Most Metastatic Colorectal Adenocarcinomas Express Less CDX2 Than Their Primaries.
Rongjun Guo, Frank Chen, Joyce Paterson, John Lynch, Amy Sands, Carl Morrison, Charles LeVea. SUNY at Buffalo, Buffalo, NY; University of Pennsylvania, Philadelphia; Roswell Park Cancer Center, Buffalo, NY
Background: CDX2 is an intestine-specific transcription factor and is used diagnostically as a tumor marker of colonic origin. Both CDX2 over-expression and decreased expression in the primary colonic adenocarcinomas have been reported previously. It is still in debate whether CDX2 is a tumor suppressor or an oncoprotein. Loss of CDX2 expression in colonic adenocarcinomas has been found associated with poor prognosis, suggesting its function as a tumor suppressor. Metastasis is a selective process through which only the cancer cell with advantageous phenotypes survives this process and grows in a site away from the primary tumor. Whether CDX2 expression is able to be sustained in the process of metastasis will provide an important clue for its role in the process of carcinogenesis. In this study, we compared CDX2 expression in metastatic and matched primary colorectal adenocarcinomas.
Design: Immunohistochemical staining against CDX2 was performed on a tissue microarray (TMA) (0.6-mm tissue cores) of 27 cases of randomly selected human colorectal adenocarcinoma specimens. Based on CDX2 expression in the primary tumor, 19 pairs of matched primary tumor and metastasis were analyzed. The percentage of cells with nuclear staining and their mean intensity level were scored. Statistical analysis was performed by two-tailed paired T test.
Results: CDX2 is expressed in 68% (19/28) of primary colorectal adenocarcinomas. Among these 19 paired primary and metastatic tumors, expression of CDX2 was completely or significantly reduced (p-value < 0.00004) in 73% (14/19) of metastatic tumors. CDX2 expression in the other 5 pairs showed no significant changes. In the 8 cases that CDX2 were not expressed in primary tumors, no CDX2 was detected in their paired metastases.
Conclusions: While most primary colorectal adenocarcinomas express CDX2, 73% of remote metastasis completely lose or decrease CDX2 expression. This phenomenon should be considered when diagnosing metastatic tumor of unknown origin. The significantly reduced CDX2 expression in metastatic colonic adenocarcinoma also supports the notion that CDX2 behaves as a tumor suppressor. To our knowledge, this is the first study comparing CDX2 expression in primary colorectal adenocarcinoma with its metastasis.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 43, Wednesday Morning