Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors
Abstract Dickkopf-1 (DKK1) is a secreted modulator of Wnt signaling that is frequently overexpressed in tumors and associated with poor clinical outcomes. DKN-01 is a humanized monoclonal therapeutic antibody that binds DKK1 with high affinity and has demonstrated clinical activity in gastric/gastro...
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Nature Portfolio
2021
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oai:doaj.org-article:386bfb9934384f32ac9a8bd2228acb372021-12-02T17:01:43ZValidation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors10.1038/s41598-021-89060-32045-2322https://doaj.org/article/386bfb9934384f32ac9a8bd2228acb372021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89060-3https://doaj.org/toc/2045-2322Abstract Dickkopf-1 (DKK1) is a secreted modulator of Wnt signaling that is frequently overexpressed in tumors and associated with poor clinical outcomes. DKN-01 is a humanized monoclonal therapeutic antibody that binds DKK1 with high affinity and has demonstrated clinical activity in gastric/gastroesophageal junction (G/GEJ) patients with elevated tumoral expression of DKK1. Here we report on the validation of a DKK1 RNAscope chromogenic in situ hybridization assay to assess DKK1 expression in G/GEJ tumor tissue. To reduce pathologist time, potential pathologist variability from manual scoring and support pathologist decision making, a digital image analysis algorithm that identifies tumor cells and quantifies the DKK1 signal was developed. Following CLIA guidelines the DKK1 RNAscope chromogenic in situ hybridization assay and digital image analysis algorithm were successfully validated for sensitivity, specificity, accuracy, and precision. The DKK1 RNAscope assay in conjunction with the digital image analysis solution is acceptable for prospective screening of G/GEJ adenocarcinoma patients. The work described here will further advance the companion diagnostic development of our DKK1 RNAscope assay and could generally be used as a guide for the validation of RNAscope assays with digital image quantification.Charles CaldwellJames B. RottmanWill PacesElizabeth BuecheSofia ReitsmaJoseph GibbVitria AdisetiyoMichael S. HaasHeidi HeathWalter NewmanJason BaumRoberto GiananiMichael H. KageyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q Charles Caldwell James B. Rottman Will Paces Elizabeth Bueche Sofia Reitsma Joseph Gibb Vitria Adisetiyo Michael S. Haas Heidi Heath Walter Newman Jason Baum Roberto Gianani Michael H. Kagey Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors |
| description |
Abstract Dickkopf-1 (DKK1) is a secreted modulator of Wnt signaling that is frequently overexpressed in tumors and associated with poor clinical outcomes. DKN-01 is a humanized monoclonal therapeutic antibody that binds DKK1 with high affinity and has demonstrated clinical activity in gastric/gastroesophageal junction (G/GEJ) patients with elevated tumoral expression of DKK1. Here we report on the validation of a DKK1 RNAscope chromogenic in situ hybridization assay to assess DKK1 expression in G/GEJ tumor tissue. To reduce pathologist time, potential pathologist variability from manual scoring and support pathologist decision making, a digital image analysis algorithm that identifies tumor cells and quantifies the DKK1 signal was developed. Following CLIA guidelines the DKK1 RNAscope chromogenic in situ hybridization assay and digital image analysis algorithm were successfully validated for sensitivity, specificity, accuracy, and precision. The DKK1 RNAscope assay in conjunction with the digital image analysis solution is acceptable for prospective screening of G/GEJ adenocarcinoma patients. The work described here will further advance the companion diagnostic development of our DKK1 RNAscope assay and could generally be used as a guide for the validation of RNAscope assays with digital image quantification. |
| format |
article |
| author |
Charles Caldwell James B. Rottman Will Paces Elizabeth Bueche Sofia Reitsma Joseph Gibb Vitria Adisetiyo Michael S. Haas Heidi Heath Walter Newman Jason Baum Roberto Gianani Michael H. Kagey |
| author_facet |
Charles Caldwell James B. Rottman Will Paces Elizabeth Bueche Sofia Reitsma Joseph Gibb Vitria Adisetiyo Michael S. Haas Heidi Heath Walter Newman Jason Baum Roberto Gianani Michael H. Kagey |
| author_sort |
Charles Caldwell |
| title |
Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors |
| title_short |
Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors |
| title_full |
Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors |
| title_fullStr |
Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors |
| title_full_unstemmed |
Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors |
| title_sort |
validation of a dkk1 rnascope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/386bfb9934384f32ac9a8bd2228acb37 |
| work_keys_str_mv |
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1718382061980483584 |