High minichromosome maintenance protein 7 proliferation indices: a powerful predictor of progression in pancreatic neuroendocrine neoplasms without distant metastasis at the time of surgery

Abstract

Pancreatic neuroendocrine neoplasms (PanNENs) have an unpredictable clinical course that varies from indolent to highly malignant. No immunohistochemical markers are available for reliable prediction of the biological behavior of early stage PanNENs. Minichromosome maintenance protein 7 (MCM7) is a putative powerful marker of cell proliferation. Whether the expression of MCM7 is related to the risk of PanNENs progression remains unclear. We assessed the clinical behavior of 156 PanNENs with respect to stage, grade, Ki-67 index, MCM7 index, and other pathologic features. A high MCM7 index was significantly associated with larger tumor size (P < .001), nonfunctioning tumor (P < .001), increased grade (P < .0001), and later TNM stage (P < .001). In multivariate analysis, G2/G3 (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.35-3.62; P < .001), stage III/IV (HR, 2.11; 95% CI, 1.31-3.41; P < .001), and MCM7 labeling index >5% (HR, 3.81; 95% CI, 1.30-11.17; P = .02) were independent negative prognostic factors related to the risk of tumor progression in stage I-IV disease. MCM7 labeling index >5% was associated with an increased risk of progression in stages I-V, I-III, and I-II. Our study confirms that MCM7 is a valuable marker for assessing the progression of PanNENs, especially in patients with early stage disease and without distant metastasis.