NanoString nCounter(R)analysis of tissue microarray punch samples from colorectal carcinomas with invasive margins of the expansive and infiltrative type

Abstract

By a classical approach, the invasive margins of colorectal carcinomas can be typed as expansive or infiltrative, the latter portending a poor prognosis. Colorectal carcinomas with infiltrative-type invasive margins have long been known for their peculiar stroma and the relative absence of a lymphohistiocytic host response, but they have not been studied with contemporary gene expression techniques. Therefore, we submitted 18 microsatellite-stable colorectal carcinomas that could be typed as having invasive margins of the infiltrative (N = 7) or expansive type (N = 11) with confidence to nanoString nCounter(R) analysis (Tumor Signaling 360 Panel). Tissue microarray punch samples were obtained from the tumors and prior to RNA extraction histological sections were prepared. The invasive margin types were mirrored surprisingly well in the two main clusters delineated by an unsupervised cluster analysis of the gene expression data, but tumor budding, the second type of colorectal carcinoma invasion phenotype, was not. Nanostring Annotation Scores were significant for signaling pathways (TGFb, PDGF, MET, FGFR), extracellular matrix remodeling, and anti-tumor immunity processes. However, any hopes that the tumour biology behind the two phenotypes of invasion could be pinpointed to differential expressions of a small set of genes were not fulfilled. Taken together, the data indeed give a molecular underpinning to the two invasion phenotypes, pointing out that matrix features and anti-tumor immunity are key. Nevertheless, we failed to gain a more detailed insight into the mechanics at work, and this may well be due to general limitations of the technology employed.