RhoA and vigilin are candidates for immunohistochemical markers for epithelioid malignant mesothelioma

Our plain-English summary of RhoA and vigilin are candidates for immunohistochemical markers for epithelioid malignant mesothelioma, by T. Hiratsuka, T. Yamamoto, A. Yoshizawa, et al (Scientific Reports, 2022).

The study

• Authors: T. Hiratsuka, T. Yamamoto, A. Yoshizawa, S. Toyokuni, T. Tsuruyama
• Journal: Scientific Reports
• Published: 2022;12(1):18519
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Diagnostic markers of malignant mesothelioma (MM) have been extensively investigated. Immunohistochemistry (IHC) markers, such as calretinin, have been used for pathologic diagnosis. However, more diagnostic markers are required to improve the specificity and sensitivity of pathologic diagnosis. This study proposed two proteins as diagnostic markers for epithelioid MM. One is RhoA, an MM mutation-susceptible locus-derived protein, and another is vigilin, a lung small cell carcinoma marker. IHC was performed using 93 MM (epithelioid, 71 cases; sarcomatoid, 13 cases; and biphasic, 9 cases), 64 lung adenocarcinoma (LAC), 60 lung squamous cell carcinoma (LSC), and 14 normal mesothelial (NM) tissues. The majority of epithelioid MM cases were positive for both RhoA and vigilin, whereas both IHCs showed lower stainability in biphasic and sarcomatoid MM. Besides, both IHCs showed significantly higher stainability for RhoA and vigilin in epithelioid MM than in LAC and LSC (p < 0.05). Chi-square tests showed that both RhoA and vigilin IHC positive rate in epithelioid MM was not significantly different from that of calretinin (p > 0.05). In the differential diagnosis of MM from lung cancer, the accuracy and specificity of RhoA, vigilin, and calretinin staining were almost equivalent. Further, H-score test showed that there was no significant difference between RhoA versus calretinin and vigilin versus calretinin in IHC positivity in epithelioid MM (p > 0.05). In conclusion, RhoA and vigilin may be candidates for immunohistochemical markers for epithelioid MM.

© 2022. The Author(s).

In plain English

This laboratory study tested whether staining for the proteins RhoA and vigilin could distinguish epithelioid malignant mesothelioma from lung cancer in tissue samples. The authors stained commercial tissue from 93 mesotheliomas (71 epithelioid, 13 sarcomatoid, 9 biphasic; pleural, pericardial and abdominal), 64 lung adenocarcinomas, 60 lung squamous cell carcinomas and normal mesothelium. Asbestos exposure was not reported. Staining results covered 58 epithelioid cases, not 71. RhoA was positive in 39 of 58 (pleural 23 of 26, abdominal 16 of 32) and vigilin in 46 of 58 (pleural 20 of 26, abdominal 26 of 32). Lung cancers were significantly less often positive: RhoA in 5 of 64 adenocarcinomas and 5 of 60 squamous cell carcinomas, vigilin in 5 of 64 and 3 of 60. Most sarcomatoid and biphasic tumours and all normal mesothelium stained negative. Calretinin, an established marker, was positive in 81%; average staining scores for RhoA and vigilin did not differ significantly from it. The authors concluded both are candidate markers but said the sample was too small to verify this and calretinin stained more definitely. Several of the article's tables disagree with each other.

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 diagnostic-marker study: immunohistochemical staining of archived tumour and normal tissue on commercial tissue microarrays
• Who was studied: Tissue samples from 93 malignant mesothelioma patients (71 epithelioid, 13 sarcomatoid, 9 biphasic). Table 1 places 39 in the pleura and 8 in the pericardium (47 under the pleura heading) and 46 in the abdominal cavity (mesentery, omentum, peritoneum). Comparison samples were 64 lung adenocarcinomas, 60 lung squamous cell carcinomas, and normal mesothelial tissue from 14 cases (28 tissues). Samples were supplied by US Biomax, Inc. (Rockville, MD). The patients' country and collection years are not stated.
• Exposure: No asbestos exposure information was reported for these patients. The study examined staining for the proteins RhoA and vigilin, compared with the existing markers D2-40 and calretinin.
• Main results:
  • In the epithelioid mesothelioma samples analysed (58, not the 71 listed in Table 1), RhoA was positive in 39 and negative in 19 (67.2%). By site, Table 2 gives 23 of 26 pleural (88%) and 16 of 32 abdominal (50%).
  • Vigilin was positive in 46 of the 58 epithelioid mesothelioma samples (79.3%). By site, Table 2 gives 20 of 26 pleural (77%) and 26 of 32 abdominal (81%).
  • In lung adenocarcinoma and lung squamous cell carcinoma, RhoA was positive in 5 of 64 and 5 of 60 samples (reported as 7% and 8%).
  • In lung adenocarcinoma and lung squamous cell carcinoma, vigilin was positive in 5 of 64 and 3 of 60 samples (8% and 5%).
  • Chi-square tests found significant differences (p less than 0.05) in RhoA positivity, and likewise in vigilin positivity, between epithelioid mesothelioma and each lung cancer type.
  • Sarcomatoid and most biphasic mesotheliomas were negative for RhoA, though Table 2 lists a few positives (pleural biphasic 3 of 10, abdominal biphasic 1 of 13, abdominal sarcomatoid 1 of 9). All sarcomatoid and biphasic samples were negative for vigilin. Normal mesothelial tissues were negative for both stains.
  • Calretinin was positive in 81% of epithelioid mesotheliomas.
  • Mean H-scores (a combined measure of staining intensity and extent) in epithelioid mesothelioma were 61.0 for RhoA, 73.4 for vigilin and 96.7 for calretinin. The differences from calretinin were not statistically significant (p = 0.24 for RhoA, p = 0.40 for vigilin).
  • For distinguishing epithelioid mesothelioma (n = 58) from lung cancer (n = 124), Table 4 gives the following accuracy, specificity and sensitivity: 0.84, 0.86 and 0.80 for RhoA; 0.89, 0.91 and 0.85 for vigilin; 0.82, 0.90 and 0.70 for calretinin. The authors described these as almost equivalent.
• The authors' conclusion: The authors concluded that RhoA and vigilin are candidate immunohistochemical markers for diagnosing epithelioid malignant mesothelioma and distinguishing it from lung cancer.
• Limitations the authors state:
  • The sample size was insufficient to verify RhoA and vigilin as diagnostic markers; the study only identifies candidates.
  • Calretinin staining was more definite than RhoA or vigilin staining, and the RhoA and vigilin staining protocols need improvement.
  • Comparisons with soft tissue tumours and reactive mesothelial tissues were not done and will be needed.

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: Epithelioid, Mesothelioma, Immunohistochemistry, Calretinin, Carcinoma, Sarcomatoid, Biphasic Mesothelioma, Lung Adenocarcinoma.

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