Background & aims

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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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前颗粒蛋白高表达的胃肠道间质瘤的临床病理特征和预后

背景与目标

众所周知，前颗粒蛋白（PGRN）可以促进多种癌细胞的肿瘤发生和增殖。然而，关于PGRN表达的胃肠道间质瘤（GIST）患者的临床病理特征知之甚少。

方法

对2007年至2017年接受根治性手术切除的GIST患者进行回顾性分析。PGRN的表达通过免疫组织化学（IHC）分析进行评估，并半定量分类（无表达，0；弱，1 +；中度，2 +；未表达）。 （3岁以上）。染色强度为2+或3+的肿瘤被认为是高PGRN表达。

结果

分析了54例患者。31名患者（57％）为男性。手术中位年龄为60岁（33-79岁），最常见的原发部位是胃（67％）。三十五例（65％）有纺锤体组织学；根据改良的美国国立卫生研究院（NIH）分类，将42例患者（78％）分为高危组。在27例患者中（50％）观察到高PGRN表达的肿瘤，上皮样/混合组织学较多（68％vs. 32％; p = 0.046），以及KIT外显子11突变（76％vs. 24％; p = 0.037） ）。PGRN高表达肿瘤患者的无复发生存率（RFS）（5年RFS的36％）与PGRN低表达肿瘤患者（96％; p<0.001）。多变量分析表明，PGRN高表达和高龄（> 60岁）是不良RFS的独立预后因素。

结论

高PGRN表达GISTs显示出更多的上皮样/混合组织学和KIT外显子11突变。在进行根治性切除的GIST患者中，PGRN过表达与RFS差相关。