Abstract 5106: Circulating MACC1 transcripts are elevated in pancreatic cancer patient blood and correlate to locally advanced disease.

Abstract

Abstract Pancreatic cancer is a highly aggressive malignancy with a 5-year survival of < 5%. Late diagnosis, lack of prognostic markers and poor response to radiation and chemotherapies all contribute to the dismal prognosis. Surgery represents the sole curative treatment option. However, success is limited by invasive growth and metastatic spread, which frequently precede the onset of clinical symptoms and hence diagnosis. Recently, we identified the novel gene metastasis-associated in colon cancer-1 (MACC1). MACC1 is a prognostic indicator for metastasis formation linked to metastasis-free survival of colorectal cancer patients. Circulating MACC1 transcripts in colorectal cancer patient plasma predict metastasis and survival. Correlations of MACC1 expression levels with tumor progression, recurrence and metastasis have meanwhile been reported for several cancers, e.g. gastric, lung and hepatocellular cancer. Here, we addressed the role of MACC1 in pancreatic cancer. Immunohistochemical analysis of MACC1 in cryosections of human pancreatic cancer revealed strong reactivity of tumour duct epithelial cells, but not in the desmoplastic stroma. In contrast, weak immunoreactivity was present in non transformed pancreatic tissues, suggesting an induction of MACC1 in pancreatic malignancy. We furthermore analyzed blood levels of circulating MACC1 transcripts in pancreatic cancer patients. Circulating MACC1 transcript levels were elevated in pancreatic cancer patients, when compared to healthy volunteers. MACC1 transcript levels furthermore correlated to peripancreatic infiltration, but not to tumour size, tumor grading or angioinvasion. Thus, MACC1 expression is induced in pancreatic cancer, which is reflected by increased circulating transcript levels in blood as well as high protein levels in the primary tumors. The correlation of MACC1 transcript levels with peripancreatic infiltration suggests a distinct function of MACC1 in pancreatic cancer cell biology, which translates into distinct clinical features of disease progression. Circulating MACC1 might therefore help to personalize treatment decisions in situations such as (neo-)adjuvant chemotherapy. Citation Format: Ulrike S. Stein, Pia Herrmann, Christian Fischer, Peter M. Schlag, Katharina Detjen. Circulating MACC1 transcripts are elevated in pancreatic cancer patient blood and correlate to locally advanced disease. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5106. doi:10.1158/1538-7445.AM2013-5106