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

Abstract

The number of genes suggested to play a role in cancer biology is rapidly increasing. To be able to test a large number of molecular parameters in sufficiently large series of primary tumours, a tissue microarray (TMA) approach has been developed where samples from up to 1000 tumours can be simultaneously analysed on one glass slide. Because of the small size of the individual arrayed tissue samples (diameter 0.6 mm), the question arises of whether these specimens are representative of their donor tumours. To investigate how representative are the results obtained on TMAs, a set of 2317 bladder tumours that had been previously analysed for histological grade and Ki67 labelling index (LI) was used to construct four replica TMAs from different areas of each tumour. Clinical follow-up information was available from 1092 patients. The histological grade and the Ki67 LI were determined for every arrayed tumour sample (4x2317 analyses each). Despite discrepancies in individual cases, the grade and Ki67 information obtained on minute arrayed samples were highly similar to the data obtained on large sections (p<0.0001). Most importantly, every individual association between grade or Ki67 LI and tumour stage or prognosis (recurrence, progression, tumour-specific survival) that was observed in large section analysis could be fully reproduced on all four replica TMAs. These results show that intra-tumour heterogeneity does not significantly affect the ability to detect clinico-pathological correlations on TMAs, probably because of the large number of tumours that can be included in TMA studies. TMAs are a powerful tool for rapid identification of the biological or clinical significance of molecular alterations in bladder cancer and other tumour types.

D2-40 and calretinin—a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation

“…Tissue microarray studies have almost always reproduced the expected biological relevance of a given biomarker, for example, the clinical significance of Ki-67 labeling index in bladder cancer, the prognostic role of steroid hormone receptor expression and Her2 neu amplification/overexpression in breast cancer as well as many other established or new associations between molecular markers and tumor phenotype or clinical outcome. 41,45,48 Also in our study, there was a high concordance of tissue microarray results and data obtained on large tissue specimens. Previous studies have found calretinin positivity in 50-100% of epithelioid malignant mesothelioma, with only very few studies showing expression frequencies below 90% on large tissue sections.…”

“…Tissue microarrays have proven highly representative in comparison with traditional evaluation through methods on large tissue samples. [40][41][42][43][44][45][46][47][48][49][50][51] …”

Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer

“…The tissue microarray technique is an accepted tool of investigation, especially when a huge number of samples are analyzed. 18,[23][24][25][26][27][28] The randomization of the study population into two subgroups allowed us to determine the best cutoffs for cytoplasmic and nuclear Mst1 expression on the first subgroup (N ¼ 599) based on the ROC curve analysis and to apply the determined cutoffs on the second subgroup (N ¼ 598) as well as on the third group (N ¼ 141). This approach has the important advantage of avoiding a scoring system that includes a subjectively selected cutoff or a complex composite scoring system.…”

Applications of array technology: identification of molecular targets in bladder cancer

“…The application of tissue microarrays represents a highthroughput approach for validation of potential novel markers for bladder cancer by immunohistochemistry or in situ hybridisation in paraffin blocks (Kononen et al, 1998;Schraml et al, 1999;Richter et al, 2000;Nocito et al, 2001). Several reports describe the rapid evaluation of targets of interest, such as cytoskeletal actinassociated gelsolin or E-cadherin (Rao et al, 2002), Na,K-ATPase or cell-cycle-related markers (Espineda et al, 2003).…”