Potential role of minichromosome maintenance protein 2 as a screening biomarker in esophageal cancer high-risk population in China

Abstract

Minichromosome maintenance proteins are novel proliferative markers that have been proposed as diagnostic markers in many cancers. We evaluated the potential role of minichromosome maintenance protein 2 as a screening biomarker and compared it with proliferating cell nuclear antigen and Ki67 in a population survey of esophageal squamous cell carcinoma. A total of 299 esophageal samples from a high-risk region in China, including 171 from an endoscopy population survey, 30 from brushing cytology, and 98 from surgery and autopsy, underwent immunostaining with minichromosome maintenance protein 2, proliferating cell nuclear antigen, and Ki67 antibodies. Minichromosome maintenance protein 2 expression was confined to the proliferative compartment of normal and abnormal esophageal epithelium and particularly manifested in the surface layer of dysplasia and carcinoma in situ. The expression of proliferating cell nuclear antigen and Ki67 was positively correlated with that of minichromosome maintenance protein 2 (r(s) >0.39, P < .01); but their positive nuclei seldom reached the surface layer, and the labeling indices were significantly lower than those for minichromosome maintenance protein 2 in dysplasia (P < .05) and carcinoma in situ (P < .001). The sensitivity and specificity of minichromosome maintenance protein 2 in diagnosing dysplasia were 91.3% and 61.8%, respectively, higher than those for proliferating cell nuclear antigen (88.4% and 47.1%) and Ki67 (78.3% and 57.8%). Nine of 10 cancer and paracancerous surface-brushing samples expressed minichromosome maintenance protein 2, and the detection was higher than that for proliferating cell nuclear antigen (8/10 and 7/10) and Ki67 (7/10 and 7/10). However, none of 10 normal surface-brushing samples expressed the 3 markers. Minichromosome maintenance protein 2 is more sensitive and specific than proliferating cell nuclear antigen and Ki67 in indicating esophageal dysplasia. Minichromosome maintenance protein 2 immunostaining combined with surface brushing could be valuable in screening patients at high risk of cancer in mass surveys.