Morphological and molecular heterogeneity in colorectal neoplasms with K-RAS mutation. A report of two cases

Approximately forty percent of colorectal cancers (CRC) are characterized by activating mutations of the K-RAS gene. Determination of K-RAS mutational status as a predictive marker for anti-EGFR therapy is usually based on the assumption of intratumoral homogeneity. We present two cases of CRC in which morphologically distinct tumor components were associated with different activating mutations of K-RAS in one patient and a mutated and a non-mutated portion in the second patient, as demonstrated by laser microdissection and consecutive molecular analyses.