Clinicopathological characteristics of patients with gastrointestinal stromal tumor according to progranulin expression.

Abstract

57 Background: As an autocrine growth factor, progranulin (PGRN) has been known to stimulate tumorigenesis and proliferation of several types of cancer cells. However, little is known about the clinicopathological features of patients with gastrointestinal stromal tumor (GIST) according to the PGRN expression. Methods: A retrospective analysis was performed for patients with GIST who underwent curative surgical resection between March 2007 and March 2018. PGRN expression in tumor cells was evaluated by immunohistochemical (IHC) analysis and semi-quantitatively categorized (no expression, 0; weak, 1+; moderate, 2+; strong, 3+). High expression was considered for tumors graded 2+ or 3+ staining intensity. Results: A total of 54 patients were analyzed, and 31 patients (57%) were male. Median age at surgery was 60 years (range, 33-79), and the most common primary site was stomach (36 patients, 67%). Spindle histology was observed in 35 patients (65%). Median tumor size was 8 cm (range, 2-47), and low mitotic count (≤ 5/50 HPF) was observed in 18 patients (33%). According to the modified NIH classification, 42 patients (78%) were grouped into high risk. With IHC evaluation, KIT and CD34 expression were observed in 51 patients (94%) and 40 patients (80%), respectively, and 27 patients (50%) had high PGRN-expressing tumors. Among the 34 patients whose tumors were genotyped, 25 patients (74%) had an exon 11 mutation, and D842V was observed in 3 patients (9%). According to the PGRN expression, high PGRN-expressing tumors had more epithelioid/mixed histology (68% vs. 32%; p = 0.046), and KIT exon 11 mutation (76% vs. 24%; p = 0.037). Regarding other clinicopathological characters, such as sex, age at surgery, primary site, size, mitotic count, risk classification, and KIT/CD34 expression, there was no significant difference between high PGRN-expressing tumors and low PGRN-expressing tumors. Conclusions: High PGRN-expressing GISTs had more epithelioid/mixed histology and more KIT exon 11 mutation in GIST patients who underwent curative surgical resection.