Dachshund 2 protein, a novel neuroendocrine marker associated with favorable tumor characteristics and clinical outcome in colorectal cancer

Abstract only e14580 Background: The dachshund (DACH) gene encodes a nuclear protein and transcription factor that regulates metazoan development of eyes, limbs, brain, gonads and endocrine tissue. DACH2, one of two human homologues, has recently been identified as a marker of poor prognosis in epithelial ovarian cancer, but its further role in tumorigenesis and expression in normal and cancerous human tissue has not been described. Methods: In this study, immunohistochemical expression of DACH2 was evaluated in tissue microarrays with tumours from 539 cases of incident colorectal cancer in the Malmö Diet and Cancer Study. Chi Square and Spearman’s correlation tests were used to explore the associations between DACH2 expression, clinicopathological characteristics and investigative parameters. Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the relationship between DACH2 expression and cancer specific survival (CSS). Furthermore, given its distinct expression in various endocrine normal tissues and tumours in the Human Protein Atlas, we also compared DACH2 expression with a standard panel of neuroendocrine markers in 20 carcinoid tumours. Results: DACH2 expression correlated negatively with TNM-stage, differentiation grade, vascular invasion and microsatellite instability, and positively with older age, distal tumour location and expression of p27, cyclin D1, p53 Ki-67 and beta-catenin. DACH2 expression was significantly associated with an improved CSS in the whole cohort and in cases with tumour located in the colon but not rectum. These associations did however not remain significant in multivariable analysis, adjusted for established clinicopathological factors. Furthermore, DACH2 was highly expressed in all examined carcinoid tumours, with a better diagnostic performance than the majority of established markers. Conclusions: Our findings demonstrate a strong link between DACH2 expression and favourable clinicopathological characteristics and outcome in CRC. Moreover, DACH2 is abundantly expressed in neuroendocrine tumours, and its utility as a diagnostic tool for this entity warrants further study.