Endocrine Abstracts

Background: The chemokine receptor CXCR4 and its associate receptor CXCR7, that modulates CXCR4 function, have been associated with tumor progression and metastasis in human cancers. In ACC, Ki67 index and ENSAT stage are the most important prognostic parameters.

Objective: To assess expression of CXCR4 and CXCR7 in adrenal cancer and correlate results with clinical outcome.

Methods: CR expression was assessed by immunohistochemistry in paraffin-embedded sections of 215 ACC tissues (174 primary tumors (PT), 18 local recurrences (LR), 23 metastases (M)). 47.4% (n=102) of patients had an initial R0 resection status. Data were correlated with metastatic status, tumor progress and survival.

Results: Staining for CXCR4 and CXCR7 was found in 85% and 82% of investigated tumors, respectively (h-score >1 in 48 and 50%). No differences were observed regarding CR staining between PT, LR and M. Patients with initial R0 resection status and a positive CXCR4 membrane staining tended to more frequently develop metastases at follow up (59 vs 41%; P=0.075). However, for the whole patient group, no significant correlation was observed between clinicopathological data and membrane staining of the CR, with neither of the CR being an independent factor of overall and progression-free survival. In contrast, strong cytoplasmic CXCR4 staining appeared to be associated with a better overall survival in multivariate analysis (130 vs 49 months, RR 0.55, P=0.046). Among the subgroup of cases with a low ENSAT stage (I and II), a strong CXCR7 membrane staining described a trend towards a better overall survival (77 vs 41 months; P=0.077).

Conclusion: Different from other malignancies, CXCR4 and CXCR7 membrane staining did not significantly influence prognosis in ACC. The observation of improved outcome in patients with strong cytoplasmic CXCR4 staining remains to be assessed in further studies.