Utility of tissue-specific transcription factors thyroid transcription factor 1 and Cdx2 in determining the primary site of metastatic adenocarcinomas to the brain.

Abstract

CONTEXT:

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To characterize the previously unpublished immunohistochemical expression of the relatively new tissue-specific transcription factor Cdx2 in metastatic adenocarcinomas to the brain.

DESIGN:

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.

• Authors: Leah B Strickland-Marmol, Andras Khoor, Sandra K Livingston, Amyn Rojiani
• Journal: Archives of pathology & laboratory medicine (Arch Pathol Lab Med) Vol. 131 Issue 11 Pg. 1686-90 (Nov 2007) ISSN: 1543-2165 [Electronic] United States
• PMID: 17979487 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• CDX2 Transcription Factor
• CDX2 protein, human
• DNA-Binding Proteins
• Homeodomain Proteins
• Keratin-20
• Keratin-7
• TTF1 protein, human
• Transcription Factors

Topics

• Adenocarcinoma (secondary)
• Brain Neoplasms (secondary)
• Breast Neoplasms (diagnosis, metabolism, pathology)
• CDX2 Transcription Factor
• Colorectal Neoplasms (diagnosis, metabolism, pathology)
• DNA-Binding Proteins (metabolism)
• Diagnosis, Differential
• Gastrointestinal Neoplasms (diagnosis, metabolism, pathology)
• Homeodomain Proteins (metabolism)
• Humans
• Keratin-20 (metabolism)
• Keratin-7 (metabolism)
• Lung Neoplasms (diagnosis, metabolism, pathology)
• Neoplasms, Unknown Primary (diagnosis, metabolism, pathology)
• Predictive Value of Tests
• Sensitivity and Specificity
• Transcription Factors