Abstract:

The tissue microarray (TMA) design generates arrays of tiny tissue samples, allowing high-throughput evaluation of protein expression in large numbers of tumors. The goal of the TMA design is to generate tissue samples that are both genetically and morphologically representative of a tumor. Here we considered two design issues. The first issue regarded the number of TMA cores to be sampled from a tumor in order to represent the genetic information in the tumor. We considered the number of TMA cores to observe the true maximum intensity of a gene in a morphologically representative region of a tumor. The result was that, with three cores sampled from a morphologically representative region of a tumor, one is guaranteed at least 95% chance of observing the true maximum intensity as long as the maximum intensity of a gene is uniformly distributed among cells in the region. The second issue regarded the morphological representativeness of TMA samples. We wanted to understand how target histology and section depth affected the probability of a morphological non-representative sample of prostate, kidney, and bladder tissues. Logistic regression was used to predict the probability of a morphologically non-representative sample at a given slide for a given target histology. Incorporating missing data into the analysis, we predicted the probability for a sample to be morphologically non-representative or missing. Using this probability, we computed the number of cores to guarantee at least one, two, or three morphologically representative and non-missing cores per pathological case. The result was that three tissue cores punched from morphologically representative targets guarantees 95% chance of obtaining at least one morphologically representative and non-missing core per pathological case through out the first 100 slides. To obtain at least three morphologically representative and non-missing cores, seven cores per pathological case are required. The recommended numbers of cores are applicable to all target histology except LNMET, PIN of prostate tissues and NORMAL, CIS, DYSPLASIA of bladder tissues with which one should sample a larger number of cores or rely on the first 25 slides for higher rates of morphologically representative samples.