Current literature suggests that strong WT1 expression in a carcinoma of unknown origin virtually excludes a breast primary. Our previous pilot study on WT1 expression in breast carcinomas has shown WT1 expression in approximately 10% of carcinomas that show mixed micropapillary and mucinous morphology (Mod Pathol 2007;20(Suppl 2):38A). To definitively assess as to what subtype of breast carcinoma might express WT1 protein, we examined 153 cases of invasive breast carcinomas. These consisted of 63 consecutive carcinomas (contained 1 mucinous tumor), 20 cases with micropapillary morphology (12 pure and 8 mixed), 6 micropapillary 'mimics' (ductal no special type carcinomas with retraction artifacts), 33 pure mucinous carcinomas and 31 mixed mucinous carcinomas (mucinous mixed with other morphologic types). Overall, WT1 expression was identified in 33 carcinomas, that is, 22 of 34 (65%) pure mucinous carcinomas and in 11 of 33 (33%) mixed mucinous carcinomas. The non-mucinous component in these 11 mixed mucinous carcinomas was either a ductal no special type carcinoma (8 cases) or a micropapillary component (3 cases). WT1 expression level was similar in both the mucinous and the non-mucinous components. The degree of WT1 expression was generally weak to moderate (490% cases) and rarely strong (o10% cases). None of the breast carcinoma subtype unassociated with mucinous component showed WT1 expression.
The distinction between breast and müllerian carcinomas from each other and from tumors with a similar cytokeratin profile can be difficult. We tested the usefulness of 2 new markers, NY-BR-1 and PAX8, by staining a variety of breast and gynecologic carcinomas, along with tumors of pancreas, bile ducts, stomach, and gastroesophageal junction. NY-BR-1 expression (ie, H score >10) was seen in 58.4% of breast carcinomas (111/190), 5.6% of müllerian carcinomas (8/142), 7% of pancreatic tumors (1/15), 0% of cholangiocarcinomas (0/22), 0% of gastric tumors (0/36), and 0% of gastroesophageal carcinomas (0/25). All 188 breast carcinomas were negative for PAX8. PAX8 expression was seen in 72.4% of müllerian tumors (105/145). All pancreatic tumors (n = 15), cholangiocarcinomas (n = 23), and gastric (n = 35) and gastroesophageal junction (n = 25) carcinomas were negative for PAX8. Addition of NY-BR-1 and PAX8 in a panel would be useful in distinguishing breast cancer, gynecologic tumors, and tumors of the upper gastrointestinal tract.
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