29/2/96

One of my surgical pathology colleagues has come to me with a very practical question, for which I am seeking the group's input. The end result would be a molecular test that can indicate whether the correct treatment is colectomy or simple endoscopically-monitored removal of a colonic mass by cauterization. Obviously, the medical, financial, and quality of life implications of such a test are large. An ongoing problem for surgical pathologists, and one that generates much pressure on them from the gastroenterologists who are usually attending on these cases, is to differentiate between colonic adenomas (usual type) and DALM lesions (DALM is Dysplasia Associated Lesion or Mass). DALM lesions are polyploid dysplastic lesions arising in a patient with inflammatory bowel disease. Adenomas progress to colon cancer over the course of many years. When found during endoscopy, the simple treatment is to remove them by cauterization. Unfortunately this ruins the histology and makes pathologic categorization as DALM or adenoma by morphologic examination difficult. On the other hand, DALM is a very serious condition that has a high rate of coexistent adenocarcinoma and can quickly progress to invasive neoplasia; it is best treated by colectomy. If a molecular test was available that could be done on colonic biopsies and could differentiate between adenomas and DALM, it would be a great boon to medicine, in that the right treatment could be administered. The right molecular test would be highly specific for one or the other (adenoma vs. DALM). Obtaining specimens is not a problem; we have many PEFFT specimens available on which to do the testing. The question is: does anyone know of a molecular difference, at the gene, transcript, or gene product level, between these two conditions that we could exploit? Has anyone done any work in this area or can you steer us to the correct papers? We thought we'd tap the group's collective knowledge before hitting the library. Please e-mail me your thoughts (including any offers of collaboration) and thank you.