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Systemic mastocytosis (SM) is a myeloid neoplasm characterized by abnormal growth and accumulation of neoplastic mast cells in at least one extracutaneous site. Clinical presentation and course are variable, most patients are developing an indolent disease and some, an aggressive/leukemic form. Because of its rarity, most physicians are unfamiliar with this disease and do not readily diagnose it. In the present retrospective study, the authors describe 12 patients diagnosed with mast cell neoplasm. Cases were selected from three institutions from Campinas and São Paulo City, Brazil. Morphological features and diagnostic pitfalls are emphasized. Patients' age ranged from 15 to 81 years (mean 51.6 years). Male and female were affected similarly (1:1). Ten patients were classified as aggressive SM, one patient as SM with an associated acute promyelocytic leukemia with t(15;17), and one patient with mast cell sarcoma. The most common clinical findings included anemia (9 patients), thrombocytopenia (3 patients), and skin lesions (3 patients). Bone marrow was involved in 11 patients at diagnosis, followed by skin (5 patients). Five morphological patterns were present: mast cell aggregates (5), plasmacytoid (4), monocytoid (2), spindle cell (2), and epithelioid/pleomorphic (1); two patients showed two histological patterns. In all cases, neoplastic cells were positive for CD117/C-KIT. C-KIT D816V mutation was present in four patients, C-KIT K509I in two, and del(7q22) in one; in five cases no mutational status was available. Despite limited resources, basically morphology and a restricted immunohistochemical panel, it is possible to diagnose mast cell neoplasm. Of note, the pathologist should recognize the different morphological variants of the disease and include adequate markers when requesting immunohistochemical studies.

Extracellular matrix (ECM) represents more than a mere intercellular cement. It is physiologically active in cell communication, adhesion and proliferation. Collagen is the most abundant protein, making up to 90% of ECM, and 30% of total protein weight in humans. Second-harmonic generation (SHG) microscopy represents an important tool to study collagen organization of ECM in freshly unfixed tissues and paraffin-embedded tissue samples. This manuscript aims to review some of the applications of SHG microscopy in Oncologic Pathology, mainly in the study of ECM of epithelial tumors. It is shown how collagen parameters measured by this technique can aid in the differential diagnosis and in prognostic stratification. There is a tendency to associate higher amount, lower organization and higher linearity of collagen fibers with tumor progression and metastasizing. These represent complex processes, in which matrix remodeling plays a central role, together with cancer cell genetic modifications. Integration of studies on cancer cell biology and ECM are highly advantageous to give us a more complete picture of these processes. As microscopic techniques provide topographic information allied with biologic characteristics of tissue components, they represent important tools for a more complete understanding of cancer progression. In this context, SHG has provided significant insights in human tumor specimens, readily available for Pathologists.

The extracellular matrix plays an important role in cellular balance, and collagen fibers are its most important component. Over the last few years, second harmonic generation (SHG) microscopy has been used for the analysis of collagen fibers in several types of gynaecological cancers, such as breast and ovarian cancer. The value of collagen parameters obtained with this technique to gain insights on the physiopathology and on the prognostic evaluation of cancer has been advocated. Herein, we have characterized the collagen fibers in squamous cell carcinoma (VSCC) and preneoplastic lesions using the SHG microscopy. Collagen parameters, quantity, organization, and uniformity, of VSCC, adjacent skin of VSCC or preneoplastic lesions were compared with values obtained in normal tissue of healthy control. There was an evident decrease in the values of collagen fiber parameters in the VSCC. Increased quantity and uniformity of tumor associated collagen fibers were associated with the presence of lymph node metastases, which suggest a prognostic value of such parameters in the evaluation of vulvar cancer.

Background Breast cancer outcomes among patients who use safety-net hospitals in the highly populated Harris County, Texas and Southeast Brazil are poor. It is unknown whether treatment delay contributes to these outcomes. Methods We conducted a retrospective cohort analysis of patients with non-metastatic breast cancer diagnosed between January 1, 2009 and December 31, 2011 at Harris Health Texas and Unicamp’s Women’s Hospital, Barretos Hospital, and Brazilian National Institute of Cancer, Brazil. We used Cox proportional hazards regression to evaluate association of time to treatment and risk of recurrence (ROR) or death. Results One thousand one hundred ninety-one patients were included. Women in Brazil were more frequently diagnosed with stage III disease (32.3% vs. 21.1% Texas; P = .002). Majority of patients in both populations had symptom-detected disease (63% in Brazil vs. 59% in Texas). Recurrence within 5 years from diagnosis was similar 21% versus 23%. Median time from diagnosis to first treatment defined as either systemic therapy (chemotherapy or endocrine therapy) or surgery, were comparable, 9.9 weeks versus 9.4 weeks. Treatment delay was not associated with increased ROR or death. Higher stage at diagnosis was associated with both increased ROR and death. Conclusion Time from symptoms to treatment was considerably long in both populations. Treatment delay did not affect outcomes. Impact Access to timely screening and diagnosis of breast cancer are priorities in these populations.

// Luis Felipe Sallum 1 , Liliana Andrade 2 , Susana Ramalho 1 , Amanda Canato Ferracini 3 , Rodrigo de Andrade Natal 4 , Angelo Borsarelli Carvalho Brito 5 , Luis Otavio Sarian 1 and Sophie Derchain 1 1 Department of Obstetrics and Gynecology, State University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, Sao Paulo, Brazil 2 Department of Pathology, University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, Sao Paulo, Brazil 3 Program in Medical Sciences, State University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, Sao Paulo, Brazil 4 Laboratory of Investigative and Molecular Pathology, State University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, Sao Paulo, Brazil 5 Laboratory of Cancer Genetics, State University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, Sao Paulo, Brazil Correspondence to: Sophie Derchain, email: fsallum@unicamp.br Keywords: cystadenocarcinoma; serous; diagnoses; survival; prognosis; Pathology Received: September 28, 2017 Accepted: February 12, 2018 Epub: February 19, 2018 Published: March 23, 2018 ABSTRACT Objective: To evaluate the diagnostic and prognostic value of the immunohistochemical expression of WT1, p53 and p16 in low- (LGSOCs) and high-grade serous ovarian carcinomas (HGSOCs). Results: HGSOC had a significantly higher proportion of advanced stage disease, higher CA125 levels, higher proportion of post-surgery residual disease and higher recurrence or disease progression. WT1 was expressed in 71.4% of LGSOCs and in 57.1% of HGSOCs ( p = 0.32). Focal and/or complete absence of p53 expression with negative p16 expression was found in 90.5% of LGSOCs, in contrast to the 88.1% of HGSOCs with diffuse or complete absence of p53 expression with positive p16 expression (

The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II – versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II – versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.

The objective of this study is to characterize arterial tissue with and without atherosclerosis by fluorescence lifetime imaging microscopy (FLIM) using Europium Chlortetracycline complex (EuCTc) as fluorescent marker. For this study, twelve rabbits were randomly divided into a control group (CG) and an experimental group (EG), where they were fed a normal and hypercholesterolemic diet, respectively, and were treated for 60 days. Cryosections of the aortic arch specimens were cut in a vertical plane, mounted on glass slides, and stained with Europium (Eu), Chlortetracycline (CTc), Europium Chlortetracycline (EuCTc), and Europium Chlortetracycline Magnesium (EuCTcMg) solutions. FLIM images were obtained with excitation at 405 nm. The average autofluorescence lifetime within plaque depositions was ~1.36 ns. Reduced plaque autofluorescence lifetimes of 0.23 and 0.31 ns were observed on incubation with EuCTc and EuCTcMg respectively. It was observed a quenching of collagen, cholesterol and TG emission spectra increasing EuCTc concentration. The drastic reduction in fluorescence lifetimes is due to a resonant energy transfer between collagen, triglycerides, cholesterol and europium complexes, quenching fluorescence.

One of the promising tools to evaluate collagen in the extracellular matrix is the second-harmonic generation microscopy (SHG). This approach may shed light on the biological behavior of cancers and their taxonomy, but has not yet been applied to characterize collagen fibers in cases diagnosed as invasive breast carcinoma (BC) of histological special types (IBC-ST). Tissue sections from 99 patients with IBC-ST and 21 of invasive breast carcinoma of no special type (IBC-NST) were submitted to evaluation of collagen parameters by SHG. Tissue microarray was performed to evaluate immunohistochemical-based molecular subtype. In intratumoral areas, fSHG and bSHG (forward-SHG and backward-SHG) collagen parameters achieved their lowest values in mucinous, papillary and medullary carcinomas, whereas the highest values were found in classic invasive lobular and tubular carcinomas. Unsupervised hierarchical cluster analysis and minimal spanning tree using intratumoral collagen parameters allowed the identification of three main groups of breast cancer: group A (classic invasive lobular and tubular carcinomas); group B (IBC-NST, metaplastic, invasive apocrine and micropapillary carcinomas); and group C (medullary, mucinous and papillary carcinomas). Our findings provide further characterization of the tumor microenvironment of IBC-ST. This understanding may add information to build more consistent tumor categorization and to refine prognostication.

Second-harmonic generation microscopy represents an important tool to evaluate extracellular matrix collagen structure, which undergoes changes during cancer progression. Thus, it is potentially relevant to assess breast cancer development. We propose the use of second-harmonic generation images of tumor stroma selected on hematoxylin and eosin–stained slides to evaluate the prognostic value of collagen fibers analyses in peri and intratumoral areas in patients diagnosed with invasive ductal breast carcinoma. Quantitative analyses of collagen parameters were performed using ImageJ software. These parameters presented significantly higher values in peri than in intratumoral areas. Higher intratumoral collagen uniformity was associated with high pathological stages and with the presence of axillary lymph node metastasis. In patients with immunohistochemistry-based luminal subtype, higher intratumoral collagen uniformity and quantity were independently associated with poorer relapse-free and overall survival, respectively. A multivariate response recursive partitioning model determined 12.857 and 11.894 as the best cut-offs for intratumoral collagen quantity and uniformity, respectively. These values have shown high sensitivity and specificity to differentiate distinct outcomes. Values of intratumoral collagen quantity and uniformity exceeding the cut-offs were strongly associated with poorer relapse-free and overall survival. Our findings support a promising prognostic value of quantitative evaluation of intratumoral collagen by second-harmonic generation imaging mainly in the luminal subtype breast cancer.

ObjectiveThe purpose of this study was to compare the immunohistochemical expression of BRCA1, Ki67, and β-catenin in women with low-grade (LGSOC) and high-grade serous ovarian carcinomas (HGSOC) and their relationship with clinicopathological features, response to platinum-based chemotherapy, and survival.MethodsFor this study, 21 LGSOC and 85 HGSOC stage I to IV cases, diagnosed and treated from 1996 to 2013 and followed-up until December 2016, were included. BRCA1, Ki67, and β-catenin expression was assessed using tissue microarray-based immunohistochemistry.ResultsWomen with HGSOC were significantly more likely to have advanced-stage disease (P < 0.001), higher CA125 levels (P < 0.001), postsurgery residual disease (P < 0.01), and higher rates of disease progression and recurrence (P = 0.001). The percentage of women with HGSOC whose tumors expressed Ki67 was significantly higher compared with women with LGSOC (P < 0.001). The expression of BRCA1 and β-catenin did not differ between LGSOC and HGSOC (P = 0.12 and P = 1.00, respectively). The clinicopathological features and the response to platinum-based chemotherapy did not differ according to the BRCA1, Ki67, and β-catenin expression in either group. In HGSOC, only International Federation of Gynecology and Obstetrics stage was independently associated with poor survival (PFS and OS).ConclusionsKi67 expression was significantly higher in HGSOC. BRCA1 and β-catenin expression did not differ between LGSOC and HGSOC samples. BRCA1, Ki67, and β-catenin expression was neither related to clinicopathological features, response to platinum-based chemotherapy, nor survival. Only International Federation of Gynecology and Obstetrics stage remained associated with poor survival in women with HGSOC.

Background Mucinous breast carcinoma is characterized by the production of variable amounts of mucin. Some studies have addressed immunohistochemical characterization of mucinous breast carcinoma using a limited set of antibodies. However, the purpose of the present study was to investigate a larger panel of markers not widely used in daily practice and to determine their pathological implications. Methods Forty patients diagnosed with mucinous breast carcinoma were enrolled. An immunohistochemical study was performed on whole sections of paraffin embedded tissue, using antibodies for the following markers: estrogen receptor alpha and beta, progesterone receptor, androgen receptor, HER2, EGFR, Ki-67, E-cadherin, β-catenin, p53, chromogranin, synaptophysin, GCDFP15, mammaglobin, and CDX2. Results The pure mucinous type was more prevalent in older patients and more frequently expressed GCDFP15. Capella type B presented more frequently with a high Ki-67 index and neuroendocrine differentiation. Although there was a lower frequency of vascular invasion and lymph node metastases in the pure type, the difference was not statistically significant. No case expressed CDX2 (a marker for gastrointestinal tumors), while 85% of the cases expressed at least one of the two typical breast markers (GCDFP15 and mammaglobin), suggesting that these markers may be reliably used for differential diagnosis. Expression of estrogen receptor beta was related to the presence of mucin cell producing lymph node metastasis, with potential prognostic and predictive value. Conclusion our findings support the immunohistochemical homogeneity of mucinous breast carcinomas because only minor differences were found when subgrouping them into Capella types A and B or into types pure and mixed.

Introduction: In breast cancer (BC), desmoplastic reaction, assembled primarily by fibroblasts, is associated with unfavorable prognosis, but the reason of this fact remains still unclear. In this context, nonlinear optics microscopy, including Fluorescence Lifetime Imaging Microscopy (FLIM), has provided advancement in cellular metabolism research. In this paper, our purpose is to differentiate BC cells metabolism with or without contact to desmoplastic reaction. Formalin fixed, paraffin embedded samples were used at different points of hematoxylin stained sections. Methodology: Sections from 14 patients with invasive ductal breast carcinoma were analyzed with FLIM methodology to NAD(P)H and FAD fluorescence lifetime on a Confocal Upright LSM780 NLO device (Carl Zeiss AG, Germany). Quantification of the fluorescence lifetime and fluorescence intensity was evaluated by SPC Image software (Becker H p< 0.05 was considered significant. Results: BC cells in contact with desmoplastic reaction presented a significantly lower NAD(P)H and FAD fluorescence lifetime. Furthermore, optical redox ratio was also lower in these tumor cells. Conclusion: Our results suggest that contact of BC cells with desmoplastic reaction increase their metabolic activity, which might explain the adverse prognosis of cases associated with higher peritumoral desmoplastic reaction.

Introduction: High-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease with high mortality. Initially most women respond to platinum chemotherapy, but rapidly many become resistant to the drug and progress to relapse and death. Better knowledge of the pathways responsible for the mechanisms of invasion and metastasis in women with HGSOC may help in the identification of prognostic biomarkers and in the development of new target therapies. The epithelial-mesenchymal transition (EMT) is an important cellular process related to invasion and metastasis. Some protein components such as the receptor tyrosine kinase, discoidin domain receptor 2 (DDR2), acting on the signal-regulated kinase 1/2 (ERK1/2) extracellular pathway, and the transcriptional co-activator yes-associated protein (YAP), acting in Hippo, are associated with EMT. In such pathways, microRNAs, such as miR-182, miR-96, and miR-9 are described as post-transcriptional regulators. Objective: To evaluate the expression of DDR2, YAP and miR-182, miR-96 and miR-9 in formalin-fixed, paraffin-embedded blocks with HGSOC, and its association with clinical, tumor, platinum response, and survival characteristics. Methods: 63 women with HGSOC stages III and IV, who underwent platinum chemotherapy from 1996 until 2013, followed up until 2016 at the Women's Hospital Prof. Dr. José Aristodemo Pinotti, Brazil, were included. All women had paraffin blocks and complete clinical data on the chart. DDR2 and YAP expression were assessed by immunohistochemistry on tissue microarray (TMA) slides and the microRNAs were evaluated by real-time polymerase chain reaction (rtPCR). For the comparison of DDR2 and YAP expression with age, CA125 serum level, post-surgery residual stage disease, and platinum response, Mann-Whitney and Fisher tests were used. Progression-free survival (PFS) and overall survival (OS) were calculated by Cox regression. The PFS and OS curves were estimated by the Kaplan-Meier method and compared by the Log-Rank test. Expression of miR and DDR2 and YAP levels were compared by the t-test. Results: DDR2 expression was high in 8 (13.7%) women. There was no association between DDR2 expression and age, stage, CA125, residual post-surgery disease, and response to platinum-based chemotherapy. PFS was significantly worse in women whose tumors had high DDR2 expression (p=0.03), but not OS (p=0.49). MiR-182 level expression was lower in the group with high DDR2 expression (p Conclusions: Low levels of miR-182 expression were associated with high expression of DDR2, which was associated with poorer DFS. These findings suggest that the ERK1/2 signaling pathway was relevant to the EMT of these HGSOCs. The role of Hippo remained indeterminate. Citation Format: Susana Oliveira Ramalho, Luis Otávio Sarian, Rodrigo Natal, Liliana Andrade, Amanda Ferracini, Marina Pavanello, Cassio Cardoso Filho, Sophie Derchain. Prognostic evaluation of components associated with epithelium-mesenchymal transition in women with serous carcinoma of high ovary grade [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B16.

Introduction: Second-Harmonic Generation microscopy (SHG) has provided progresses in extracellular matrix research, mainly regarding automated analysis of collagen fibers. Nodular sclerosis-classical Hodgkin lymphoma (NS) often has a rich collagen deposition, which remains poorly explored in its biological significance and potential prognostic role. The aim of this study was to characterize the collagen component of NS using SHG, and to investigate its clinical value. Methods: Hematoxylin and eosin stained slides from 53 consecutive samples of paraffin embedded NS tissue were analyzed by SHG imaging in an Inverted Zeiss LSM 780-NLO. HIV-positive individuals were excluded. For comparative purposes, 11 reactive lymph nodes (RL) were also randomly selected. In each slide, 3 capsular areas and 3 sclerotic regions (perinodular septa - PS - in NS and fibrotic foci around germinal centers in RL) were chosen. Collagen near blood vessels was not considered. We evaluated quantity, uniformity and organization of the fibers with ImageJ and OrientationJ plug-in in 4 hotspots from each image. Shapiro-Wilk test was used to assess data normality, while t-tests and Pearson correlations were performed to analyze collagen parameters between two groups. Overall survival (OS) was defined as time from diagnosis until death from the disease or last follow-up. Event-free survival (EFS) was set as time from diagnosis until progressive disease, death from the disease or last follow-up. Collagen data were used in survival analyses as continuous variables (in Cox-hazards model) or categorical ones (by choosing the mean value as a threshold for Kaplan-Meier curves and log-rank test). Significance was set at p Results: NS patients were mostly female (58.5%). The mean and median values of age at diagnosis were, respectively, 33 and 29 years (range: 14-82 years). Forty-two patients (79.2%) had B-symptoms, while bulky disease was seen in 23 cases (43.3%). Bone marrow was infiltrated in 4 patients (7.5%). Based on the International Prognostic Score (IPS), patients were stratified as follows: 39 (73.5%) as low-risk (IPS ≤ 3) and 14 (26.5%) as high-risk (IPS > 3). The first-line treatment was ABVD in 40 cases (75.5%) and BEACOPP in 13 patients (24.5%). Radiotherapy was performed in 27 (50.9%) patients. Tumor PS presented more dense (p The presence of high-risk IPS was associated with a shorter EFS (p=0.002), but had no relationship to OS. Collagen parameters had no impact on EFS. However, in univariate Cox regression, higher collagen quantity (p=0.04) in PS was the only factor associated with a worse OS. When only high-risk IPS cases were analyzed in Cox regression model, PS collagen had association with unfavorable OS regarding higher collagen quantity (p=0.03) and uniformity (p Conclusion: Collagen parameters in NS have distinct features than in RL and affect clinical presentation of the tumor. Moreover, collagen quantity and uniformity in cases with high-risk IPS were associated with survival, which indicates that incorporation of collagen information might be relevant in the prognostication of NS. Figure 1. Survival curve of high-risk patients (n=14) stratified according to the perinodular collagen (pCOL) quantity threshold. Figure 1. Survival curve of high-risk patients (n=14) stratified according to the perinodular collagen (pCOL) quantity threshold. Disclosures No relevant conflicts of interest to declare.

Introduction: Follicular lymphoma (FL) is the second most prevalent non-Hodgkin lymphoma worldwide, and is characterized by an indolent course and frequent relapses. Better understanding of FL has shown that angiogenesis (AG) has an important role in its progression to a more aggressive form. The most important mediator of AG is the vascular endothelial growth factor (VEGF), which is encoded by a polymorphic gene. It is already known that allele C of the VEGF 2578C/A polymorphism (rs699947) is related to higher serum concentration of VEGF compared to the A allele. The roles of this genetic polymorphism in clinical manifestations and outcome of FL are still unknown, and therefore these were the aims of the present study. Methods: Our analysis included 86 consecutive FL patients seen at diagnosis at the university hospital. The patients were treated with 6 to 8 cicles of R-CHOP. The clinical data of these patients were obtained from medical records. Genomic DNA was extracted from peripheral blood samples, and genotyping of the VEGF -2578C/A (rs699947) polymorphism was performed with real-time qPCR. Overall-survival (OS) was defined as time from diagnosis until death from any cause or last follow-up. The differences between groups were analyzed by the logistic regression model. Kaplan-Meier and log-rank analyses were used to assess survival information from the patients’ data. Furthermore, we examined survival data using univariate Cox proportional hazards regression, with the respective hazard ratios (HR) and 95% Confidence Intervals (CIs). Adjustement of Cox regression for clinical features was also performed. A p-value smaller than 0.05 was used to denote statistical significance. Results: The FL patients had a mean age of 56.2 years at diagnosis. The majority of the patients were caucasians (87.6%), and there was an equivalent distribution between genders: 43 male and 43 female patients (50% each). Thirty-nine (45.3%) patients had B-symptoms and 48 (54.7%) had no B-symptoms at diagnosis. Sixty-three (73.2%) patients presented at diagnosis with tumors of III or IV Ann Arbor stage, and 30 (34.8%) had bone marrow infiltration. Follicular Lymphoma International Prognostic Index (FLIPI) was assessed and patients were classified as follows: low-risk FLIPI (≤ 1 point) was seen in 34 cases (39.5%), medium-risk FLIPI (2 points) in 28 cases (32.5%), and high-risk FLIPI ( ≥ 3 points) was seen in 24 patients (27.9%). The VEGF 2578CC genotype was more common in patients with B-symptoms at diagnosis than in those without B-symptoms (51.2% versus 29.7%, p=0.04). The frequency of VEGF 2578CC genotype was also higher in patients with high-risk FLIPI than in those with medium and low-risk FLIPI (58.3% versus 32.2%, p=0.03). We found no association between genotypes and bone marrow infiltration at diagnosis. Considering clinical course of the patients, Kaplan Meier curves of OS showed that at 60 months of follow up, B-symptoms at diagnosis (65.2% of OS versus 87.1%, p=0.02), high-risk FLIPI (52.5% of OS versus 90%, p=0.002), and 2578CC genotype (62.1% of OS in 2578CC patients versus 89.4% in 2578CA plus 2578AA patients, p=0.01) had negative impacts on outcome. In univariate Cox analysis, presence of B-symptoms (p=0.03, HR=3.2, 95% CI: 1.09-9.38), high-risk FLIPI (p=0.01, HR= 3.91, 95% CI: 1.38-11.03) and 2578CC genotype (p=0.02, HR=3.70, 95% CI: 1.16-11.82) were also associated with a worse outcome. The prognostic role of the abovementioned polymorphism was still present after adjustment for age (p=0.04, HR=3.23, 95% CI:1.01-10.36) and Ann Arbor stage (p=0.02, HR=3.58, 95% CI:1.1-11.6) in univariate regression. After adjustment for FLIPI status as a whole, only a trend of association of 2578CC genotype with a worse outcome was found in the study (p=0.05, HR=3.24, 95% CI: 0.95-13.05). Conclusion: Our results present, for the first time, preliminary evidence that FL patients with the VEGF 2578CC genotype, related to higher production of VEGF, are more likely to develop aggressive form of the disease at diagnosis, and to succumb earlier to death. We recognize, however, that our study is based on a small sample size and that more numerous cohorts should be analyzed in order to assess additional associations. Also, further studies, such as correlations between relevant AG genes and tumor vascularization, should be done in order to clarify this issue in the context of FL. Disclosures No relevant conflicts of interest to declare.