Expression of the HER4 isoform CYT2 correlates to improved survival in bladder cancer patients lacking Estrogen receptor
Abstract:The epidermal growth factor receptor HER4 consists of several isoforms. The isoform HER4 JM-a/CYT2 undergoes intracellular cleavage and the released peptide in complex with the Estrogen receptor α (ER-α) act as a transcription factor. Previous studies indicate an improved survival in bladder cancer patients expressing HER4. Now we question the importance of the expression of the individual isoforms of HER4 and the expression of ER-α.
Quantitative mRNA assays specific for HER4 isoforms JM-a, JM-b, CYT1, and CYT2 as well as ER-α were established and used to analyse tumour samples from 86 bladder cancer patients. Expression of the isoforms was compared to overall survival with a median follow up time of 39.2 months.
No HER4 expression was encountered in 58% (n=50) of the bladder cancer samples. HER4 positive samples (n=36) were all of the JM-a/CYT2 type. In addition the CYT1 isoform was observed in half of these samples. As previously described the expression of HER4 (n=36) was associated to improved survival (P=0.008) and the expression correlated inversely to tumour stage, grade, and type (all P<0.05). ER-α was expressed in 37% (n=32) of the samples while 63% (n=54) were negative of ER-α. A survival benefit was observed only for patients expressing HER4 JM-a/CYT2 but no ER-α (n=17, P=0.007). When HER4 and ER-α was co-expressed no difference in survival was observed (n=19, P=0.347).
We show that the HER4 isoform JM-a/CYT2 or a combination of JM-a/CYT1 and JM-a/CYT2 are expressed in bladder cancer biopsies. Expression of the JM-a/CYT1 and JM-b isoforms seems insignificant. Interestingly, expression of HER4 JM-a/CYT2 is related with a favourable prognosis but only in patients with no expression of ER-α.
Document Type: Abstract
Publication date: 2008-05-01