Malignancies associated with GIST: a retrospective study with molecular analysis of KIT and PDGFRA

Mayr, N. Patrick; Märkl, Bruno; Agaimy, Abbas; Kriening, Bernadette; Dintner, Sebastian; Schenkirsch, Gerhard; Schneider‐Stock, Regine

doi:10.1007/s00423-019-01773-2

Cited by 16 publications

(27 citation statements)

References 23 publications

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“…Screening by the two authors (Waidhauser J and Bornemann A) resulted in 126 eligible papers. In addition, one study on 188 GIST patients that was performed at our institute by Mayr et al[15] and had not been published by the time of the literature search was included. Of the 130 selected publications, 108 were case reports and 22 were case series or retrospective and prospective studies (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…GIST can occur in the setting of genetic syndromes such as neurofibromatosis 1[9], Carney triad[10], or familial GIST[11] and, in these cases, frequently come along with other benign or malignant neoplasias. In recent years, though, there has been increasing evidence of second neoplasia in patients with sporadic GIST[12-15]. Several retrospective studies and case series have been published on this topic, complemented by many case reports and a few reviews, but so far to our knowledge, no meta-analysis or systematic reviews have been conducted.…”

Section: Introductionmentioning

confidence: 99%

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Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia

Waidhauser¹,

Bornemann²,

Trepel

et al. 2019

WJG

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BACKGROUND In recent years, increasing evidence of second neoplasms associated with gastrointestinal stromal tumors (GIST) has been found. Numerous case reports, mostly retrospective studies and a few reviews, have been published. To our knowledge, however, no systematic review or meta-analysis of the existing data has been performed so far. AIM To prepare a compilation, as complete as possible, of all reported second tumor entities that have been described in association with GIST and to systematically analyze the published studies with regard to frequency, localization, and types of GIST-associated neoplasms. METHODS The MEDLINE and EBSCO databases were searched for a combination of the keywords GIST/secondary, synchronous, coincident/tumor, neoplasm, and relevant publications were selected by two independent authors. RESULTS Initially, 3042 publications were found. After deletion of duplicates, 1631 remained, and 130 papers were selected; 22 of these were original studies with a minimum of 20 patients, and 108 were case reports. In the 22 selected studies, comprising a total number of 12050 patients, an overall rate of GIST-associated neoplasias of 20% could be calculated. Most second neoplasias were found in the gastrointestinal tract (32%) and in the male and female urogenital tract (30%). The specific risk scores of GISTs associated with other tumors were significantly lower than those without associated neoplasias. CONCLUSION In this first systematic review, we could confirm previously reported findings of a more than coincidental association between GIST and other neoplasias. The question whether there is an underlying causal association will need further investigation. Our data suggest that even GIST with a very low risk of disease progression should prompt screening for second neoplasia and subsequent frequent controls or extended staging.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia

Waidhauser¹,

Bornemann²,

Trepel

et al. 2019

WJG

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“…GASTROINTESTINAL STROMAL TUMORS (GIST) are of gastrointestinal mesenchymal tissue origin, as proposed for the by Mazur and Clark in 1983 1 . Current studies generally conclude that GIST is a potentially malignant disease 2,3 . According to the commonly used classification method, the risk of GIST invasion is stratified into four levels considered very low, low, intermediate, and high, based on the following four factors: surgical GIST size, mitotic number, tumor site, and rupture 4 .…”

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confidence: 99%

MRITexture‐Based Models for Predicting Mitotic Index and Risk Classification of Gastrointestinal Stromal Tumors

Yang

Zheng

Dong

et al. 2020

Magnetic Resonance Imaging

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Background Treatment regimens and prognoses of gastrointestinal stromal tumors (GIST) are quite different for tumors in different risk categories. Accurate preoperative grading of tumors is important for avoiding under‐ or overtreatment. Purpose To develop and validate an MRI texture‐based model to predict the mitotic index and its risk classification. Study Type Retrospective. Population Ninety‐one patients with histologically‐confirmed GIST; 64 patients in a training cohort, and 27 patients in a test cohort. Field Strength/Sequence T2‐weighted imaging (T2WI), diffusion‐weighted imaging (DWI), and dynamic contrast‐enhanced three‐dimensional volumetric interpolated breath‐hold examination (3D‐VIBE) at 1.5T. Assessment GIST images were manually segmented by two independent radiologists using ITK‐SNAP software and MRI features were extracted using Pyradiomics. Two pathologists reviewed the tissue specimens of the tumors to identify the mitotic index and risk classification in consensus. Statistical Tests The least absolute shrinkage and selection operator (LASSO) regression method was used to select texture features. A logistic regression model was established based on the radiomic score (radscore), tumor location, and maximum diameter to predict tumor classification and develop a nomogram. Receiver operator characteristic (ROC) curves were used to evaluate the ability of the nomogram to distinguish between two tumors with different risk classifications, and a calibration curve was used to evaluate the consistency between the predicted risk and the actual risk. Results The texture signature achieved high efficacy in predicting the mitotic index area under the curve ([AUC], 0.906; 95% confidence interval [CI]: 0.813, 0.961). A nomogram for prediction of the risk classification of GIST, which incorporated this texture signature together with maximum tumor diameter and location, allowed good discrimination in the training cohort (AUC, 0.878; 95% CI: 0.769, 0.960) and the validation cohort (AUC, 0.903; 95% CI: 0.732, 0.922). Data Conclusion The texture‐based model can be used to predict GIST mitotic index and risk classification preoperatively. Level of Evidence 2. Technical Efficacy Stage 3

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“…The mutation rates in these trials are higher than those in a study based on the Polish Clinical GIST Registry (82.2%) (10) and a European multicenter analysis (85.1%) (11), but lower than that in a study of Chinese cases (93.8% overall, 89.1% for KIT and 4.7% for PDGFRA) conducted by Wang et al (28). KIT mutations have been reported to be associated with a high risk of progression (18,24,27). The proportion of high-risk subtypes in the single-center study conducted by Wang et al (28) was higher than that in the present series (42.5 vs. 29.1%, respectively), which explains the relatively lower frequency of KIT mutations in the present data.…”

Section: Univariate Multivariate ------------------------------------mentioning

confidence: 62%

Mutational characteristics of gastrointestinal stromal tumors: A single‑center analysis of 302 patients

Liang

et al. 2021

Oncol Lett

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Gastrointestinal stromal tumors (GISTs) represent a spectrum of tumors characterized by variable behaviors and activating mutations in KIT proto-oncogene, receptor tyrosine kinase ( KIT ) or platelet derived growth factor receptor α ( PDGFRA ) genes. However, whether genotype analysis should be regarded as a prognostic indicator remains unclear. In the present study, clinicopathological data and the mutation phenotypes of KIT and PDGFRA genes were assessed in a series of 302 patients with GISTs at a single center. Univariate and multivariate Cox regression analyses were performed to identify the clinicopathological and mutational factors associated with relapse-free survival (RFS) in patients who had undergone complete primary GIST resection. KIT and PDGFRA mutations were identified in 233 (77.2%) and 30 (9.9%) cases, respectively. The following clinicopathological parameters were significantly associated with a shorter RFS: Male, non-gastric tumor origin, larger tumor size (>5 cm), high mitotic activity (>5/50 high-power fields), necrosis and epithelioid morphology. Tumors at non-gastric sites, with high National Institutes of Health risk classification, high World Health Organization (WHO) grade and KIT deletion involving codons 557/558/559 exhibited a significantly higher risk of progression. In the Cox regression model, KIT deletion involving codons 557/558/559, non-gastric origin and high WHO grade were independent indicators of RFS. The adverse prognosis associated with KIT deletions involving codons 557/558/559 was also observed for gastric GISTs. Conversely, spindle morphology, KIT exon 11 substitution and PDGFRA exon 18 mutation were associated with a longer RFS and lower rate of relapse. Furthermore, the coexistence of KIT exon 11 deletion and exon 13 duplication was observed in one tumor, with adverse prognostic features. Heterogeneity affecting morphology, immunostaining and genotype was identified in 4 cases. In addition, the presence of succinate dehydrogenase-deficient GIST was found in 5 cases (3.6%). In conclusion, the tumor genotype with regard to KIT and PDGFRA mutations exhibited prognostic significance for the risk of GIST progression and may be helpful for the optimization of tailored adjuvant therapy.

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Malignancies associated with GIST: a retrospective study with molecular analysis of KIT and PDGFRA

Cited by 16 publications

References 23 publications

Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia

Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia

MRITexture‐Based Models for Predicting Mitotic Index and Risk Classification of Gastrointestinal Stromal Tumors

Mutational characteristics of gastrointestinal stromal tumors: A single‑center analysis of 302 patients

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