Soluble AXL is ubiquitously present in malignant serous effusions

Our plain-English summary of Soluble AXL is ubiquitously present in malignant serous effusions, by K. Flem Karlsen, E. McFadden, V.A. Flørenes, et al (Gynecologic Oncology, 2019).

The study

• Authors: K. Flem Karlsen, E. McFadden, V.A. Flørenes, B. Davidson
• Journal: Gynecologic Oncology
• Published: 2019;152(2):408-415
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: The objective of this study was to analyze the expression level and clinical role of soluble AXL (sAXL) in cancers affecting the serosal surfaces, with focus on ovarian carcinoma.

Methods: sAXL protein expression by ELISA was analyzed in 572 effusion supernatants, including 424 peritoneal, 147 pleural and 1 pericardial specimens.

Results: sAXL was overexpressed in peritoneal effusions compared to pleural and pericardial specimens (p < 0.001). sAXL levels were additionally significantly higher in effusions from patients with ovarian carcinoma, malignant mesothelioma and breast carcinoma compared to specimens from patients with other cancers (predominantly carcinomas of lung, gastrointestinal or uterine corpus/cervix origin) or benign reactive effusions (p < 0.001). sAXL was further overexpressed in high-grade serous carcinoma (HGSC; n = 373) compared to low-grade serous carcinoma (LGSC; n = 32; p = 0.036). In HGSC, sAXL levels were significantly lower in post-chemotherapy effusions compared to primary diagnosis pre-chemotherapy specimens (p = 0.002). sAXL levels in HGSC were unrelated to chemoresponse at diagnosis, progression-free survival or overall survival. Levels were similarly unrelated to survival in LGSC and breast carcinoma.

Conclusions: sAXL is widely expressed in malignant effusions, particularly in ovarian and breast carcinoma and in malignant mesothelioma. sAXL is overexpressed in HGSC compared to LGSC and its levels are lower following exposure to chemotherapy. However, sAXL levels are not informative of chemoresponse or survival.

Copyright © 2018 Elsevier Inc. All rights reserved.

In plain English

This laboratory study from the Norwegian Radium Hospital in Oslo measured soluble AXL (sAXL), a protein shed from cells, in fluid from 572 effusions (abnormal fluid collections) submitted for diagnosis between 1998 and 2013. Of these, 424 were peritoneal, 147 pleural and 1 pericardial. Most (437) came from ovarian carcinoma, and 24 came from malignant mesothelioma. The study did not look at asbestos exposure. sAXL was found in all 572 samples. Levels were higher in peritoneal than in pleural or pericardial effusions (median 1555 vs 1221 pg/mL). They were also higher in effusions from ovarian carcinoma (median 1550), malignant mesothelioma (median 1519) and breast carcinoma (median 1435) than in other cancers (median 323) or benign reactive effusions (median 165). In high-grade serous ovarian carcinoma, levels were higher than in low-grade serous carcinoma and lower after chemotherapy. However, levels were not linked to survival in high-grade serous carcinoma, low-grade serous carcinoma or breast carcinoma. The authors concluded that sAXL has a limited role in identifying patients with clinically aggressive disease. They questioned its diagnostic value because values varied widely within each group.

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 analysis of stored effusion fluid samples, with clinical and survival data for patients with ovarian high-grade serous carcinoma
• Who was studied: 572 effusion specimens (424 peritoneal, 147 pleural, 1 pericardial) submitted to the Department of Pathology, Norwegian Radium Hospital, Oslo, Norway, from 1998 to 2013; included 373 high-grade serous carcinoma effusions from 299 patients
• Exposure: No asbestos or other environmental or occupational exposure was studied. The factor measured was soluble AXL protein in cell-free effusion fluid, using an ELISA test.
• Main results:
  • sAXL was detected in all 572 effusions, at levels from 23 pg/mL to 138.325 ng/mL
  • Peritoneal effusions (n = 424) had higher sAXL than pleural/pericardial effusions (n = 148): median 1555 vs 1221 pg/mL, p less than 0.001
  • Effusions from ovarian carcinoma, malignant mesothelioma and breast carcinoma had significantly higher sAXL than those from other cancers or benign reactive effusions
  • Range and median sAXL by group: ovarian (437 cases) 49–138,325, median 1550 pg/mL; breast (51) 373–3108, median 1435; malignant mesothelioma (24) 671–2467, median 1519; benign reactive (21) 23–3456, median 165; other cancers (39) 50–1729, median 323
  • sAXL was higher in high-grade serous carcinoma than in low-grade serous carcinoma (mean rank 206.57 vs 161.42, p = 0.036)
  • In high-grade serous carcinoma (364 specimens), sAXL was higher in pre-chemotherapy than in post-chemotherapy effusions (mean rank 197.11 vs 161.66, p = 0.002)
  • In patients with high-grade serous carcinoma, sAXL was unrelated to overall survival (p = 0.366)
  • In patients with high-grade serous carcinoma, sAXL was not informative of progression-free survival (p = 0.25)
  • In the multivariate analysis of patients with high-grade serous carcinoma, sAXL had no independent role for overall survival (p = 0.143)
  • In patients with low-grade serous carcinoma (n = 31) and breast carcinoma (n = 42) effusions, sAXL showed no association with survival
• The authors' conclusion: The authors concluded that sAXL levels are unrelated to chemoresponse or survival, suggesting a limited role for sAXL in identifying patients with clinically aggressive disease
• Limitations the authors state:
  • Samples were stored over a broad span of time, which may have affected sAXL levels
  • The diagnostic relevance of the differences between groups is questionable because values varied widely within each group
  • There are no true normal controls, because an effusion is always a pathological finding

Topics

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

Medical terms in this study, explained in our Lexicon: Serosal Surface, Carcinoma, Pericardial, Malignant Mesothelioma, Chemotherapy, Progression-Free Survival, Overall Survival.

Related studies

• Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival — K. Brenne, D.A. Nymoen, et al. (2012)
• Targeted inhibition of multiple receptor tyrosine kinases in mesothelioma — W.B. Ou, C. Hubert, et al. (2011)
• Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma — K. Brusegard, H.T. Stavnes, et al. (2012)
• Hepatocyte nuclear factor-1β is not a specific marker of clear cell carcinoma in serous effusions — B. Davidson (2014)
• Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma — J. Andrici, J. Jung, et al. (2016)
• Calretinin. A selective marker of normal and neoplastic mesothelial cells in serous effusions — M.C. Barberis, M. Faleri, et al. (1997)

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