Limitations of tissue microarrays compared with whole tissue sections in survival analysis

Abstract

Abstract. Tissue microarray (TMA) is a promising technique in the evaluation of immunohistochemical markers in tumors and may be used as an alternative for whole sections. However, only a few studies have correlated a clinical outcome with both TMA and results obtained from whole sections. This study compared immunostaining for Ki-67 and p16 in TMA (3 cores from each specimen) and whole sections of 171 cases of stage III epithelial ovarian cancer with clinical data. A high expression of Ki-67 was identified in 85.0, 85.5, 85.8, 90.5 and 84% of cores 1, 2 and 3, TMAs and whole tissue sections, respectively. A high p16 expression was found in 36.5, 31.4, 30.3, 46.3 and 31.0% of cores 1, 2 and 3, TMAs and whole tissue sections, respectively. The high expression of Ki-67 and p16 in whole tissue sections significantly correlated with that of Ki-67 and p16 in core 1 (P<0.0001 and P<0.0001, respectively), core 2 (P<0.0001 and P<0.0001, respectively), core 3 (P<0.0001 and P<0.0001, respectively), and TMAs (P<0.0001 and P<0.0001, respectively). In univariate analysis, a high expression of Ki-67 and p16 in two of the cores; TMA and the whole tissue sections were significantly correlated to diseaserelated survival (Ki-67: P=0.008, 0.012, 0.012 and 0.0001, respectively, and p16: P=0.0007, 0.0005, 0.0008 and 0.005, respectively). However, in the multivariate analysis only Ki-67 on whole tissue sections retained an independent prognostic significance (P=0.025). We concluded that more studies, with a higher number of cores, are necessary to determine the efficacy of TMA in reflecting the prognostic value of different antibodies. Morever, evaluation of this method is crucial for each type of tumor and each separate antigen. It is also essential to confirm the clinical correlations on the whole sections before investigating the same parameters on TMA.

Clinicopathological characteristics of oestrogen receptor negative, progesterone receptor positive breast cancers: re-evaluating subsets within this group

“…TMAs were introduced by Kononen in 1998,42 and involves cutting out 0.6–2 mm tissue cores from FFPE tissue and reinserting them into a recipient TMA block containing samples from different patients, thus greatly decreasing the amount of archival tissue required for a particular study, preserving tissue for other research or diagnostic needs, conserving reagents and saving time reviewing the cases. Since only a portion of tissue is analysed, there are concerns if TMAs are representative of the whole tumour,43 44 in particular, in tumours with intratumoural heterogeneity 45 46. However, validation studies comparing TMAs with whole tissue sections have demonstrated a concordance rate of >95% with the use of two to three 0.6 mm cores rather than the use of a single core, as well as minimising decrease in study subjects due to loss of cores during processing 44 47–49.…”

Expression of ZNF148 in different developing stages of colorectal cancer and its prognostic value

“…Moreover, TMA technology has the advantage that hundreds of specimens are processed simultaneously using identical conditions, thereby conserving reagents, saving time, and decreasing the amount of archival tissue. 24 However, the main limitation of TMA is that the amount of tissue analyzed using this technique is limited and may not be representative of the entire specimen, especially in CRC, in which intratumoral heterogeneity exists. 25 The results of the current study indicate that, although ZNF148 expression in CRC occurs during the progression of normal mucosa to adenocarcinoma, this expression is consecutively downregulated from stage I to stage III CRC and is inversely associated with CRC metastasis and good postoperative survival.…”

Tissue Microarray Is a Reliable Tool for the Evaluation of HER2 Amplification in Breast Cancer

“…Variability between batches is considerably reduced, since specimens can be simultaneously processed using identical conditions (8,9). Furthermore, the TMA technique significantly reduces the reagents and technical time required for staining (22,23). This is particularly attractive for expensive and time-consuming techniques such as FISH.…”

“…This is particularly attractive for expensive and time-consuming techniques such as FISH. The amount of tissue needed is also reduced (23).…”