The diagnostic role of PTEN and ARID1A in serous effusions

Our plain-English summary of The diagnostic role of PTEN and ARID1A in serous effusions, by B. Davidson, M. Pinamonti, D. Cuevas, et al (Virchows Archiv, 2018).

The study

• Authors: B. Davidson, M. Pinamonti, D. Cuevas, A. Holth, P. Zeppa, T. Hager, J. Wohlschlaeger, M. Tötsch
• Journal: Virchows Archiv
• Published: 2018;472(3):425-432
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of this study was to analyze the diagnostic role of PTEN and ARID1A in effusion cytology. Effusions (n = 279), consisting of 226 carcinomas (70 ovarian, 64 breast, 36 lung, and 15 uterine corpus carcinomas; 41 carcinomas of other origin) and 53 malignant mesotheliomas, were analyzed for PTEN and ARID1A expression using immunohistochemistry. PTEN was preserved in 166 (59%) tumors, partially lost in 38 (14%), and absent in 75 (27%), with lower expression in malignant mesotheliomas compared to carcinomas, though not significantly (p = 0.084). ARID1A was preserved in 243 (88%) tumors, partially lost in 18 (6%), and absent in 18 (6%). The majority of tumors with absent ARID1A were ovarian carcinomas, predominantly of clear cell or low-grade serous type. Reactive mesothelial cells in carcinoma specimens were uniformly positive for both proteins. ARID1A mutation analysis showed no mutations in eight analyzed specimens negative by immunohistochemistry. Loss of PTEN and ARID1A expression is highly specific for malignancy in effusion pathology. Loss of PTEN is not informative of organ of origin, whereas absence of ARID1A should raise suspicion of an ovarian primary.

In plain English

This laboratory study asked whether two proteins, PTEN and ARID1A, help pathologists diagnose cancer in fluid that collects around the lungs, abdomen or heart (serous effusions). The authors stained 279 malignant effusions. Most came from a hospital in Oslo, Norway, collected from 1998 to 2008, and the rest from centers in Italy, Austria, Denmark and Germany. There were 226 carcinomas and 53 malignant mesotheliomas of the epithelioid or biphasic type. The article does not report asbestos exposure. Across all 279 tumors, PTEN was absent in 75 and partly lost in 38. PTEN was lower in mesothelioma than in carcinomas, but the difference was not statistically significant (p = 0.084). ARID1A was absent in 18 tumors and partly lost in 18. Among the 53 mesotheliomas it was absent in 3. Most tumors lacking ARID1A were ovarian carcinomas, mainly clear cell and low-grade serous. In the carcinoma specimens, non-cancerous (reactive) mesothelial cells stained uniformly for both proteins. Gene testing of eight ARID1A-negative specimens found no mutations. The authors concluded that loss of either protein appears highly specific for malignancy but of low to moderate sensitivity.

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: Diagnostic laboratory study (immunohistochemical staining of archived effusion cell blocks), with gene sequencing of a small subset
• Who was studied: 279 malignant serous effusions: 226 carcinomas (70 ovarian, 64 breast, 36 lung, 15 uterine corpus, 41 of other origin) and 53 malignant mesotheliomas of epithelioid or biphasic type (14 peritoneal, 39 pleural effusions). 210 specimens came from the Norwegian Radium Hospital, Oslo (1998–2008). The rest came from Trieste (32), Graz (20), Ålborg (8), Essen (5) and Salerno (4).
• Exposure: No asbestos or other fiber exposure was studied or reported. Tumor cells were tested by immunohistochemistry for the proteins PTEN and ARID1A.
• Main results:
  • All 279 tumors, PTEN: preserved in 166 (59%), partially lost in 38 (14%), absent in 75 (27%). Expression was lower in mesothelioma than in all carcinomas, but not statistically significantly (p = 0.084).
  • Mesothelioma specimens (n = 53), PTEN: preserved in 24, partly lost in 14, absent in 15.
  • All 279 tumors, ARID1A: preserved in 243 (88%), partially lost in 18 (6%), absent in 18 (6%). Expression did not differ between mesothelioma and carcinomas (p = 0.974).
  • Mesothelioma specimens (n = 53), ARID1A: preserved in 46, partly lost in 4, absent in 3.
  • Most tumors with absent ARID1A were ovarian carcinomas, mainly clear cell and low-grade serous types.
  • Across the six major tumor groups, PTEN expression was highest in breast carcinoma, and differences between groups were statistically significant (p < 0.001).
  • In the carcinoma specimens examined, reactive (non-cancerous) mesothelial cells were uniformly positive for both proteins. The authors reported specificity of 100% in their series.
  • Sanger sequencing of eight effusions negative for ARID1A by staining found no ARID1A mutations.
• The authors' conclusion: The authors concluded that loss of PTEN and ARID1A appears highly specific, though of low to moderate sensitivity, for malignancy in effusions. Loss of PTEN does not indicate the organ of origin. Absence of ARID1A should raise suspicion of an ovarian primary; the body of the article adds ovarian or peritoneal carcinoma, or alternatively mesothelioma.
• Limitations the authors state:
  • Few endometrioid carcinomas of ovarian or uterine corpus origin were included, although these tumors are known to carry PTEN and ARID1A mutations.
  • Sensitivity for detecting malignancy would be limited, because PTEN was lost in more than half of cases and ARID1A in only 12%.
  • The authors questioned how far these markers are needed, since robust markers for reactive mesothelial cells and leukocytes are already widely available.
  • The sequencing covered only parts of the ARID1A gene. Mutations elsewhere in the gene might be found by next-generation sequencing.
  • Carcinomas of other origin were left out of the statistical analysis because there were too few of them.

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: Cytology, Carcinoma, Mesothelioma, Immunohistochemistry, Reactive Mesothelial Hyperplasia, Pathology.

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)
• The diagnostic role of BAP1 in serous effusions — B. Davidson, M. Tötsch, et al. (2018)
• Expression of thyroid transcription factor-1 in malignant pleural effusions — A. Khoor, A.L. Byrd-Gloster, et al. (2011)
• Analysis of expression of PTEN/PI3K pathway and programmed cell death ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) — S. Cedrés, S. Ponce-Aix, et al. (2016)
• Exploratory analysis of activation of PTEN-PI3K pathway and downstream proteins in malignant pleural mesothelioma (MPM) — S. Cedrés, M.A. Montero, et al. (2012)
• First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications — M.W. Löffler, J. Steinhilber, et al. (2018)

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