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CD44 and CD44v6 downregulation in clinical prostatic carcinoma: relation to Gleason grade and cytoarchitecture
A M De Marzo1, C Bradshaw, J Sauvageot
1Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.
Background:
Altered expression of CD44 has been implicated in tumor progression and metastasis in multiple neoplasms.
Methods:
CD44 expression in archival tissues of prostate carcinoma was examined by immunohistochemistry with monoclonal antibodies against core CD44 and the RNA splice variant CD44v6 (v6).
Results:
Core CD44 expression was reduced in the majority of primary neoplastic foci (n = 94) and loss of expression correlated with increasing Gleason grade. Staining for v6 was absent in most carcinomas and metastases. Expression of core CD44 in pelvic lymph node (n = 27) and bone metastases (n = 21) was significantly reduced. In addition, CD44 expression correlated with cytoarchitecture. Tall columnar tumor cells typically stained positively, yet more rounded cells forming cribiform structures or nests showed reduced expression. All cases of high-grade prostatic intraepithelial neoplasia were positive for core CD44 yet, there was decreased expression in cribiform and micropapillary variants.
Conclusions:
The majority of clinically relevant human prostatic carcinomas and metastases downregulate expression of CD44. Additional studies to determine whether CD44 cell surface expression relates to clinical outcome independent of other established clinicopathologic risk factors are warranted.