Expressions of RelA and RelB, c-Kit/PDGFRA mutation status in gastrointestinal stromal tumors and their clinical significance

CHEN Hao; DAI Hanjue; XU Jingjing; CHENG Li; GUO Feng

doi:10.3969/j.issn.1009-0460.2018.03.006

Abstract：Objective To investigate the correlation between RelA and RelB expression, c-Kit/PDGFRA mutation status and the clinicopathological features in patients with gastrointestinal stromal tumors (GIST ). Methods Retrospective data from 132 GIST patients submitted to surgical resection and pathologically confirmed as GIST were collected. Immunohistochemical analysis was performed for RelA and RelB by using primary antibodies. c-Kit and PDGFRA mutation status was analyzed by direct sequencing. The correlation between RelA and RelB expression, c-Kit/PDGFRA mutation status and the clinicopathological features was analyzed by Chisquare test. Results The positive rates of RelA and RelB were 65.2％ (86/132) and 54.5％ (72/132), respectively. The high positive rates of RelA in patients with high NIH risk score were 76.0％, which higher than 58.5％ of those classified into the non-high risk group (P = 0.041). However, the expression of RelB was not correlated with NIH risk score(P＞0.05). And the expression of RelA and RelB was not correlated with gender, age, tumor location, tumor size, tumor necrosis and tumor ulcers. Hot spot mutations in c-Kit and PDGFRA were detected in 82 (62.1％) patients, including 74 (56.1％) c-Kit mutations and 8 (6.1％) PDGFRA mutations. The positive rate of RelA was 70.7％ in patients with c-Kit/PDGFRA mutation, which was higher than 56.0％ in those with wild-type c-Kit/PDGFRA(P=0.085). And the expression of RelB was not correlated with c-Kit/PDGFRA mutation status (P＞0.05). The total mutation rate of c-Kit/PDGFRA gene was 78.6％ in patients with tumor diameter>10 cm, which was higher than 57.7％ in those with tumor diameter≤10 cm (P=0.043). The overall mutation rate of c-Kit/PDGFRA was 76.0％ in patients with high NIH risk score, which was higher than 53.7％ in those with lower risk (P = 0.01). The mutation rate of c-Kit/PDGFRA in CD34 positive and DOG-1 positive patients was 70.8％ and 64.1％, which was higher than 44.2％(P = 0.003) and 0(P = 0.038) of the corresponding negative patients, respectively. However, the mutation rate of c-Kit/PDGFRA genes in MBP and Desmin positive patients was 52.5％ and 30.8％, respectively, lower than 76.9％ (P=0.005) and 69.8％ (P＜0.001) of the corresponding negative patients. Conclusion RelA positive or c-Kit/PDGFRA mutation may be valuable indicators of poor outcome in GIST. Immunohistochemical biomarker CD34 (+) along with DOG-1 (+) may be positive diagnostic factors for c-Kit/PDGFRA-mutant GSIT, while MBP (+) and Desmin (+) might can serve as negative diagnostic factors for c-Kit/PDGFRA-mutant GSIT.