Thyroid Transcription Factor-1 in Primary CNS Tumors

Abstract

In diagnostic pathology thyroid transcription factor-1 (TTF-1) is used as a relatively specific and sensitive diagnostic marker of thyroid and lung adenocarcinomas and lung carcinoids but has also been demonstrated in minor proportions of carcinomas from other organs as well as nonepithelial neoplasms. Two antibody clones are widely used for TTF-1 demonstration, 8G7G3/1 and SPT24, the latter being the most sensitive. Few studies have addressed the occurrence of TTF-1 in central nervous system (CNS) tumors with highly divergent results, a major reason for which seems to be use of different clones. Based on multitissue blocks we analyzed the TTF-1 expression in a series of 155 CNS tumors comparing antibody clones 8G7G3/1 and SPT24 in optimized protocols on the Benchmark Ultra stainer. With clone SPT24 TTF-1 staining was observed in 13 cases (8%). Among astrodendroglial and oligodendroglial tumors, TTF-1 expression was found in 10 of 56 grades III to IV tumors (18%), as opposed to 0 of 47 grades I to II tumors (0%). The TTF-1 expression in positive tumors was generally weak to moderate and focal (mean histoscore 28, range: 2 to 120). TTF-1 positivity was inversely correlated to the expression of nestin. Among 52 other CNS tumors, TTF-1 expression was found in 1 of 3 central neurocytoma (the only CNS tumor with a moderate, diffuse staining), 1 of 18 ependymal tumors, and 1 of 5 choroid plexus tumors, whereas 4 pineal tumors, 11 meningiomas, 8 embryonal tumors, and 4 mixed neuronal-glial tumors all were negative. None of the 155 tumors stained with the 8G7G3/1 antibody clone. TTF-1 expression in primary brain tumors should be taken into consideration when interpreting brain tumors of uncertain origin.

An Unusual Oncocytic Sellar Neoplasm in a Patient with Birt-Hogg-Dubé Syndrome

“…More recently, TTF-1 nuclear positivity has also been described in SCO (Lee, Tihan, Scheithauer, Zhang, & Gonatas, 2009;Mlika et al, 2011;Ogiwara et al, 2011;; however this is not specific to SCO as TTF-1 is also expressed in other primary brain tumors, and generally those arising in the sellar and third ventricular regions (Kristensen, Nielsen, & Vyberg, 2011;Lee et al, 2009;Zamecnik, Chanova, & Kodet, 2004). It is important to note that these studies have described variable expression of TTF-1 in SCO and other primary brain tumors with both the SPT24 and the 8G7G3/1 clones; in general if positive, the SPT24 clone tends to show stronger expression than the 8G7G3/1 clone.…”

Ttf-1 may not be a reliable marker for differentiating metastasis from brain tumors

“…TTF-1 is a reliable marker for the lung and thyroid, although TTF-1 expression was also identified in urothelial carcinoma, prostate, stomach, salivary gland carcinomas (6), colorectal carcinomas (6,19), ovarian epithelial neoplasms (20) and uterine tumors (21). In addition, TTF-1 expression was described in primary central nervous system tumors in a few studies (5,(12)(13)(14)(15).…”

“…Clone 8G7G3/1 has been used since 1996, whereas clone SPT24 became available later (5). Most studies have shown high specificity for clone 8G7G3/1, while clone SPT24 seems to have higher sensitivity but less specificity (10).…”

“…However, TTF-1 expression has been described in tumors from other sites, particularly colorectal carcinoma, gynecological tumors, urothelial carcinoma, prostate, stomach, and salivary gland carcinoma and primary central nervous system tumors (5)(6)(7)(8). The presence of TTF-1 expression in primary brain tumors is largely unclear and has not been clearly specified yet.…”

Neuropathology of brain metastases

“…[324154] There are reports of TTF-1 positivity in primary CNS neoplasms, although in most diagnostic considerations for metastatic NUP, TTF-1 is negative or only weakly and focally positive. [25] A greater specificity is obtained by combining markers, with most primary lung adenocarcinomas being CK7-positive, CK20-negative, and TTF-1-positive [Figure 9]. [21] Thyroid carcinomas have a similar expression profile; however, they have distinct architectural features and are rarely included in the differential of CNS NUP.…”