Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade

The number of genes suggested to play a role in cancer biology is rapidly i ncreasing, To be able to test a large number of molecular parameters in suf ficiently large series of primary tumours, a tissue microarray (TMA) approa ch has been developed where samples from up to 1000 tumours can be simultan eously analysed on one glass slide. Because of the small size of the indivi dual arrayed tissue samples (diameter 0.6 mm), the question arises of wheth er these specimens are representative of their donor tumours. To investigat e how representative are the results obtained on TMAs, a set of 2317 bladde r tumours that had been previously analysed for histological grade and Ki67 labelling index (LI) was used to construct four replica TMAs from differen t areas of each tumour. Clinical follow-up information was available from 1 092 patients. The histological grade and the Ki67 LI were determined fbr ev ery arrayed tumour sample (4 x 2317 analyses each). Despite discrepancies i n individual cases, the grade and Ki67 information obtained on minute array ed samples were highly similar to the data obtained on large sections (p <0 .0001). Most importantly, every individual association between grade or Ki6 7 LI and tumour stage or prognosis (recurrence, progression, tumour-specifi c survival) that was observed in large section analysis could be fully repr oduced on all four replica TMAs, These results show that intra-tumour heter ogeneity does not significantly affect the ability to detect clinico-pathol ogical correlations on TMAs, probably because of the large number of tumour s that can be included in TMA studies. TMAs are a powerful tool for rapid i dentification of the biological or clinical significance of molecular alter ations in bladder cancer and other tumour types. Copyright (C) 2001 John Wi ley & Sons, Ltd.