COX-2 and Ki-67 immunohistochemical markers in the assessment of long-standing ulcerative colitis associated dysplasia.

ABSTRACT

INTRODUCTION: Malignancy in LUC (long-standing ulcerative colitis) presumably evolves through a chronic inflammation-dysplasia-adeno-carcinoma sequence in which a multitude of yet not fully understood factors takes part. AIM: To assess ulcerative colitis (UC) associated dysplasia and to distinguish regenerative changes from premalignant ones using immunohistochemical (IHC) markers. MATERIALS AND METHODS: We studied 80 LUC biopsy specimens 20 high-grade dysplasia (HGD), 20 low-grade dysplasia (LGD), 20 indefinite for dysplasia, 20 regenerative atypia. We used anti-COX-2 and Ki-67 antisera (Dako, Carpinteria, USA) to perform immunohistochemical staining by the labeled Streptavidin-Biotin method, and then assessed and graded staining intensity and distribution using previously described scoring systems. Statistical analysis was made using chi-square test and SPSS application. A p-value <0.05 was considered significant. RESULTS: In LGD, most of the cases had middle and top Ki-67 localization of the staining. For HGD, we found to be characteristic the top and surface staining of the crypts and no case of basal immunostaining. COX-2 immunostaining was positive (total score >=3) in 72.5% of all the UC cases studied. In non-dysplastic lesions (regenerative atypia), COX-2 expression was negative and as the pathologic process progressed towards dysplasia/malignant transformation, COX-2 expression became positive with a progressive increase of the total score. CONCLUSIONS: A combination of enhanced colonoscopic surveillance and IHC markers those are more sensitive for dysplasia might be the optimal way to manage the increased colorectal cancer (CRC) risk in LUC patients. Further studies to find additional prognostic parameters will provide valuable insights into the behavior of LUC.