Dachshund Homolog 1 Is Associated with Colorectal Carcinogenesis
Qiuying Shi, Grace Guzman, Virgilia Macias, Kongming Wu, Hui Xie, Roshan Patel, Anish Shah, Andre Kajdacsy-Balla, Wancai Yang. University of Illinois at Chicago, Chicago, IL
Background: The human dachshund homolog 1 (DACH1) gene is located in chromosome 13 and encodes a protein composed of two highly conserved domains, dachshund domain 1 and 2, engaging in multiple context-dependent complexes that activate or repress transcription, and regulate cell proliferation and differentiation. DACH1 expression is reduced in a variety of human tumors. Reduced DACH1 expression predicts poor outcomes of breast and endometrial cancer patients. The expression levels and the role of DACH1 in colorectal cancer are largely unknown. Our aims were to characterize DACH1 expression in normal, hyperplastic, dysplastic, and carcinomatous colon tissues; and to determine any relation of DACH1 expression to colon carcinogenesis.
Design: A colorectal progression tissue microarray (TMA) was designed and constructed for evaluation of 173 normal, 130 hyperplastic, 60 dysplastic and 222 adenocarcinoma cores obtained from 131 cases of colorectal carcinoma patients and normal control tissues. Standard immunohistochemistry using anti-human DACH1 was performed. The immunostaining intensity was analyzed as: 0, no staining; 1, weak staining; 2, intermediate staining; 3, strong staining. A composite index was calculated based on the combination of intensity and percentage for each core (range 0-300). Statistical analysis using repeated measures ANOVA by SAS was performed.
Results: DACH1 staining of colon is predominantly cytoplasmic, nuclear, or both nuclear and cytoplasmic. There was absent or very weak staining in normal colonic mucosa, and few positive cells were seen at the base of crypt at the proliferating zone. The staining indices in normal, hyperplasia, dysplasia and cancers were 26, 56, 124 and 161, respectively. The differences among groups were significant (p<0.0001).
Conclusions: Our results show that there is a progression of DACH1 immunoexpression in normal colon, hyperplasia, dysplasia, and colorectal carcinoma, suggesting that DACH1 plays a role in colorectal carcinogenesis. This study uncovers a novel role for DACH1 as an oncogene in colorectal carcinogenesis, unlike that of the tumor suppressor role of DACH1 that has been reported in hormone-responsive breast and endometrial cancers. Further studies using a larger cohort to investigate the correlation between DACH1 expression in various tumor grades, stages, and metastases status, are necessary to stratify prognosis, and to determine whether DACH1 is indeed an oncogene in colorectal carcinogenesis.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 76, Tuesday Afternoon