ERBB2 Mutations Characterize a Subgroup of Muscle-invasive Bladder Cancers with Excellent Response to Neoadjuvant Chemotherapy

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• 作者：Floris H. Groenendijk^a ; Jeroen de Jong^b ; ^&dagger ; ; Elisabeth E. Fransen van de Putte^c ; ^&dagger ; ; Magali Michaut^a ; Andreas Schlicker^a ; Dennis Peters^d ; Arno Velds^e ; Marja Nieuwland^e ; Michel M. van den Heuvel^f ; Ron M. Kerkhoven^e ; Lodewijk F. Wessels^a ; Annegien Broeks^d ; Bas W.G. van Rhijn^c ; René ; Bernards^a ; Michiel S. van der Heijden^a ; ^g ; ^{ms.vd.heijden@nki.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ERBB2 ; ERCC2 ; Muscle-invasive bladder cancer ; Neoadjuvant chemotherapy ; Response
• 刊名：European Urology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：69
• 期：3
• 页码：384-388
• 全文大小：1900 K

文摘

A pathologic complete response to neoadjuvant chemotherapy (NAC) containing platinum is a strong prognostic determinant for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive molecular characterization of bladder cancer, associations of molecular alterations with treatment response are still largely unknown. We selected pathologic complete responders (ypT0N0; n = 38) and nonresponders (higher than ypT2; n = 33) from a cohort of high-grade MIBC patients treated with NAC. DNA was isolated from prechemotherapy tumor tissue and used for next-generation sequencing of 178 cancer-associated genes (discovery cohort) or targeted sequencing (validation cohort). We found that 9 of 38 complete responders had erb-b2 receptor tyrosine kinase 2 (ERBB2) missense mutations, whereas none of 33 nonresponders had ERBB2 mutations (p = 0.003). ERBB2 missense mutations in complete responders were mostly confirmed activating mutations. ERCC2 missense mutations, recently found associated with response to NAC, were more common in complete responders; however, this association did not reach statistical significance in our cohort. We conclude that ERBB2 missense mutations characterize a subgroup of MIBC patients with an excellent response to NAC.

Patient summary

In this report we looked for genetic alterations that can predict the response to neoadjuvant chemotherapy (NAC) in bladder cancer. We found that mutations in the gene ERBB2 are exclusively present in patients responding to NAC.