Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma
Histopathologic assessment of high-risk endometrial cancer (EC) suffers from intersubject variability and poor reproducibility. The pragmatic classification in four molecular subgroups helps to overcome these limits, showing a significant prognostic value. The “no specific molecular profile” (NSMP)...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/21/5429 |
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| author | Antonella Ravaggi Davide Capoferri Laura Ardighieri Iacopo Ghini Federico Ferrari Chiara Romani Mattia Bugatti Laura Zanotti Stephanie Vrede Germana Tognon Johanna M. A. Pijnenborg Enrico Sartori Stefano Calza Eliana Bignotti Franco Odicino |
| author_facet | Antonella Ravaggi Davide Capoferri Laura Ardighieri Iacopo Ghini Federico Ferrari Chiara Romani Mattia Bugatti Laura Zanotti Stephanie Vrede Germana Tognon Johanna M. A. Pijnenborg Enrico Sartori Stefano Calza Eliana Bignotti Franco Odicino |
| author_sort | Antonella Ravaggi |
| collection | DOAJ |
| description | Histopathologic assessment of high-risk endometrial cancer (EC) suffers from intersubject variability and poor reproducibility. The pragmatic classification in four molecular subgroups helps to overcome these limits, showing a significant prognostic value. The “no specific molecular profile” (NSMP) is the most heterogeneous EC subgroup, requiring further characterization to better guide its clinical management. DNA sequencing of POLE exonuclease domain and immunohistochemistry for PMS2, MSH6, and p53 were performed in order to stratify a cohort of 94 high-risk EC patients in the four molecular subgroups. Moreover, a panel of seven additional biomarkers was tested. Patients were found to be 16% POLE-mutated, 36% mismatch repair-deficient, 27% p53-abnormal, and 21% NSMP. In the multivariable model, molecular groups confirmed their significant association with disease-specific survival and progression-free survival, with p53-abnormal and NSMP endometrial cancer characterized by poor outcomes. Among the additional evaluated biomarkers, L1CAM was the only one with a significant prognostic value within the NSMP subgroup. NSMP/L1CAM-positive patients experienced the worst outcome and were “early-relapsing” after platinum-based chemotherapy, with a significantly shorter platinum-free interval compared to L1CAM-negative patients. L1CAM appears to be a promising candidate as a prognostic and predictive biomarker in the high-risk NSMP subgroup, which is actually known to lack specific molecular markers. |
| first_indexed | 2024-03-09T19:11:53Z |
| format | Article |
| id | doaj.art-07e96ab8557a49dc9ba33081a3b145a6 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T19:11:53Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-07e96ab8557a49dc9ba33081a3b145a62023-11-24T04:04:17ZengMDPI AGCancers2072-66942022-11-011421542910.3390/cancers14215429Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial CarcinomaAntonella Ravaggi0Davide Capoferri1Laura Ardighieri2Iacopo Ghini3Federico Ferrari4Chiara Romani5Mattia Bugatti6Laura Zanotti7Stephanie Vrede8Germana Tognon9Johanna M. A. Pijnenborg10Enrico Sartori11Stefano Calza12Eliana Bignotti13Franco Odicino14Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, ItalyDepartment of Pathology, ASST Spedali Civili di Brescia, 25123 Brescia, ItalyDepartment of Pathology, ASST Spedali Civili di Brescia, 25123 Brescia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, ItalyAngelo Nocivelli’ Institute of Molecular Medicine, ASST Spedali Civili di Brescia, University of Brescia, 25121 Brescia, ItalyDepartment of Pathology, ASST Spedali Civili di Brescia, 25123 Brescia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, ItalyDepartment of Obstetrics and Gynecology, Radboudumc, 6525 GA Nijmegen, The NetherlandsDivision of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, 25123 Brescia, ItalyDepartment of Obstetrics and Gynecology, Radboudumc, 6525 GA Nijmegen, The NetherlandsDepartment of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, ItalyUnit of Biostatistics and Bioinformatics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalyAngelo Nocivelli’ Institute of Molecular Medicine, ASST Spedali Civili di Brescia, University of Brescia, 25121 Brescia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, ItalyHistopathologic assessment of high-risk endometrial cancer (EC) suffers from intersubject variability and poor reproducibility. The pragmatic classification in four molecular subgroups helps to overcome these limits, showing a significant prognostic value. The “no specific molecular profile” (NSMP) is the most heterogeneous EC subgroup, requiring further characterization to better guide its clinical management. DNA sequencing of POLE exonuclease domain and immunohistochemistry for PMS2, MSH6, and p53 were performed in order to stratify a cohort of 94 high-risk EC patients in the four molecular subgroups. Moreover, a panel of seven additional biomarkers was tested. Patients were found to be 16% POLE-mutated, 36% mismatch repair-deficient, 27% p53-abnormal, and 21% NSMP. In the multivariable model, molecular groups confirmed their significant association with disease-specific survival and progression-free survival, with p53-abnormal and NSMP endometrial cancer characterized by poor outcomes. Among the additional evaluated biomarkers, L1CAM was the only one with a significant prognostic value within the NSMP subgroup. NSMP/L1CAM-positive patients experienced the worst outcome and were “early-relapsing” after platinum-based chemotherapy, with a significantly shorter platinum-free interval compared to L1CAM-negative patients. L1CAM appears to be a promising candidate as a prognostic and predictive biomarker in the high-risk NSMP subgroup, which is actually known to lack specific molecular markers.https://www.mdpi.com/2072-6694/14/21/5429high-risk endometrial carcinomamolecular classificationNSMPL1CAMprognosisplatinum-based adjuvant chemotherapy |
| spellingShingle | Antonella Ravaggi Davide Capoferri Laura Ardighieri Iacopo Ghini Federico Ferrari Chiara Romani Mattia Bugatti Laura Zanotti Stephanie Vrede Germana Tognon Johanna M. A. Pijnenborg Enrico Sartori Stefano Calza Eliana Bignotti Franco Odicino Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma Cancers high-risk endometrial carcinoma molecular classification NSMP L1CAM prognosis platinum-based adjuvant chemotherapy |
| title | Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma |
| title_full | Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma |
| title_fullStr | Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma |
| title_full_unstemmed | Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma |
| title_short | Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma |
| title_sort | integrated biomarker analysis reveals l1cam as a potential stratification marker for no specific molecular profile high risk endometrial carcinoma |
| topic | high-risk endometrial carcinoma molecular classification NSMP L1CAM prognosis platinum-based adjuvant chemotherapy |
| url | https://www.mdpi.com/2072-6694/14/21/5429 |
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