preoperative c reactive protein and thrombocyte count as potential markers for longterm survival in ovarian cancer

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Atypical aleukemic presentation of large granular lymphocytic leukemia: a case report

Cristina Bagacean,1,2 Adrian Tempescul,3 Mariana Patiu,1,4 Bogdan Fetica,4 Horia Bumbea,5,* Mihnea Zdrenghea1,4,* 1Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Laboratory of Immunology and Immunotherapy, University Hospital Brest, 3Department of Hematology, Institute of Cancerology and Hematology, Brest University Medical School, Brest, France; 4Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, 5Department of Hematology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania *These authors contributed equally to this work Abstract: Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disorder of transformed natural killer or T-cells attributed to chronic exposure to the proinflammatory cytokine IL-15. Diagnosis of the majority of T-cell LGLL is established by documenting clonal large granular lymphocytes (LGLs) in peripheral blood, by morphology and immunophenotype. The proteasome inhibitor bortezomib is known to target molecular pathways downstream of the IL-15 receptor signaling and has been proposed as a therapy in these patients. We report an uncommon presentation of LGLL with chronic neutropenia lacking typical blood LGLs, which failed to respond to bortezomib but obtained a very good partial remission with a classical methotrexate regimen. Keywords: large granular lymphocytes, lymphoproliferative, Felty, neutropenia, bortezomi

Baseline blood immunological profiling differentiates between Her2– breast cancer molecular subtypes: implications for immunomediated mechanisms of treatment response

Oana Tudoran,1,2,* Oana Virtic,2,* Loredana Balacescu,1,2 Carmen Lisencu,3 Bogdan Fetica,4 Claudia Gherman,1 Ovidiu Balacescu,1 Ioana Berindan-Neagoe1,2,5 1Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof Dr Ion Chiricuţă”, 2Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 3Department of Radiotherapy I, 4Department of Pathology, The Oncology Institute “Prof Dr Ion Chiricuţă”, 5Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania *These authors contributed equally to this work Purpose: Breast cancer patients’ response to treatment is highly dependent on the primary tumor molecular features, with triple-negative breast tumors having the worst prognosis of all subtypes. According to the molecular features, tumors stimulate the microenvironment to induce distinct immune responses, baseline immune activation being associated with higher likelihood of pathologic response. In this study, we investigated the deconvolution of the immunological status of triple-negative tumors in comparison with luminal tumors and the association with patients’ clinicopathological characteristics.Patients and methods: Gene expression of 84 inflammatory molecules and their receptors were analyzed in 40 peripheral blood samples from patients with Her2- primary breast cancer tumors. We studied the association of triple-negative phenotype with age, clinical stage, tumor size, lymph nodes, and menopausal status.Results: We observed that more patients with estrogen (ER)/progesterone (PR)-negative tumors had grade III, while more patients with ER/PR-positive tumors had grade II tumors. Gene expression analysis revealed a panel of 14 genes to have differential expression between the two groups: several interleukins: IL13, IL16, IL17C and IL17F, IL1A, IL3; interleukin receptors: IL10RB, IL5RA; chemokines: CXCL13 and CCL26; and cytokines: CSF2, IFNA2, OSM, TNSF13.Conclusion: The expression levels of these genes have been previously shown to be associated with reduced immunological status; indeed, the triple-negative breast cancer patients presented with lower counts of lymphocytes and eosinophils than the ER/PR-positive ones. These results contribute to a better understanding of the possible role of antitumor immune responses in mediating the clinical outcome. Keywords: triple-negative breast cancer, gene expression, molecular mechanism, immunological status, clinical outcom

Impact of clinical factors and surgical outcome on long-term survival in high-grade serous ovarian cancer: a multicenter analysis

Introduction: Long-term survivors of ovarian cancer are a unique group of patients in whom prognostic factors for long-term survival have been poorly described. Such factors may provide information for a more personalized therapeutic approach. The objective of this study is to determine further characteristics of long-term survivors with high-grade serous ovarian cancer. Methods: Long-term survivors were defined as patients living longer than 8 years after first diagnosis and were recruited within seven high volume centers across Europe from November 1988 to November 2008. The control group included patients with high-grade serous ovarian cancer with less than 5 years' survival identified from the systematic 'Tumorbank ovarian cancer' database. A subanalysis of Charité patients only was performed separately for in-depth analysis of tumor dissemination. Propensity score matching with nearest-neighbor caliper width was used to match long-term survivors and the control group regarding age, FIGO stage, and residual tumor. Results: A total of 276 patients with high-grade serous ovarian cancer were included, divided into 131 long-term survivors and 145 control group patients. After propensity score matching and multivariable adjustment, platinum sensitivity (p=0.002) was an independent favorable prognostic factor whereas recurrence (p<0.001) and ascites (p=0.021) were independent detrimental predictors for long-term survival. Significantly more long-term survivors tested positive for mutation in the BRCA1 gene than the BRCA2 gene (p=0.016). Intraoperatively, these patients had less tumor involvement of the upper abdomen at initial surgery (p=0.024). Complexity of surgery and surgical techniques were similar in both cohorts. Conclusion: Platinum sensitivity constitutes a favorable factor for long-term survival whereas tumor involvement of the upper abdomen, ascites, and recurrence have a negative impact. Based on clinical estimation, long-term survival is associated with combinations of clinical, surgical, and molecular factors