Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm
TGCTs represent a model of curable disease afflicting especially young men. Defining tumor biological characteristics is crucial to increase current knowledge and tailor the best clinical management. Ki67, a potential prognostic marker, still exhibits heterogenous associations with patient outcomes,...
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MDPI AG
2022-02-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/2/264 |
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| author | Beatriz Chaves Lourenço Catarina Guimarães-Teixeira Bianca C. T. Flores Vera Miranda-Gonçalves Rita Guimarães Mariana Cantante Paula Lopes Isaac Braga Joaquina Maurício Carmen Jerónimo Rui Henrique João Lobo |
| author_facet | Beatriz Chaves Lourenço Catarina Guimarães-Teixeira Bianca C. T. Flores Vera Miranda-Gonçalves Rita Guimarães Mariana Cantante Paula Lopes Isaac Braga Joaquina Maurício Carmen Jerónimo Rui Henrique João Lobo |
| author_sort | Beatriz Chaves Lourenço |
| collection | DOAJ |
| description | TGCTs represent a model of curable disease afflicting especially young men. Defining tumor biological characteristics is crucial to increase current knowledge and tailor the best clinical management. Ki67, a potential prognostic marker, still exhibits heterogenous associations with patient outcomes, thus bringing the need of corroboration with larger cohorts in clinical practice. LSD1, an epigenetic enzyme, represents a future target for epigenetic drugs that may lower treatment-associated morbidity. This study aimed to assess Ki67/LSD1 immunoexpression across all TGCT histological subtypes and correlate it with clinicopathological features. Results were compared with an in silico analysis of the TCGA database. Immunohistochemistry for Ki67 and LSD1 was carried out in a cohort of 157 TGCT tumor samples and assessed using a digital pathology algorithm. LSD1 protein expression was explored in TGCT cell lines, including ATRA-differentiated clones. There was a significant positive correlation between Ki67 and LSD1 H-scores (r<sub>s</sub> = 0.182, <i>p</i> = 0.037). Ki67 positivity percentage and H-score were significantly higher in non-seminomas (<i>p</i> = 0.0316 and 0.0113, respectively). Expression was not significantly different according to clinicopathological features, including stage, IGCCCG prognosis-based system, or relapse/progression-free survival, which was corroborated by in silico analysis. Our study, making use of digital image analysis, does not confirm the utility of these biomarkers in a daily practice cohort. Although not affecting patient outcome in our cohort, LSD1 is expressed overall in TGCTs, suggesting sensitivity to LSD1 inhibitors. |
| first_indexed | 2024-03-09T21:34:27Z |
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| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T21:34:27Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-8e08acaee67b43998175064ed7b20b912023-11-23T20:46:39ZengMDPI AGLife2075-17292022-02-0112226410.3390/life12020264Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology AlgorithmBeatriz Chaves Lourenço0Catarina Guimarães-Teixeira1Bianca C. T. Flores2Vera Miranda-Gonçalves3Rita Guimarães4Mariana Cantante5Paula Lopes6Isaac Braga7Joaquina Maurício8Carmen Jerónimo9Rui Henrique10João Lobo11Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), 4200-072 Porto, PortugalCancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, PortugalCancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, PortugalCancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, PortugalDepartment of Pathology, Portuguese Oncology Institute of Porto (IPOP), 4200-072 Porto, PortugalDepartment of Pathology, Portuguese Oncology Institute of Porto (IPOP), 4200-072 Porto, PortugalDepartment of Pathology, Portuguese Oncology Institute of Porto (IPOP), 4200-072 Porto, PortugalDepartment of Urology, Portuguese Oncology Institute of Porto (IPOP), 4200-072 Porto, PortugalDepartment of Medical Oncology, Portuguese Oncology Institute of Porto (IPOP), 4200-072 Porto, PortugalCancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, PortugalDepartment of Pathology, Portuguese Oncology Institute of Porto (IPOP), 4200-072 Porto, PortugalDepartment of Pathology, Portuguese Oncology Institute of Porto (IPOP), 4200-072 Porto, PortugalTGCTs represent a model of curable disease afflicting especially young men. Defining tumor biological characteristics is crucial to increase current knowledge and tailor the best clinical management. Ki67, a potential prognostic marker, still exhibits heterogenous associations with patient outcomes, thus bringing the need of corroboration with larger cohorts in clinical practice. LSD1, an epigenetic enzyme, represents a future target for epigenetic drugs that may lower treatment-associated morbidity. This study aimed to assess Ki67/LSD1 immunoexpression across all TGCT histological subtypes and correlate it with clinicopathological features. Results were compared with an in silico analysis of the TCGA database. Immunohistochemistry for Ki67 and LSD1 was carried out in a cohort of 157 TGCT tumor samples and assessed using a digital pathology algorithm. LSD1 protein expression was explored in TGCT cell lines, including ATRA-differentiated clones. There was a significant positive correlation between Ki67 and LSD1 H-scores (r<sub>s</sub> = 0.182, <i>p</i> = 0.037). Ki67 positivity percentage and H-score were significantly higher in non-seminomas (<i>p</i> = 0.0316 and 0.0113, respectively). Expression was not significantly different according to clinicopathological features, including stage, IGCCCG prognosis-based system, or relapse/progression-free survival, which was corroborated by in silico analysis. Our study, making use of digital image analysis, does not confirm the utility of these biomarkers in a daily practice cohort. Although not affecting patient outcome in our cohort, LSD1 is expressed overall in TGCTs, suggesting sensitivity to LSD1 inhibitors.https://www.mdpi.com/2075-1729/12/2/264germ cell tumorstesticular cancerbiomarkershistopathologyprognosisKi67 |
| spellingShingle | Beatriz Chaves Lourenço Catarina Guimarães-Teixeira Bianca C. T. Flores Vera Miranda-Gonçalves Rita Guimarães Mariana Cantante Paula Lopes Isaac Braga Joaquina Maurício Carmen Jerónimo Rui Henrique João Lobo Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm Life germ cell tumors testicular cancer biomarkers histopathology prognosis Ki67 |
| title | Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm |
| title_full | Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm |
| title_fullStr | Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm |
| title_full_unstemmed | Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm |
| title_short | Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm |
| title_sort | ki67 and lsd1 expression in testicular germ cell tumors is not associated with patient outcome investigation using a digital pathology algorithm |
| topic | germ cell tumors testicular cancer biomarkers histopathology prognosis Ki67 |
| url | https://www.mdpi.com/2075-1729/12/2/264 |
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