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Different Cutoff Values for Thyroid Transcription Factor-1 Antibodies in the Diagnosis of Lung Adenocarcinoma

Smits, Alexander J.J. MD*,†; Vink, Aryan MD, PhD; Tolenaars, Gerda BSc*; Herder, Gerarda J.M. MD, PhD; Kummer, Jean Alain MD, PhD*

Applied Immunohistochemistry & Molecular Morphology: July 2015 - Volume 23 - Issue 6 - p 416–421
doi: 10.1097/PAI.0000000000000099
Research Articles

With the use of more specific treatments and targeted therapies for non–small cell lung carcinoma, distinction between adenocarcinoma (ADC) or squamous cell carcinoma (SCC) becomes increasingly important. For this, the key technique is an immunohistochemical panel in which a thyroid transcription factor-1 (TTF-1) antibody is often used. Two different TTF-1 clones (8G7G3/1 and SPT24) are used in daily practice, which appear to have different sensitivities and specificities. The aim of this study was to assess the differences between these clones and to identify the optimal cutoff value for correctly diagnosing primary or metastatic lung ADC. 182 pulmonary (109 lung ADCs, 62 lung SCCs, 11 lung metastases) and 115 extrapulmonary (36 metastatic lung ADCs, 79 nonpulmonary tumors) samples were stained with both TTF-1 antibodies. The percentage of tumor cells with nuclear staining was scored in categories of <1%, 1% to 5%, 6% to 25%, 26% to 50%, 51% to 75%, and 76% to 100%. The staining was further assessed as weak or strong. The sensitivity and specificity were calculated at different cutoff values. Applying the same cutoff value for positivity to both clones resulted in a significant difference between the clones at all cutoff values, with a lower sensitivity of 8G7G3/1 at high cutoff values and a lower specificity of SPT24 at low cutoff values. However, when the optimal cutoff value was used for each clone (>5% staining for 8G7G3/1 and >50% strong staining for SPT24), no significant difference in sensitivity (0.79 vs. 0.82) or specificity (0.98 vs. 0.98) was detected, making the clones equally useful for reliably diagnosing lung ADC.

Supplemental Digital Content is available in the text.

Departments of *Pathology

Pulmonary Diseases, St. Antonius Hospital, Nieuwegein

Department of Pathology, University Medical Center, Utrecht, the Netherlands

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Supported by a grant from the Oncology Center of the St. Antonius Hospital, Nieuwegein, the Netherlands.

The authors declare no conflict of interest.

Reprints: Jean Alain Kummer, MD, PhD, Department of Pathology, St. Antonius Hospital, P.O. Box 2500, Nieuwegein 3430 EM, the Netherlands (e-mail:

Received February 9, 2014

Accepted April 3, 2014

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.