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

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.

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A modification of NIH consensus criteria to better distinguish the highly lethal subset of primary localized gastrointestinal stromal tumors: A subdivision of the original high-risk group on the basis of outcome

Surgery ◽

10.1016/j.surg.2007.01.024 ◽

2007 ◽

Vol 141 (6) ◽

pp. 748-756 ◽

Cited By ~ 58

Author(s):

Hsuan-Ying Huang ◽

Chien-Feng Li ◽

Wen-Wei Huang ◽

Tsung-Hui Hu ◽

Ching-Nan Lin ◽

...

Keyword(s):

High Risk ◽

Gastrointestinal Stromal Tumors ◽

Risk Group ◽

High Risk Group ◽

Stromal Tumors ◽

Nih Consensus Criteria

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Gastrointestinal Stromal Tumors With KIT Exon 11 Deletions Are Associated With Poor Prognosis

Gastroenterology ◽

10.1053/j.gastro.2006.01.043 ◽

2006 ◽

Vol 130 (6) ◽

pp. 1573-1581 ◽

Cited By ~ 150

Author(s):

Johanna Andersson ◽

Per Bümming ◽

Jeanne M. Meis–Kindblom ◽

Harri Sihto ◽

Nina Nupponen ◽

...

Keyword(s):

Gastrointestinal Stromal Tumors ◽

Poor Prognosis ◽

Stromal Tumors ◽

Exon 11

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Epithelioid/mixed phenotype in gastrointestinal stromal tumors with KIT mutation from the stomach is associated with accelerated passage of late phases of the cell cycle and shorter disease-free survival

Modern Pathology ◽

10.1038/modpathol.2010.188 ◽

2010 ◽

Vol 24 (2) ◽

pp. 248-255 ◽

Cited By ~ 10

Author(s):

Florian Haller ◽

Judith Cortis ◽

Joel Helfrich ◽

Silke Cameron ◽

Philipp Schüler ◽

...

Keyword(s):

Cell Cycle ◽

Gastrointestinal Stromal Tumors ◽

Disease Free Survival ◽

Kit Mutation ◽

Free Survival ◽

Stromal Tumors ◽

Mixed Phenotype ◽

Disease Free

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Imatinib in the Management of Multiple Gastrointestinal Stromal Tumors Associated With a Germline KIT K642E Mutation

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-1393-iitmom ◽

2007 ◽

Vol 131 (9) ◽

pp. 1393-1396

Author(s):

Janet Graham ◽

Maria Debiec-Rychter ◽

Christopher L. Corless ◽

Robin Reid ◽

Rosemarie Davidson ◽

...

Keyword(s):

Gastrointestinal Stromal Tumors ◽

Interstitial Cells Of Cajal ◽

Germline Mutations ◽

Mesenchymal Tumors ◽

Stromal Tumors ◽

Pdgfra Gene ◽

Oncogenic Mutations ◽

Esophageal Tumors ◽

Exon 11 ◽

Cells Of Cajal

Abstract Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gut and are distinguished by expression of CD117 (c-Kit). Oncogenic mutations in the KIT or PDGFRA gene are detected in approximately 85% of sporadic GISTs. In recent years, examples of familial GIST have been reported in which germline mutations of KIT or PDGFRA result in multiple GISTs, skin disorders, and other abnormalities. The most common germline mutations are in KIT exon 11, mutations in exons 8 and 17 have also been described, and there are 2 families with germline PDGFRA mutations. We present a case in which a germline KIT exon 13 mutation (K642E) was discovered in a patient with multiple GISTs of rectum, small intestine, and esophagus, as well as diffuse hyperplasia of the interstitial cells of Cajal. To our knowledge, this is only the second germline example of this particular mutation. The patient's esophageal tumors were stabilized with imatinib.

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Meta-Analysis on the Efficacy and Safety of Laparoscopic Surgery for Large Gastric Gastrointestinal Stromal Tumors

The American Surgeon ◽

10.1177/0003134820951482 ◽

2020 ◽

pp. 000313482095148

Author(s):

Miao Yu ◽

Deng-chao Wang ◽

Jian Wei ◽

Yue-hua Lei ◽

Zhao-jun Fu ◽

...

Keyword(s):

Gastrointestinal Stromal Tumors ◽

Laparoscopic Resection ◽

Meta Analysis ◽

Disease Free Survival ◽

Operation Time ◽

Intraoperative Blood Loss ◽

Open Resection ◽

Free Survival ◽

Stromal Tumors ◽

Disease Free

Background The aim of this study was to conduct a meta-analysis comparing the safety and feasibility of laparoscopic versus open resection for gastric gastrointestinal stromal tumors (GISTs) larger than 5 cm. Method We searched the Cochrane Library, PubMed, and Embase for relevant articles. Randomized and nonrandomized clinical trials were identified and included in this study. Searching for related articles on large GIST (>5 cm) for laparoscopic resection (laparoscopic group [LAPG]) and open resection (open group [OG]), RevMan 5.3 was used for data analysis, comparing 2 groups of operation time, intraoperative blood loss, complications, length of hospital stay, recurrence rate, disease-free survival, and overall survival. Results Seven studies including 440 patients were identified for the meta-analysis. Meta-analysis revealed that LAPG had less bleeding, shorter postoperative hospital stay, and a better 5-year disease-free survival. There was no significant difference between LAPG and OG in operation time, postoperative complications, recurrence rate, and overall survival. Conclusion Laparoscopic resection of large (>5 cm) GIST is safe and feasible and has the advantages of less intraoperative blood loss and fast postoperative recovery, with a good outcome in the recent oncology.

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CT texture analysis can be a potential tool to differentiate gastrointestinal stromal tumors without KIT exon 11 mutation

European Journal of Radiology ◽

10.1016/j.ejrad.2018.07.025 ◽

2018 ◽

Vol 107 ◽

pp. 90-97 ◽

Cited By ~ 10

Author(s):

Fei Xu ◽

Xiaohong Ma ◽

Yichen Wang ◽

Yuan Tian ◽

Wei Tang ◽

...

Keyword(s):

Texture Analysis ◽

Gastrointestinal Stromal Tumors ◽

Stromal Tumors ◽

Ct Texture Analysis ◽

Exon 11 ◽

Potential Tool

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Long-term Survival among Patients with Gastrointestinal Stromal Tumors Diagnosed after Another Malignancy: A SEER Population-Based Study

10.21203/rs.2.21309/v1 ◽

2020 ◽

Author(s):

Chaoyong Shen ◽

Chengshi Wang ◽

Tao He ◽

Zhaolun Cai ◽

Xiaonan Yin ◽

...

Keyword(s):

Gastrointestinal Stromal Tumors ◽

Population Based ◽

Clinicopathological Characteristics ◽

Second Primary ◽

Primary Malignancy ◽

Clinicopathologic Characteristics ◽

Term Survival ◽

Stromal Tumors ◽

Group A

Abstract BACKGROUND: To explore overall survival (OS) and GISTs-specific survival (GSS) among cancer survivors developing a second primary gastrointestinal stromal tumors (GISTs). METHODS: We conducted a cohort study, where patients with GISTs after another malignancy (AM-GISTs, n=851) and those with only GISTs (GISTs-1, n=7660) were identified from the Surveillance, Epidemiology, End Results registries (1988-2016). Clinicopathologic characteristics and survival were compared between the two groups. RESULTS: The most commonly diagnosed first primary malignancy was prostate cancer (27.7%), followed by breast cancer (16.2%). OS among AM-GISTs was significantly inferior to that of GISTs-1: 10-year OS was 40.3% vs. 50.0%, (p<0.001); A contrary finding was observed for GSS (10-year GSS: 68.9% vs. 61.8%, p=0.002). In the AM-GISTs group, a total of 338 patients died, of which 26.0% died of their initial cancer and 40.8% died of GISTs. Independent of demographics and clinicopathological characteristics, mortality from GISTs among AM-GISTs patients was decreased compared with their GISTs-1 counterparts (HR, 0.71; 95% CI, 0.59-0.84; p<0.001); whereas OS was inferior among AM-GISTs (HR, 1.11; 95% CI, 0.99-1.25; p=0.085). CONCLUSIONS: AM-GISTs patients have decreased risk of dying from GISTs compared with GIST-1. Although another malignancy history does not seemingly affect OS for GISTs patients, clinical treatment of such patients should be cautious.

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