HER2 Blockade in Metastatic Collecting Duct Carcinoma (CDC) of the Kidney: A Case Report

Bronchud, Miguel H.; Castillo, S.; Romaní, Santiago Escriva de; Mourelo, Santiago; Fernández, Alejandra; Baena, Cecilia; Murillo, Jesús; Julia, Joan C; Esquius, J.; Romero, Rubén; Andreu, Xavier

doi:10.1159/000345041

Cited by 23 publications

(11 citation statements)

References 21 publications

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“…Further, triple combination of bevacizumab, gemcitabine and cisplatin/carboplatin has been reported to be effective in terms of progression-free survival and overall survival as compared to platinum-based chemotherapy [ 50 ]. Additionally, double HER2 blockade has been shown to have activity in disseminated CDC [ 51 ]. In the majority of CDC cases, surgical treatment did not result in cure [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Collecting duct carcinoma of the kidney is associated withCDKN2Adeletion andSLCfamily gene up-regulation

et al. 2016

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The genetic landscape and molecular features of collecting duct carcinoma (CDC) of the kidney remain largely unknown. Herein, we performed whole exome sequencing (WES) and transcriptome sequencing (RNASeq) on 7 CDC samples (CDC1 −7). Among the 7 samples, 4 samples with matched non-tumor tissue were used for copy number analysis by SNP array data. No recurrent somatic SNVs were observed except for MLL, which was found to be mutated (p.V297I and p.F407C) in 2 samples. We identified somatic SNVs in 14 other cancer census genes including: ATM, CREBBP, PRDM1, CBFB, FBXW7, IKZF1, KDR, KRAS, NACA, NF2, NUP98, SS18, TP53, and ZNF521. SNP array data identified a CDKN2A homozygous deletion in 3 samples and SNV analysis showed a non-sense mutation of the CDKN2A gene with unknown somatic status. To estimate the recurrent rate of CDKN2A abnormalities, we performed FISH screening of additional samples and confirmed the frequent loss (62.5%) of CDKN2A expression. Since cisplatin based therapy is the common treatment option for CDC, we investigated the expression of solute carrier (SLC) family transporters and found 45% alteration. In addition, SLC7A11 (cystine transporter, xCT), a cisplatin resistance associated gene, was found to be overexpressed in 4 out of 5 (80%) cases of CDC tumors tested, as compared to matched non-tumor tissue. In summary, our study provides a comprehensive genomic analysis of CDC and identifies potential pathways suitable for targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Collecting duct carcinoma of the kidney is associated withCDKN2Adeletion andSLCfamily gene up-regulation

et al. 2016

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“…У пациента мужского пола с метастатической карциномой собирательного протока с большим количеством отдаленных метастазов была обнаружена мутация HER2, подходящая для терапии трастузумабом и лапатинибом. Через две недели лечения наблюдалось значительное уменьшение метастазов и уменьшение размеров основной опухоли [24]. Это позволяет сделать вывод о том, что успешное лечение ПКК может быть проведено с использованием анти-HER2-таргетной терапии.…”

Section: лабораторные и экспериментальные исследованияunclassified

Integral Analysis of Genomic and Transcriptomic Changes in Clear Cell Renal Cell Carcinoma in the Russian Population

et al. 2020

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Renal cell carcinoma (Rcc) is the most common form of kidney cancer, accounting for about 90 % of cancers in the kidney. clear cell renal cell carcinoma (ccRcc) is the most common histological type of Rcc. clear cell renal cell carcinoma is characterized by specific genomic and transcriptomic aberrations in the tumor. We performed a targeted sequencing of key oncogenes and a genome-wide expression study in 58 patients with Rcc belonging to a population of the western part of the Russian Federation. the integrative analysis of genomics and transcriptome data revealed that the NFkβ nuclear complex, ERBB2 receptor, and tP53 transcription factor were the key regulators of observed changes in the expression. We also carried out the analysis of the mutational landscape in key genes associated with cancer. We found the difference in the molecular mechanisms of Rcc between different populations, since the detected expression regulators were not previously described as expression mediators in Rcc. since the ERBB2 receptor is a highly attractive target for therapeutic interventions of breast cancer, we will eventually be able to develop new treatment modalities for Rcc.

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“…Likewise, HER2 overexpression and/or gene amplification has also been observed in 0–25% of urothelial carcinoma [ 20 ], and it has been considered a target suitable for trastuzumab treatment [ 21 ]. HER2 overexpression in CDC has been reported only in a few studies, more specifically in two case-reports [ 22 , 23 ] and one small cohort of 11 cases [ 24 ]. Since the lack of effective adjuvant treatment, improved molecular characterization of CDCs, and identifying novel targets that can provide new therapeutic options will be crucial to improve patient outcomes from the perspective of a precision medicine approach.…”

Section: Introductionmentioning

confidence: 99%

Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication

Costantini

Amoreo

Torregrossa

et al. 2020

Cancers

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Collecting duct carcinoma (CDC) is rare and aggressive histology of kidney cancers. Although different therapeutic approaches have been tested, the 2-year survival remains very poor. Since CDC exhibits overlapping features with urothelial carcinoma, the analysis of shared molecular alterations could provide new insights into the understanding of this rare disease and also therapeutic options. We collected 26 CDC cases, and we assessed HER2 protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in-situ hybridization (FISH) according to 2018 ASCO/CAP HER2-testing recommendations. Six out of twenty-six (23%) tumors showed HER2 positive staining. In particular, 3+ score was present in 2/6 cases (33%), 2+ in 3/6 cases (50%) and 1+ in 1/6 cases (17%). The 6 HER2+ tumors were also analyzed by FISH to assess gene copy number. One out of six CDC with IHC 3+ was also HER2 amplified, showing an average HER2 copy number ≥4.0 (10.85) and a HER2/CEP17 ratio ≥ (5.63), while the 5/6 cases were HER2 negative. Based on the 2018 ASCO/CAP guidelines overall, 2/26 CDC cases (8%) were HER2+. The present study provides evidence for testing, in future studies, HER2 to assess its clinical value as a novel target for the treatment of this highly malignant cancer.

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HER2 Blockade in Metastatic Collecting Duct Carcinoma (CDC) of the Kidney: A Case Report

Cited by 23 publications

References 21 publications

Collecting duct carcinoma of the kidney is associated withCDKN2Adeletion andSLCfamily gene up-regulation

Collecting duct carcinoma of the kidney is associated withCDKN2Adeletion andSLCfamily gene up-regulation

Integral Analysis of Genomic and Transcriptomic Changes in Clear Cell Renal Cell Carcinoma in the Russian Population

Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication

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