TY - JOUR
T1 - BAP1, Wilms' tumor 1, and calretinin in predicting survival and response to first-line chemotherapy in patients with pleural mesothelioma
AU - Yuce, Tuna Han
AU - Ak, Guntulu
AU - Metintas, Selma
AU - Dundar, Emine
AU - Roe, Oluf Dimitri
AU - Panou, Vasiliki
AU - Metintas, Muzaffer
N1 - © 2024. The Author(s).
PY - 2024/1/27
Y1 - 2024/1/27
N2 - PURPOSE: There are currently no methods to predict response to chemotherapy in pleural mesothelioma (PM). The aim of this study is to investigate the predictive and prognostic role of BAP1, WT1 and calretinin expression and their combinations in pre-treatment tumor samples by immunohistochemical (IHC) staining.METHODS: The study included consecutive PM patients treated with chemotherapy alone at a University hospital between 2009 and 2020. BAP1 analyses were performed on formalin-fixed, paraffin-embedded tumor tissue samples of the patients, while WT1 and calretinin information were obtained from the histopathological diagnosis records.RESULTS: Of the total 107 patients included, 64% had loss of BAP1 expression, whereas 77% had WT1 and 86% had calretinin expression. Patients with the presence of BAP1 expression, one or both of the other two markers, or loss of expression of all three markers (unfavorable status) were more likely to not respond to chemotherapy than those with the presence of all three markers or loss of BAP1 expression and expression of one or two other markers (favorable status) (p = 0.001). Median survival time of patients with favorable and unfavorable status was 15 ± 1.7 and 8.0 ± 2.4 months, respectively (p = 0.027). After adjustment for histopathology and stage, loss of BAP1 (HR = 0.54, 95%CI 0.35-0.83), WT1 (1.75, 1.06-2.90), calretinin (2.09, 1.14-3.84) expression and favourable panel (0.50, 0.27-0.92) was associated with prognosis.CONCLUSIONS: The IHC biomarkers BAP1, WT1, and calretinin, used in the routine diagnosis of PM and their combinations, are the first biomarkers associated with response to chemotherapy and may be a useful tool to select patients for first-line platinum pemetrexed treatment in PM patients. Validation in a large cohort is ongoing.
AB - PURPOSE: There are currently no methods to predict response to chemotherapy in pleural mesothelioma (PM). The aim of this study is to investigate the predictive and prognostic role of BAP1, WT1 and calretinin expression and their combinations in pre-treatment tumor samples by immunohistochemical (IHC) staining.METHODS: The study included consecutive PM patients treated with chemotherapy alone at a University hospital between 2009 and 2020. BAP1 analyses were performed on formalin-fixed, paraffin-embedded tumor tissue samples of the patients, while WT1 and calretinin information were obtained from the histopathological diagnosis records.RESULTS: Of the total 107 patients included, 64% had loss of BAP1 expression, whereas 77% had WT1 and 86% had calretinin expression. Patients with the presence of BAP1 expression, one or both of the other two markers, or loss of expression of all three markers (unfavorable status) were more likely to not respond to chemotherapy than those with the presence of all three markers or loss of BAP1 expression and expression of one or two other markers (favorable status) (p = 0.001). Median survival time of patients with favorable and unfavorable status was 15 ± 1.7 and 8.0 ± 2.4 months, respectively (p = 0.027). After adjustment for histopathology and stage, loss of BAP1 (HR = 0.54, 95%CI 0.35-0.83), WT1 (1.75, 1.06-2.90), calretinin (2.09, 1.14-3.84) expression and favourable panel (0.50, 0.27-0.92) was associated with prognosis.CONCLUSIONS: The IHC biomarkers BAP1, WT1, and calretinin, used in the routine diagnosis of PM and their combinations, are the first biomarkers associated with response to chemotherapy and may be a useful tool to select patients for first-line platinum pemetrexed treatment in PM patients. Validation in a large cohort is ongoing.
KW - Biomarkers
KW - Biomarkers, Tumor/metabolism
KW - Calbindin 2
KW - Humans
KW - Kidney Neoplasms
KW - Lung Neoplasms/metabolism
KW - Mesothelioma, Malignant
KW - Mesothelioma/drug therapy
KW - Pleural Neoplasms/drug therapy
KW - Tumor Suppressor Proteins/metabolism
KW - Ubiquitin Thiolesterase
KW - WT1 Proteins/analysis
KW - Wilms Tumor
KW - Calretinin
KW - Chemotherapy response
KW - Mesothelioma
KW - WT1
KW - BAP1
UR - http://www.scopus.com/inward/record.url?scp=85183400652&partnerID=8YFLogxK
U2 - 10.1007/s00432-023-05565-6
DO - 10.1007/s00432-023-05565-6
M3 - Journal article
C2 - 38280040
SN - 0171-5216
VL - 150
JO - Journal of cancer research and clinical oncology
JF - Journal of cancer research and clinical oncology
IS - 2
M1 - 38
ER -