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

Our plain-English summary of Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma, by S. Inaguma, J. Lasota, Z. Wang, et al (Human Pathology, 2018).

The study

• Authors: S. Inaguma, J. Lasota, Z. Wang, P. Czapiewski, R. Langfort, J. Rys, J. Szpor, P. Waloszczyk, K. Okoń, W. Biernat, H. Ikeda, D.S. Schrump, R. Hassan, M. Miettinen
• Journal: Human Pathology
• Published: 2018;71:1-7
• Cited by: 50 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

Copyright © 2017 Elsevier Inc. All rights reserved.

In plain English

This laboratory study examined tumor tissue from 175 diffuse malignant pleural mesotheliomas (148 epithelioid, 15 biphasic, 12 sarcomatoid). The researchers stained it for ALCAM, ALDH1 and SALL4, which the authors describe as cancer stem cell markers, and for PD-L1, an immune-related protein. Asbestos exposure was not examined. ALCAM was found in 43 of 175 tumors (25%) and PD-L1 in 57 (33%). ALDH1 was found in only 2 tumors and SALL4 in 3. Survival was analyzed for 66 patients. Median survival was 7.0 months when tumors showed ALCAM on the cell membrane, versus 22.5 months otherwise. It was 6.0 months with PD-L1-positive tumors, versus 18.0 months without. Patients whose tumors had both markers had a median of 4 months, versus 36.0 months for those with neither. In a combined statistical analysis, ALCAM (hazard ratio 3.26, 95% confidence interval 1.80 to 5.92) and PD-L1 (hazard ratio 2.34, 95% confidence interval 1.26 to 4.33) were identified as potential independent risk factors. The authors concluded that these markers could be useful for prognosis and treatment planning. They noted that they lacked complete staging and treatment information.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (immunohistochemical) study of tumor tissue samples, with survival analysis using log-rank tests and Cox proportional hazards regression
• Who was studied: 175 diffuse malignant pleural mesotheliomas: 148 epithelioid, 15 biphasic, 12 sarcomatoid. Thirty came from patients in a clinical trial at the National Institutes of Health, and 145 were additional anonymous tumors. Survival was analyzed for 66 of these patients, who were followed for as long as 120 months. Dates of collection are not stated.
• Exposure: No asbestos or other environmental exposure was studied. The factors examined were tumor expression of the proteins ALCAM, ALDH1, SALL4 and PD-L1, scored as positive at a 5% cut-off. PD-L1 in tumor-associated immune cells was also assessed.
• Main results:
  • ALCAM was expressed on the cell membrane in 43 of 175 mesotheliomas (25%).
  • PD-L1 was expressed in 57 of 175 tumors (33%), with a median of 60% of cells positive.
  • The authors describe the association between ALCAM and PD-L1 expression as mild but statistically significant (P = .04).
  • PD-L1 was found on tumor-associated immune cells in 35 cases (20%).
  • ALDH1 was expressed in only 2 cases (1%) and SALL4 in only 3 cases (2%).
  • Survival analyses were done on 66 mesothelioma patients.
  • Median survival was 7.0 months for patients whose tumors expressed ALCAM on the cell membrane, versus 22.5 months for those without ALCAM expression or with cytoplasmic labeling only (P < .01).
  • Median survival was 6.0 months for patients with PD-L1-expressing tumors, versus 18.0 months without PD-L1 (P < .01).
  • Patients whose tumors expressed both ALCAM and PD-L1 had a median survival of 4 months, versus 36.0 months for those without ALCAM or PD-L1 (P < .01). Survival in the double-positive group did not differ significantly from the ALCAM-positive/PD-L1-negative group (P = .20) or the ALCAM-negative/PD-L1-positive group (P = .31).
  • In multivariate Cox regression, ALCAM was a potential independent risk factor: hazard ratio 3.26, 95% CI 1.80 to 5.92, P < .01.
  • In the same model, PD-L1 was also a potential independent risk factor: hazard ratio 2.34, 95% CI 1.26 to 4.33, P < .01.
  • No significant difference in clinical outcome was found among the tumor histology groups.
  • PD-L1 positivity was 40% (6/15) in biphasic, 42% (5/12) in sarcomatoid and 31% (46/148) in epithelial mesotheliomas. The authors found no clear association between PD-L1 and histology.
• The authors' conclusion: The authors concluded that ALCAM and PD-L1 expression in malignant pleural mesothelioma is associated with shorter survival, and that these markers could be useful in determining prognosis and planning treatment.
• Limitations the authors state:
  • Patient clinical information, such as complete tumor staging and treatment, was limited, so these could not be included in the survival model.
  • Many samples were small biopsy specimens that gave no information for staging.
  • The authors said a larger study might clarify the relationship between PD-L1 expression and tumor histology.
  • The authors said further experimental investigation is needed to confirm that some PD-L1-positive mesothelioma cells may have stem cell-like properties.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: PD-L1, Pleural Mesothelioma, Malignant Mesothelioma, Pleura, Angiogenesis, Metastasis, STEM, Epithelioid.

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• Shorter Survival in Malignant Pleural Mesothelioma Patients With High PD-L1 Expression Associated With Sarcomatoid or Biphasic Histology Subtype: A Series of 214 Cases From the Bio-MAPS Cohort — S. Brosseau, C. Danel, et al. (2019)
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• High tumor cell platelet-derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma — H. Ollila, J. Paajanen, et al. (2021)
• PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma — B.H. Nguyen, R. Montgomery, et al. (2018)
• Determination of PD-L1 expression in effusions from mesothelioma by immuno-cytochemical staining — M.S.I. Mansour, T. Seidal, et al. (2017)

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