Intratumoral heterogeneity of MIB-1 labelling index in gastric gastrointestinal stromal tumor (GIST)

Background The MIB-1 labelling index (LI) is used as a prognostic indicator for gastrointestinal stromal tumors (GISTs). However, whether a biopsy-based LI represents the entire tumor is uncertain, because the LI is not always homogeneous. In this study, we examined the extent and characteristics of LI heterogeneity in gastric GISTs. Methods We analyzed ten c-kit-positive gastric GISTs with diameters exceeding 3 cm, of which six were multilobular and four were unilobular. For MIB-1-immunostained sections, continuous digital images were obtained through the maximum diameter of the lobules. We obtained LIs for images by carrying out computer-assisted image analysis, and calculated the means and standard deviations (SDs) of the LIs for the lobules. For each lobule, intralobular heterogeneity was evaluated on the basis of the SD. For multilobular tumors, interlobular heterogeneity was assessed on the basis of the mean LI difference between lobules. Results The SDs, which ranged from 0.8% to 9.8%, indicated intralobular heterogeneity. Moreover, considerable interlobular heterogeneity was noted in five (83%) of the six multilobular GISTs, in which the maximum interlobular mean LI difference ranged from 9.6% to 27.2%. Notably, although the high maximum mean LI (14.1%–32.3%) showed that these five GISTs were high-grade tumors, they also contained at least one lobule showing a low-grade mean LI value (2.7%–5.1%). Conclusion Gastric GISTs often show intralobular or interlobular MIB-1 LI heterogeneity. In multilobular GISTs, multiple biopsy samples may be required for the accurate evaluation of tumor grade.