Molecular pathways and pathomorphology of colorectal cancers

Colorectal carcinomas (CRCs) evolve through multiple pathways. These pathways may be defined based on two molecular features: (1) chromosomal instability and (2) chromosomal stability. Tumors showing chromosomal stability evolve through the so-called microsatellite instability pathway. These types of tumors show different clinico-pathological features and need different therapy so very important to separate them. As Hematoxylin-Eosin (HE) based histology is influenced by the different genetic alterations of a tumor, it is reasonable that different gene expression profiles result in different HE morphology. Our aim was to find specific histomorphological features specific for colorectal tumors showing different molecular features. We analyzed the clinicopathological parameters of 324 colorectal carcinomas, 26 hereditary non-polyposis colorectal cancers, 32 sporadic high-level microsatellite-instable (MSI-H) cancers and 266 microsatellite-stable or low-level microsatellite-instable (MSI-L) cancers among them. Our results showed that we could recognize different genetic types of tumors on the base of clinicopathological features like patient's age, tumor localization and histological characteristics of CRCs. Main histological parameters help in differentiation are inflammatory background, nuclear features and pattern of infiltration. Clinical parameters like clinical stage and localization and careful histological analysis helps to select molecular method to define molecular features and to select the most appropriate therapy of a given tumor.