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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
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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
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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)