Prognostic Impact of Immunohistochemical and Molecular Expression of the Endocytosis Receptor LRP1 in Colonic Adenocarcinomas

Colorectal cancer (CRC) is a major public health problem in France and worldwide. CRC is the third most common cancer in incidence and mortality in France. The vast majority of these cancers are adenocarcinomas that arise sporadically and develop from precursor lesions: adenoma. All CRC with the same disease stage do not have the same prognosis. Various parameters have been identified as factors influencing the prognosis and allows adjustment of the treatment. The poor histoprognostic factors are the presence of tumor vessels and nerves invasion or the mucinous adenocarcinoma subtype. At the molecular level, the presence of microsatellite instability (MSI) improves the prognosis, while the presence of a BRAF mutation is an independent poor prognostic factor.

Low density lipoprotein related Protein Receptor 1 (LRP-1) is a multifunctional endocytic receptor that belongs to the family of LDL receptors. He is involved in the clearance of enzymes responsible for the degradation of the extracellular matrix: the matrix proteases. This role of matrix proteolysis modulator associated with a function of cell migration regulator give to this protein an anticancer role. The antitumor property of LRP-1 has been demonstrated in thyroid cancers in vitro. In these studies, loss of LRP-1 expression or a decrease in the LRP-1 activity was correlated with an increase of cancer cells migration and invasion. However, the opposite effect was observed in prostate cancer cell lines.

The clinical impact of the level of LRP-1 expression on overall survival of cancer patients has been assessed in two studies: one on patients suffering from hepatocellular carcinoma and one on patients suffering from primitive lung adenocarcinomas. In both studies, the decrease of immunohistochemical and gene expression of LRP-1 correlated with overall survival decrease. In CRC, only one immunohistochemical expression study of LRP-1 has been published to date. This study shows that adenocarcinomatous cells express LRP-1, but in nearly half the cases, weaker than in normal colonic cells. The clinical and prognostic impact of LRP-1 expression in colon cancer and its association with a particular molecular or morphological profile has not been studied to date.

In this work, the investigators will study the immunohistochemical and genic expression of LRP-1 in a well-characterized series of CRC.

The main objective of this study is to study by genic and immunohistochemical approaches the role of LRP-1 in the aggressiveness of colon adenocarcinomas.