Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation
Abstract Intratumoral heterogeneity (ITH) is spatial, phenotypic, or molecular differences within the same tumor that have important implications for accurate tumor classification and assessment of predictive biomarkers. The Canadian Ovarian Experimental Unified Resource (COEUR) has created a cohort...
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Nature Portfolio
2025-01-01
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| author | Aline Talhouk Derek S. Chiu Liliane Meunier Kurosh Rahimi Cécile Le Page Monique Bernard Diane Provencher David G. Huntsman Anne Marie Mes Masson Martin Köbel |
| author_facet | Aline Talhouk Derek S. Chiu Liliane Meunier Kurosh Rahimi Cécile Le Page Monique Bernard Diane Provencher David G. Huntsman Anne Marie Mes Masson Martin Köbel |
| author_sort | Aline Talhouk |
| collection | DOAJ |
| description | Abstract Intratumoral heterogeneity (ITH) is spatial, phenotypic, or molecular differences within the same tumor that have important implications for accurate tumor classification and assessment of predictive biomarkers. The Canadian Ovarian Experimental Unified Resource (COEUR) has created a cohort of 437 FFPE tissue specimens from 108 tubo-ovarian high-grade serous carcinoma (HGSC) patients to quantify ITH across the anatomical sites and between primary and recurrence. We quantified the ITH of six clinically used immunohistochemical diagnostic and prognostic biomarkers (WT1, p53, p16, PR, CD8, and Ki67). Markers were stained on tissue microarrays and scored using a continuous or categorical interpretation of staining patterns. Two-way random effect and nested intraclass correlation were used to assess continuous markers, and Gwet’s AC1 was used for categorical markers. All biomarkers showed at least substantial agreement over several spatial comparisons, with WT1, p53 and p16 showing almost perfect agreement for most spatial comparisons. Similarly, categorical WT1, p53 and p16 showed almost perfect agreement for temporal comparisons, while the agreement for primary versus recurrence for PR, CD8 and Ki67 was only fair. We provide power calculations to achieve reliability of > 0.60 and recommend testing emerging protein biomarkers to see whether they reach a clinically acceptable benchmark level of ITH. |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-35ad9ec698f449c08e695a82577c224e2025-01-26T12:32:48ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-024-82206-zQuantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translationAline Talhouk0Derek S. Chiu1Liliane Meunier2Kurosh Rahimi3Cécile Le Page4Monique Bernard5Diane Provencher6David G. Huntsman7Anne Marie Mes Masson8Martin Köbel9Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of British ColumbiaDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of British ColumbiaCentre de Recherche du Centre Hospitalier de l’Universite de Montreal (CRCHUM), Institut du cancer de MontrealCentre de Recherche du Centre Hospitalier de l’Universite de Montreal (CRCHUM), Institut du cancer de MontrealCentre de Recherche de I’IUSMMCentre de Recherche du Centre Hospitalier de l’Universite de Montreal (CRCHUM), Institut du cancer de MontrealCentre de Recherche du Centre Hospitalier de l’Universite de Montreal (CRCHUM), Institut du cancer de MontrealDepartment of Pathology and Laboratory Medicine, University of British ColumbiaCentre de Recherche du Centre Hospitalier de l’Universite de Montreal (CRCHUM), Institut du cancer de MontrealDepartment of Pathology and Laboratory Medicine, University of CalgaryAbstract Intratumoral heterogeneity (ITH) is spatial, phenotypic, or molecular differences within the same tumor that have important implications for accurate tumor classification and assessment of predictive biomarkers. The Canadian Ovarian Experimental Unified Resource (COEUR) has created a cohort of 437 FFPE tissue specimens from 108 tubo-ovarian high-grade serous carcinoma (HGSC) patients to quantify ITH across the anatomical sites and between primary and recurrence. We quantified the ITH of six clinically used immunohistochemical diagnostic and prognostic biomarkers (WT1, p53, p16, PR, CD8, and Ki67). Markers were stained on tissue microarrays and scored using a continuous or categorical interpretation of staining patterns. Two-way random effect and nested intraclass correlation were used to assess continuous markers, and Gwet’s AC1 was used for categorical markers. All biomarkers showed at least substantial agreement over several spatial comparisons, with WT1, p53 and p16 showing almost perfect agreement for most spatial comparisons. Similarly, categorical WT1, p53 and p16 showed almost perfect agreement for temporal comparisons, while the agreement for primary versus recurrence for PR, CD8 and Ki67 was only fair. We provide power calculations to achieve reliability of > 0.60 and recommend testing emerging protein biomarkers to see whether they reach a clinically acceptable benchmark level of ITH.https://doi.org/10.1038/s41598-024-82206-zOvarian cancerHigh-grade serousIntratumoral heterogeneityTP53CD8WT1 |
| spellingShingle | Aline Talhouk Derek S. Chiu Liliane Meunier Kurosh Rahimi Cécile Le Page Monique Bernard Diane Provencher David G. Huntsman Anne Marie Mes Masson Martin Köbel Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation Scientific Reports Ovarian cancer High-grade serous Intratumoral heterogeneity TP53 CD8 WT1 |
| title | Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation |
| title_full | Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation |
| title_fullStr | Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation |
| title_full_unstemmed | Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation |
| title_short | Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation |
| title_sort | quantifying intratumoral biomarker heterogeneity in tubo ovarian high grade serous carcinoma to optimize clinical translation |
| topic | Ovarian cancer High-grade serous Intratumoral heterogeneity TP53 CD8 WT1 |
| url | https://doi.org/10.1038/s41598-024-82206-z |
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