Pathology – Research and Practice 207 (2011) 686–690 Contents lists available at SciVerse ScienceDirect Pathology – Research and Practice journa l h omepage: www.elsevier.d e/prp Original article Thyroid transcription factor-1 expression in colorectal adenocarcinomas Matthias Dettmer a , Tae Eun Kim b , Chan Kwon Jung b,∗ , Eun Sun Jung b , Kyo Young Lee b , Chang Suk Kang b a Department of Pathology and Laboratory Medicine, University of Pittsburgh, Pittsburgh, PA, USA b Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea a r t i c l e i n f o Article history: Received 8 August 2011 Accepted 29 August 2011 Keywords: Colorectal cancer Immunohistochemistry TTF1 protein Cytokeratin CDX2 protein a b s t r a c t Although thyroid transcription factor-1 (TTF-1) immunoreactivity is considered as a specific marker of lung and thyroid neoplasms, it may be positive in a proportion of extrapulmonary adenocarcinomas. This study examined the expression of TTF-1 in 555 colorectal adenocarcinomas using three commercial mon- oclonal antibodies: clone SPT24 (Novocastra) and 8G7G3/1 (Dako and Cell Marque), and compared the TTF-1 staining with other immunohistochemical markers, cytokeratin (CK) 7, CK 20, caudal-type home- obox transcription factor 2 (CDX2), and MUC2. The clinicopathological prognostic factors were compared with the TTF-1 expression status. Nuclear TTF-1 staining was detected in 24 cases (4.3%) with the SPT24 antibody and 18 cases (3.2%) with the 8G7G3/1 antibody. All cases positive for 8G7G3/1 were also posi- tive for SPT24. CDX2 was expressed constantly in all 24 TTF-1-positive colorectal cancers, whereas CK7, CK20, and MUC2 were detected in 2 (8.3%), 23 (95.8%), and 8 (33.3%) cases, respectively. There was no correlation between TTF-1 expression and clinicopathological significance. To avoid potential pitfalls, TTF-1 should be interpreted in conjunction with the clinical setting, histological features, and the results of other markers, such as CK7, CK20, and CDX2. MUC2 can be used as supplementary information to confirm difficult cases. © 2011 Elsevier GmbH. All rights reserved. Introduction Thyroid transcription factor-1 (TTF-1) is essential for the devel- opment and differentiation of the thyroid gland, lung, and ventral forebrain [4]. In follicular cells of the thyroid, TTF-1 regulates the expression of the genes responsible for the production of thyroglob- ulin, thyroperoxidase, thyrotropin receptor, and sodium iodide symporter [4]. In the lung, TTF-1 is expressed in alveolar type II and Clara epithelial cells, and regulates the expression of surfac- tant proteins, Clara cell secretory protein, and ATP-binding-cassette transporter A3 genes [4]. In the brain, TTF-1 is expressed in the neu- rons of the hypothalamus and controls telencephalic interneuron specification and migration during development [5,23]. Therefore, genetic mutations of the TTF-1 gene can lead to neurological, thy- roid, or pulmonary problems [6]. Metastatic carcinoma from a tumor with an unknown origin is a frequent problem encountered in daily clinical practice. To provide a correct diagnosis for the treating clinician and to ensure ade- quate patient treatment, the pathologists use a range of different ∗ Corresponding author at: Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea. Tel.: +82 2 2258 1622; fax: +82 2 2258 1628. E-mail address: ckjung@catholic.ac.kr (C.K. Jung). immunohistochemical markers [9]. Among them, cytokeratin (CK) 7, a 54-kD type II simple keratin, is present in most lung adenocar- cinomas, whereas it is rare in colorectal cancer (CRC). CK7 is often used in combination with CK20, a 46-kD low molecular weight ker- atin, and is very helpful in distinguishing CRC from a primary lung cancer [7,17]. Mucin core polypeptides are observed throughout the gastrointestinal tract where they are responsible for the mucus- gel layer. MUC2 is secreted by goblet cells. In general, it is expressed at similar levels as CK7, CK20, and CDX-2. A higher percentage of signet ring carcinomas is positive for MUC2 [22]. TTF-1 is widely used as an immunohistochemical marker for follicular derived thyroid cancers, pulmonary adenocarcinomas, and small cell carcinomas [9]. Its diagnostic usefulness is well- known among pathologists because it is rarely observed outside the lung and thyroid [11,13,15]. On rare occasions, the expression of TTF-1 has been reported in primary adenocarcinomas and neu- roendocrine carcinomas of other organs [12,20,30]. Although TTF-1 expression in CRC has been described previously [8,21,30], there have been no large systematic studies of the prevalence of this phenomenon, and little is known about the impact of the differ- ent antibodies and clones used to detect TTF-1 expression. More studies will be needed to better understand the diagnostic and functional roles of the TTF-1 immunoreactivity in CRC. To better understand this field, this study investigated TTF-1 immunoreac- tivity with three commercially available antibodies in 555 patients 0344-0338/$ – see front matter © 2011 Elsevier GmbH. All rights reserved. doi:10.1016/j.prp.2011.08.009