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

• Published in: PloS one Vol. 16; no. 1; p. e0245153
• Main Authors: Do, In-Gu, Jung, Kyung Uk, Koo, Dong-Hoe, Lee, Yun-Gyoo, Oh, Sukjoong, Kim, Kyungeun, Kim, Dong-Hoon, Sohn, Jin Hee, Son, Byung Ho, Lee, Sung Ryol, Shin, Jun Ho, Kim, Hyung Ook, Kim, Hungdai, Chun, Ho-Kyung, Serrero, Ginette, Yoo, Chang Hak
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.01.2021; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Biology and Life Sciences; Cancer; Cell proliferation; Connective tissue tumors; Development and progression; Disease-Free Survival; Female; Gastrointestinal cancer; Gastrointestinal Neoplasms - metabolism; Gastrointestinal Neoplasms - mortality; Gastrointestinal Neoplasms - pathology; Gastrointestinal Neoplasms - surgery; Gastrointestinal Stromal Tumors - metabolism; Gastrointestinal Stromal Tumors - mortality; Gastrointestinal Stromal Tumors - pathology; Gastrointestinal Stromal Tumors - surgery; Gastrointestinal tumors; Gene Expression Regulation, Neoplastic; Glycoproteins; Health aspects; Hematology; Histology; Hospitals; Humans; Internal medicine; Kinases; Male; Medicine; Medicine and Health Sciences; Middle Aged; Multivariate analysis; Mutation; Neoplasm Proteins - biosynthesis; Oncology; Pathology; Patient outcomes; Prognosis; Progranulins - biosynthesis; Research and Analysis Methods; Retrospective Studies; Risk groups; Surgery; Survival Rate; Tumorigenesis; Tumors; Vascular endothelial growth factor; South Korea; Melbourne Victoria Australia; Australia; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0245153

Progranulin (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. A 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. Fifty-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%; p<0.001). Multivariate analysis showed that high PGRN expression and old age (>60 years) were independent prognostic factors for poor RFS. High 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.