An immunohistochemical comparison of two TTF-1 monoclonal antibodies in atypical squamous lesions and sarcomatoid carcinoma of the lung, and pleural malignant mesothelioma

Our plain-English summary of An immunohistochemical comparison of two TTF-1 monoclonal antibodies in atypical squamous lesions and sarcomatoid carcinoma of the lung, and pleural malignant mesothelioma, by S. Klebe, A. Swalling, L. Jonavicius, et al (Journal of Clinical Pathology, 2016).

The study

• Authors: S. Klebe, A. Swalling, L. Jonavicius, D.W. Henderson
• Journal: Journal of Clinical Pathology
• Published: 2016;69(2):136-41
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Unlabelled: Immunohistochemical detection of thyroid transcription factor-1 (TTF-1) plays an important role in the diagnosis and subclassification of non-small cell carcinomas of the lung in biopsy and some cytology samples, specifically for identification of squamous cell carcinoma (classically negative) and non-mucinous adenocarcinoma (positive in most cases) and for discrimination between lung adenocarcinoma and pleural malignant mesothelioma (classically negative).

Aims And Methods: We carried out a comparison of the widely used mouse monoclonal TTF-1 antibody based on the 8G7G3/1 clone versus the more recently introduced rabbit monoclonal antibody (MAb) based on the SP141 clone.

Results: Both antibodies labelled alveolar epithelium in normal lung parenchyma, but the SP141 antibody also labelled bronchial mucosal basal cells. All 13 cases of atypical squamous lesions (including one case of bronchial squamous dysplasia) were negative with the 8G7G3/1 antibody, but 6/13 cases of squamous carcinoma/dysplasia showed positive nuclear labelling with the SP141 antibody in the same tissue biopsy. All 35 cases of adenocarcinoma of the lung were positive with both antibodies. For 12 cases of sarcomatoid carcinoma of the lung, two cases were labelled with the 8G7G3/1 antibody, whereas positive labelling of 4/12 cases was observed with SP141. All 66 cases of epithelioid malignant mesothelioma were negative with both antibodies, but 8/19 cases of sarcomatoid mesothelioma showed positive nuclear labelling with the SP141 antibody (0/19 with 8G7G3/1).

Conclusions: Our findings indicate differences in the rates of positive and negative labelling with these two antibodies, and suggest the potential for misclassification of a proportion of squamous carcinomas of the lung as adenocarcinoma, and for misdiagnosis of some sarcomatoid mesotheliomas as sarcomatoid carcinoma of the lung. If the results of SP141 are assigned overriding significance, our findings further indicate that in isolation, neither negative labelling with either 8G7G3/1 or SP141 nor positive labelling with the SP141 MAb discriminates between sarcomatoid carcinoma and sarcomatoid mesothelioma, whereas positive labelling with the 8G7G3/1 MAb favours a diagnosis of sarcomatoid carcinoma. The literature suggests that these seemingly 'aberrant' results with the SP141 antibody are not 'false' positives, but rather real detection of low levels of TTF-1 protein in a broader range of tumours than is widely recognised.

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In plain English

This laboratory study used pathology files at Flinders Medical Centre in Adelaide, South Australia, to compare two antibodies that detect a protein called TTF-1. Pathologists use this stain to help classify lung cancers and to tell lung adenocarcinoma from pleural malignant mesothelioma. Tissue from the same blocks was stained with the 8G7G3/1 antibody and the newer SP141 antibody. Cases included 85 mesotheliomas (66 epithelioid, 19 sarcomatoid), 35 lung adenocarcinomas, 13 atypical squamous lesions and 12 sarcomatoid lung carcinomas. Both antibodies stained all 35 adenocarcinomas and none of the 66 epithelioid mesotheliomas. SP141 stained 6 of 13 squamous lesions (8G7G3/1: 0 of 13), 4 of 12 sarcomatoid carcinomas (8G7G3/1: 2 of 12) and 8 of 19 sarcomatoid mesotheliomas (8G7G3/1: 0 of 19). The authors concluded that SP141 staining alone did not reliably separate sarcomatoid lung carcinoma from sarcomatoid mesothelioma, whereas positive 8G7G3/1 staining strongly favoured sarcomatoid carcinoma. They suggested SP141 may detect very low, real levels of TTF-1. They noted that systematic data on actual TTF-1 levels in these tumours were lacking. Asbestos exposure was not studied.

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 comparison of two immunohistochemical antibodies (diagnostic stains) applied in parallel to archived pathology cases
• Who was studied: Cases from SA Pathology files at Flinders Medical Centre, Adelaide, South Australia, May 2014 to May 2015 (professional and medicolegal referrals and in-house biopsies). There were 85 malignant mesotheliomas (66 epithelioid, 19 sarcomatoid), 12 poorly differentiated squamous cell carcinomas plus one bronchial dysplasia, and 35 lung adenocarcinomas. For sarcomatoid lung carcinoma, the search was extended back to 1992, giving 12 cases.
• Exposure: No asbestos or other exposure was studied. The comparison was between two TTF-1 monoclonal antibodies: mouse 8G7G3/1 (Dako) and rabbit SP141 (Ventana).
• Main results:
  • Lung adenocarcinoma: all 35 cases were positive with both antibodies.
  • Squamous lesions (12 squamous cell carcinomas and 1 bronchial squamous dysplasia): 0/13 were positive with 8G7G3/1 and 6/13 (about 46%) with SP141.
  • SP141 also stained the nuclei of basal cells in the bronchial lining.
  • Sarcomatoid carcinoma of the lung (spindle-cell component only): 2/12 (17%) were positive with 8G7G3/1 and 4/12 (about 33%) with SP141.
  • Epithelioid malignant mesothelioma: all 66 cases were negative with both antibodies.
  • Sarcomatoid mesothelioma: 0/19 were positive with 8G7G3/1 and 8/19 (about 42%) with SP141. The SP141-positive cases included one desmoplastic mesothelioma with weak to focally moderate staining.
• The authors' conclusion: The authors concluded that, on its own, neither positive nor negative SP141 staining of a pleural sarcomatoid tumour reliably distinguished sarcomatoid lung carcinoma from pleural sarcomatoid mesothelioma. Positive 8G7G3/1 staining, in their view, was evidence against sarcomatoid mesothelioma and strongly favoured sarcomatoid carcinoma. They suggested that SP141 positivity may reflect high sensitivity for very low levels of TTF-1 protein, with a risk of misclassifying some sarcomatoid mesotheliomas and some squamous carcinomas.
• Limitations the authors state:
  • The authors knew of no systematic data on actual TTF-1 levels in sarcomatoid lung carcinomas and sarcomatoid mesotheliomas, so true and false positive or negative rates could not be estimated.
  • The authors noted that comparison with TTF-1 mRNA levels, which they called the ideal 'gold standard', was not possible because such data for these sarcomatoid tumours are unavailable.

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: Thyroid Transcription Factor-1 (TTF-1), Monoclonal, Sarcomatoid, Carcinoma, Malignant Mesothelioma, Biopsy, Cytology, Squamous Cell Carcinoma.

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