TTF1 expression in normal lung neuroendocrine cells and related tumors: immunohistochemical study comparing two different monoclonal antibodies

Abstract

Thyroid transcription factor-1 (TTF1) regulates lung morphogenesis and differentiation, and its immunohistochemical expression is used for identifying lung neoplasms. The 8G7G3/1 antibody has been used in previous studies, but a different and more sensitive anti-TTF1 antibody, named SPT24, has become commercially available. Since the immunohistochemical expression of TTF1 in normal lung neuroendocrine (NE) cells has not been previously investigated and its utility in the diagnosis of lung NE tumors is a controversial issue, we studied the TTF1 expression in normal adult and fetal lungs, in 83 pulmonary NE neoplasms, in 131 non-lung NE tumors and in 36 metastases from these neoplasms using these two antibodies. A TTF1 immunoreactivity was demonstrated in normal fetal and adult NE cells when using the SPT24 clone. Conversely, using the 8G7G3/1 antibody, only rare fetal neuroendocrine cells were TTF1 positive while adult NE cells were negative. The SPT24 clone identified TTF1 expression in more carcinoids, most of them peripherally located, and poorly differentiated NE carcinomas than the 8G7G3/1 clone. Non-pulmonary well-differentiated NE tumors were negative for both antibodies. Among the 45 non-pulmonary poorly differentiated NE carcinomas 11% were positive for 8G7G3/1 and 18% for SPT24. TTF1 expression in metastases perfectly reflected that detected in the related primary tumors. Our results indicate that the SPT24 antibody is more sensitive than the 8G7G3/1 clone for labeling lung carcinoids and it appears particularly useful in detecting peripheral neoplasms. In addition, the expression of TTF1 in normal NE cells suggests a possible role for the transcription factor in their development and differentiation.

Phenotyping of pulmonary carcinoids and a Ki-67-based grading approach

“…TTF-1 has been recommended to detect the primary site in metastatic disease in the lung [15]. Expression of TTF-1 in PC is reported with 0-80% in TC and 0-100% in ATC [16][17][18][19][20]. Fig.…”

“…Some studies applied scoring systems with a 5-10% cutoff for immunoreactive cells [18][19][20], which results in a lower percentage rate of positive cases compared to studies which even considered few stained cells as positive. The reported differences of TTF-1 positivity in PC could also be attributed to different staining protocols, antibody concentrations, and the selection of cases.…”

Breast Metastasis as the First Clinical Manifestation of Ileal Neuroendocrine Tumor. A Challenging Diagnosis with Relevant Clinical Implications

“…CDX2 immunoreactivity may suggest a possible primary NET in the stomach or small bowel. TTF1 expression may help in identifying lung carcinoids as primary malignancies [23], although TTF1 is not expressed in 100 % of pulmonary carcinoids [32].…”

Neuroendocrine tumours—challenges in the diagnosis and classification of pulmonary neuroendocrine tumours

“…TTF-1 positivity has been reported in up to 95% of pulmonary carcinoids, with stronger staining in spindle cell carcinoids 22–24. However, choice of TTF-1 antibody has been shown to influence staining percentages 25. A further problem may arise in small crushed biopsies where the cytological details and mitotic figures of a possible carcinoid tumour cannot be adequately assessed.…”