Comparison of Proliferation Indices in Glioblastoma Multiforme by Whole Tissue Section vs Tissue Microarray

Abstract

Tissue microarrays (TMAs) reduce the amount of tissue analyzed with the assumption that protein and gene expression patterns are homogeneous throughout tumors. Many tumor types, including glioblastoma multiforme (GBM), are heterogeneous in many regards, including cell proliferation. We retrospectively compared Ki-67 labeling indices (LIs) determined by whole tissue section (WTS) vs TMA in a series of 50 GBMs from 45 patients. A paired t test indicated that the difference between average LIs obtained from a TMA vs a WTS was not significant (P = .51). There was no correlation between TMA and WTS (r = 0.042; P = .77), indicating that the methods yielded very different results in individual tumors. The Ki-67 LI did not always correlate with the tissue section in an individual tumor; however, when evaluating a large number of tumors on a TMA, the LI range and mean LI were roughly comparable with the LI range and mean LI determined from the WTS. In an attempt to increase throughput expression profiling of tumor samples, tissue microarray (TMA) can be used. It is a method of harvesting small cores of tissue and placing them in an array on a recipient block, such that hundreds of cases can be easily analyzed simultaneously. 1 The reflex criticism of this technique is that the small amount of tissue analyzed may not be representative of the tumor, particularly in heterogeneous tumors. Constituting approximately 25% of all intracranial tumors, glioblastoma multiforme (GBM) is the most common primary tumor of the central nervous system. This highly malignant neoplasm grows quickly, and, without therapy, 95% of patients die within 3 months of diagnosis. 2 Among neuroepithelial tumors, it generally is difficult to identify prognostic factors among high-grade tumors, ie, factors that predict why a small subset of patients with GBM survive longer. In GBM, besides age, Karnofsky performance status, and location, no other prognostic factors have been reliably identified that influence survival. Sex, tumor size, preoperative conditions, specific neurologic findings, extent of tumor resection, diverse histologic features of the resected tumor, response to radiotherapy, reoperation, and postoperative adjuvant treatment each have been regarded as significant by some authors and relatively unimportant by others. 3-13