non-recurrence in a sub-group of eight patients, representing 5 1.7% of patients with non-recurrent disease. In normal bladder mucosa. CK20 expression was restricted to the terminally- differentiated superficial cell. In eight CK20-positive tumours which showed no recurrence at 5 years, CK20 expression was either restricted to, or most intense in, the luminal cells of the papillae. This pattern of expression was not seen in any of the 15 tumours from the recurrent group. Disruption of normal CK20 expression was highly significantly correlated with recurrent tumours. These results suggest that changes in the expression of differentiation-associated antigens, such as CK20, may be useful in predicting benign versus malignant behaviour and may, therefore, be useful in defining treatment strategies. Keywords: cytokeratin, bladder, transitional cell carcinoma, immunohistology Introduction At the time of initial presentation, approximately 70% of transitional cell carcinomas (TCC) are designated as superficial (TNM categories Ta, T1)’. Of these, approxi- mately half will not have breached the epithelial basement membrane and hence are defined as non- invasive carcinomas (TNM category T,). In other organ systems, the diagnosis of carcinoma is only made in the presence of stromal invasion although precursor lesions, such as carcinoma in situ, are well recog- nized. Furthermore, most malignant tumours have benign counterparts. Hence, there are clear clinical and pathological distinctions between squamous cell Address for correspondence: Dr J. Southgate. Imperial Cancer Research Fund Cancer Medicine Research Unit, St James’sUniversity Hospital. Leeds zyxwvutsrq LS9 zyxwvutsrqp 7TF. UK. papillomas and carcinomas. By contrast, in the bladder, the diagnosis of papilloma is rarely, if ever, made. In practice, all tumours, whether invasive or not, are labelled carcinomas. The reason for this is that approximately 50% of the non-invasive tumours will recur within 3 years and 3% will progress to muscle invasive disease’. Apart from the poorly differentiated (grade 3) tumours which are recognized for their potentially aggressive behaviour. conventional histo- pathological examination cannot reliably identify patients at risk for recurrence or progression from those who will suffer no further disease (reviewed by Hall et al.’). As a consequence, approximately 50% of tumours which will not recur are ‘overdiagnosed’ and overtreated as carcinomas, with the corresponding psychological impact on the patient. Hence, there is an acute need to identify markers which may 169 Q 1995 Blackwell Science Limited.