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2020 CUA Abstracts





        inhibitors (ICIs) are not so high in metastatic RCC. Here, we focused on   Reference
        DEAD/H-box helicase gene DDX41 as potential therapeutic biomarker   1.   Thompson L. Pheochromocytoma of the Adrenal gland Scaled
        of ICIs in RCC. DDX41 functions as DNA sensor that depends on the   Score (PASS) to separate benign from malignant neoplasms: A
        stimulator of interferon genes (STING) to sense pathogenic DNA and   clinicopathologic and immunophenotypic study of 100 cases. Am
        directly binds DNA and STING. It functions through the STING and the   J Surg Pathol 2002;26:551-66. https://doi.org/10.1097/00000478-
        downstream effectors, such as  interferon regulatory factor 3 (IRF3), lead-  200205000-00002
        ing to the expression of type I IFNs.
        Methods: We aimed to investigate the effect of DDX41 in ccRCC using   MP-3.13
        public database and in vitro experiment. We investigated the genetic
        alterations in DDX41, TMEM173 (encoding STING), and IRF3 in patients   Role of lactate dehydrogenase (LDH) in identifying relapse for
        with ccRCC using the data sets from The Cancer Genome Atlas (TCGA)   patients with stage I testis cancer on active surveillance 2
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        including 446 complete samples. To assess the DDX41 function, we estab-  Adam Bobrowski , Lauren Landoni , Lynn Anson-Cartwight , Aaron
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        lished DDX41 overexpressing 786-O and Caki-1 cells and performed   Hansen , Peter Chung , Phillippe Bedard , Padraig Warde , Michael A.
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        RNA sequence.                                        Jewett , Martin O’Malley , Joan Sweet , Robert J. Hamilton
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        Results: The genetic alterations in DDX41, TMEM173, and IRF3 were   Faculty  of  Medicine,  University  of  Toronto,  Toronto,  ON,
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        found respectively in 49 (11%), 28 (5.8%), and 23 (5.2%) samples.   Canada;  Departments of Surgery and Surgical Oncology (Urology),
        Enhanced expression of DDX41 mRNA is associated with worse progno-  Princess Margaret Hospital, University Health Network, University of
                                                                                     3
        sis, as well as TMEM173 and IRF3. Each enhanced expression of DDX41,   Toronto, Toronto, ON, Canada;  Department of Medical Oncology,
        TMEM173, and IRF3 mRNA significantly correlates with increased PD-1-  Princess Margaret Hospital, University Health Network, University of
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        cording gene. In vivo experiments shows that enhanced DDX41 expres-  Toronto, Toronto, ON, Canada;  Department of Radiation Oncology,
        sion cause enrichment of E2F target gene sets in both 786-O and Caki-1   Princess Margaret Hospital, University Health Network, University of
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        cell lines.                                          Toronto, Toronto, ON, Canada;  Department of Diagnostic Radiology,
        Conclusions: Expression of DDX41 might be a potential biomarker for   Princess Margaret Hospital, University Health Network, University of
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        predicting the response of anti PD-1 therapy in ccRCC.  Toronto, Toronto, ON, Canada;  Department of Pathology, Princess
        References                                           Margaret Hospital, University Health Network, University of Toronto,
            1.   Liu X, Wang C. The emerging roles of the STING adaptor pro-  Toronto, ON, Canada
               tein in immunity and diseases. Immunology 2016;147:285-91.   Introduction: Tumor markers alpha-fetoprotein (AFP), human chorionic
               https://doi.org/10.1111/imm.12561             gonadotropin (hCG), and lactate dehydrogenase (LDH) have played a key
            2.   Cancer Genome Atlas Research Network. Comprehensive   role in diagnosis, staging, prognosis, and therapeutic response in testis
               molecular characterization of clear-cell renal cell carcinoma.   cancer. Nonetheless, LDH has weak sensitivity and very weak specificity,
               Nature 2013;499:43-9. https://doi.org/10.1038/nature12222  which can lead to falsely elevated results that cause anxiety for patients
                                                             on surveillance. We explored the utility of LDH in identifying relapse
                                                             among stage I seminomatous and non-seminomatous germ cell tumors
        MP-3.12                                              (NSGCT) on surveillance.
        Clinical severity of resected pheochromocytoma and its relation   Methods: Subjects were selected from a prospectively maintained data-
        to Pheochromocytoma of the Adrenal Gland Scaled Score (PASS)  base from December 1980 to August 2019 and followed according to
        Jiefei Yao , Luke Witherspoon , Eric Belanger , Neal E. Rowe 1  published surveillance algorithms. The link between LDH elevation and
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        1 Surgery-Urology, University of Ottawa, Ottawa, ON, Canada;  Pathology,   relapse was examined. We noted if LDH elevation was the sole indicator
                                                  2
        The Ottawa Hospital, Ottawa, ON, Canada              of relapse. The rate of false positive LDH elevation was assessed in the
        Introduction: Pheochromocytoma (PCC) is a rare catecholamine secreting   non-relapsed cohort.
        tumor that often arises from the adrenal medulla. While only a small por-  Results: A total of 1753 patients (1077 seminoma and 676 NSGCT) were
        tion of tumors are malignant, many are associated with classic signs and   studied. Among seminomas, 183 patients (17%) relapsed at a median of
        symptoms, including, hypertension, tachycardia, headache, and palpita-  15 months. The most common mode of relapse detection was imaging
        tions. The Pheochromocytoma of the Adrenal Gland Scale Score (PASS)   alone (83%). Tumor marker elevation alone was noted in 1.6%. LDH was
        was developed by Thompson in 2002.  This scoring system is based on the   elevated in 27 (15%) cases at relapse but never in isolation as the sole
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        presence of 12 different histological parameters to aid the identification of   indicator of relapse. Of the 676 NSGCT patients, 175 (26%) experienced
        malignant tumors. PASS ≥4 is thought to have an increased potential for   disease relapse at a median of 7.9 months. The most common mode of
        malignancy, while <4 is favored to be benign. The relationship between   relapse detection was imaging alone (42%). LDH was elevated in 26
        PASS and other features of PCC has not been described. Our study aimed   (15%) cases at relapse and, like in seminoma, never in isolation as the
        to assess the relationship between PASS and presentation severity.  sole indicator of relapse. Among non-relapsing NSGCT patients diagnosed
        Methods: We performed a retrospective chart review on all resected PCCs   from January 2000 (n=312), 234 (75%) registered at least one false posi-
        in a tertiary center from 2008–2018. Demographics, operative details,   tive LDH, and 160 (52%) had multiple false positive LDH values. This
        pre/postoperative courses, and histopathology information were collected.   translates into an average of 2.9 false positives per patient.
        Any histological specimens were assigned a PASS.     Conclusions: LDH did not independently contribute to early relapse
        Results: Sixty-four resected tumors were identified and only two cases   detection in stage I seminoma or NSGCT. False positive values were
        (PASS 4 and 12) were malignant. Mean PASS was 5.4 (0–15); 61% had   commonly documented in non-relapsing NSGCT. Based on these results,
        PASS ≥4. ICU admission occurred in seven patients, with average PASS   we advocate no longer measuring LDH in stage I surveillance.
        of 8.6 vs. 5.1 in non-ICU (p=0.0264). Average max intraoperative systolic
        blood pressure for PASS <4 and ≥4 was 178 mmHg and 183 mmHg,
        respectively (p=0.67). Average PASS for incidentally detected PCC vs.
        symptomatic was 5.45 and 5.44, respectively (p=0.99).
        Conclusions: Patients with an asymptomatic presentation of PCC did not
        have different PASS than patients with symptoms. However, PASS was
        higher in patients identified to have the most extreme clinical presenta-
        tion (ICU admission). While our data suggests a role for PASS beyond
        prediction of metastatic potential, further studies involving patients from
        multiple centers is needed.
        S94                                     CUAJ • June 2020 • Volume 14, Issue 6(Suppl2)
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