890

CCNA2

cyclin A2;CCNA2;cyclin A2

cyclin-A|cyclin-A2

4q27

protein-coding

Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997-1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers' results was good or even very good, with kappa values 0.71-0.87. The agreement of TMA and large section results was good with kappa value 0.62-0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale.

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.