UEGJournal Abstracts 2021 - 109

Tuesday, October 5, 2021
Monday, October 4, 2021
Sunday, October 3, 2021
Aims & Methods: We studied endogenous ROBO1 expression and overexpression
of a flurorescently tagged ROBO1 in two different PDAC cell lines
(Panc-1 and T3M-4) by confocal microscopy (with Airyscan). Knockdown
of ROBO1 and actin-regulatory genes was obtained by siRNA, validated by
RT-PCR and phenotypic effects were analyzed using microscopy. Effects
on RhoA were monitored using a GFP-Anillin AHPH biosensor.
Results: Immunofluorescent analysis of the subcellular distribution in
two PDAC cell lines revealed that ROBO1 localized at filopodia, lamellipodia
or ruffles, and adherens junctions (AJ), overlapping with dynamic
F-actin structures. ROBO1 loss resulted in disorganization of cell junction-
associated F-actin and disturbance of AJ, phenocopying interference with
the RhoA/ABI/Diaph1/actomyosin axis that regulates actin dynamics. In
fact, ROBO1 promotes the concentration of RhoA-GTP at AJ. In addition to
AJ, ROBO1 also supports the formation of actin-rich cell membrane protrusions.
Conclusion:
Together, these results reveal that ROBO1 regulates actin cytoskeletal
organization at pancreatic tumor cell peripheries. This is a first
step in unravelling the role of ROBO1 in pancreatic cancer.
References: 1. Biankin et al. Pancreatic cancer genomes reveal aberrations
in axon guidance pathway genes. Nature. 2012;491(7424):399-405
2. Pinho et al. ROBO2 is a stroma suppressor gene in the pancreas and acts
via TGF-beta signalling. Nat Commun. 2018;9(1):5083
Disclosure: nothing to declare
Endoscopic management of hereditary and
inflammatory conditions
16:00-17:00 / Hall 8
OP146
MUTYH-ASSOCIATED POLYPOSIS: GENOTYPE-PHENOTYPE
CORRELATIONS
P. Currais1, P. Lage2, I. Rosa3, P. Rodrigues4
C. Albuquerque5
, I. Claro3
1Portuguese Institute Oncology Gastroenterology, Lisboa,
Portugal, 2
Instituto Portugues de Oncologia de Lisboa, EPE
Dept. de Gastroenterologie, Gastroenterology, Lisboa, Portugal,
3
Instituto Português de Oncologia de Lisboa Francisco Gentil,
Gastrenterologia, Lisboa, Portugal, 4
Instituto Português de
Oncologia de Lisboa Francisco Gentil, Familiar Cancer Risk Clinic,
Lisboa, Portugal, 5
Instituto Português de Oncologia de Lisboa
Francisco Gentil, UIPM, Lisboa, Portugal
Contact E-Mail Address: pedro_currais@live.com.pt
Introduction: MUTYH-associated polyposis (MAP) is a recessively inherited
disease characterized by the presence of two pathogenic mutations
in the MUTYH gene. European caucasian population presents two mutational
hotspots, Y179C and G396D. This disorder is associated with a high
lifetime risk of developing adenomas and colorectal cancer (CRC) and a
modest risk of extra-colonic cancers. It is recommended to start colonic
surveillance at age 18-20 years to prevent CRC and gastroduodenal surveillance
at age 30-35 years. Previous studies have demonstrated different
phenotypes, according to the location of the germline mutations.
Aims & Methods: To evaluate colonic phenotype, extra-colonic cancers,
treatment and outcomes of MAP patients and to analyze genotype-phenotype
correlations.
Retrospective unicentric study evaluating all the families with MAP followed
in the familial cancer risk clinic of a tertiary Center regarding their
demographic data, germline mutations, surgical/endoscopic treatment,
histopathology of tumors and subsequent endoscopic surveillance.
Vol. 9 | October 2021
OP147
SIZE AND MULTIPLICITY ARE RISK FACTORS FOR THE RECURRENCE OF
HIGH-RISK ADENOMAS IN A COLORECTAL CANCER SCREENING COHORT
J. Zessner-Spitzenberg1,2
A. Szymanska1,2
A. Hinterberger1,2
, E. Waldmann1,2
, A. Asaturi1,2, L.-M. Rockenbauer1,2
, B. Majcher1,2
, L. Jiricka3
,
,
, M. Trauner1, M. Ferlitsch1,2
1Medical University of Vienna, Department of Internal Medicine
III, Division of Gastroenterology and Hepatology, Vienna, Austria,
2
Medical University of Vienna, Center for
Austrian Society for Gastroenterology, Quality Assurance Working
Group, Vienna, Austria, 3
Medical Statistics, Informatics and Intelligent Systems, Institute of
Clinical Biometrics, Vienna, Austria
Contact E-Mail Address: jasmin.zessner-spitzenberg@meduniwien.ac.at
Introduction: Surveillance colonoscopy after initial screening is recommended
for patients presenting with characteristics of polyps encountered
on index examination, including lesion size, count or the presence of
high-grade dysplasia. A proportion of patients develop recurring adenomas
within a given follow-up interval, and little is known of the determinants
of high-risk adenoma recurrence.
Aims & Methods: The aim of this cohort study was to identify the number
of patients harboring high-risk adenomas at follow-up when high-risk adenomas
were present at baseline colonoscopy, and to examine possible
109
, B. Filipe5
,
Results: 91 patients with biallelic mutations from 89 MAP families were
evaluated as well as 103 at-risk relatives with monoallelic mutations.
Regarding MAP patients (51.6% male; mean age: 47 years old, interval:
22-86), at diagnosis, 51.6% had >30 polyps, both adenomas (77%) and
hyperplastic/serrated lesions and 59.3% (54/91) were submitted to surgery,
32/91 due to CCR and 22/91 due to polyposis. Gastric fundic gland
polyps were present in 6.6% of patients and 8.8% had duodenal adenomas.
Extra-colonic cancers were present in 10/91 (11%) patients (2 sebaceous
glands, 4 papillary thyroid, 4 breast). During a median follow-up of
43 months, all patients not submitted to surgery developed additional
polyps (9.9% had >30 polyps), 2 CRC were diagnosed and 9 patients died
(3 from unrelated events). The most frequent germline mutations were
G396D/G396D in 30/91 (33%), Y179C/Y179C in 16/91 (17.5%) and Y179C/
G396D in 15/91 (16.4%) patients. In multivariable analysis, MAP patients
with Y179C/Y179C had a higher risk of having >30 colonic polyps (p=0.023,
OR 1.06-1.22) as well as gastric (p=0.04, OR 1.12-1.34) and duodenal polyps
(p=0.01, OR 1.34-1.78) at diagnosis. No association was found between
genotype and age at CRC diagnosis, presence of extra-colonic cancers or
mortality. From 103 relatives with monoallelic mutations (55.3% male;
mean age: 31 years-old, interval: 19-83), 24/103 performed colonoscopy
and 11/24 (45.8%) had colorectal adenomas. At diagnosis, 10.7% (11/103)
had 1-10 colonic polyps and 1 patient had CCR and was submitted to surgery.
Only 4.4% and 1% had gastric fundic gland polyps and duodenal adenomas,
respectively. Extra-colonic cancers were present in 5/103 (4,9%)
patients (2 sebaceous glands, 2 duodenal and 1 ovarian). During a median
follow-up of 12 months, 1.9% (2/103) developed 10-30 polyps and 5.8%
(6/103) 1-10 polyps. No CRC was diagnosed and only 1 patient died during
follow-up (unrelated event). The most frequent mutations in this group
were: G396D in 48/103 (46.6%) and Y179C in 37/103 (35.9%).
Conclusion: Our study confirms that patients with Y179C biallelic mutation
present a higher risk for colonic, gastric and duodenal polyps. These
findings highlight the importance of genotype-phenotype correlation with
potential implications in management of PAM patients. Also the elevated
number of adenomas in the monoallelic carriers validates the surveillance
proposed.
Disclosure: Nothing to disclose.

UEGJournal Abstracts 2021

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