Claudin Expression in Invasive Lobular Carcinoma with an Emphasis on Pleomorphic Lobular Carcinoma
Shaolei Lu, Kamaljeet Singh, Shamlal Mangray, Rose Tavares, Renee Monahan, Jianhong Li, Murray Resnick, Evgeny Yakirevich. The Warren Alpert Medical School of Brown University, Providence, RI
Background: Claudins are involved in the formation of tight junctions in epithelial cells. The role of claudins in breast epithelial physiology is traditionally thought to be in maintaining cellular adhesion, polarity, and barrier function. Invasive lobular carcinomas of the breast are characterized by loss of cell adhesion. The goal of this study was to evaluate the expression patterns of claudins 1,3,4,7,and 8 in invasive lobular carcinoma (ILC) with an emphasis on pleomorphic lobular carcinoma (PLC).
Design: Fifty eight cases of invasive lobular carcinoma were retrieved from the archives of Rhode Island Hospital including 35 cases of classic ILC (CLC) and 23 cases of PLC. Paraffin embedded tissue microarrays were analyzed for IHC expression of E-cadherin and claudins 1,3,4,7, and 8. The immunoreactivity was assessed based on a combined score of the extent and intensity on a scale of 0-3+.
Results: Normal breast luminal cells exhibited membranous claudin staining for all of the claudins studied. In the carcinoma tissue the staining pattern was similar to that in the normal breast with a predominant membranous staining. Loss of E-cadherin immunoreactivity was detected in all cases in both groups. Negative to weak claudin 1 staining was detected in the vast majority (94%) of CLC and 96% of PLC. Loss of claudin 3 expression was similar in CLC and PLC (79% and 78%, respectively). In contrast to claudins 1 and 3, claudins 4, 7, and 8 were significantly overexpressed (2-3+) in CLC (100%, 61%, 97%, respectively), and PLC (100%, 67%, 94%, respectively). Strong (3+) claudin 4 expression was significantly more frequent in PLC as opposed to CLC (65% and 30%, respectively, P=0.013). Similar to claudin 4, strong claudin 8 expression was more frequently seen in PLC than in CLC (47% and 10%, respectively, P=0.0031). There was a trend between claudin 4 overexpression and poor patient survival (P=0.2).
Conclusions: This study is the first to examine expression of the claudin protein family in ILC. Low expression levels of claudins 1 and 3 are in keeping with loss of other adhesion proteins in ILC. Overexpression of claudins 4, 7, and 8 is an unexpected phenomenon in lobular carcinoma and suggests that these proteins may be involved in progression to more aggressive tumor type. In view of the results of this study, it is likely that the traditional view of adhesion proteins being lost in ILC will need to be revised in the case of claudins. ILC may be added to the group of solid tumors where claudin expression is paradoxically increased.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 39, Monday Morning