Thyroid Transcription Factor (TTF-1) Expression in Breast Carcinomas
JN Robens, LC Goldstein, AM Gown, SJ Schnitt. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; PhenoPath Laboratories, Seattle, WA
Background: Immunostaining for thyroid transcription factor-1 (TTF-1) is frequently used to help assess the site of origin of metastatic carcinomas. TTF-1 is most frequently expressed by carcinomas of thyroid and lung origin. Furthermore, it has been assumed that expression of TTF-1 in a carcinoma excludes the possibility of a breast origin. We have recently encountered in our consultation practice three cases of invasive breast carcinoma (confirmed by clinical findings and other immunophenotypic features) that demonstrated unequivocal expression of TTF-1. Two of these cases had neuroendocrine features on H and E-stained sections (confirmed by chromogranin and synaptophysin immunostains); the third case had apocrine features on H and E-stained sections. However, the frequency with which TTF-1 expression is observed in breast carcinomas is unknown. The purpose of this study, therefore, was to evaluate the prevalence of TTF-1 staining in an unselected series of breast carcinomas.
Design: We performed immunostaining for TTF-1 (clone SPT24, Leica/Novacastra, 1:400 dilution) following heat induced epitope retrieval in 305 breast cancer cases submitted to a reference laboratory for routine estrogen receptor (ER), progesterone receptor (PR), and/or HER2 immunostaining. Cases were considered TTF-1 positive if they showed any nuclear staining for this marker.
Results: TTF-1 expression in tumor cell nuclei was seen in 4 of 305 of the breast cancers studied (1.3%). In 3 of the 4 cases, TTF-1 expression was weak and focal. In the fourth case, strong TTF-1 expression was seen in the nuclei of both invasive carcinoma and associated ductal carcinoma in situ. Of note, these 4 TTF-1 positive breast cancers varied with regard to their histologic type, histologic grade and ER, PR and HER2 status.
Conclusions: In this study, TTF-1 expression was seen in just over 1% of breast carcinomas and was most often focal and weak. There were no histologic features or ER/PR/HER2 profile that were particularly associated with the presence of TTF-1 staining in these cases. Thus, while diffuse, strong TTF-1 expression in a carcinoma likely excludes a breast origin, the presence of TTF-1 immunoreactivity cannot by itself be used to rule out a breast origin in a carcinoma of unknown primary site. These results emphasize once again the potential pitfall of relying on the results of a single immunostain to establish the site of origin of a carcinoma in a patient without a known primary site.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 33, Monday Morning