Gloor, Beat

Karamitopoulou, Evanthia

Lugli, Alessandro

Perren, Aurel

Zlobec, Inti

Bern Open Repository and Information System (BORIS)

source: https://doi.org/10.48350/47044 | downloaded: 17.2.2023Objective: To identify mutational biomarkers using next-generation sequencing (NGS) and endoscopic samples for stratifi-cation of Barrett Esophagus (BE) patients at increased risk ofdysplasia.Method: Ion Torrent AmpliSeq Cancer Panel was used to screen formutations in 46 cancer genes. Sixteen samples were tested: Intesti-nal metaplasia from 6 patients (IM-P) with concomitant high-gradedysplasia (HGD)/adenocarcinoma (EAC) and HGD/EAC in 3 pa-tients; IM of 7 patients followed for at least 2 years without anydysplasia (IM-N). Ion torrent suite software and ANNOVAR wereused for analysis.Results: The most frequent mutations in IM and HGD/EAC weredetected in TP53 spanning codons 150 to 280. Four of 6 IM-Ppatients had TP53 mutations in IM samples and in HGD/EACtested. None of the 7 IM-N patients had TP53 mutations. Sensitiv-ity of TP53 mutation for presence of concomitant dysplasia was67 % and specificity was 100 %.Conclusion: DNA from routine endoscopic samples can be efficientlyused to simultaneously detect multiple mutations by NGS. TP53 muta-tions were frequently detected in IM of patients with HGD/EAC but not inpatients who did not progress to HGD/EAC, suggesting that TP53 muta-tional testing may be useful to identify IM-P patients who may benefitfrom closer surveillance.OFP-03-002Amplification but not translocation of ALK is a frequent event inesophageal cancerP. Birner**Medizin. Universität Wien, Inst. für Pathologie, AustriaObjective: Translocations of ALK have been demonstrated in a variety ofhuman malignancies, and the corresponding fusion-proteins are potentialtherapeutical targets. Aim of this study was to investigate ALK genestatus in a large cohort of esophageal squamous cell carcinoma (SCC)and adenocarcinoma (AC).Method: ALK status was investigated in 117 SCCs and 136 ACs byfluorescence in situ hybridization (FISH), and ALK protein expression byimmunohistochemistry. Data on expression of ALK downstream effectortyrosine −705 phosphorylated STAT3 (pSTAT3) was available from aprevious study.Results: FISH was successfull in 251 cases. No ALK translocationswere found, while 14/135 (12.1 %) of SCCs and 14/116 (10.4 %)of ACs showed ALK amplifications. Concomitant EML4 amplifica-tions were present in 27/28 cases with ALK amplifications. Threecases showed EML4 translocations not involving ALK. None of thetumors with ALK amplification showed ALK protein expression,and no correlation with clinical parameters, survival or pSTAT3expression was observed.Conclusion: While ALK translocations are not present in esophagealcancer, ALK amplifications are common events. Since ALK amplifiedbreast cancer cells were shown to respond to ALK inhibitors, ALKamplified esophageal cancers might be considered as possible candidatesfor therapies targeting ALK.OFP-03-003MALDI imaging mass spectrometry for proteomic segmentation oftumor heterogeneity in gastric cancer tissuesB. Balluff**Leiden University Medical Cent, The NetherlandsObjective: A high clonal diversity within a patient’s tumor is an impor-tant factor for the evolution of the disease and the clinical management ofthe patient with regard to cancer relapse and response to therapy(Marusyk, Nat Rev Cancer. 2012 Apr 19;12(5):323–34). The identifica-tion and molecular characterization of the tumor’s clonal diversity istherefore of high clinical relevance.Method: In this study, matrix-assisted laser desorption/ionization(MALDI) imaging mass spectrometry was used to identify clini-cally relevant tumor subpopulations in gastric cancer. MALDIimaging allows the unlabeled in situ measurement of hundreds ofmolecules (like proteins) within their histomorphological context oftissue sections (Balluff, Gastroenterology. 2012 Sep;143(3):544–9.e1-).Results: Spatially-resolved, tumor-specific proteomic data was ac-quired from 63 intestinal-type gastric cancer patients by MALDIimaging. The resulting data underwent a novel statistical procedure(Jones, PLoS One. 2011;6(9):e24913) which results in a spatialsegmentation of areas within a tumor section based on their molec-ular similarity. Correlation of the molecular signatures of the seg-mented tumor areas with clinical data resulted in the identificationof clinically relevant tumor subpopulation in terms of prognosis andmetastasis.Conclusion: Our results highlight the usefulness of MALDI imaging incombination with advanced statistical approaches for detecting novel andclinical relevant information from tumor tissues.OFP-03-005Increased tumor-budding/CD8+ lymphocytes ratio is associated withmetastasis and venous invasion in Pancreatic Ductal Adenocarcinoma(PDAC)E. Karamitopoulou*, I. Zlobec, A. Perren, B. Gloor, A. Lugli*University of Bern, Institute of Pathology, SwitzerlandObjective: T-Lymphocytes can be a major part of tumor microen-vironment, especially at the area of tumor-host interaction wheretumor progression, reflected by epithelial-mesenchymal transition(EMT) and its hallmark tumor-budding is taking place. Our aimwas to determine the role of CD8+lymphocytes in correlation withtumor-budding in PDAC.Method: Double immunostaining for AE1-AE3/CD8 was performed ona multipunch tissue microarray of 120 well-characterized PDACs.Tumor-buds, CD8+ and tumor-budding/CD8+ lymphocytes indices wereevaluated and associated with clinico-pathological features, follow-upand adjuvant therapy information.Results: There was a strong negative correlation between the number ofbuds and CD8+ counts (p=0.01). Increased numbers of tumor-buds wereassociated with venous invasion (p=0.0272) and reduced overall survival(p=0.0147). Low CD8+ peritumoral lymphocytes showed only a mar-ginal association with metastasis (p=0.0683). Tumor-budding/CD8+lym-phocytes ratio was strongly associated with venous invasion (p=0.0078)and metastasis (p=0.0452). No intratumoral CD8+lymphocytes weredetected.Conclusion: Low counts of CD8+ peritumoral lymphocytes in themicro-environment of PDAC promote EMT as reflected by tumor-budding and facilitate tumor progression, since tumor-buds seem todisplay metastatic potential only when coupled by decreased countsof CD8+lymphocytes. However, unlike to other tumor types, noprognostic effect was found, probably reflecting the fact of theabsence of intratumoral CD8+lymphocytes.OFP-03-006Various carcinogenetic pathways may be involved in colorectal serratedpolyposisE. Courcet*, A. Aline-Fardin, P. Cervera, J.-F. Fléjou*Hôpital Saint-Antoine, Service d’Anatomie Pathologiqu, Paris, FranceObjective: Serrated polyposis (SP) is considered as a model leadingto colorectal cancer (CRC) through the serrated pathway. However,the precise morphological and molecular steps are still incompletelyunderstood. We aimed to characterize the morphological and mo-lecular abnormalities in a series of SP, in CRC and in precancerouslesions.106 Virchows Arch (2013) 463:101–352

Increased tumor-budding/CD8+lymphocytes ratio is associated with metastasis and venous invasion in Pancreatic Ductal Adenocarcinoma

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