Usefulness of Thyroid Transcription Factor-1 Immunohistochemical Staining in the Differential Diagnosis of Primary Pulmonary Tumors of Dogs

Abstract

Abstract. In a previous study, we characterized the reactivity of monoclonal antibody (MoAb) 8G7G3/1 to thyroid transcription factor-1 (TTF-1) in canine thyroid tumors. In this study, we have examined the reactivity of this antibody in 120 canine pulmonary tumors, including 78 primary epithelial tumors. Tissues had been fixed in formalin and routinely processed for histopathology. Nuclear staining for TTF-1 was detected in 64.2% of primary pulmonary epithelial tumors. The most common TTF-1-reactive tumor types were bronchioloalveolar carcinomas and bronchogenic carcinomas. Staining was diffuse, heterogeneous, or patchy. Nonpulmonary, metastatic epithelial tumors, except two of two thyroid carcinomas, did not react with antibody 8G7G3/1. Mesotheliomas and other mesenchymal tumors were also negative for this marker. A reduction or loss of reactivity was apparent in pulmonary epithelial tumors archived in paraffin blocks for 7-8 years. There was slight reduction in the number of positive cells or the intensity of the reaction in control tissues fixed longer than 1 week. On the basis of our limited studies and the human literature, it appears that MoAb 8G7G3/1 to TTF-1 is a highly specific (with the exception of thyroid tumors) and moderately sensitive marker for canine pulmonary epithelial tumors.Key words: Dogs; immunohistochemistry; lungs; neoplasia; thyroid transcription factor-1.Pulmonary neoplasms are uncommon in dogs, with a prevalence of 0.1-0.9% in the overall canine population; however, when only aging dogs are considered, the percentage of animals with pulmonary tumors may reach 25%. 41 The lung is a common place for metastases of nonpulmonary neoplasms. Metastatic tumors can resemble primary pulmonary tumors microscopically, 9 making it challenging to determine the origin of the tumor on the basis of routine histopathology. Thyroid transcription factor-1 (TTF-1) is a 38-kDa homeodomain containing nuclear protein that is a member of the Nkx2 gene family. It plays a role in transcriptional activation during embryogenesis in the thyroid, diencephalon, and respiratory epithelium. 5,13,22 Thyroglobulin-producing cells, C cells, and parathyroid cells from different species express TTF-1. 15,18,39 In the lung, TTF-1 activates surfactant proteins and Clara cell secretory protein gene promoters. 5 TTF-1 is necessary for lung epithelial morphogenesis. 23 In the human fetal lung, TTF-1 is detected in nonciliated cells in airways and in type-I and type-II pneumocytes; 36 in neonates and adults, TTF-1 is primarily expressed in type-II alveolar cells and nonciliated bronchiolar epithelial cells. 16,21,36 Thyroid and pulmonary tumors of humans express TTF-1. 2,3,6,8,[10][11][12][19][20][21]26,27,37,38,42,43 Metastatic pulmonary carcinomas also express TTF-1. 14,17,25,[33][34][35] We recently reported the detection of TTF-1 in most canine thyroid follicular neoplasms and in approximately half of canine C-cell tumors. 32 During that study, we observed TTF-1 reactivity in some pulmonary neoplasms. In this study, we examin...

Immunohistochemistry characterization of a bronchioloalveolar carcinoma mixed subtype in cat

“…The lung is one of the main sites of metastases and, it is often difficult to distinguish primary pulmonary tumors from metastasis (7,11). In our case, the absence of lesions in other organs corroborates that the neoplastic lesion is primary of the lung.…”

“…TTF-1 is a protein originally identified in follicular cells of the thyroid, but was also found in respiratory cells and areas of the developing brain (7). TTF-1 has been described as a highly specific marker in lung adenocarcinomas in human and dog (7,11). D'Costa et al, (2) showed a labeling specificity of 66.7% in feline lung tumors and it was the highest percentage when compared with other antibodies Surfactant A (SP-A) (50%), Epidermal growth factor receptor (EGFR) (20.8%) and p53 (25%), suggesting the importance of these protein as marker to support the diagnosis of pulmonary tumors in the cat.…”

“…In contrast, is an infrequent found in domestic animals (2,11). Spontaneous lung tumors are more frequently in dogs, cats and sheep (6,8).…”

Suggested Guidelines for Immunohistochemical Techniques in Veterinary Diagnostic Laboratories

“…Determination of immunoreactivity in other neoplasms that would be included in the differential diagnosis (e.g., oral spindle cell sarcomas). 46,48,50,53 iii. Comparison of immunoreactivity between nonneoplastic and neoplastic tissues (antigen expression may be lost or expressed de novo in the neoplastic phenotype).…”

Immunohistochemical Characterization of a Pulmonary Large-Cell Carcinoma in a Dog

“…20 Its prevalence in retrospective studies is variable: 0/40 (0%), 7 18/218 (8.2%), 10 33/210 (15.7%), 11 or 2/120 (1.6%). 13 This variability is probably because of the fact that several previously reported cases were actually malignant histiocytosis, a neoplasm with similar histologic features: round cells with abundant eosinophilic or foamy cytoplasm and the presence of multinucleated giant cells. 3 Large-cell carcinomas have not been well characterized, in contrast with other uncommon pulmonary tumors, such as adenosquamous carcinoma 15 and small-cell carcinoma.…”