The adhesion molecule CD44v6 is associated with a high risk for local recurrence in adult soft tissue sarcomas

Abstract

Summary In many malignant diseases the expression levels of CD44 and its splice variant v6 (CD44v6) have been associated with the prognosis. The purpose of this study was to investigate the clinical significance of CD44 in adult soft tissue sarcomas (STS). 133 STS patients with a limb or superficial trunk tumour treated at the Helsinki University Central Hospital in 1987-1993 with a median follow-up time of 68 months were included in this study. The expression of CD44 and CD44v6 was determined immunohistochemically on paraffin-embedded tumour samples. 95% of the tumours expressed CD44 and CD44v6 was detected in 57%. Strong CD44 expression was associated with low grade (P = 0.04) and small tumour size (P = 0.02). In diploid tumours the CD44 expression was correlated with low S-phase fraction (P = 0.001). High expression of both, CD44 in general as well as that of CD44v6, predicted a higher risk for local recurrence (CD44: P = 0.01 and CD44v6: P = 0.05). Low CD44v6 content of the primary tumour correlated with poor survival (P = 0.02). Determining the expression of CD44 or CD44v6 in a primary STS could be a valuable tool for selecting the group of patients who might benefit from intensified local tumour treatment.

Prognostic factors in soft tissue sarcomaTissue microarray for immunostaining, the importance of whole-tumor sections and time-dependence

“…These levels were similar to those previously reported, although comparisons are difficult, since the methods of assessment, and the cut-off levels differ [83,108,135]. A high CD44 expression was also a strong prognostic factor for metastasis in our series of 140 mixed STS with a HR of 2.4, but not in the series of 201 MFH (Table 17).…”

“…In a series of 47 STS, Kahara et al [83] demonstrated that most sarcomas expressed CD44s, but that the isoform CD44v6 was more commonly expressed in high-grade tumors, and this isoform was also correlated to a shorter metastasis-free survival. Also Maula et al [108] found that high CD44s expression, and particularly the isoform CD44v6 was associated with an increased risk of LR, but not with survival.…”

“…Several CD44 sequences exist because of alternative splicing and post-translational modification. Up-regulation of CD44 has been found in many cancer types, including lymphomas, colorectal cancer, renal cancer, and head and neck tumors [11,83,108,123,135,176]. A prognostic importance of CD44 expression in STS has been suggested in two studies [83,135].…”

“…A high CD44 expression was also a strong prognostic factor for metastasis in our series of 140 mixed STS with a HR of 2.4, but not in the series of 201 MFH (Table 17). Although up-regulation of CD44 has been shown in several tumor types, such as cancers, lymphomas and mesenchymal tumors, the prognostic value of CD44 is seemingly conflicting as both improved and impaired survival has been found [11,83,108,123,135,176]. CD44 is encoded by a single gene, but multiple isoforms of CD44 are generated by alternative splicing.…”

“…The univariate analysis, performed in a subset of 124 tumors and with adequate local treatment, showed that tumors with cyclin A expression had a HR of 3.6 for development of LR (Table 14). Data on IHC expression in relation to LR are scarce, but Maula et al [108] demonstrated an increased risk of LR for the isovariant CD44v6, but not for overall CD44 immunoreactivity in a series of 133 mixed STS and Heslin et al [67] studied the markers Ki-67, p53, mdm2 and Rb in 121 mixed STS without detecting any significant correlation to the risk of LR.…”