Variability in HER2 expression between primary colorectal cancer and corresponding metastases

Shan, Lina; Lv, Yiming; Bai, Bingjun; Huang, Xuefeng; Zhu, Hongbo

doi:10.1007/s00432-018-2744-z

Cited by 21 publications

(9 citation statements)

References 24 publications

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“…In studies to determine prognostic markers for colorectal cancer and investigating the corresponding LN metastases, the expression patterns of some of the markers showed to be heterogeneous between the PT and LN metastases. While the expression of p53 has been documented to be similar between PT and LN metastases, the EGFR and HER2 expression differed significantly [6, 8, 9]. This differences in EGFR and HER2 expression indicate that the PT does not accurately reflect the metastasis situation and we need the information of the LN metastases, which might have important clinical implications.…”

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confidence: 99%

Tumor stroma as contributing factor in the lymph node metastases process?

2019

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confidence: 99%

Tumor stroma as contributing factor in the lymph node metastases process?

2019

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“…In addition, Shan et al 12 evaluated HER2 amplification in the liver and nodal metastases demonstrating poorer concordance overall, including 63% among liver metastases ( κ = 0.32), while nodal metastases were somewhat higher at 90% ( κ = 0.48). The authors importantly cited that HER2 overexpression was most commonly seen in KRAS wild‐type patients, suggesting that genomic events may not be isolated, and, therefore, a linear relationship may not always be observed if alterations are linked or coexpressed.…”

Section: Discussionmentioning

confidence: 99%

“…Because the possibility of chance agreement cannot be excluded, assessment of concordance (expressed as an absolute ratio) can be best put into context using the reported κ value. Such measurement has been infrequently utilized in previous publications in this realm of study 12 …”

Section: Discussionmentioning

confidence: 99%

“…Whole‐exome sequencing between primary colon lesions and associated metastases has demonstrated great variation, supporting hypotheses of subclonal expansion among metastatic lesions 7,8 . In the clinical setting, more convenient DNA sequencing technologies have permitted rapid assessment of commonly described CRC mutations, and variable rates of concordance between primary disease and liver metastases have been similarly reported 9‐13 . Moreover, this issue is further complicated by the fact that some genomic alterations appear to be more stable across primary and hepatic metastatic lesions than others.…”

Section: Introductionmentioning

confidence: 99%

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High mutational concordance between primary colorectal tumors and associated pulmonary metastases

Corsini

Datar

Mitchell

et al. 2020

Journal of Surgical Oncology

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Background and Objectives: Precision medicine has altered the management of colorectal cancer (CRC). However, the concordance of mutational findings between primary CRC tumors and associated pulmonary metastases (PM) is not welldescribed. This study aims to determine the concordance of genomic profiles between primary CRC and PM.Methods: Patients treated for colorectal PM at a single institution from 2000 to 2017 were identified. Mutational concordance was defined as either both wild-type or both mutant alleles in lung and colorectal lesion; genes with opposing mutational profiles were reported as discordant. Results: Thirty-eight patients met inclusion criteria, among whom KRAS, BRAF, NRAS, MET, RET, and PIK3CA were examined for concordance. High concordance was demonstrated among all evaluated genes, ranging from 86% (KRAS) to 100% concordance (NRAS, RET, and MET). De novo KRAS mutations were detected in the PM of 4 from 35 (11%) patients, 3 of whom had previously received anti-epidermal growth factor receptor (EGFR) therapy. Evaluation of Cohen's κ statistic demonstrated moderate to perfect correlation among evaluated genes. Conclusions: Because high intertumoral genomic homogeneity exists, it may be reasonable to use primary CRC mutational profiles to guide prognostication and targeted therapy for PM. However, the possibility of de novo KRAS-mutant PM should be considered, particularly among patients previously treated with anti-EGFR therapy. K E Y W O R D S colorectal cancer, concordance, genes, mutations, pulmonary metastases F I G U R E 2 Mutational concordance by a gene with concordant specimens in light/dark blue and discordant samples in light/dark red. WT, wild-type [Color figure can be viewed at wileyonlinelibrary.com] 986 | CORSINI ET AL. CONFLICT OF INTERESTSThe authors declare that there are no conflict of interests. DATA AVAILABILITY STATEMENTDeidentified patient data, as well as plan of statistical analyses, which underlie the results reported in this investigation will be made available upon request immediately upon publication for up to 36 months. Requests from investigators with methodologically sound research proposals will be granted for specific analyses outlined within such proposals or meta-analyses.Requests for data sharing should be submitted to the corresponding author. ORCIDErin M. Corsini http://orcid.org/0000-0003-4715-0244 988 | CORSINI ET AL.

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“…The Cancer Genome Atlas (TCGA) project detected HER2 alterations in around 7% of patients affected by CRC, especially in RAS and BRAF wild-type tumors [93]. Although controversial, HER2 overexpression has been observed more frequently in high tumor mutational burden and advanced T stage [86], while some studies evidenced a significant discordance between primary tumors and metastases, suggesting the loss of HER2 positivity during disease progression [94,95]. Moreover, HER2 status has been related to sidedness and, more frequently, HER2-amplified primary tumors have been located in the rectum, as well as in the left colon [96][97][98].…”

Section: Her2 Alterations In Acrcmentioning

confidence: 99%

Beyond RAS and BRAF: HER2, a New Actionable Oncotarget in Advanced Colorectal Cancer

Guarini

Grassi²,

Pezzicoli

et al. 2021

IJMS

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The human epidermal growth factor receptor 2 (HER2) is a well-established oncogenic driver and a successful therapeutic target in several malignancies, such as breast and gastric cancers. HER2 alterations, including amplification and somatic mutations, have also been detected in a small but not negligible subset of patients affected by advanced colorectal cancer (aCRC). However, to date, there are no available oncotargets in this malignancy beyond RAS and BRAF that are available. Here we present an overview on the present predictive and prognostic role of HER2 expression in aCRC, as well as on its consequent potential therapeutic implications from preclinical investigations towards ongoing trials testing anti-HER2 agents in aCRC. While HER2′s role as a molecular predictive biomarker for anti-EGFR therapies in CRC is recognized, HER2 prognostic value remains controversial. Moreover, thanks to the impressive and growing body of clinical evidence, HER2 is strongly emerging as a new potential actionable oncotarget in aCRC. In conclusion, in the foreseeable future, HER2-targeted therapeutic strategies may integrate the algorithm of aCRC treatment towards an increasingly tailored therapeutic approach to this disease.

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Variability in HER2 expression between primary colorectal cancer and corresponding metastases

Abstract: The present study showed a high rate of discordance in matched pairs of primary tumors and metastases, suggesting that the accurate evaluation of HER2 status is essential before any therapeutic decision.

Cited by 21 publications

References 24 publications

Tumor stroma as contributing factor in the lymph node metastases process?

Tumor stroma as contributing factor in the lymph node metastases process?

High mutational concordance between primary colorectal tumors and associated pulmonary metastases

Beyond RAS and BRAF: HER2, a New Actionable Oncotarget in Advanced Colorectal Cancer

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