Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling.

TLDR

Colon and ovarian cancers are hard to differentiate in the abdomen, and distinguishing them is crucial for selecting appropriate therapies. The study aimed to identify molecular markers that enable differential diagnosis of colon versus ovarian adenocarcinomas. A multistep protocol was employed, beginning with 60 NCI cancer cell lines, then using cDNA microarrays, resequencing, Affymetrix chips, reverse‑phase protein microarrays, and finally validating candidate markers on clinical tumor tissue microarrays. The approach identified villin as a colon cancer marker and moesin as an ovarian cancer marker, both matching or exceeding the performance of existing markers and demonstrating that the multistep process can yield additional diagnostic, prognostic, and therapeutic markers.

Abstract

Colon and ovarian cancers can be difficult to distinguish in the abdomen, and the distinction is important because it determines which drugs will be used for therapy. To identify molecular markers for that differential diagnosis, we developed a multistep protocol starting with the 60 human cancer cell lines used by the National Cancer Institute to screen for new anticancer agents. The steps included: (a) identification of candidate markers using cDNA microarrays; (b) verification of clone identities by resequencing; (c) corroboration of transcript levels using Affymetrix oligonucleotide chips; (d) quantitation of protein expression by "reverse-phase" protein microarray; and (e) prospective validation of candidate markers on clinical tumor sections in tissue microarrays. The two best candidates identified were villin for colon cancer cells and moesin for ovarian cancer cells. Because moesin stained stromal elements in both types of cancer, it would probably not have been identified as a marker if we had started with mRNA or protein profiling of bulk tumors. Villin appears at least as useful as the currently used colon cancer marker cytokeratin 20, and moesin also appears to have utility. The multistep process introduced here has the potential to produce additional markers for cancer diagnosis, prognosis, and therapy.