CDX-2 and MIB-1 expression in the colorectum: correlation with morphological features of adenomatous lesions.
Tumours of the gastrointestinal (GI) tract, of which 70% arise in the colorectum, are a major cause of morbidity and mortality worldwide. Transformation from normal to malignant mucosa is a multistep process involving specific gene mutations and is called the adenoma-carcinoma sequence. Histologically, adenomas are of three types (tubular, tubulovillous and villous) and the extent of mucosal cellular abnormality of three grades (mild, moderate and severe). Cellular proliferation is a marker of malignant potential in many tissues. In the colon, cellular proliferation is partly controlled by the CDX-2 gene, a homeobox gene expressed in differentiated cells of the intestine that has proto-oncogenic potential in murine models. In the stomach, CDX-2 is expressed in intestinal metaplasia and decreasing expression through tumourogenesis shows its tumour suppressor potential. Down-regulation in colorectal cancer cell lines is also observed. This is a retrospective study of colorectal adenomas, and haematoxylin and eosin (H&E) and immunocytochemical staining for CDX-2 and MIB-1 (a cell proliferation marker) are performed on each case. Comment is made on the morphological features (adenoma type and dysplasia severity) and the grade of CDX-2 and MIB-1 expression. This study showed that dysplasia severity is linked to cellular proliferation (P=0.011) but adenoma type was not (P=0.54). CDX-2 was not linked to the morphological features discussed (P=0.11 and P=0.16) and CDX-2 and MIB-1 expression showed no correlation. Increased cell proliferation (MIB-1 expression) was seen in increasingly dysplastic adenomatous lesions of the colorectum. CDX-2 had no link to morphological features or cell proliferation of the dysplastic mucosa.
Woodland
J G
JG
Department of Cellular Pathology, Royal Berkshire Hospital, London Road, Reading, Berkshire RG1 5AN. james.woodland@rbbh-tr.nhs.uk
D000236:Adenoma / Q000737:chemistry* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D000071616:CDX2 Transcription Factor; D002455:Cell Division / Q000502:physiology; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015534:Trans-Activators / Q000032:analysis*
D015415:Biomarkers; D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D015534:Trans-Activators