Editorial Comment to Annexin A1 expression is correlated with malignant potential of renal cell carcinoma

In this issue of International Journal of Urology, Yamanoi et al. have evaluated the expression of annexin A1 (ANXA1) on renal cell carcinoma (RCC) cell membranes by immunohistochemistry in 22 cases of clear cell RCC (ccRCC), two cases of papillary RCC, two cases of chromophobe RCC and one multilocular RCC. The authors found significantly better disease-free survival in the ANXA1negative group (n = 14) compared with the ANXA1-positive group (n = 12). The same observation was made in ccRCC cases with significantly better disease-free survival in ANXA1-negative ccRCC (n = 10) than in ANXA1-positive ccRCC (n = 11). Even though the number of clinical cases was limited, this work provides valuable information using clinical samples and clinicopathological data from RCC patients seen at a single hospital who received no neoadjuvant or adjuvant molecular targeted therapy. To date, there are only a few published studies that investigate the significance of ANXA1 expression in RCC. Zimmermann et al. examined ANXA1 immunostaining in 33 ccRCC, and found that positive ANXA1 immunostaining correlated with higher clinical stage, higher Fuhrman grade and poor prognosis. Niinivirta et al. examined ANXA1 cytoplasmic staining in 77 metastatic RCC cases treated with nephrectomy followed by sunitinib therapy in the firstor second-line setting. Cytoplasmic ANXA1-negative cases (25/77, 32%) showed better progression-free survival and overall survival than cytoplasmic ANXA1-positive cases. Niinivirta et al. concluded that cytoplasmic expression of ANXA1 was a negative predictive marker for sunitinib treatment in metastatic RCC patients. ANXA1 is reported to be overexpressed in many cancers, and has various roles in cancer development, proliferation, invasion and metastasis. ANXA1 shows specific patterns of expression and subcellular localization in each cancer type. Nuclear localization of ANXA1 is associated with the poor prognosis of patients with oral squamous cell carcinoma and gastric adenocarcinoma. It would be of great importance to examine ANXA1 expression and specific subcellular localization in RCC samples in a much larger cohort. ANXA1 is also implicated in inflammation, immune response and homeostasis of the tissue microenvironment. No studies that examine the role of ANXA1 in immune checkpoint blockade therapy in cancer have been published. It would be of great interest to examine the correlation between ANXA1 expression and therapeutic efficacy of immune checkpoint blockade therapy in advanced RCC patients. Despite the limitation of a small cohort, the current study by Yamanoi et al. raises many potentially important research directions to pursue in the development of new diagnostic methods for the treatment of advanced RCC patients.