Atypical pituitary adenomas – investigation and validation of the 2004 who criteria

Abstract

Introduction In 2004, the WHO added a new subgroup of pituitary adenoma, ‘atypical’ pituitary adenoma, which may be associated with aggressive behaviour. The features of this subgroup include an elevated mitotic index, Ki-67 index of >3% and extensive nuclear staining for p53. However these criteria have not been validated clinically. Aims To investigate and validate the WHO 2004 criteria on a large Australian cohort of patients who have undergone surgery for a pituitary adenoma. Study Designs We identified 117 patients who had surgery between 2000 and 2009 for which clinical follow-up was available. Of these, archived paraffin embedded tissue was available for 115 cases. Mitotic rate, Ki-67 and p53 expression were scored. Comparison was made with clinical outcome. Results Early results, so far, indicate that the degree of p53 expression is an insensitive marker for aggressive behaviour. We anticipate completing our study of Ki-67 and mitotic index by the end of December 2012. Conclusion In our study, the early indications are that p53 has poor sensitivity to predict aggressive behaviour in pituitary adenomas. The validation of Ki-67 and mitotic index in atypical pituitary adenomas is proceeding and we anticipate completing this analysis during December 2012. In 2004, the WHO added a new subgroup of pituitary adenoma, ‘atypical’ pituitary adenoma, which may be associated with aggressive behaviour. The features of this subgroup include an elevated mitotic index, Ki-67 index of >3% and extensive nuclear staining for p53. However these criteria have not been validated clinically. To investigate and validate the WHO 2004 criteria on a large Australian cohort of patients who have undergone surgery for a pituitary adenoma. We identified 117 patients who had surgery between 2000 and 2009 for which clinical follow-up was available. Of these, archived paraffin embedded tissue was available for 115 cases. Mitotic rate, Ki-67 and p53 expression were scored. Comparison was made with clinical outcome. Early results, so far, indicate that the degree of p53 expression is an insensitive marker for aggressive behaviour. We anticipate completing our study of Ki-67 and mitotic index by the end of December 2012. In our study, the early indications are that p53 has poor sensitivity to predict aggressive behaviour in pituitary adenomas. The validation of Ki-67 and mitotic index in atypical pituitary adenomas is proceeding and we anticipate completing this analysis during December 2012.