Increased expression of Chitinase 3-like 1 and microvessel density predicts metastasis and poor prognosis in clear cell renal cell carcinoma.

Abstract

Increasing evidence demonstrated that Chitinase 3-like 1 (hereafter termed CHI3L1 or YKL-40) was highly expressed and tightly associated with human tumor development and progression. However, its precise role in clear cell renal cell carcinoma (hereafter termed RCC) remains to be delineated. In the present study, we investigated the relationship between CHI3L1 expression and microvessel density (MVD), a reflection of angiogenesis, with metastasis and prognosis in patients with clear cell renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of clear cell RCC from 73 patients who had undergone radical nephrectomy were stained immunohistochemically with specific antibodies against CHI3L1 and CD34. CHI3L1 immunostaining was semi-quantitatively estimated based on the proportion (percentage of positive cells) and intensity. MVD was determined with CD34-stained slides. The expression pattern of CHI3L1 and MVD was compared with the clinicopathological variables. Twenty patients had either synchronous or metachronous metastases and 12 died during the follow-up. CHI3L1 intensity was significantly correlated with tumor size (P = 0.005), TNM stage (P = 0.027), M stage (P = 0.011), grade (P = 0.014), and metastasis (synchronous or metachronous; P < 0.001). The CHI3L1 proportion (P = 0.038) and MVD (P = 0.012) were significantly correlated with metastasis. MVD was correlated with CHI3L1 intensity (r = 0.376, P = 0.001) and CHI3L1 proportion (r = 0.364, P = 0.002). There was no difference in the expression of CHI3L1 and MVD between primary and metastatic sites. The survival of patients with higher CHI3L1 intensity was significantly worse than that of patients with lower CHI3L1 intensity. Multivariate analyses indicated that only M stage was an independent prognostic factor for cancer-specific survival and CHI3L1 expression was not an independent factor. Taken altogether, increased expression of CHI3L1 and MVD is associated with metastasis and a worse prognosis in clear cell RCC. CHI3L1 expression is correlated with MVD. The results suggest that CHI3L1 may be important in the progression and angiogenesis of clear cell RCC and CHI3L1 might be a novel strategy for therapy of the patients with RCC.