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Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma

Diffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune r... Full description

Journal Title: Human pathology 2018-01, Vol.71, p.1-7
Main Author: Inaguma, Shingo
Other Authors: Lasota, Jerzy , Wang, Zengfeng , Czapiewski, Piotr , Langfort, Renata , Rys, Janusz , Szpor, Joanna , Waloszczyk, Piotr , Okoń, Krzysztof , Biernat, Wojciech , Ikeda, Hiroshi , Schrump, David S , Hassan, Raffit , Miettinen, Markku
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: United States: Elsevier Inc
ID: ISSN: 0046-8177
Link: https://www.ncbi.nlm.nih.gov/pubmed/28811252
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title: Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma
format: Article
creator:
  • Inaguma, Shingo
  • Lasota, Jerzy
  • Wang, Zengfeng
  • Czapiewski, Piotr
  • Langfort, Renata
  • Rys, Janusz
  • Szpor, Joanna
  • Waloszczyk, Piotr
  • Okoń, Krzysztof
  • Biernat, Wojciech
  • Ikeda, Hiroshi
  • Schrump, David S
  • Hassan, Raffit
  • Miettinen, Markku
subjects:
  • Adult
  • Aged
  • ALCAM, activated leukocyte cell adhesion molecule (CD166)
  • ALDH1A1, aldehyde dehydrogenase 1A1 (ALDH1)
  • ALDH1A1, aldehyde dehydrogenase, 1A1
  • Antigens, CD - biosynthesis
  • Apoptosis
  • Article
  • Autoimmune diseases
  • B7-H1 Antigen - biosynthesis
  • Biomarkers, Tumor - analysis
  • Cell Adhesion Molecules, Neuronal - biosynthesis
  • Female
  • Fetal Proteins - biosynthesis
  • Histology
  • Humans
  • Immunoglobulins
  • Ligands
  • Lung cancer
  • Lung Neoplasms - pathology
  • Male
  • Medical prognosis
  • Mesothelioma
  • Mesothelioma - pathology
  • Mesothelioma, Malignant
  • Middle Aged
  • MPM, malignant pleural mesothelioma
  • PD-L1 (CD274), programmed cell death ligand 1
  • PD-L1, programmed cell death ligand 1 (CD274)
  • Pleural Neoplasms - pathology
  • Prognosis
  • Proportional Hazards Models
  • Proteins
  • SALL4, spalt-like transcription factor 4
  • Software
  • Statistical analysis
  • Stem cells
  • Studies
  • Tumors
ispartof: Human pathology, 2018-01, Vol.71, p.1-7
description: Diffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4. The PD-L1 (CD274)/PD-1 (PDCD1, CD279) pathway is crucial for the modulation of immune responses in normal cells. Nevertheless, pathologic activation of the PD-L1/PD-1 pathway participates in immune evasion by tumor cells. Many PD-L1–expressing tumor cells have been identified in different types of cancer, including malignant mesothelioma. In this study, 175 well-characterized primary diffuse pleural mesotheliomas, including the epithelioid (n = 148), biphasic (n = 15), and sarcomatoid (n = 12) histotypes, were evaluated immunohistochemically for cancer stem cell markers (ALCAM, ALDH1, and SALL4) and PD-L1 expression. Twenty-five percent of the mesotheliomas (43/175) expressed ALCAM, whereas ALDH1 and SALL4 positivity was seen in 1% to 2% of cases. Thirty-three percent of the analyzed tumors (57/175) contained PD-L1–positive cells. Overall survival was significantly decreased in the cohort of patients with ALCAM- or PD-L1–positive tumors (both P < .01). Furthermore, the multivariate Cox hazards regression analysis identified ALCAM and PD-L1 (both P < 0.01) as potential independent risk factors. Thus, a combination of these 2 markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma. •PD-L1 and stem cell marker expressions were analyzed in malignant mesotheliomas.•PD-L1 and ALCAM were expressed in 33% and 25% of mesothelioma cases, respectively.•The Cox proportional hazards model identified these proteins as independent risk factors for death.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0046-8177
fulltext: fulltext
issn:
  • 0046-8177
  • 1532-8392
url: Link


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titleExpression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma
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creatorInaguma, Shingo ; Lasota, Jerzy ; Wang, Zengfeng ; Czapiewski, Piotr ; Langfort, Renata ; Rys, Janusz ; Szpor, Joanna ; Waloszczyk, Piotr ; Okoń, Krzysztof ; Biernat, Wojciech ; Ikeda, Hiroshi ; Schrump, David S ; Hassan, Raffit ; Miettinen, Markku
creatorcontribInaguma, Shingo ; Lasota, Jerzy ; Wang, Zengfeng ; Czapiewski, Piotr ; Langfort, Renata ; Rys, Janusz ; Szpor, Joanna ; Waloszczyk, Piotr ; Okoń, Krzysztof ; Biernat, Wojciech ; Ikeda, Hiroshi ; Schrump, David S ; Hassan, Raffit ; Miettinen, Markku
descriptionDiffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4. The PD-L1 (CD274)/PD-1 (PDCD1, CD279) pathway is crucial for the modulation of immune responses in normal cells. Nevertheless, pathologic activation of the PD-L1/PD-1 pathway participates in immune evasion by tumor cells. Many PD-L1–expressing tumor cells have been identified in different types of cancer, including malignant mesothelioma. In this study, 175 well-characterized primary diffuse pleural mesotheliomas, including the epithelioid (n = 148), biphasic (n = 15), and sarcomatoid (n = 12) histotypes, were evaluated immunohistochemically for cancer stem cell markers (ALCAM, ALDH1, and SALL4) and PD-L1 expression. Twenty-five percent of the mesotheliomas (43/175) expressed ALCAM, whereas ALDH1 and SALL4 positivity was seen in 1% to 2% of cases. Thirty-three percent of the analyzed tumors (57/175) contained PD-L1–positive cells. Overall survival was significantly decreased in the cohort of patients with ALCAM- or PD-L1–positive tumors (both P < .01). Furthermore, the multivariate Cox hazards regression analysis identified ALCAM and PD-L1 (both P < 0.01) as potential independent risk factors. Thus, a combination of these 2 markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma. •PD-L1 and stem cell marker expressions were analyzed in malignant mesotheliomas.•PD-L1 and ALCAM were expressed in 33% and 25% of mesothelioma cases, respectively.•The Cox proportional hazards model identified these proteins as independent risk factors for death.
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1EISSN: 1532-8392
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languageeng
publisherUnited States: Elsevier Inc
subjectAdult ; Aged ; ALCAM, activated leukocyte cell adhesion molecule (CD166) ; ALDH1A1, aldehyde dehydrogenase 1A1 (ALDH1) ; ALDH1A1, aldehyde dehydrogenase, 1A1 ; Antigens, CD - biosynthesis ; Apoptosis ; Article ; Autoimmune diseases ; B7-H1 Antigen - biosynthesis ; Biomarkers, Tumor - analysis ; Cell Adhesion Molecules, Neuronal - biosynthesis ; Female ; Fetal Proteins - biosynthesis ; Histology ; Humans ; Immunoglobulins ; Ligands ; Lung cancer ; Lung Neoplasms - pathology ; Male ; Medical prognosis ; Mesothelioma ; Mesothelioma - pathology ; Mesothelioma, Malignant ; Middle Aged ; MPM, malignant pleural mesothelioma ; PD-L1 (CD274), programmed cell death ligand 1 ; PD-L1, programmed cell death ligand 1 (CD274) ; Pleural Neoplasms - pathology ; Prognosis ; Proportional Hazards Models ; Proteins ; SALL4, spalt-like transcription factor 4 ; Software ; Statistical analysis ; Stem cells ; Studies ; Tumors
ispartofHuman pathology, 2018-01, Vol.71, p.1-7
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0Inaguma, Shingo
1Lasota, Jerzy
2Wang, Zengfeng
3Czapiewski, Piotr
4Langfort, Renata
5Rys, Janusz
6Szpor, Joanna
7Waloszczyk, Piotr
8Okoń, Krzysztof
9Biernat, Wojciech
10Ikeda, Hiroshi
11Schrump, David S
12Hassan, Raffit
13Miettinen, Markku
title
0Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma
1Human pathology
addtitleHum Pathol
descriptionDiffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4. The PD-L1 (CD274)/PD-1 (PDCD1, CD279) pathway is crucial for the modulation of immune responses in normal cells. Nevertheless, pathologic activation of the PD-L1/PD-1 pathway participates in immune evasion by tumor cells. Many PD-L1–expressing tumor cells have been identified in different types of cancer, including malignant mesothelioma. In this study, 175 well-characterized primary diffuse pleural mesotheliomas, including the epithelioid (n = 148), biphasic (n = 15), and sarcomatoid (n = 12) histotypes, were evaluated immunohistochemically for cancer stem cell markers (ALCAM, ALDH1, and SALL4) and PD-L1 expression. Twenty-five percent of the mesotheliomas (43/175) expressed ALCAM, whereas ALDH1 and SALL4 positivity was seen in 1% to 2% of cases. Thirty-three percent of the analyzed tumors (57/175) contained PD-L1–positive cells. Overall survival was significantly decreased in the cohort of patients with ALCAM- or PD-L1–positive tumors (both P < .01). Furthermore, the multivariate Cox hazards regression analysis identified ALCAM and PD-L1 (both P < 0.01) as potential independent risk factors. Thus, a combination of these 2 markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma. •PD-L1 and stem cell marker expressions were analyzed in malignant mesotheliomas.•PD-L1 and ALCAM were expressed in 33% and 25% of mesothelioma cases, respectively.•The Cox proportional hazards model identified these proteins as independent risk factors for death.
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0Adult
1Aged
2ALCAM, activated leukocyte cell adhesion molecule (CD166)
3ALDH1A1, aldehyde dehydrogenase 1A1 (ALDH1)
4ALDH1A1, aldehyde dehydrogenase, 1A1
5Antigens, CD - biosynthesis
6Apoptosis
7Article
8Autoimmune diseases
9B7-H1 Antigen - biosynthesis
10Biomarkers, Tumor - analysis
11Cell Adhesion Molecules, Neuronal - biosynthesis
12Female
13Fetal Proteins - biosynthesis
14Histology
15Humans
16Immunoglobulins
17Ligands
18Lung cancer
19Lung Neoplasms - pathology
20Male
21Medical prognosis
22Mesothelioma
23Mesothelioma - pathology
24Mesothelioma, Malignant
25Middle Aged
26MPM, malignant pleural mesothelioma
27PD-L1 (CD274), programmed cell death ligand 1
28PD-L1, programmed cell death ligand 1 (CD274)
29Pleural Neoplasms - pathology
30Prognosis
31Proportional Hazards Models
32Proteins
33SALL4, spalt-like transcription factor 4
34Software
35Statistical analysis
36Stem cells
37Studies
38Tumors
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1Lasota, Jerzy
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3Czapiewski, Piotr
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6Szpor, Joanna
7Waloszczyk, Piotr
8Okoń, Krzysztof
9Biernat, Wojciech
10Ikeda, Hiroshi
11Schrump, David S
12Hassan, Raffit
13Miettinen, Markku
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titleExpression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma
authorInaguma, Shingo ; Lasota, Jerzy ; Wang, Zengfeng ; Czapiewski, Piotr ; Langfort, Renata ; Rys, Janusz ; Szpor, Joanna ; Waloszczyk, Piotr ; Okoń, Krzysztof ; Biernat, Wojciech ; Ikeda, Hiroshi ; Schrump, David S ; Hassan, Raffit ; Miettinen, Markku
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3ALDH1A1, aldehyde dehydrogenase 1A1 (ALDH1)
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5Antigens, CD - biosynthesis
6Apoptosis
7Article
8Autoimmune diseases
9B7-H1 Antigen - biosynthesis
10Biomarkers, Tumor - analysis
11Cell Adhesion Molecules, Neuronal - biosynthesis
12Female
13Fetal Proteins - biosynthesis
14Histology
15Humans
16Immunoglobulins
17Ligands
18Lung cancer
19Lung Neoplasms - pathology
20Male
21Medical prognosis
22Mesothelioma
23Mesothelioma - pathology
24Mesothelioma, Malignant
25Middle Aged
26MPM, malignant pleural mesothelioma
27PD-L1 (CD274), programmed cell death ligand 1
28PD-L1, programmed cell death ligand 1 (CD274)
29Pleural Neoplasms - pathology
30Prognosis
31Proportional Hazards Models
32Proteins
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abstractDiffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4. The PD-L1 (CD274)/PD-1 (PDCD1, CD279) pathway is crucial for the modulation of immune responses in normal cells. Nevertheless, pathologic activation of the PD-L1/PD-1 pathway participates in immune evasion by tumor cells. Many PD-L1–expressing tumor cells have been identified in different types of cancer, including malignant mesothelioma. In this study, 175 well-characterized primary diffuse pleural mesotheliomas, including the epithelioid (n = 148), biphasic (n = 15), and sarcomatoid (n = 12) histotypes, were evaluated immunohistochemically for cancer stem cell markers (ALCAM, ALDH1, and SALL4) and PD-L1 expression. Twenty-five percent of the mesotheliomas (43/175) expressed ALCAM, whereas ALDH1 and SALL4 positivity was seen in 1% to 2% of cases. Thirty-three percent of the analyzed tumors (57/175) contained PD-L1–positive cells. Overall survival was significantly decreased in the cohort of patients with ALCAM- or PD-L1–positive tumors (both P < .01). Furthermore, the multivariate Cox hazards regression analysis identified ALCAM and PD-L1 (both P < 0.01) as potential independent risk factors. Thus, a combination of these 2 markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma. •PD-L1 and stem cell marker expressions were analyzed in malignant mesotheliomas.•PD-L1 and ALCAM were expressed in 33% and 25% of mesothelioma cases, respectively.•The Cox proportional hazards model identified these proteins as independent risk factors for death.
copUnited States
pubElsevier Inc
pmid28811252
doi10.1016/j.humpath.2017.04.032
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