Thyroid transcription factor 1 in pulmonary adenocarcinoma

Abstract

Aims: To discover whether variations in thyroid transcription factor 1 (TTF-1) staining in different subtypes and patterns of pulmonary adenocarcinoma are related to the putative origin of the tumour. In addition, to confirm the specificity of TTF-1 for pulmonary (as opposed to other sites) adenocarcinoma, to examine the possible prognostic relevance of TTF-1 positivity in lung cancer, and to review this laboratory's experience of TTF-1 in diagnostic practice. Materials/Methods: In total, 128 primary lung adenocarcinomas, 106 primary non-pulmonary adenocarcinomas, and 37 pulmonary non-adenocarcinoma tumours were studied. In addition, 100 cases where TTF-1 was used in routine surgical pathology practice were investigated. Immunoperoxidase staining was performed on formalin fixed, paraffin wax embedded sections using anti-TTF-1 antibody. Staining was evaluated semiquantitatively using the frequency and intensity of nuclear positivity. Results: None of the 106 non-pulmonary adenocarcinomas expressed TTF-1 and only three of the 37 nonadenocarcinoma lung cancers, all neuroendocrine carcinomas, were positive. Of the pulmonary adenocarcinomas, 75% were strongly positive for TTF-1. Mucinous (two of six) and poorly differentiated adenocarcinomas (four of 10) were less likely to stain. Of the peripheral adenocarcinomas, 33 of 37 were positive, whereas only seven of 14 of those of bronchial origin stained strongly. Atypical adenomatous hyperplasia strongly expressed TTF-1. No ''false positives'' were encountered in the 100 routine diagnostic cases. Conclusion: Positive TTF-1 staining is useful in the differential diagnosis of pulmonary adenocarcinomas. TTF-1 may be a lineage marker for tumours arising from the peripheral airway or alveolar epithelium and has no prognostic relevance.

Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin

“…Some mentions of non-terminal respiratory unit type adenocarcinoma or central bronchial adenocarcinoma have been made. [7][8][9][10] An old study by Edwards 8 suggested three subtypes of adenocarcinoma according to its location: groups I to III. Group I was designated as parenchymal adenocarcinoma and group II as bronchial adenocarcinoma.…”

“…Only a few studies have focused on this issue. [5][6][7][8][9][10] Recently, peripheral adenocarcinoma has been defined as terminal respiratory unit adenocarcinoma. [11][12][13] Their clinicopathological characteristics are generally well defined.…”

DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers

“…For example, thyroid transcription factor 1 (TITF1) in the novel hotspot at 14q12-q13 is known to be overexpressed specifically in lung adenocarcinoma, the predominate subtype of NSCLC from which the 27 cell lines in our study were derived (Fabbro et al, 1996). This gene encodes a homeodomain transcription factor that is involved in regulating pulmonary development and gene expression (Apergis et al, 1998) and has been proposed to be a lineage marker for tumors arising from the peripheral airway (Stenhouse et al, 2004). Adenocarcinomas that express TITF1 are dependent on its persistent expression for survival (Tanaka et al, 2007).…”

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

“…Carcinomas arising from lung and thyroid also show frequent TTF-1 expression. 1,2 As the lung is one of the most common sites of metastasis, TTF-1 is considered as a reliable marker to distinguish between primary lung carcinoma and lung metastasis, especially when dealing with an adenocarcinoma or a large-cell carcinoma. [3][4][5][6] It is also considered as a reliable marker in the differential diagnosis between pleural localization of lung origin carcinoma and malignant mesothelioma.…”