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

Abstract

Thyroid transcription factor-1 (TTF-1) is considered as a reliable marker for differential diagnosis in distinguishing primary adenocarcinomas of the lung from extrathoracic origins. We previously reported the first case of lung metastasis of colorectal origin, with nuclear expression of TTF-1. As most previous studies were performed on series of extrathoracic primary tumors, we raised the question of a possible role of lung microenviroment in TTF-1 expression. We investigated the rate of TTF-1 expression in lung metastases of extrathoracic adenocarcinomas and compared results of immunohistochemistry performed with different primary antibodies. Two different clones of antibodies (8G7G1/1 from Dako, SPT24 from Novocastra) raised against TTF-1 were used on 56 lung-metastatic malignant tumors, 41 from colorectal origin. A series of primary colorectal (90 cases) and primary pulmonary adenocarcinomas (86 cases) were also investigated. Four of 41 (10%) lung metastases of colorectal adenocarcinomas displayed a nuclear staining for TTF-1 with SPT24 clone. Three of the four positive cases displayed similar nuclear staining in primary and/or other extrathoracic metastatic sites as well as four of 90 (5%) primary colorectal adenocarcinomas, ruling out the role of lung microenvironment. None of them was positive with 8G7G1/1 clone. Sensitivity between two sets of antibodies was compared in 86 primary pulmonary adenocarcinomas. Nuclear staining was detected in 72 cases (84%) with Novocastra's antibody and 56 cases (65%) with Dako's. Significant discordance was observed (Po 0.01). These results suggest that the diagnostic virtue of TTF-1 detection depends on the used antibody's clone. The SPT24 clone seems to have a stronger affinity for TTF-1 protein but may lead to a few positive colorectal adenocarcinomas. Keywords: TTF-1; lung; carcinoma; metastasis; colorectal Thyroid transcription factor-1 (TTF-1) is a tissuespecific transcription factor expressed in the epithelial cells of thyroid and lung (type II pneumocytes and Clara cells). 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. 7 Two main commercial available clones of monoclonal antibodies have been raised against TTF-1 for immunohistochemical use, 8G7G1/1 and SPT24, their diagnostic value in determining the lung or thyroid origin of adenocarcinoma has not yet been compared. Most of the studies show the high specificity of TTF-1 detection and have been published used the 8G7G1/1 clone. We previously reported one case of lung metastasis of colorectal origin, which showed a focal nuclear staining with the anti-TTF-1 antibody (clone SPT24)...

Thyroid transcription factor-1 expression in ovarian epithelial neoplasms

“…6,[19][20][21][22][23] TTF-1 positivity has also been reported in 2 of 27 ependymomas arising in the third ventricle, 24 4 of 5 invasive ductal carcinomas of the breast, 25 1 of 66 gastric cancers, 12 4 of 41 colorectal adenocarcinomas, 26 and 4 of 7 colonic adenocarcinomas. 27 In the gynecologic tract, TTF-1 expression has been noted in 2 of 166 ovarian carcinomas (1 mixed serous and endometrioid adenocarcinoma and 1 serous carcinoma) in a tissue microarray study, 10 1 of 16 ovarian cancers (cell block of cytology fluid), 11 1 of 8 endometrial cancers, 12 and 1 of 14 primary peritoneal serous carcinomas.…”

Molecular pathological predictive diagnostics in a patient with non‑small cell lung cancer treated with crizotinib therapy: A case report

“…In the present study, the tumor morphology and results of immunohistochemical examinations (TTF1, CK7 and cdx2) were not unambiguous, and from a differential diagnostic point of view, the metastatic tumor origin (11)(12)(13), e.g., the stomach, was also considered. HER2/neu gene amplification was assessed by FISH during the diagnostic process.…”

Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms

“…100,118 Moreover, TTF-1 has also been found to be positive in a subset of colorectal carcinomas. 11 In a study of 555 colorectal adenocarcinomas, TTF-1 was positive in 18 (3.2%) and 24 cases (4.3%), using the 8G7G3/1 and SPT24 clones, respectively. 119 For other extrapulmonary adenocarcinomas, PAX8 has also been recently proposed as a third immunomarker used alongside TTF-1 and napsin A to distinguish primary lung adenocarcinomas from metastatic neoplasms.…”

“…However, the SPT24 TTF-1 clone may also show an affinity for colorectal adenocarcinomas. 11 Napsin A, a relatively new cytoplasmic IHC marker for pulmonary adenocarcinoma, is an aspartic proteinase involved 12 in the maturation of surfactant protein B that has an expression thought to be regulated by TTF-1. 13 Napsin A has been shown to be superior to TTF-1 in distinguishing primary lung adenocarcinomas from other carcinomas (except for renal cell carcinoma, 14,15 clear cell carcinomas of the gynecologic tract, 16,17 and thyroid carcinomas 15 ).…”