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Background The extent of tubular lesions and recruitment of inflammatory cells is belived to be and important predictor of renal function in immune- mediated glomerulonephritis (1) such as Lupus Nephritis (LN). The response of the renal tubules to proteinuria is implicated in progression of renal disease (2). Kidney Injury Molecule 1 (KIM-1), a recently discovered transmembrane tubular protein, is markedly induced in acute kidney injury and chronic kidney disease. KIM-1 is an ideal biomarker because is not expressed in normal kidney but specifically expressed in injured proximal tubular cells and such expression persist until the damage cells recovered (3). Objectives The role of KIM-1 in LN remains elusive. In this study, we examined the correlation between gene expression of KIM-1 in the urinary sediment and biopsy of patients (P) with NL diagnosis, and the relationship between KIM-1 expression and urine Protein/Creatinine ratio (P/C). Methods Twenty two kidney biopsies and 28 urine samples from 20 P with LN (17 F/3 M, age 33,55±12,28; Range: 15-72) were evaluated. Kidney biopsies were classified according to ISN/RPS scoring system (4). Urine samples from LN patients were divided as P/C <1 (Group I, N=12) and P/C >1 (Group II, N=16), and urine samples from healthy individuals (Group III, N=17) were analized as control. Levels of gene expression of KIM-1 were evaluated using Quantitative Real Time PCR (QPCR). All amplifications were carried out in duplicate and threshold cycle (Ct) scores were averaged for calculations of relative expression values. The Ct scores were normalized against Ct scores by subtracting the corresponding β2Microglobuline (β2M) control, or DCt=Ct,gene- Ct,B2M. A Spearman’s rank-order correlations (r) was used to test associations between gene expression levels in biopsy and urine pairs samples. To test for differential gene expression between groups a variance analysis (ANOVA) was performed. Results We observed a significant correlation between biopsy and urine, Spearman r=0,6838 (p=0.0005). There were a statistically significant difference in the expression of KIM-1 between groups (p=0,0110). After ANOVA test, we observed that the levels of mRNA of KIM-1 in Group II were higher than those from Group I and there were higher than Group III. Conclusions There was no expression of KIM-1 in normal urine. In LN, urinary KIM-1 gene expression is closely related to tissue KIM-1 and correlates with the severity of tubular interstitial injury. Quantitation of urinary KIM-1 is likely to be a nobel noninvasive and sensitive method for the evaluation of kidney injury in P with LN. References Zheng L, et al. Journal of Histochemistry and Cytochemistry. 56(5): 517-529, 2008. Hill G, et al. Kidney International. 60: 1893-1903, 2001. Hou W, et al. Transplantation Reviews. 24:143-146, 2010. Weening JJ, et al. Kidney International. 65 (2): 521-530, 2004. Disclosure of Interest None Declared

BackgroundLupus Nephritis (LN) is one of the most severe forms of systemic lupus erythematosus (SLE) (1). Angiotensinogen (AGT) gene encodes the only glycoprotein known to be a precursor of the vasopresor angiotensin II (Ang II). Ang II is also a growth factor and a profibrogenic cytokine (2). In kidney transplantation AGT has been founded down expressed in biopsies with chronic allograft dysfunction (3). In LN, AGT deserves evaluation.ObjectivesTo investigate AGT expression in biopsies and urines from LN patients.Methods32 biopsies/urines paired from 32 LN patients was included. Kidney biopsies were evaluated according to the ISN/RPS classification system. Levels of AGT were evaluated using Quantitative Real Time PCR. Threshold cycle (Ct) scores were averaged for calculations of relative expression values. The Ct scores were normalized against Ct scores by subtracting β2Microglobuline control, or ΔCt=Ct,gene- Ct,B2M. Data expressed as ΔCt are inversely proportional to gene expression level. Nonparametric Mann Whitney test analysis and Anova with Bonferroni test were performed.Results26 (81.3%) patients were female with a mean age at biopsy time of 31.9±29 years. The SLEDAI at the time of biopsy was 10.5 (IQR 0–15.7) and SLICC ≥1 in 13 (32.5%), hypocomplementemia 13/31 (41.9%) and positive DNA in 11/29 (37.9%) patients. Biopsies from patients with proteinuria ≥0.5 and renal failure (n=23), proteinuria isolated (n=14), LN remission (n=9), renal failure (n=7) and nephrotic syndrome (n=2) were performed. The mean value of ΔCt AGT gene expression in renal biopsy was 4.50 (IQR 3.51 – 5.67) and AGT in urine samples was 13.94 (IQR 11.66 – 17.89).Table 1.AGT gene expression in biopsies and urines samplesClass I/Class IIClass IVClass V/VIp Normal BiopsiesBiopsiesBiopsiesBiopsies n=3n=6n=12n=10p ΔCt AGT Biopsies*5,573,675,344,350,02(3,60–5,57)(2,19–5,37)(4,75–10,93)(3,45–4,57)ΔCt AGT Urines**14,1111,1916,7715,060,01(12,44–14,11)(9,53–11,59)(12,88–18,25)(12,16–17,62)*p<0,05 class IV vs II; **p<0,05 Class IV vs II.Table 2.AGT gene expression in biopsies according proteinuria levelsProteinuria ≤0,5Proteinuria >0,5p ΔCt AGT Biopsies3,60 (3,34–4,41)4,79 (3,73–6,39)0,04ConclusionsIn the present study we found a potential utility of AGT mRNA levels in samples of active vs remission LN patients. Prospective studies are needed for confirming these results.References Yajuan Li et al. Biomarkers Profiling for Lupus Nephritis. Genomics Proteomics Bioinformatics 11; 158–165, 2013.Eriguchi M et al. Assessment of urinary angiotensinogen as a marker of podocyte injury in proteinuric nephropathies. Am J Physiol Renal Physiol 310: F322–F333, 2016.Mas V et al. Establishing the molecular pathways involved in chronic allograft nephropathy for testing new non-invasive diagnostic markers. Transplantation. 83:448–57, 2007. Disclosure of InterestNone declared

Background: Phenotype plays an important role in BC biology and outcome. We evaluated the characteristics and outcomes of clinical stages I-III BC patients with recurrence according to the IHC phenotype: ER or PR+/HER2-; HER2+ (regardless the ER and PR status) and triple negative (ER-/PR-/HER2-), to determine the influence of phenotype in the SNC recurrence. Methods: We reviewed 1,232 clinical stage I-III BC treated at INEN (2000-2002). Phenotypes were categorized by IHC into [ER+ and/or PR+, HER2-], [ER-, PR-, HER2-] and [HER2+ (regardless ER/PR status)]. Patients were classified in 3 risk groups (recursive partitioning analysis [RPA]; Gaspar et al. Int J Radiat Oncol Biol Phys 1997;37:745) according to 4 criteria: those with Karnofsky Performance Status (KPS) less than 70 (Class III), those with a KPS of or more, aged less than 65, with a controlled primary, no other systemic metastases (Class I), all other patients (Class II). We used Kaplan-Meier estimates for comparing CNS-free metastases survival and survival after CNS recurrence according to IHC phenotype or classes. Results: A median follow-up of 7.6 years; 416 (33.8%) patients had local, regional or distant disease dissemination, and 454 (36.9%) deaths were registered. In total, 62 (5.0%) patients developed CNS metastases (60 cases of cerebral and 2 of meningeal metastases), 36 (2.9%) of whom had developed CNS metastases as the site of first recurrence. 12 (2.1%), 31 (7.7%) and 19 (7.5%) were ER or PR+/HER2-, HER2+ and triple negative, respectively. CNS metastases free survival shown significant differences between ER or PR+/HER2-, HER2+ and Triple negative (97.3%, 89.6% y 90.5%, respectively; P&lt;0.001). Main multivariate predictive factor was IHC phenotype (P&lt;0.001), using [ER or PR+/HER2-] as reference, other phenotypes were expressed by hazard ratios (HR); [HER2+] (HR=3.8, 95%CI; 1.9 - 7.4), triple-negative (HR=4.0, 95%CI; 1.9-8.4). In regard to the RPA groups, 3 (4.9%) were class I, 28 (45.9%) class II and 30 (49.2%) class III. Median survival after CNS recurrence was 12.9, 6.1 and 2.8 for RPA Class I,II and III, respectively]; however there was not significant differences (p=0.085). In the multivariate analysis for OS after SNC metastases, only phenotype was significant and Triple Negative have the higher risk (HR=2.064; IC95% 0.94 — 4.531; P=0.023), Risk groups have not significant effect (P=0.088). Phenotype and outcome Conclusion: IHC phenotype is a strong risk factor for outcome; triple negative, and Class III breast cancer patients present a shorter time to CNS recurrence and survival after CNS recurrence than other IHC phenotypes and other risk groups. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-14-02.

ObjectivesTo evaluate BLyS as biomarker in disease activity in urinary sample and renal biopsy from patients with LN.MethodsRetrospective study. Between June 2009 and October 2013, 32 patients with SLE and LN fullfilling SLE classification criteria of ACR 1997 were included. The renal biopsies were evaluated according to the ISN/RPS classification system. The gene expression levels of BLyS were quantified using Quantitative Real Time PCR (QPCR). The relative quantification method was used for analysis, where Ct was normalized to an endogenous control β2Microglobulina (β2M) (ΔCt BLyS). The data expressed as ΔCt are inversely proportional to gene expression level. The value of BLyS is expressed as median (M) and interquartile range (IQR) for filing a non-normal distribution.Results26 (81.3%) patients were female with a mean age at diagnosis of 26.9±13 years and 31.9±29 years at the time of renal biopsy. The SLEDAI at the time of biopsy was 10.5 (IQR 0–15.7) and SLICC ≥1 in 13 (32.5%), hypocomplementemia 13/31 (41.9%) and positive DNA in 11/29 (37.9%) patients. Biopsies from patients with proteinuria ≥0.5 and renal failure (RF) (n=23, 71.9%), proteinuria isolated (n=14, 43.8%), LN remission. The value of the BLyS gene expression in renal biopsy was 8.09 (IQR 7.37–9.16) and BLyS in urinary sample was 6.45 (IQR 5.62–7.76).Table 1.BLyS gene expression in urinary sample and renal biopsy according to clinical and histological findingsVariablesΔCt BLyS UrinarypΔCt BLyS Biopsyp SLEDAI =0/ SLEDAI ≥6 7.52 (6.59–11.19)/5.94 (5.52–7.08) 0.04 8.03 (6.90–10.20)/8.15 (7.35–9.10)0.82Bx LN in remission/LN active 7.52 (6.59–11.19)/5.94 (5.52–7.08) 0.04 8.03 (6.90–10.20)/8.15 (7.35–9.10)0.82MDRD ≥60/ MDRD ≤60 6.76 (6.018.12)/5.60 (5.16–7.19) 0.04 8.03 (6.95–8.95)/8.41 (7.45–13.40)0.42Proteinuria ≤0.5/Proteinuria ≥0.5 7.52 (6.59–11.19)/5.94 (5.52–7.08) 0.04 8.03 (6.90–10.20)/8.15 (7.35–9.10)0.82Without tubular atrophy in Bx /Tubular atrophy in Bx 7.83 (6.43–11.67)/6.14 (5.51–7.24) 0.03 8.16 (6.44–8.52)/8.09 (7.42–10.55)0.53Table 2.BLyS gene expression in urinary sample and renal biopsy according to the classification of LNClass I/Normal BxClass II BxClass IV BxClass V/VI BxP ΔCt BLyS Renal Biopsy7.56 (6.50–7.56)8.41 (7.36–10.37)7.95 (7.37–10.04)8.28 (7.37–11.80)0.88ΔCt BLyS Urinary*** 7.28 (9.95–7.28) 8.41 (7.36–10.37) 5.65 (5.45–6.40) 6.34 (5.74–7.32) 0.003 ***p<0.05 Class I/normal with class IV, Class II with IV, class II with V/VI.ConclusionsBLyS detection in urinary samples could be a potential biomarker for predicting lupus nephritis activity. Our data confirm that the BLyS as urinary biomarker is present in patients with active renal disease especially in patients with proliferative glomerulonephritis.Disclosure of InterestNone declared