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371 Background: Inflammation plays a key role in the pathophysiology of many diseases, including cancer. Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, it is unknown the prognostic impact of systemic inflammation markers in patients with GEP-NETs treated with PRRT. Methods: We conducted an observational, retrospective, multicentric study of 40 patients with GEP-NET treated with PRRT belonging to GGNET (Galician Research Group on Neuroendocrine Tumors) network at Nuclear Medicine Department of Santiago de Compostela University Hospital (Spain). The systemic inflammatory markers were calculated as follows: NLR = neutrophil count/lymphocyte count, PLR = platelet count/lymphocyte count, MLR= monocyte count/lymphocyte count, ALB= albumin levels and dNLR = neutrophil count/ (leucocytes count – neutrophils count). For the calculation of the different ratios, baseline analysis and after the second dose were used. The cut-off values were determined as the median of each values, correlating them with progression-free survival (PFS). Results: Data from 40 patients (pts) treated between 2016 and 2020 were recorded. Median age was 63.5 years (range 41-85) and 55% were male. Baseline ECOG PS 0/1/2 was 15 (37.5%)/16 (40%)/9 (22.5%). Tumor location was intestinal 26 pts (65%), pancreas 11 pts (27.5%) and unknown origin 3 pts (7.5%). 15 pts (37.5%) were functioning. Tumor grade G1/G2/G3 were 17 pts (42.5%)/ 20 pts (50%)/ 3 pts (7.5%), and Ki 67 20%/unknown were 11 pts (27.5%)/ 21 pts (52.5%)/ 3 pts (7.5%)/ 5 pts (12.5%), respectively. The most frequent site of metastasis was liver 32 pts (80%), lymph nodes 19 pts (47.5%), peritoneum 11 pts (27.5%) and bone 10 pts (25%). Surgery: 22 pts (55%) primary tumor surgery and 8 pts (20%) metastasectomy. Previous systemic treatments included somatostatin analogs (SSA) 40 pts (100%), everolimus 26 pts (65%) and sunitnib 11 pts (27.5%), others 7 pts (17.5%). The baseline cutoff-values for NLR was 2.61, for PLR 110.14, for MLR 0.31, for ALB 4.2. and for dNLR 1.71. The cutoff-values after the 2nd dose for NLR was 2.3, for PLR 2.15, for MLR 0.3, for ALB 4.2 and for dNLR 1.48. With a median follow up of 21 months, 14 pts (35%) had died. Median PFS was 27.2 m (95% CI 16.0-38.4m) and OS was not reached (NR). Pts with baseline higher NLR (>2.61 vs. 1.71 vs.

e13061 Background: Smoking is the leading cause of avoidable death in the world. Although controversial for years, current prospective studies suggest that smoking increases the risk of cancer in women with a deleterious BRCA1/2 mutation. Actually, we have very limited information about tobacco habit among BRCA1/2 carriers. Methods: We report an observational retrospective study of a consecutive sample of 198 BRCA1/2 carriers studied between April 2014 and March 2018 at the Family Cancer Clinic of the University Hospital of Coruña (NW-Spain). The main objective of the study is to know the prevalence of smoking in BRCA1/2 women, and to determine if carriers undergoing risk-reducing surgeries (RRS) abandon their tobacco habit as part of the primary prevention strategy. Results: The sample includes 136 patients affected by cancer (84% breast, 19% ovary) and 62 healthy women. During their follow-up [Median = 22, (1-43) months], 85 carriers underwent RRS (29% mammary, 54% prophylactic salpingo-oophorectomy, 16% both). At first visit, 46 were active smokers, 47 ex-smokers, 77 non-smokers and 28 did not specify their habit. The percentage of smokers and never smokers is similar between sick and healthy BRCA1/2 carriers, presenting a greater proportion of former smokers among those affected of cancer (30% vs. 23%), and of active smokers among healthy women (35% vs. 23%) [p > 0.5)]. Moreover, 23% of BRCA1/2 carriers are active smokers despite a previous diagnosis of cancer. RRS are not associated to a greater tobacco cessation, persisting in the habit 18% of the women that underwent any preventive surgery (p > 0.5). Conclusions: Smoking habit is high (55%) among BRCA1/2 carriers followed at our family cancer clinic. At least 23% of our BRCA1/2 positive women are active smokers despite a previous diagnosis of cancer.The performance of aggressive RRS is not associated with greater abandonment of tobacco in carriers, persisting in the smoking habit 18% of operated women.It is essential to improve anti-tobacco strategies in family cancer consultations if we want to be efficient in the management of high-risk cancer individuals.

12043Background: The determination of monitoring Circulating Tumor Cells (CTC) in patients (pts) with metastatic breast cancer (MBC) is a well-established prognostic marker of efficacy/tolerance. W...

468 Background: Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in genitourinary tumors (GT). The aim of this work was identify aberrantly expressed miRNAs potentially useful for CTC detection in blood samples from patients with GT to assess their potential clinical significance, and to gain a greater understanding of the mechanisms driving tumor progression. Methods: We examined blood levels of 92 microRNAs in 113 metastatic patients: prostate (mP), renal cell carcinoma (mRCC), bladder tumors (mB) and healthy volunteers (HV) (N=18) using SYBR-green-based microRNA RT-qPCR arrays (Exiqon). Array design was made by literature review and bioinformatics approach using free databases. Relative Expression Software Tool (REST) and SPPS 21.0 were used to data processing and analysis. Results: microRNAs differential expressed between tumors and HV (only up-regulated miRNAs are shown in Table). Conclusions: microRNAs in the circulation are relatively stable, very accessible, low invasive and easily testable biomarkers. These results suggest that our bioinformatic approach is an useful high-throughput method to identified tumors-associated miRNAs. The selected miRNAs should be further evaluated for their potential as markers for CTC detection, prognosis and therapeutic outcome. Further studies of precision and sensitivity on these markers in this GT population will clarify its role as novel stable blood-based markers. [Table: see text]

451 Background: Renal cell carcinoma (RCC) is known to be resistant to chemotherapy. There is need for the identification of biomarkers capable to determine RCC prognosis factors and metastatic potential obtainable from non-invasive or minimally invasive techniques. Our aim was to derive predictive models which could predict more accurately than any one factor alone. Methods: To studythe cascade of events leading to the formation and progression of RCC, we assessed 29 markers by immunohistochemistry and qRT-PCR using tissue micro-array (TMA). Results: Multivariate logistic regression showed the best proteins combination for node status (NOTCH1 and GLUT5) and pelvis invasion (EGFR and DLL3). ROC curve analyses were made to analyse the accuracy of the best candidate proteins; it should be noted NOTCH1 and GLUT5 for node status prediction (AUC=0.833, 95% CI, 0.744-0.922; p

e22171 Background: We previously have studied differentially microRNA expression levels related to hormone refractory and sensitive prostate cancer cell lines (VCap and LNCap respectively). Now, we investigated circulating miRNAs differentially expressed between metastatic prostate adenocarcinomas (mPA) and healthy controls (HC) that may serve as novel diagnostic and/or prognosis markers. Methods: Using SYBR-green-based custom microRNA RT-qPCR arrays technology (Exiqon), we compared the expression levels of miRNAs in blood samples from 18 HC and 48 mPA. Results: Among a panel of 92 candidates we found 41 underexpressed (UE) and 8 overexpressed (OE) miRNAs. The level of significance was p

e15542 Background: Renal cell carcinoma (RCC) is known to be resistant to chemotherapy. The need for the identification of biomarkers capable of determining RCC prognosis factors and metastatic potential that are obtainable from non-invasive or minimally invasive techniques are desirable. The purpose from this analysis was to derive predictive models which could predict more accurately than any one factor alone. Methods: By tissue micro-array (TMA) technology we assessed 29 markers involved in the cascade of events leading to the formation and progression of this disease. The ability of multivariate logistic regression to improve the diagnostic accuracy for RCC by combining determinations of proteins markers and pathological variables was evaluated. Univariate analysis was used to select factors (p

e15076 Background: The characterization of factors involved in the etiology of renal cell carcinoma (RCC) may lead to the identification of new targets for therapy and prognostic markers. Recent data indicate that Notch family members can be expressed by malignant RCC cells and this expression may have potential use as a strong prognostic factor. The aim of this study was to investigate the potential of Notch family members as prognostic markers for stage IV patients. Methods: We analyzed, by means of immunohistochemistry and quantitative polymerase chain reaction, protein and mRNA levels of 4 Notch family members in tumor specimens obtained from 48 patients with stage IV RCC. Clinicopathological data for these patients were evaluated. A 34% of the population had hypertension, 7.3% had hypothyroidism, 19.5% were diabetic, 7.7% prediabetic, and 22% showed hyperlipidemia. RCC specimens included clear cell RCC: 34; papillary: 3; mixed: 1; undifferentiated: 1; hypernephroma: 1.The association among biomarkers and clinicopathological factors were explored using One-Way ANOVA test and non-parametric statistics, Mann-Whitney U and Kruskal-Wallis tests. Results: Relative expression of Nocth3 and Notch4 transcript levels were elevated 25-fold in clear cell RCC tumors when compared with normal kidney tissues. Notch1 and Notch2 were overexpressed at protein level in clear cell RCC (p>0.05). Those renal tumors with right localization showed highest levels of Notch4 protein (p=0.096). Notch2 overexpression was associated with patients who had undergone nefrectomy (p=0.038). Finally, Bonferroni post-hoc statistic test showed us a statistically significant association (p = 0.020) between Nocth1 protein expression levels and patients with medium risk prognosis. Conclusions: These results show a deregulated expression of Notch receptors in RCC and suggest a role for this pathway in the progression of this tumoral pathology.

e15079 Background: Many studies have demonstrated genetic and environmental factors lead to renal cell carcinoma (RCC) occurring during a protracted period of tumorigenesis. It seemed suitable identify and characterize potential molecular markers appearing during of tumorigenesis which might provide rapid and effective possibilities for early detection of RCC. Methods: We assessed using quantitative real-time PCR (qPCR) the profile of 32 markers involved in the cascade of events leading to the formation and progression of RCC: invasiveness, angiogenesis and antiapoptotic mechanisms. RNA of quality was obtained in 90% of samples (N=80, 64/80 clear RCC, 8/80 papillary RCC and 8/80 chromophobe RCC) to carry out the study of gene expression. Nonparametric tests (Pearson's correlation coefficient test and Spearman's rho test, Kruskal — Wallis and Mann — Whitney) and Bonferroni post-hoc test were applied for statistical data analysis. Additionally, a knowledgebase of biological pathways, Reactome, was used to superimpose our quantitative expression data. Results: Statistical analysis comparing medians and means showed the following candidates as the best gene predictors related to different pathological variables (histological type, number of involved nodes, renal pelvis invasion, lymphatic vessels invasion and rupture of the renal capsule): Hif1-α (p

405 Background: MicroRNAs (miRNAs), a class of small RNAs, have been intensely investigated recently because of their important regulatory role in gene expression. Circulating miARNs are potential biomarkers for cancer not only abundant in blood, but also very stable, which are important prerequisites as clinical biomarkers. Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in genitourinary renal tumors. The aim of this work is identify miRNAs potentially useful for CTC detection in blood samples from patients with renal tumors to assess their potential clinical significance. Methods: We examined blood levels of three miRNAs, let-7c, miR-200c and miR-31 in 48 patients with renal tumors with locally advanced or metastatic disease and 18 healthy persons using quantitative real-time PCR. The clinicopathologic characteristics of the population under consideration include among other: sex, age, tumor location, histological type, Fuhrman grade, tumor size, number of involved nodes, tumor stage, time to progression and overall survival. Results: We found that the median levels of miRNAs, let-7c, miR-200c and miR-31 were significantly higher in patients with renal tumors than those in healthy controls (p=.002, p=.000 and p=.004, respectively). Receiver-operator characteristic (ROC) curve analyses indicate that these blood miRNAs may be useful markers for discriminating patients with renal tumors from healthy controls (AUC=.750, AUC=.853 and AUC=.738, respectively). Conclusions: miRNAs in the circulation are relatively stable, very accessible, low invasive and easily testable biomarkers. Our results suggest let-7c, miR-200c and miR-31 as novel stable blood-based markers for renal cancer detection. This work was supported by Grants PI07/0477 from Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III.S. Díaz Prado is supported by an Isidro Parga Pondal research contract by Xunta de Galicia (A Coruña, Galicia, Spain). Cancer research in our laboratory is supported by the “Fundación do CHU A Coruña”.

We present a patient with severe idiopathic aplastic anemia with no previous chromosomal abnormalities who developed trisomy 21 and monosomy 7 during treatment with intravenous (i.v.) cyclosporine. The abnormal karyotype disappeared when the drug was changed to the oral form. This cytogenetic aberration, previously unreported in association with cyclosporine, may reflect either a direct drug effect or the emergence of a hidden myelodysplastic cell clone subject to preferential survival during immunosuppression.

Cytogenetic studies of the peripheral blood and marrow of a patient with chronic granulocytic leukemia in blastic transformation revealed the following abnormalities: 1) a Philadelphia chromosome with the usual 9:22 translocation; 2) a three break rearrangement (insertion) of chromosome #11; and 3) a deletion of the short arm in chromosome #16. Clinical and hematologic remission developed after three courses of intermittent chemotherapy with transient but complete bone marrow aplasia. Studies performed during remission revealed two cellular clones. One had the same karyotype already described and the second showed only a Ph1 chromosome. We postulate that the pretreatment clone evolved from Ph1-positive cells in this patient with chronic granulocytic leukemia during a short, undiagnosed stable phase. Treatment allowed the reappearance of the Ph1-positive clone. The second abnormal clone was apparently partially eradicated but normal cells did not repopulate the bone marrow, suggesting that either the Ph1-positive cells were greatly resistant to therapy or that there were no remaining normal myelogenous stem cells. In addition, we found that there have been few reports of abnormalities involving chromosomes #11 and #16, and that an inserting chromosome #11 has never been reported.

Herein we give clinical support to the theory of a common origin of multiple endocrine adenomatosis. Accurate clinical evaluation of a patient suspected to have endocrine neoplasia requires the search for a much wider range of potential endocrine tumors. Such an approach is now made possible by the radioimmunoassay. Chromosome patterns and histocompatibility antigens are reviewed in a family with the disease.