Temporal Effect on PD‐L1 Detection and Novel Insights Into Its Clinical Implications in Non–Small Cell Lung Cancer
ABSTRACT Objectives Several studies rely on archived tissue blocks to assess the PD‐L1 scores; however, a detailed analysis of potential variations of scores between fresh and archived tissue blocks still lacks. In addition, the prognostic implications of PD‐L1 in lung cancers have not yet been comp...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-10-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.70262 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849733800247951360 |
|---|---|
| author | Gopal P. Pathak Rashmi Shah Mathieu Castonguay Angela Cheng John Fris Rowan Murphy Gail Darling Alexander Ednie Daniel French Harry Henteleff Aneil Mujoomdar Madelaine Plourde Alison Wallace Zhaolin Xu |
| author_facet | Gopal P. Pathak Rashmi Shah Mathieu Castonguay Angela Cheng John Fris Rowan Murphy Gail Darling Alexander Ednie Daniel French Harry Henteleff Aneil Mujoomdar Madelaine Plourde Alison Wallace Zhaolin Xu |
| author_sort | Gopal P. Pathak |
| collection | DOAJ |
| description | ABSTRACT Objectives Several studies rely on archived tissue blocks to assess the PD‐L1 scores; however, a detailed analysis of potential variations of scores between fresh and archived tissue blocks still lacks. In addition, the prognostic implications of PD‐L1 in lung cancers have not yet been completely understood. Here, we aimed to investigate the temporal variation in PD‐L1 scores from clinical samples and the clinical implications of PD‐L1 in non–small cell lung cancer (NSCLC). Methods NSCLC cases from January 2005 to June 2023 were considered for this study, and PD‐L1 scores in archived and fresh tissue blocks were analyzed. Association of PD‐L1 with various driver mutations was explored, and implications of PD‐L1 in progression‐free survival (PFS) and overall survival (OS) were analyzed. Results Our study revealed a significant disparity in PD‐L1 scores between archived and fresh tissue blocks, and a temporal variation in scores within 6 months of tissue acquisition. Advanced‐stage primary tumors, metastatic lymph nodes, and visceral pleural invasion revealed higher PD‐L1 expression as presented by tumor proportion score (TPS). Notably, in fully resected stage I/II NSCLC cases, OS was better in the high PD‐L1 (≥ 50% TPS) cohort with driver mutations compared to cases without driver mutations (hazard ratio—0.5129, 95% confidence interval 0.2058–1.084, p = 0.0779). In contrast, high PD‐L1 was associated with worse OS compared to no PD‐L1 (< 1% TPS) (hazard ratio—2.431, 95% confidence interval 1.144–6.656, p = 0.0242) in the cohort without driver mutations. Furthermore, the presence of a KRAS mutation favored the outcome of anti‐PD‐L1/PD1 immunotherapy in advanced NSCLC. Conclusion PD‐L1 detection from tissue blocks was found to vary temporally, urging for a prioritized consideration for patients with marginal scores when archived blocks are employed for its detection. Prognostic roles of PD‐L1 were associated with driver mutations, and KRAS mutations favored the outcome of anti‐PD‐L1/PD1 therapy in advanced NSCLC. |
| format | Article |
| id | doaj-art-ff5a5695ce2448108b9d6431f5d82b1b |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-ff5a5695ce2448108b9d6431f5d82b1b2025-08-20T03:07:57ZengWileyCancer Medicine2045-76342024-10-011319n/an/a10.1002/cam4.70262Temporal Effect on PD‐L1 Detection and Novel Insights Into Its Clinical Implications in Non–Small Cell Lung CancerGopal P. Pathak0Rashmi Shah1Mathieu Castonguay2Angela Cheng3John Fris4Rowan Murphy5Gail Darling6Alexander Ednie7Daniel French8Harry Henteleff9Aneil Mujoomdar10Madelaine Plourde11Alison Wallace12Zhaolin Xu13Department of Pathology QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDepartment of Pathology QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDepartment of Pathology QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDepartment of Pathology QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDepartment of Pathology QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDivision of Thoracic Surgery QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDivision of Thoracic Surgery QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDivision of Thoracic Surgery QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDivision of Thoracic Surgery QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDivision of Thoracic Surgery QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDivision of Thoracic Surgery QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDivision of Thoracic Surgery QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDivision of Thoracic Surgery QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaDepartment of Pathology QEII Health Sciences Centre and Dalhousie University Halifax Nova Scotia CanadaABSTRACT Objectives Several studies rely on archived tissue blocks to assess the PD‐L1 scores; however, a detailed analysis of potential variations of scores between fresh and archived tissue blocks still lacks. In addition, the prognostic implications of PD‐L1 in lung cancers have not yet been completely understood. Here, we aimed to investigate the temporal variation in PD‐L1 scores from clinical samples and the clinical implications of PD‐L1 in non–small cell lung cancer (NSCLC). Methods NSCLC cases from January 2005 to June 2023 were considered for this study, and PD‐L1 scores in archived and fresh tissue blocks were analyzed. Association of PD‐L1 with various driver mutations was explored, and implications of PD‐L1 in progression‐free survival (PFS) and overall survival (OS) were analyzed. Results Our study revealed a significant disparity in PD‐L1 scores between archived and fresh tissue blocks, and a temporal variation in scores within 6 months of tissue acquisition. Advanced‐stage primary tumors, metastatic lymph nodes, and visceral pleural invasion revealed higher PD‐L1 expression as presented by tumor proportion score (TPS). Notably, in fully resected stage I/II NSCLC cases, OS was better in the high PD‐L1 (≥ 50% TPS) cohort with driver mutations compared to cases without driver mutations (hazard ratio—0.5129, 95% confidence interval 0.2058–1.084, p = 0.0779). In contrast, high PD‐L1 was associated with worse OS compared to no PD‐L1 (< 1% TPS) (hazard ratio—2.431, 95% confidence interval 1.144–6.656, p = 0.0242) in the cohort without driver mutations. Furthermore, the presence of a KRAS mutation favored the outcome of anti‐PD‐L1/PD1 immunotherapy in advanced NSCLC. Conclusion PD‐L1 detection from tissue blocks was found to vary temporally, urging for a prioritized consideration for patients with marginal scores when archived blocks are employed for its detection. Prognostic roles of PD‐L1 were associated with driver mutations, and KRAS mutations favored the outcome of anti‐PD‐L1/PD1 therapy in advanced NSCLC.https://doi.org/10.1002/cam4.70262checkpoint inhibitordriver mutationimmunotherapyNSCLCPD‐L1 |
| spellingShingle | Gopal P. Pathak Rashmi Shah Mathieu Castonguay Angela Cheng John Fris Rowan Murphy Gail Darling Alexander Ednie Daniel French Harry Henteleff Aneil Mujoomdar Madelaine Plourde Alison Wallace Zhaolin Xu Temporal Effect on PD‐L1 Detection and Novel Insights Into Its Clinical Implications in Non–Small Cell Lung Cancer Cancer Medicine checkpoint inhibitor driver mutation immunotherapy NSCLC PD‐L1 |
| title | Temporal Effect on PD‐L1 Detection and Novel Insights Into Its Clinical Implications in Non–Small Cell Lung Cancer |
| title_full | Temporal Effect on PD‐L1 Detection and Novel Insights Into Its Clinical Implications in Non–Small Cell Lung Cancer |
| title_fullStr | Temporal Effect on PD‐L1 Detection and Novel Insights Into Its Clinical Implications in Non–Small Cell Lung Cancer |
| title_full_unstemmed | Temporal Effect on PD‐L1 Detection and Novel Insights Into Its Clinical Implications in Non–Small Cell Lung Cancer |
| title_short | Temporal Effect on PD‐L1 Detection and Novel Insights Into Its Clinical Implications in Non–Small Cell Lung Cancer |
| title_sort | temporal effect on pd l1 detection and novel insights into its clinical implications in non small cell lung cancer |
| topic | checkpoint inhibitor driver mutation immunotherapy NSCLC PD‐L1 |
| url | https://doi.org/10.1002/cam4.70262 |
| work_keys_str_mv | AT gopalppathak temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT rashmishah temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT mathieucastonguay temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT angelacheng temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT johnfris temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT rowanmurphy temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT gaildarling temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT alexanderednie temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT danielfrench temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT harryhenteleff temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT aneilmujoomdar temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT madelaineplourde temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT alisonwallace temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer AT zhaolinxu temporaleffectonpdl1detectionandnovelinsightsintoitsclinicalimplicationsinnonsmallcelllungcancer |