[730] CDX2 Expression and Previously Undescribed CDX1 Expression in Primary Gastrointestinal and Metastatic Carcinoid Tumors: An Immunohistochemical Study of 43 Cases

Raveena Reddy, Richard Iverson, Bradley Brimhall, Steve Bigler, Xinchun Zhou, Zelda He, Lafarra Young-Gaylor. University of Mississippi Medical Center, Jackson, MS

Background: CDX1 and CDX2 are homeobox genes which encode for transcription factors essential for intestinal organogenesis. CDX2 has been demonstrated in gastrointestinal (GI) carcinoid tumors whereas CDX1 has never been tested. The aim of this study was to evaluate the expression of CDX1 in GI carcinoid tumors, the relative site-specificity of CDX1 and CDX2, and to determine their patterns of expression in both paired and unpaired analyses of primary carcinoid tumors and metastases.
Design: Immunohistochemical study of CDX1 and CDX2 transcription factors was performed on tissue microarrays from 32 archival tumor samples and on recuts from 11 archival paraffin embedded tissue sections of primary gastrointestinal (GI) carcinoids and extra-gastrointestinal (EGI) tract metastases from the years 1990-2011. Specimens were categorized as either primary tumors or metastases and also by anatomic location as foregut, midgut, hindgut, or EGI. The Fisher Exact test was employed to determine the statistical significance of differences in the proportion of positive immunoperoxidase staining between members of each category.
Results: The proportion of specimens staining positively was higher in metastases compared to primary tumor for both CDX1 (55% vs. 41%) and CDX2 (76% vs. 69%). Neither of these differences achieved statistical significance. The percentage of positively staining specimens differed for each marker depending on the anatomic location.

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Site of tumors	CDX1 (%)	CDX2 (%)
Foregut	25	50
Midgut	26	90
Hindgut	57	11
EGI	71	89

Differences in staining were statistically significant for CDX1 midgut vs. EGI (p=0.018) and CDX2 midgut vs. hindgut (p=0.0001) as well as hindgut vs. EGI (p=0.0002). CDX1 expression was the highest in hindgut, and CDX2 expression was the highest in midgut compared to other GI locations.
Conclusions: Carcinoid tumors originating in different sites have similar histologic features. Immunoperoxidase markers with differential expression may prove useful in distinguishing the origin of metastatic carcinoids. In our study, both CDX1 and CDX2 exhibited differential expression based on anatomic location and metastatic status of tumor. Our results, like others, demonstrate that CDX2 expression persists in metastases with similar findings in CDX1 expression. Retention of these markers in neoplastic endocrine cells, in contrast to the downregulation in colon cancer, has unknown significance. The potential use of CDX1 as a more sensitive marker for hindgut tumors needs more studies.
Category: Gastrointestinal

Wednesday, March 21, 2012 9:30 AM

Poster Session V # 72, Wednesday Morning