Utility of tissue-specific transcription factors thyroid transcription factor 1 and Cdx2 in determining the primary site of metastatic adenocarcinomas to the brain.
BACKGROUND
Brain metastases of adenocarcinoma of unknown primary pose a diagnostic dilemma to the surgical pathologist. Although the most common source in these cases is the lung, determining a primary source is difficult on routinely stained slides. Immunohistochemical stain panels including differential cytokeratins, hormone receptors, and breast-specific proteins are commonly used in these cases. Recently, attention has turned to tissue-specific transcription factors, such as thyroid transcription factor 1 (TTF-1) and Cdx2, in the appraisal of metastatic adenocarcinomas.


OBJECTIVE
To characterize the previously unpublished immunohistochemical expression of the relatively new tissue-specific transcription factor Cdx2 in metastatic adenocarcinomas to the brain.


METHODS
We reviewed the surgical pathology files of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla, and retrieved 38 consecutive cases of metastatic adenocarcinoma (22 pulmonary, 10 breast, 6 gastrointestinal [2 esophagus/gastroesophageal junction, 4 colorectal]) to the brain with confirmation of the primary site by chart review and histologic evaluation. Sections were immunohistochemically stained with antibodies to TTF-1, Cdx2, and cytokeratins 7 and 20 by standard methods.


RESULTS
Specificities and positive predictive values for Cdx2 and TTF-1 equaled 100% for metastatic gastrointestinal and pulmonary adenocarcinomas, respectively. The negative predictive value of Cdx2 was also very high at 97%.


CONCLUSIONS
Cdx2 is a specific and valuable tool for the surgical pathologist when faced with the common problem of metastatic adenocarcinoma of unknown primary. In conjunction with TTF-1, cytokeratin 7, and cytokeratin 20, Cdx2 can accurately differentiate the most common sources of metastatic adenocarcinoma to the brain.
Strickland-Marmol
Leah B
LB
University of South Florida Department of Pathology, 12901 Bruce B. Downs Blvd, MDC Box 11, Tampa, FL 33612, USA. Leah.Strickland-Marmol@med.va.gov
Khoor
Andras
A
Livingston
Sandra K
SK
Rojiani
Amyn
A
D000230:Adenocarcinoma / Q000556:secondary*; D001932:Brain Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D000071616:CDX2 Transcription Factor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003937:Diagnosis, Differential; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D053554:Keratin-20 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D014157:Transcription Factors
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D053554:Keratin-20; D053552:Keratin-7; C504003:TTF1 protein, human; D014157:Transcription Factors