Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer
Abstract Introduction Gastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications. Method...
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2024-12-01
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| Online Access: | https://doi.org/10.1186/s12885-024-13236-z |
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| author | Jefim Brodkin Tuomas Kaprio Jaana Hagström Alli Leppä Arto Kokkola Caj Haglund Camilla Böckelman |
| author_facet | Jefim Brodkin Tuomas Kaprio Jaana Hagström Alli Leppä Arto Kokkola Caj Haglund Camilla Böckelman |
| author_sort | Jefim Brodkin |
| collection | DOAJ |
| description | Abstract Introduction Gastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications. Methods We classified a cohort of 283 gastric cancer patients undergoing surgery at Helsinki University Hospital between 2000 and 2009. We constructed a tumour tissue microarray immunostained for the following markers: microsatellite instability (MSI) markers MSH2, MSH6, MLH1, and PMS2; p53; E-cadherin; and EBERISH. Results In the univariate survival analysis for disease-specific survival, the Epstein–Barr virus (EBV) -positive subtype exhibited the worst prognosis with a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.19–5.25, p = 0.016) compared with the most benign subtype, chromosomal instability (CIN). Using TCGA’s classification, the genetically stable (GS) and MSI subtypes exhibited a worse survival compared with CIN (HR 1.73 [95% CI 1.15–2.60], p = 0.009 and HR 1.74 [95% CI 1.06–2.84], p = 0.027, respectively). Using the ACRG classification, the p53 aberrant subtype exhibited the best prognosis, whereas wild-type p53, MSI, and the epithelial–mesenchymal transition (EMT) subtypes exhibited poorer prognoses (EMT: HR 1.90 [95% CI 1.30–2.77], p < 0.001) when compared with aberrant p53. Conclusions Immunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed. |
| format | Article |
| id | doaj-art-79ec27d220a64f77ad169c0ed924ff3c |
| institution | OA Journals |
| issn | 1471-2407 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-79ec27d220a64f77ad169c0ed924ff3c2025-08-20T02:30:56ZengBMCBMC Cancer1471-24072024-12-0124111210.1186/s12885-024-13236-zPrognostic effect of immunohistochemically determined molecular subtypes in gastric cancerJefim Brodkin0Tuomas Kaprio1Jaana Hagström2Alli Leppä3Arto Kokkola4Caj Haglund5Camilla Böckelman6Translational Cancer Medicine Research Program, Faculty of Medicine, University of HelsinkiTranslational Cancer Medicine Research Program, Faculty of Medicine, University of HelsinkiTranslational Cancer Medicine Research Program, Faculty of Medicine, University of HelsinkiDepartment of Surgery, University of Helsinki and Helsinki University HospitalDepartment of Surgery, University of Helsinki and Helsinki University HospitalTranslational Cancer Medicine Research Program, Faculty of Medicine, University of HelsinkiTranslational Cancer Medicine Research Program, Faculty of Medicine, University of HelsinkiAbstract Introduction Gastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications. Methods We classified a cohort of 283 gastric cancer patients undergoing surgery at Helsinki University Hospital between 2000 and 2009. We constructed a tumour tissue microarray immunostained for the following markers: microsatellite instability (MSI) markers MSH2, MSH6, MLH1, and PMS2; p53; E-cadherin; and EBERISH. Results In the univariate survival analysis for disease-specific survival, the Epstein–Barr virus (EBV) -positive subtype exhibited the worst prognosis with a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.19–5.25, p = 0.016) compared with the most benign subtype, chromosomal instability (CIN). Using TCGA’s classification, the genetically stable (GS) and MSI subtypes exhibited a worse survival compared with CIN (HR 1.73 [95% CI 1.15–2.60], p = 0.009 and HR 1.74 [95% CI 1.06–2.84], p = 0.027, respectively). Using the ACRG classification, the p53 aberrant subtype exhibited the best prognosis, whereas wild-type p53, MSI, and the epithelial–mesenchymal transition (EMT) subtypes exhibited poorer prognoses (EMT: HR 1.90 [95% CI 1.30–2.77], p < 0.001) when compared with aberrant p53. Conclusions Immunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed.https://doi.org/10.1186/s12885-024-13236-zGastric cancerImmunohistochemistrySurvivalEpstein–Barr virus |
| spellingShingle | Jefim Brodkin Tuomas Kaprio Jaana Hagström Alli Leppä Arto Kokkola Caj Haglund Camilla Böckelman Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer BMC Cancer Gastric cancer Immunohistochemistry Survival Epstein–Barr virus |
| title | Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer |
| title_full | Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer |
| title_fullStr | Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer |
| title_full_unstemmed | Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer |
| title_short | Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer |
| title_sort | prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer |
| topic | Gastric cancer Immunohistochemistry Survival Epstein–Barr virus |
| url | https://doi.org/10.1186/s12885-024-13236-z |
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