Cyclin A predicts metastatic potential of rectal neuroendocrine tumors.

Rectal neuroendocrine tumors (NETs) are rare tumors representing 10% to 15% of gastroenteropancreatic NETs. The grade of these tumors, according to the World Health Organization (WHO) 2010 classification and based on Ki-67 index and mitotic count, correlates with their metastatic potential. We studied the expression of a cell cycle regulatory protein, cyclin A, in rectal NETs. Our tumor series of rectal NETs comprised 73 tumors, of which 71 cases were available for immunohistochemistry. We assessed how well expression of cyclin A predicts the occurrence of metastatic lesions. Expression of cyclin A correlated well with metastatic potential because all tumors with high expression (≥5%) were metastatic. Cyclin A expression and WHO 2010 grade were independent prognostic factors. Cyclin A failed to recognize 3 metastatic tumors classified as grade 2 tumors. On the other hand, 2 grade 2 tumors with low expression of cyclin A remained local. The WHO 2010 classification showed excellent prognostic accuracy for rectal NETs. Additional reliable prognostic tools would nevertheless be valuable. This study showed cyclin A expression to correlate well with metastatic potential. Both cyclin A and WHO 2010 grade were very specific in identifying patients at risk for metastasis (100% versus 96%). Grade was more sensitive (100% versus 60%). Tumors with strong expression of both cyclin A and Ki-67 were all metastatic, and these patients will require careful monitoring and may benefit from adjuvant therapy.