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

By a classical approach, the invasive margins of colorectal carcinomas can be typed as expansive or infiltrative, the latter portending a poor prognosis. To gain insight into the tumor biology behind these morphological features, 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® analysis (Tumor Signaling 360™ Panel). Tissue microarray punch samples were obtained from the tumors and prior to RNA extraction histological sections were prepared. In an unsupervised cluster analysis of the gene expression data, 9 tumors, all of which expansive-types, were assigned to cluster 1, and all 7 cases with infiltrative-type margins to cluster 2 which also included 2 expansive-type cancers. Thus, invasive margin-types were mirrored in gene expressions; however, tumor budding, the second type of colorectal carcinoma invasion phenotype, was not. Nanostring Annotation Scores were significant (p < 0.05) for signaling pathways (TGFb, PDGF, MET, FGFR), extracellular matrix remodeling, and anti-tumor immunity processes, but any hopes that the tumor 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.