PLoS ONE (Jan 2021)

Clinicopathological characteristics and outcomes of gastrointestinal stromal tumors with high progranulin expression.

  • In-Gu Do,
  • Kyung Uk Jung,
  • Dong-Hoe Koo,
  • Yun-Gyoo Lee,
  • Sukjoong Oh,
  • Kyungeun Kim,
  • Dong-Hoon Kim,
  • Jin Hee Sohn,
  • Byung Ho Son,
  • Sung Ryol Lee,
  • Jun Ho Shin,
  • Hyung Ook Kim,
  • Hungdai Kim,
  • Ho-Kyung Chun,
  • Ginette Serrero,
  • Chang Hak Yoo

DOI
https://doi.org/10.1371/journal.pone.0245153
Journal volume & issue
Vol. 16, no. 1
p. e0245153

Abstract

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Background & aimsProgranulin (PGRN) is known to promote tumorigenesis and proliferation of several types of cancer cells. However, little is known about the clinicopathological features of patients with gastrointestinal stromal tumors (GISTs) with regard to PGRN expression.MethodsA retrospective analysis was performed on patients with GISTs who underwent curative surgical resection between 2007 and 2017. PGRN expression was evaluated by immunohistochemical (IHC) analysis and semi-quantitatively categorized (no expression, 0; weak, 1+; moderate, 2+; strong, 3+). Tumors with a staining intensity of 2+ or 3+ were considered high PGRN expression.ResultsFifty-four patients were analyzed; 31 patients (57%) were male. The median age at surgery was 60 years (range, 33-79), and the most common primary site was the stomach (67%). Thirty-five patients (65%) had spindle histology; 42 patients (78%) were separated as a high-risk group according to the modified National Institutes of Health (NIH) classification. High PGRN-expressing tumors were observed in 27 patients (50%), had more epithelioid/mixed histology (68% vs. 32%; p = 0.046), and KIT exon 11 mutations (76% vs. 24%; p = 0.037). Patients with high PGRN-expressing tumors had a worse recurrence-free survival (RFS) (36% of 5-year RFS) compared to those with low PGRN-expressing tumors (96%; p60 years) were independent prognostic factors for poor RFS.ConclusionsHigh PGRN-expressing GISTs showed more epithelioid/mixed histology and KIT exon 11 mutations. PGRN overexpression was significantly associated with poor RFS in patients with GISTs who underwent curative resection.