Gastric GISTs: Analysis of c-Kit, PDGFRA and BRAF mutations in relation to prognosis and clinical pathological characteristics of patients - A GIRCG study

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• 作者：L. Capelli^a ; E. Petracci^b ; V. Quagliuolo^c ; L. Saragoni^d ; P. Colombo^e ; P. Morgagni^f ; D. Calistri^a ; A. Tomezzoli^g ; M. Di Cosmo^h ; F. Rovielloⁱ ; C. Vindigni^j ; A. Coniglio^k ; V. Villanacci^l ; M. Catarci^m ; L. Coppolaⁿ ; S. Alfieri^o ; R. Ricci^p ; C. Capella^q ; S. Rausei^r ; D. Gulino^b ; D. Amadori^s ; P. Ulivi^a ; ^{paola.ulivi@irst.emr.it" class="auth_mail" title="E-mail the corresponding author} ; on behalf of the Italian Gastric Cancer Research Group (GIRCG)
• 关键词：GISTs ; KIT ; PDGFRA ; BRAF ; Prognostic factors ; Mutation
• 刊名：European Journal of Surgical Oncology (EJSO)
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：42
• 期：8
• 页码：1206-1214
• 全文大小：233 K

文摘

Gastric gastrointestinal stromal tumors (GISTs) represent a subgroup of GISTs with a better prognosis than those located in other areas. In this retrospective study we performed a molecular characterization of a large series of patients with gastric GISTs in relation to clinical–pathological characteristics and prognosis.

Methods

DNA was extracted from paraffin-embedded sections from 221 gastric GIST patients submitted to surgery. Exons 9, 11, 13 and 17 of m>KITm>, exons 12 and 18 of m>PDGFRAm> and exons 11 and 15 of m>BRAFm> were analyzed by direct sequencing. Cox regression analysis adjusted for clinical–pathological factors was performed to evaluate m>KITm> and m>PDGFRAm> mutations in relation to the composite endpoint of relapse or death.

Results

m>KIT and PDGFRAm> mutations were observed in 119 (53.8%) and 56 (25.3%) patients, respectively, whereas 46 (20.8%) patients had wild type (wt) disease. Univariable analyses showed that a high Miettinen risk category and the presence of ulceration and m>KITm> deletions were associated with increased risk of relapse or death (p < 0.001; p = 0.0389 and p = 0.002, respectively). After adjusting for Miettinen risk score, m>KITm> deletions remained an independent prognostic factor (HR_adj = 2.65, 95% CI [1.15–6.13], p = 0.023). Moreover, m>KITm> deletions in exon 11 codons 557, 558 or 559 were associated with a higher risk of relapse or death than wt tumors (HR_adj = 3.29 95% CI [1.64–6.64], p = 0.001).

Conclusions

m>KITm> deletions in exon 11, especially those involving codons 557, 558 or 559, were correlated with a more aggressive gastric GIST phenotype and increased risk of relapse or death.