N YAP 1, T ONG 1, A RAZACK 1, G GOBE 2, R RAJANDRAM 1,2
1Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 2Kidney Disease Research Collaborative, Faculty of Medicine, University of Queensland, and Translational Research Institute, Brisbane, Australia
Introduction: CD14 is involved in production of cytokines, chemokines and growth factors. Its role in the pathogenesis of renal cell carcinoma (RCC) is unclear. The aim here was to compare CD14 staining in clear cell RCC (ccRCC) and matched non-cancer kidney, as well as in the serum soluble CD14 (sCD14) levels, with survival prognosis.
Methods: CD14 expression was assessed in sections from 88 patients using immunohistochemistry of ccRCC and adjacent matched non-cancer kidney. Staining intensity and localisation was established using Aperio ImageScope morphometry. Serum sCD14 was evaluated for 39 ccRCC patients and 38 non-cancer controls using ELISA. CD14 levels were compared according to tumour characteristics and survival.
Results: The majority of ccRCC were of tumour-node-metastasis (TNM) stage I (54.5%) and Fuhrman grade 2 (60.2%). Median positive pixel immunopositivity (%) for CD14 was higher in ccRCC (15.41 [9.37 – 22.02]) compared to adjacent non-cancer kidney (6.14 [3.85 -8.41]). Non-cancer kidney was, however, significantly associated with tumour staging and survival prognosis (P<0.05). Serum sCD14 median concentration (mg/mL) was significantly higher in ccRCC patients (2.11 [1.80-2.74]) compared to non-cancer controls (1.77 [1.54-2.02]) (P<0.01) and significantly associated with tumour staging and worse survival prognosis (P<0.01). Serum sCD14 was significantly associated with adverse outcomes for overall survival (OS) (hazards ratio [HR] 2.95; 95% confidence interval [CI 1.38-6.32]; P<0.01) and disease-specific survival (DSS) (HR 4.24; 95% CI 1.77-10.14; p<0.01) even when adjusted; OS (HR 3.15; 95% CI 1.04-9.57; p<0.05) and DSS (HR 11.40; 95% CI 1.36-95.81; p<0.05).
Conclusions: CD14 positive immune cell infiltrates, even in non-cancer tissue adjacent to the cancer, may play a part in ccRCC progression. The levels in peri-tumoral tissue and serum could be prospective prognostic indicators.
Retnagowri Rajandram obtained her PhD in Medicine from University of Queensland in 2009 at 25. She is currently an academic staff with University of Malaya in Malaysia for over 10 years. Her research niche areas include Urological cancers and diseases. She is well-versed in molecular biology techniques and an advocate for translational research. She completed research attachments at Oxford, United Kingdom and Harvard Medical School/Beth Israel Deaconess Medical Centre, Boston. In the last several years she received numerous awards for her contribution to her research field and for collaborating with various professionals especially clinicians.