Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach
Gastric adenocarcinoma (GAC) is a heterogeneous disease and at least two major studies have recently provided a molecular classification for this tumor: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ARCG). Both classifications quote four molecular subtypes, but these subtypes o...
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MDPI AG
2021-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/15/3722 |
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| author | Till Daun Ronny Nienhold Aino Paasinen-Sohns Angela Frank Melanie Sachs Inti Zlobec Gieri Cathomas |
| author_facet | Till Daun Ronny Nienhold Aino Paasinen-Sohns Angela Frank Melanie Sachs Inti Zlobec Gieri Cathomas |
| author_sort | Till Daun |
| collection | DOAJ |
| description | Gastric adenocarcinoma (GAC) is a heterogeneous disease and at least two major studies have recently provided a molecular classification for this tumor: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ARCG). Both classifications quote four molecular subtypes, but these subtypes only partially overlap. In addition, the classifications are based on complex and cost-intensive technologies, which are hardly feasible for everyday practice. Therefore, simplified approaches using immunohistochemistry (IHC), in situ hybridization (ISH) as well as commercially available next generation sequencing (NGS) have been considered for routine use. In the present study, we screened 115 GAC by IHC for p53, MutL Homolog 1 (MLH1) and E-cadherin and performed ISH for Epstein–Barr virus (EBV). In addition, sequencing by NGS for TP53 and tumor associated genes was performed. With this approach, we were able to define five subtypes of GAC: (1) Microsatellite Instable (MSI), (2) EBV-associated, (3) Epithelial Mesenchymal Transition (EMT)-like, (4) p53 aberrant tumors surrogating for chromosomal instability and (5) p53 proficient tumors surrogating for genomics stable cancers. Furthermore, by considering lymph node metastasis in the p53 aberrant GAC, a better prognostic stratification was achieved which finally allowed us to separate the GAC highly significant in a group with poor and good-to-intermediate prognosis, respectively. Our data show that molecular classification of GAC can be achieved by using commercially available assays including IHC, ISH and NGS. Furthermore, we present an integrative workflow, which has the potential to overcome the uncertainty resulting from discrepancies from existing classification schemes. |
| first_indexed | 2024-03-10T09:17:34Z |
| format | Article |
| id | doaj.art-1e925ab8a2824897aca00cf4173c0d40 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:17:34Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1e925ab8a2824897aca00cf4173c0d402023-11-22T05:26:43ZengMDPI AGCancers2072-66942021-07-011315372210.3390/cancers13153722Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative ApproachTill Daun0Ronny Nienhold1Aino Paasinen-Sohns2Angela Frank3Melanie Sachs4Inti Zlobec5Gieri Cathomas6Institute of Pathology, Cantonal Hospital Basel-Land, 4410 Liestal, SwitzerlandInstitute of Pathology, Cantonal Hospital Basel-Land, 4410 Liestal, SwitzerlandInstitute of Pathology, Cantonal Hospital Basel-Land, 4410 Liestal, SwitzerlandInstitute of Pathology, Cantonal Hospital Basel-Land, 4410 Liestal, SwitzerlandInstitute of Pathology, Cantonal Hospital Basel-Land, 4410 Liestal, SwitzerlandInstitute of Pathology, University of Bern, 3008 Bern, SwitzerlandInstitute of Pathology, Cantonal Hospital Basel-Land, 4410 Liestal, SwitzerlandGastric adenocarcinoma (GAC) is a heterogeneous disease and at least two major studies have recently provided a molecular classification for this tumor: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ARCG). Both classifications quote four molecular subtypes, but these subtypes only partially overlap. In addition, the classifications are based on complex and cost-intensive technologies, which are hardly feasible for everyday practice. Therefore, simplified approaches using immunohistochemistry (IHC), in situ hybridization (ISH) as well as commercially available next generation sequencing (NGS) have been considered for routine use. In the present study, we screened 115 GAC by IHC for p53, MutL Homolog 1 (MLH1) and E-cadherin and performed ISH for Epstein–Barr virus (EBV). In addition, sequencing by NGS for TP53 and tumor associated genes was performed. With this approach, we were able to define five subtypes of GAC: (1) Microsatellite Instable (MSI), (2) EBV-associated, (3) Epithelial Mesenchymal Transition (EMT)-like, (4) p53 aberrant tumors surrogating for chromosomal instability and (5) p53 proficient tumors surrogating for genomics stable cancers. Furthermore, by considering lymph node metastasis in the p53 aberrant GAC, a better prognostic stratification was achieved which finally allowed us to separate the GAC highly significant in a group with poor and good-to-intermediate prognosis, respectively. Our data show that molecular classification of GAC can be achieved by using commercially available assays including IHC, ISH and NGS. Furthermore, we present an integrative workflow, which has the potential to overcome the uncertainty resulting from discrepancies from existing classification schemes.https://www.mdpi.com/2072-6694/13/15/3722gastric cancerprognosismolecular classificationimmunohistochemistryin situ hybridizationnext generation sequencing |
| spellingShingle | Till Daun Ronny Nienhold Aino Paasinen-Sohns Angela Frank Melanie Sachs Inti Zlobec Gieri Cathomas Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach Cancers gastric cancer prognosis molecular classification immunohistochemistry in situ hybridization next generation sequencing |
| title | Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach |
| title_full | Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach |
| title_fullStr | Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach |
| title_full_unstemmed | Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach |
| title_short | Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach |
| title_sort | combined simplified molecular classification of gastric adenocarcinoma enhanced by lymph node status an integrative approach |
| topic | gastric cancer prognosis molecular classification immunohistochemistry in situ hybridization next generation sequencing |
| url | https://www.mdpi.com/2072-6694/13/15/3722 |
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