Histone mRNA in situ hybridization and Ki 67 immunohistochemistry in pediatric adrenocortical tumors

Adrenocortical tumors in the pediatric population are rare. Classification of these tumors as adenomas or carcinomas using histological criteria is often difficult. Immunohistochemical expressions of proliferative markers are currently under investigation for utilization in the differential diagnosis and prediction of clinical outcomes. The value of histone proteins as prognostic markers in adrenocortical tumors has not yet been elucidated. We evaluated the histological features, immunohistochemical staining of Ki 67, and in situ hybridization for histone mRNA in 30 pediatric adrenocortical tumors. We investigated the relationship between these parameters and the prognosis. Using the classification proposed by Weiss, 19 tumors were classified as carcinomas and 11 as adenomas. Ki 67 and histone mRNA labeling indices (LIs, the percentage of Ki 67-positive and histone mRNA-positive tumor cells, respectively) were significantly higher in carcinomas than in adenomas (Ki 67 LI was 14.62+/-5.79 in adenomas and 20.35+/-6.23 in carcinomas, p=0.02. Histone mRNA LI was 1.73+/-1.71 in adenomas and 6.62+/-2.28 in carcinomas, p=0.00). The proliferative activity assessed by histone mRNA was lower than that assessed by Ki 67 in both diagnostic groups. The cut off point for the diagnosis of malignancy was found to be 14.55 for Ki 67 LI and 5.75 for histone mRNA LI. A correlation was found between a histone mRNA LI>or=5 and poor prognosis (recurrence, metastasis, or death). We concluded that the proliferative activity of the tumor assessed by Ki 67 and histone mRNA may assist in differentiating adrenocortical adenomas and carcinomas. In addition, our results suggest that the most reliable parameter to predict prognosis in pediatric adrenocortical tumors is the histone mRNA LI.