Furthermore, in clinical
breast, ovarian and prostate cancer specimens, increased TLR9 expression was associated with decreased tumour differentiation [10–13]. It has also been demonstrated that stimulation of TLR9-expressing cancer cells with synthetic TLR9-ligands increases their in AR-13324 vitro invasion which is associated with the down-regulation of tissue inhibitor of metalloproteinases-3 (TIMP3) and the up-regulation of matrix metalloproteinase-13 (MMP-13) activity. Although bacterial DNA, similar to the synthetic CpG-sequence containing TLR9-ligands, also induces invasion in TLR9 expressing cancer cells in vitro, the natural TLR9-ligand that might induce invasion for example in breast cancers, remains unknown [10, 11]. In the normal kidney, TLR9 expression has been detected in the renal tubules and interstitial tissue, while the CBL0137 purchase tubulointerstitial and
glomerular expression has been detected in lupus nephritis . Previously, TLR9 has been associated with renal disease, such as glomerulonephritis  and lupus nephritis . To our knowledge, there are no previous studies of TLR9 expression in RCC. However, the efficacy of a synthetic TLR9-agonist has been studied in a clinical trial in advanced metastatic RCC. This compound was found to have only modest antitumour activity . The aim of this study was to investigate TLR9 expression in RCCs and to evaluate the prognostic significance of TLR9 immunostaining in RCCs. Material and methods Patients This retrospective clinical cohort consisted of 152 patients with 77 (51%) females and 75 (49%) males who underwent XAV-939 in vitro surgery for primary renal cell carcinoma between the years 1990 and 1999, at the Oulu University Hospital. All clinical data and patient follow-up details were collected from patient records and re-evaluated by the same urologist (HR). Seven patients PLEKHM2 (5%) were operated by resection and 145 (95%) by radical nephrectomy. At the time of the diagnosis, the median age of the patients was 63 years
old (range 29-86 years) and the mean age was 62 (SD ± 11 years). The median and mean follow-up times were 90 (range 0-209) months and 90 (SD ± 63) months, respectively. Complete information was obtained from all patients. During the follow-up period, 44 (29%) patients died of RCC, 40 (26%) died of other causes and 68 (45%) were still alive. The distribution of the clinicopathological parameters of the tumours has been previously described [18, 19]. Of the patients, 6 (4%) had lymph node metastases and 18 (12%) had distant metastases. The stage of the tumours was assigned using the TNM staging of RCC . T and N classes were determined by the pathological evaluation of primary tumour and resected lymph nodes. Further, N class and M class were assessed by radiological evaluation performed before primary operation. The abdominal ultrasound was done for every patient and in addition, abdominal computed tomography (CT) was performed for 125 patients (82%).