Biphasic GISTs reveal the early mechanisms in GIST high-grade transformation

To study the very early changes in high-grade transformation of gastrointestinal stromal tumors (GISTs), 17 biphasic GISTs, with a transitional status in which low-grade and high-grade parts coexist, were collected from 263 continuous cases (6.5%). Nucleic acids of each part were retrieved for gene expression profiling. By definition, biphasic GISTs contained two populations of neoplastic cells that were (1) morphologically different, either in abrupt or gradual transition to the other, and (2) showed a dramatic change in mitotic activity, which was defined as either (a) one population had ≤ 5 mitoses per 5 mm2 (AJCC G1) and the other had > 5 mitoses per 5 mm2 (AJCC G2), or (b) both populations were AJCC G1, but the difference in mitotic activity was equal to or more than 3 per 5 mm2, or (c) both populations were AJCC G2, but the low-grade part was in the range of > 5 and ≤ 10 mitoses per 5 mm2 and the high-grade part exceeded it by equal to or more than 5 mitoses per 5 mm2. In each case, selected low-grade area, high-grade area and normal smooth muscle area (as control) were manually microdissected. RNA was extracted with the RecoverAll™ Total Nucleic Acid Isolation Kit FFPE (Life Technologies, Taipei, Taiwan).