Abstracts / 51 (2015) e1–e36
Background: We sought to study the diagnostic efficiency of an echodopplerography in the assessment of prevalence of tumoural invasion in patients with cancer of the stomach at a presurgical stage. Methods: The study included 32 patients with cancer of the stomach of various localisations. Findings: At the site of the stomach tumour, blood flow in the celiac artery was increased by 1.5 times in 23 (72%) patients. In the superior mesenteric artery, blood flow increased by 1.2 times in 18 (56%) patients and in the left gastric artery and splenic vein, blood flow increased by 1.3 times in 15 (47%) patients. This increase was accompanied by a tendency towards a decrease in the resistance index. In 15 (47%) patients, strengthened hypervascularisation of the affected stomach wall with involvement of all layers and a simultaneous decrease in blood flow in the main vessels was observed, indicative of germination of the tumoural process in the surrounding structures. Characteristic symptoms of stomach cancer included existence of an atypical vascularisation of various intensities in stomach and tumour walls at CDM (PD). Interpretation: Echodopplerography improves diagnostic efficiency and facilitates decision making regarding the operability of a stomach tumour and treatment planning.
http://dx.doi.org/10.1016/j.ejca.2015.06.085
P0145 S100A9, AN EARLY ORAL CANCER RECURRENCE MARKER, EXERTS A PRO-TUMOUR EFFECT THROUGH MYELOID CELL RECRUITMENT AND IL-6 PRODUCTION L.-W. Wu *, W.-Y. Fang, Y.-W. Chen, J.-R. Hsiao, C.-S. Liu, K.-C. Chang, Y.-Z. Kuo, S.-T. Tsai. National Cheng Kung University, Taiwan Background: S100A9 is a calcium-binding protein with two EF-hands that is frequently deregulated in several cancer types. Although several putative functions are proposed for S100A9, its biological role, particularly in oral cancer cells, remains elusive. Methods: The purpose of this study was to investigate the clinical impact of S100A9 deregulation in oral cancer, and the intracellular and extracellular role of S100A9 in oral cancer cells, endothelial cells, and monocytes. Findings: Immunohistochemical staining showed frequent S100A9 deregulation in both tumour cells and their stroma. High S100A9 expression in stroma was positively associated with not only poor differentiation and tumour recurrence but also reduced recurrence-free survival among early-stage oral cancer patients, suggesting a role of S100A9 in oral cancer recurrence. In addition to the enhancement of cell migration and invasion in vitro, ectopic S100A9 expression promoted xenograft tumorigenesis as well as myeloid cell accumulation and IL-6 production in these tumours. The increase of serum S100A9 was associated with the severity of several inflammatory disorders. We also detected a significant increase of serum S100A9 in early-stage but not late-stage oral cancer patients. Extracellular S100A9 protein enhanced monocyte transendothelial migration and angiogenic activity in addition to tumour cell invasion. Co-culture experiments showed that S100A9-mediated release of IL-6 requires the crosstalk of tumour cells with monocytes. Early-stage oral cancer patients with high S100A9 expression as well as high CD68+ immune cell infiltrates in tumour stroma had shortest recurrence-free survival, suggesting the possibility of using both S100A9 and CD68 as prognostic markers.
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Interpretation: Together, intracellular and extracellular S100A9 exerts a tumour-promoting role in oral carcinogenesis. Tumour-derived S100A9 depends on stromal cells to positively regulate IL-6 expression in orchestrating the composition of a pro-tumour growth microenvironment. Understanding the potential role of S100A9 in oral cancer and stromal cells should facilitate the development of new therapeutic approaches against oral cancer. http://dx.doi.org/10.1016/j.ejca.2015.06.086
P0154 AGE-RELATED DISPARITY IN IMMEDIATE PROGNOSIS OF PATIENTS WITH TRIPLE-NEGATIVE BREAST CANCER: A POPULATION-BASED STUDY FROM SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS (SEER) CANCER REGISTRIES W. Zhu a, E. Perez b, R. Hong a, Q. Li a, B. Xu a,*. a Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China, b Mayo Clinic, USA Background: Triple-negative breast cancer (TNBC) has been demonstrated to carry poor prognosis, but whether or not there exists any age-related variation in TNBC outcomes has yet to be elucidated. The current population-based study investigated the early survival pattern of elderly women with TNBC and identified outcome-correlated factors. Methods: We searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled female primary non-metastatic TNBC cases. The patients were subdivided into elderly (P70 years) and young groups (<70 years). The survival status of elderly patients was compared with that of the younger women. The primary and secondary endpoints were cancer-specific survival and overall survival, respectively. Findings: 9908 female TNBC patients diagnosed from 2010 to 2011 were included in the current study (20.4% elderly). Elderly patients exhibited distinctly worse overall (log-rank p < 0.001) and cancer-specific survival (log-rank p < 0.001) than their young counterparts. Advanced age at diagnosis (P70 years) was significantly predictive of poor outcome in terms of overall survival (hazard ratio 3.042; 95% CI 2.474–3.740; p < 0.001) and cancer-specific survival (hazard ratio 2.125; 95% CI 1.664–2.713; p < 0.001). Elderly patients with TNBC were less likely to receive radiation (odds ratio 0.678; 95% CI 0.609–0.754; p < 0.001) and showed a tendency for less surgery (OR 0.894; 95% CI 0.694–1.151; p = 0.384). Interpretation: Elderly patients with TNBC displayed higher early mortality within the first 2 years of diagnosis compared with younger individuals. The observed lower rate of loco-regional treatment might be associated with worse outcome for these patients. http://dx.doi.org/10.1016/j.ejca.2015.06.087
P0155 EFFECT OF PRETREATMENT ANAEMIA ON OUTCOMES OF CHINESE WOMEN WITH BREAST CANCER RECEIVING NEOADJUVANT CHEMOTHERAPY W. Zhu, B. Xu *. Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
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Abstracts / 51 (2015) e1–e36
Background: Anaemia related to adjuvant chemotherapy might predict worse survival in patients with breast cancer. The present population-based study investigated the effect of pretreatment anaemia on pathological response and long-term prognosis of breast cancer patients receiving neoadjuvant chemotherapy. Methods: From 1999 to 2011, 655 patients with operable or locally advanced breast cancer who underwent neoadjuvant chemotherapy before definitive surgery were reviewed. The patients were subdivided into anaemic (baseline haemoglobin [Hb] <12.0 g/dl) and non-anaemic (Hb P12.0 g/dl) groups. Comparison was made between anaemic and non-anaemic groups concerning the rate of pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). Logistic and Cox regression models were used to determine the predictive value of pretreatment anaemia in outcomes of patients undergoing neoadjuvant chemotherapy. Findings: 166 women (25.3%) were anaemic before treatment. Patients in the anaemic group were less likely to achieve pCR after neoadjuvant chemotherapy than their non-anaemic counterparts (odds ratio 0.428, 95% confidence interval (CI) 0.198–0.927, p = 0.031). Patients with baseline anaemia displayed inferior 10-year RFS (59.1% versus 66.0%, p = 0.022 by log-rank), OS (75.3% versus 90.9%, p < 0.001) and CSS (82.4% versus 94.4%, p < 0.001) compared with those without. Of note, when stratified by radiotherapy history, anaemia-related disparities in relapse and survival were maintained in patients undergoing radiotherapy rather than those who were not receiving such treatment. After adjustment for confounders, pretreatment anaemia was shown to correlate with elevated risk of relapse (hazard ratio 1.517, 95% CI 1.120–2.055, p = 0.007), cancer-specific mortality (hazard ratio 3.152, 95% CI 1.784–5.569, p < 0.001), and all-cause mortality (hazard ratio 2.886, 95% CI 1.766–4.716, p < 0.001). Interpretation: Pretreatment anaemia exerted a moderately adverse effect on pathological response to neoadjuvant chemotherapy as well as survival status in breast cancer. Further studies are warranted to optimise the treatment of cancer-related anaemia and improve the prognosis of this subgroup of patients. http://dx.doi.org/10.1016/j.ejca.2015.06.088
P0157 ROLE OF HERV-K NP9 PROTEIN TRANSACTIVATION IN AIDS-RELATED KAPOSI’S SARCOMA L. Dai a,b, Y. Cao a, Y. Chen a, C. Parsons b, Z. Qin a,b,*. a Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, USA, b East Hospital, Tongji University School of Medicine, China Background: Kaposi’s sarcoma-associated herpesvirus (KSHV) is the aetiological agent of Kaposi’s sarcoma, which preferentially arise in patients with AIDS. Although the introduction of combined antiretroviral therapy (cART) has dramatically reduced the incidence of Kaposi’s sarcoma, it remains a significant burden of morbidity and mortality in patients with AIDS. KSHV infection is necessary, but not sufficient to cause Kaposi’s sarcoma, indicating that microenvironmental factors are also required. Human endogenous retrovirus sequences (HERVs) constitute up to 8% of human genome and have resided in human genome for several million years. Interestingly, not all HERVs remain silent passengers; some, especially the HERV type K (HERV-K), have been found to be transactivated frequently in a variety of inflammatory diseases and human cancers. The HERV-K NP9 protein has been shown to be exclusively present in some tumours
and has the oncogenic functions via regulating multiple signalling pathways. However, the role of HERV-K NP9 transactivation in viral oncogenesis, in particular in Kaposi’s sarcoma, and the potential value as a therapeutic target remain unknown. Methods: We investigated the interaction between KSHV and HERV-K NP9. Findings: We found that KSHV de novo infection or ectopic expression of KSHV-encoded Latency-associated Nuclear Antigen (LANA) protein transactivate HERV-K NP9 from human primary endothelial cells (the major cellular components within Kaposi’s sarcoma). We noted a higher level of HERV-K transactivation in peripheral blood mononuclear cells (PBMCs) from our cohort of HIV-positive/KSHV-positive patients than those from HIV-positive/KSHV-negative patients. Abundant NP9 expression was noted in Kaposi’s sarcoma tissue collected from HIV-positive patients. Further data indicate that the transactivation of NP9 is responsible for cell invasiveness and anchorage-independent growth of KSHV-infected endothelial cells. Interpretation: Our data provide insights into the contribution of HERV-K NP9 transactivation to KSHV pathogenesis and tumorigenesis, and provide the framework for developing novel strategies targeting NP9 transactivation for improved treatment and/or prevention of Kaposi’s sarcoma in high-risk HIV-positive patients. http://dx.doi.org/10.1016/j.ejca.2015.06.089
P0158 TAI CHI CHUAN ENHANCES CYTOKINE EXPRESSION LEVELS AND PSYCHOLOGICAL FACTORS IN POSTCHEMOTHERAPY BREAST CANCER PATIENTS William Tsang a, Louis W.C. Chow b, Wings T.Y. Loo b,*, Qing Liu b. Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, b UNIMED Medical Institute and Organisation for Oncology and Translational Research, Hong Kong a
Background: This study investigated the effects of Tai Chi Chuan on biological markers and psychological factors of patients diagnosed with advanced invasive ductal carcinoma. Methods: 105 breast cancer patients, aged 32–42 years, and 50 healthy female participants, aged 26–36 years, were recruited for this study. Patients underwent a mastectomy for invasive ductal carcinoma, and completed four cycles of FEC (500 mg/m2 fluorouracil, 75 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide) chemotherapy. Peripheral blood was drawn from participants to analyse biological markers such as white blood cell (WBC) and red blood cell (RBC) count and cytokine levels (IL-2, IL4, IL6, IFN-c and TNF-a). Following treatment, the patients participated in a TCC program for 12 months and biomarkers in patients were measured. A psychological factor-based questionnaire was also conducted. Findings: After 12 months of TCC, the levels of cytokines of patients and healthy groups showed no statistically significant differences. The total WBC count was 7.55 ± 1.25 (versus 8.04 ± 1.05 in the healthy group, p < 0.05), and the total RBC count was 4.62 ± 1.25 (versus 4.99 ± 0.87 in healthy controls, p < 0.05). Patients also noted improvements in short term memory. Interpretation: TCC exercise can be used as a physical and mental treatment for the rehabilitation of post-treatment breast cancer patients for psychological and biological improvements. http://dx.doi.org/10.1016/j.ejca.2015.06.090