Familial Adenomatosis Polyposis Research Articles

Superficial fibromas with CTNNB1 mutation.

Superficial fibromas are a group of mesenchymal spindle cell lesions with pathomorphological heterogeneity and diverse molecular backgrounds. In part, they may be indicators of an underlying syndrome. Among the best-known entities of superficial fibromas is Gardner fibroma, a plaque-like benign tumor, which is associated with APC germline mutations and occurs in patients with familial adenomatosis polyposis (Gardner syndrome). Affected patients also have an increased risk to develop desmoid fibromatosis (DTF), a locally aggressive neoplasm of the deep soft tissue highly prone to local recurrences. Although a minority of DTFs occur in the syndromic context and harbor APC germline mutations, most frequently their underlying molecular aberration is a sporadic mutation in Exon 3 of the CTNNB1 gene. Up to date, a non-syndromic equivalent to Gardner fibroma carrying a CTNNB1 mutation has not been defined. Here, we present two cases of (sub-)cutaneous tumors with a hypocellular and collagen-rich Gardner fibroma-like appearance and pathogenic, somatic CTNNB1 mutations. We aim to differentiate these tumors from other fibromas according to their histological appearance, immunohistochemical staining profile and underlying somatic CTNNB1 mutations. Furthermore, we distinguish them from locally aggressive desmoid fibromatosis regarding their biological behavior, prognosis and indicated therapeutic strategies. Consequently, we call them CTNNB1-mutated superficial fibromas as a sporadic counterpart lesion to syndromic Gardner fibromas.

SAT509 The Clinical Significance of Cribriform Morular Thyroid Carcinoma

Abstract Disclosure: G. Soh: None. K. Sek: None. S. Yang: None. M. Nga: None. S. Mok: None. We present two young (aged below 30) female patients who were diagnosed with the rare cribriform morular thyroid carcinoma. Both patients presented with neck swellings and underwent total thyroidectomy for the thyroid malignancies. The histological diagnosis prompted subsequent genetic evaluation. Both patients demonstrated genotypic and phenotypic evidence of familial adenomatosis polyposis (FAP) syndrome. One of the patients had a mutation which resulted in a premature translational stop signal in the adenomatous polyposis coli (APC) gene. She was eventually diagnosed with adenocarcinoma in 2 colonic polyps and underwent a curative pan-proctocolectomy. The other patient was diagnosed clinically with FAP as she had multiple (30-40) colonic polyps which were tubular adenomas. She had a variant of unknown significance in the APC gene. She declined surgery and remained on colonoscopic surveillance. Both patients’ thyroid cancers are in clinical remission. While uncommon, diagnosing cribriform-morular thyroid carcinoma is significant as 25 to 30% of patients harbour genetic mutations in the APC gene on chromosome 5q21. This is associated with FAP syndrome, an autosomal dominant genetic syndrome characterized by young-onset colonic polyposis, usually of malignant potential. Additionally, these patients may exhibit features of Gardner’s syndrome, a subset of FAP syndrome in which patients can develop extra-colonic manifestations such as osteomas of the mandible and supernumerary teeth. Histologically, cribriform morular thyroid carcinoma are well circumscribed and show a variable combination of follicular, cribriform, papillary, trabecular, solid and morular patterns. There is nuclear and cytoplasmic staining for beta catenin, as the inactivating APC mutation causes a loss of beta catenin destruction complex, impeding beta catenin degradation and increasing its nuclear translocation. This is a key event in thyroid tumorigenesis. The diagnosis of cribriform morular thyroid carcinoma should alert the clinician about the possibility of FAP with consideration for further clinical and genetic evaluation to confirm the diagnosis. References1)Cameselle-Teijeiro, J. M., Peteiro-González, D., Caneiro-Gómez, J., Sánchez-Ares, M., Abdulkader, I., Eloy, C., Melo, M., Amendoeira, I., Soares, P., & Sobrinho-Simões, M. (2018). Cribriform-morular variant of thyroid carcinoma: A neoplasm with distinctive phenotype associated with the activation of the Wnt/β-catenin pathway. Modern Pathology, 31(8), 1168–1179. https://doi.org/10.1038/s41379-018-0070-2 2)Peiling Yang, S., & Ngeow, J. (2016). Familial non-medullary thyroid cancer: Unraveling the Genetic Maze. Endocrine-Related Cancer, 23(12). https://doi.org/10.1530/erc-16-0067 Presentation Date: Saturday, June 17, 2023

A huge solitary duodenal hamartoma A rare endoscopic finding

Duodenal polyps are not commonly observed and are typically associated with conditions such as Familial adenomatosis polyposis or Peutz-Jeghers syndrome. However, there are rare instances where duodenal polyps may be encountered as isolated polyps, causing gastrointestinal symptoms.

Famitinib for familial adenomatous polyposis-associated aggressive desmoid tumors: A single-center exploratory study.

10513 Background: Desmoid tumour (DT) is a common extra-intestinal manifestation of familial adenomatosis polyposis (FAP), with high risk of recurrence and became the second leading cause of FAP patients’ death. The treatment of FAP-associated DTs are limited. Famitinib is a orally bioavailable, tyrosine kinase inhibitor against VEGFR-2, PDGFR, c-kit, and FGFR, and has shown antitumor activity in these patients (pts). Methods: This is a prospective, single arm study of FAP pts with progressing DT per RECIST v1.1, treated with famitinib 20 mg QD since 11/2021. The primary endpoint was objective response rate (ORR), with secondary endpoints of safety, progression-free survival (PFS), and quality of life (EORTC QLQ C30). We also collected the FFPE slices of DTs to test both genetic and proteomic backgrounds of pts with different therapeutic results. Results: Between Nov 24, 2021 and Aug 8, 2022, 11 pts were enrolled and evaluated every 9 weeks. The median follow-up time was 9.4 m (6.6 to 14.9 m). The median age was 36 (28-53) and 45% were male. Nine pts were diagnosed with intra-abdominal (IA) tumors while two had extra-abdominal (EA) DTs. Eight had stage III-IV DTs with rapid growth and severe symptoms. 10 of them had history of intestinal resection. Two pts were treated with dacarbazine and epirubicin before enrollment, while one patient received radiotherapy before famitinib. Five pts achieved partial response (PR) and six achieved stable disease (SD), with a median time to response of 7.0 months. The ORR was 45.5% and the disease control rate (DCR) was 100%. The 6-month PFS rate was 91%. The ORR of pts with IA DTs was 55.6%. Of adverse events (AEs) with famitinib, 87% were grade 1/2, the most frequently reported being hypertension (73%), neutropenia (64%), bilirubinemia (55%) and proteinuria (36%). Mean global health status/QoL before and after 6 months’ treatment was 58.3 vs 75.8 ( P= 0.09). Of all 11 pts, germline APC mutations scattered from codon 457 to 1578, and five of them detected somatic APC mutations from codon 547 to 1896 in DTs. Correlative study analysis will be presented. Conclusions: Famitinib demonstrated promising efficacy and a favorable safety profile in FAP-associated aggressive DTs.

S3467 Primary Duodenal Adenocarcinoma: A Rare Malignancy

Introduction: Primary duodenal adenocarcinoma (PDA) is extremely rare, representing 0.3 – 1% of all gastrointestinal malignancies. It poses a significant challenge to the physicians due to late non-specific symptoms that delays the diagnosis. Surgical resection is the only treatment option although PDA with distant or nodal metastasis have a very poor prognosis. Case Description/Methods: A 33-year-old male patient presented with epigastric abdominal pain, nausea, vomiting, lipase > 2000, elevated LFTs and hyperbilirubinemia, consistent with acute pancreatitis. CT abdomen and pelvis revealed an irregular mass in the second and third portion of the duodenum near ampulla, dilation of pancreatic and common bile duct along with multiple hepatic lesions, consistent with metastatic malignancy. EGD showed non bleeding duodenal ulcer along with enlarged lymph nodes in the peripancreatic region. Biopsy of the ulcer was suggestive of moderately differentiated invasive duodenal adenocarcinoma with background of high-grade dysplasia. Due to metastatic malignancy, patient was started on folinic acid, fluorouracil and oxaliplatin without undergoing surgery. Percutaneous biliary drain was placed with resolution of pancreatitis and hyperbilirubinemia. Patient also completed a course of antibiotics due to pseudomonas bacteremia and sepsis secondary to pancreatic phlegmon that was drained. Pain was management with fentanyl patch and oral opioids. Patient was later discharged home with outpatient follow up. Discussion: This case highlights the importance of primary duodenal adenocarcinoma (PDA) which is a very rare malignancy. Its etiology is unknown, however patients with familial adenomatosis polyposis, Peutz-Jeghers syndrome, Crohn’s and celiac disease are at higher risk. Due to non-specific symptoms including anorexia, postprandial fullness, nausea, vomiting, jaundice and abdominal pain, early diagnosis is a challenge for physicians. PDA is most commonly seen in second part of the duodenum with an incidence of 50 -70%. It can be diagnosed with the help of contrast imaging studies along with EGD and biopsy. Management is usually surgical resection with tumors of the second part of the duodenum, proximal and distal infiltrating tumors requiring pancreaticoduodenectomy to ensure radical resection. Lymphovascular invasion, lymph node metastasis and perineural invasion are features associated with poor prognosis and high mortality. For unresectable tumors, palliative surgery or endoscopic treatment is usually indicated.

Gardner Syndrome With Breast Desmoid Tumors

A young woman with familial adenomatosis polyposis presented with a history of pain and progressive enlargement of bilateral breast masses for a decade. She was diagnosed with left breast desmoid tumor via percutaneous biopsy and has since undergone multiple additional percutaneous breast biopsies and surgical excisional biopsies. She underwent multiple treatment regimens for recurrent bilateral breast desmoid tumors, including methotrexate/vinblastine, tamoxifen, doxorubicin, sunitinib, and pazopanib, with ultimate disease progression for all therapies.

Akkermansia muciniphila in inflammatory bowel disease and colorectal cancer.

Akkermansia muciniphila in inflammatory bowel disease and colorectal cancer.

Metformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer.

Simple SummaryHyperactivation of the canonical Wnt and inactivation of the Hippo pathway are well-known genetic backgrounds for familial adenomatosis polyposis (FAP) and colorectal cancer (CRC), although the reciprocal regulation between those pathways is not yet clear. In this study, we found that Axin2, a bona fide downstream target of canonical Wnt, activates the Hippo pathway in APC-mutated CRC, limiting the therapeutic potential of niclosamide on advanced CRC through the inactivation of the Hippo pathway. To overcome the limitation, we combined niclosamide with AMPK activator metformin to activate Hippo and found that this combination synergistically suppressed canonical Wnt and activated Hippo in APC-mutated CRC. Using patient-derived cancer organoid and an APC-MIN mice model, we found the combinatory approach to be effective for APC-mutated CRC. Our results provide not only the reciprocal link between Wnt and Hippo in APC-mutated CRC, but they also provide an effective therapeutic approach with clinically available drugs for FAP and CRC patients.The Wnt and Hippo pathways are tightly coordinated and understanding their reciprocal regulation may provide a novel therapeutic strategy for cancer. Anti-helminthic niclosamide is an effective inhibitor of Wnt and is now in a phase II trial for advanced colorectal cancer (CRC) patients. We found that Axin2, an authentic target gene of canonical Wnt, acts as aYAP phosphorylation activator in APC-mutated CRC. While niclosamide effectively suppresses Wnt, it also inhibits Hippo, limiting its therapeutic potential for CRC. To overcome this limitation, we utilized metformin, a clinically available AMPK activator. This combinatory approach not only suppresses canonical Wnt activity, but also inhibits YAP activity in CRC cancer cells and in patient-derived cancer organoid through the suppression of cancer stemness. Further, combinatory oral administration suppressed in vivo tumorigenesis and the cancer progression of APC-MIN mice models. Our observations provide not only a reciprocal link between Wnt and Hippo, but also clinically available novel therapeutics that are able to target Wnt and YAP in APC-mutated CRC.

Solitary hamartomatous duodenal polyp in an infant

Abstract Duodenal polyps are uncommon. They are usually syndromic seen commonly with Familial adenomatosis polyposis or Peutz-Jegher's syndrome, but maybe seen as a solitary non-syndromic polyp presenting with gastrointestinal symptoms. Few cases of Solitary duodenal hamartomatous polyps have been seen in adults, but to the best of our knowledge never in an infant. We hereby report a case of a 6week old infant who presented with bilious vomiting, weight loss and dehydration. Radiological investigations revealed an obstructive duodenal polyp. Duodenotomy and excision proved curative.

An update on the CNS manifestations of brain tumor polyposis syndromes.

Cancer predisposition syndromes are associated with an increased risk of developing primary malignancies. Here we discuss those which are associated with an increased risk of tumors of the central nervous system (CNS) and gastrointestinal (GI) tract. These can be grouped into those in which the CNS tumors predominate versus those in which the GI cancers predominate. The former include constitutional mismatch repair deficiency (CMMRD) syndrome, Li-Fraumeni syndrome (LFS), and Cowden syndrome (CS) while the latter include familial adenomatosis polyposis 1 (FAP1), Lynch syndrome and polymerase proofreading-associated polyposis syndrome (PPAP). Tumor specificity does exist as medulloblastoma occur in FAP, LFS and CMMRD while glioma are most commonly seen in all replication repair-deficient genes and LFS. Choroid plexus carcinoma is strictly observed in LFS while Cowden syndrome patients develop Lhermitte Duclos disease or meningioma. In each syndrome, specific types of low-grade and high-grade gastrointestinal cancers can occur, but these will be discussed elsewhere. Underlying cancer predisposition syndromes are important to consider when faced with brain tumors, particularly in the pediatric and young adult age groups, as identification of an underlying germ line mutation may change the upfront management of the patient and has implications for future cancer surveillance for both the patient and potentially affected family members. Considerations of family history, presence of skin lesions and consanguinity provide valuable information in identifying patients at potential increased risk.

APC gene analysis in familial adenomatosis polyposis: 3 new mutations in Turkish population

APC gene analysis in familial adenomatosis polyposis: 3 new mutations in Turkish population

Familial adenomatosis polyposis–related desmoid tumours treated with low-dose chemotherapy: results from an international, multi-institutional, retrospective analysis

IntroductionDesmoid tumour (DT) is a locally aggressive fibroblastic proliferative disease representing the most common extraintestinal manifestation of familial adenomatosis polyposis (FAP). As data on the activity of chemotherapy in these patients are limited, we examined the outcomes of patients treated with low-dose methotrexate (MTX)+vinca alkaloids (vinorelbine or vinblastine).Patients and methodsWe retrospectively reviewed clinical and outcome data from all patients with confirmed FAP-associated DTs treated with weekly MTX+vinca alkaloids in seven European sarcoma reference centres between January 2000 and December 2018. Radiological responses were assessed using RECIST V.1.0 and V.1.1. The Kaplan-Meier method associated to the log-rank test was used to estimate and compare survival curves.ResultsWe identified 37 patients (median age 29 years, range 7–44). According to RECIST, 20/37 (54.1%) patients achieved partial response (PR), 15/37 (40.5%) patients had stable disease and 2/37 (5.4%) had progressive disease as best response. Overall, the median progression-free survival (PFS) was 6.5 years (range, 0.3–12.1 years). In the subset of patients achieving PR as best response, the median PFS was not reached. In a subset of 11 patients with progressive disease offered MTX+vinca alkaloids rechallenge (after chemotherapy withdrawal following prolonged disease control), the disease control rate was 100%, resulting in a median PFS after rechallenge of 5.8 years.ConclusionsThis is the largest series on the activity of low-dose chemotherapy in patients with FAP-related DT. In this population, MTX+vinca alkaloids is an active combination, as already reported in patients with sporadic DT.

Medulloblastomas associated with an APC germline pathogenic variant share the good prognosis of CTNNB1-mutated medulloblastomas.

Medulloblastomas may occur in a predisposition context, including familial adenomatosis polyposis. Medulloblastomas related to a germline pathogenic variant of adenomatous polyposis coli (APC) remain rare and poorly described. Their similarities with sporadic WNT medulloblastomas still require description. We performed a multicentric retrospective review of 12 patients treated between 1988 and 2018 for medulloblastoma with an identified or highly suspected (personal or familial history) APC germline pathogenic variant. We report personal and familial history APC gene pathogenic variants whenever available: clinical and histologic characteristics of the medulloblastoma, treatments, and long-term outcome, including second tumor and late sequelae. Medulloblastomas associated with APC pathogenic variants are mainly classic (11/11 patients, 1 not available), nonmetastatic (10/12 patients) medulloblastomas, with nuclear immunoreactivity for ß-catenin (9/9 tested cases). Ten of 11 assessable patients are disease free with a median follow-up of 10.7 years (range, 1-28 y). Secondary tumors included desmoid tumors in 7 patients (9 tumors), 1 thyroid carcinoma, 2 pilomatricomas, 1 osteoma, 1 vertebral hemangioma, and 1 malignant triton in the radiation field, which caused the only cancer-related death in our series. Medulloblastomas associated with an APC pathogenic variant have an overall favorable outcome, even for metastatic tumors. Yet, long-term survival is clouded by second tumor occurrence; treatment may play some role in some of these second malignancies. Our findings raise the question of applying a de-escalation therapeutic protocol to treat patients with APC germline pathogenic variants given the excellent outcome, and reduced intensity of craniospinal irradiation may be further evaluated.

Modulating PKCα Activity to Target Wnt/β-Catenin Signaling in Colon Cancer.

Inactivating mutations of the tumor suppressor Adenomatosis Polyposis Coli (APC), which are found in familial adenomatosis polyposis and in 80% of sporadic colorectal cancers (CRC), result in constitutive activation of the Wnt/β-catenin pathway and tumor development in the intestine. These mutations disconnect the Wnt/β-catenin pathway from its Wnt extracellular signal by inactivating the APC/GSK3-β/axin destruction complex of β-catenin. This results in sustained nuclear accumulation of β-catenin, followed by β-catenin-dependent co-transcriptional activation of Wnt/β-catenin target genes. Thus, mechanisms acting downstream of APC, such as those controlling β-catenin stability and/or co-transcriptional activity, are attractive targets for CRC treatment. Protein Kinase C-α (PKCα) phosphorylates the orphan receptor RORα that then inhibits β-catenin co-transcriptional activity. PKCα also phosphorylates β-catenin, leading to its degradation by the proteasome. Here, using both in vitro (DLD-1 cells) and in vivo (C57BL/6J mice) PKCα knock-in models, we investigated whether enhancing PKCα function could be beneficial in CRC treatment. We found that PKCα is infrequently mutated in CRC samples, and that inducing PKCα function is not deleterious for the normal intestinal epithelium. Conversely, di-terpene ester-induced PKCα activity triggers CRC cell death. Together, these data indicate that PKCα is a relevant drug target for CRC treatment.

Prevalence and risk factors for fundic gland polyps

The incidence of fundic gland polyps (FGPs) is increasing rapidly and has surpassed hyperplastic polyps to become the most common epithelial gastric polyps in Western countries and China.1, 2 They are usually multiple, small (1-5 mm), transparent, and sessile; the background gastric mucosa is typically normal.3 FGPs are more prevalent among females and are often located in the gastric fundus and body. There are two types of FGPs: sporadic and syndromic (in association with familial adenomatosis polyposis). Although different in their genetic and molecular backgrounds, sporadic and syndromic FGPs are histologically and histochemically indistinguishable. Syndromic FGPs occur in the presence of inherited germline mutation in the adenomatous polyposis coli (APC) gene plus the acquisition of a somatic mutation, leading to complete inactivation of the APC tumor suppressor gene.4 Familial adenomatosis polyposis should be excluded by colonoscopy if FGPs are numerous, large (>1 cm), or dysplasic.3 For sporadic FGPs, up to 23% are associated with proton pump inhibitor (PPI) use.5, 6 A recent review with meta-analysis indicated that long-term use of PPIs (≥12 months) increased the risk of FGPs (pooled odds ratio [confidence interval]: 3.81 [2.78-5.24] for the fixed effects model and 2.88 [0.97-8.55] for the random effects model).7 The risk was even higher if the exposure duration was more than 48 months (pooled odds ratio: 4.02). There is no or inverse association with Helicobacter pylori infection.1, 3 FGPs rarely harbor dysplastic lesions. A study in the USA of 35 372 FGPs found that only 0.3% had low-grade dysplasia.5 Moreover, even syndromic FGPs rarely progress to cancer.8 Once epithelial gastric polyps are found at initial endoscopy, it is important to sample polyps and/or normal-appearing gastric mucosa to establish histological diagnosis and to define who needs surveillance. Biopsies from the background antrum and corpus mucosa could rule out atrophic gastritis, intestinal metaplasia, dysplasia, and H. pylori infection. All these information is important for the management of other epithelial gastric polyps, including hyperplastic polyp, adenoma, and type 1 or 2 gastric neuroendocrine tumors.3 Once sporadic FGPs are diagnosed, routine endoscopic surveillance is not recommended in the absence of dysplasia. There is still no consensus on the indication of endoscopy resection of sporadic FGPs. However, many experts suggest the removal of FGPs larger than 10 mm.3 Few studies have considered risk factors other than age, gender, PPIs, and H. pylori infection for sporadic FGPs. A recent one-center, endoscopy-based retrospective study in Taiwan indicated the incidence of FGPs increased from 0.6% in 2010 to 1.3% in 2015.9 The controls were age- and gender-matched subjects who received upper endoscopy during the similar period with the cases. The authors found the presence of liver cirrhosis, gastric ulcer, duodenal ulcer (adjusted odds ratio: 0.18, 0.28, and 0.35, respectively, all P < 0.001), but not reflux esophagitis, were inversely associated with FGP risk. FGPs are commonly seen in patients with relatively healthy gastric mucosa. This is an interesting finding that implies causative factors to gastric mucosa, including cirrhosis and peptic ulcers, which could reduce the formation of FGPs, probably through the facilitation of glandular outflow. However, more than 30% of H. pylori status was missing, and the information of PPI exposure was less than adequate in this study. Future studies are necessary to support this finding and the proposed mechanism behind it. The author declares no conflict of interest.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis.

HuR is an RNA-binding protein implicated in immune homeostasis and various cancers, including colorectal cancer. HuR binding to AU-rich elements within the 3' untranslated region of mRNAs encoding oncogenes, growth factors, and various cytokines leads message stability and translation. In this study, we evaluated HuR as a small-molecule target for preventing colorectal cancer in high-risk groups such as those with familial adenomatosis polyposis (FAP) or inflammatory bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and colorectal cancer, but not in patients with IBD-dysplasia. Intraperitoneal injection of the HuR small-molecule inhibitor MS-444 in AOM/DSS mice, a model of IBD and inflammatory colon cancer, augmented DSS-induced weight loss and increased tumor multiplicity, size, and invasiveness. MS-444 treatment also abrogated tumor cell apoptosis and depleted tumor-associated eosinophils, accompanied by a decrease in IL18 and eotaxin-1. In contrast, HuR inhibition in APCMin mice, a model of FAP and colon cancer, diminished the number of small intestinal tumors generated. In this setting, fecal microbiota, evaluated by 16S rRNA gene amplicon sequencing, shifted to a state of reduced bacterial diversity, with an increased representation of Prevotella, Akkermansia, and Lachnospiraceae Taken together, our results indicate that HuR activation is an early event in FAP-adenoma but is not present in IBD-dysplasia. Furthermore, our results offer a preclinical proof of concept for HuR inhibition as an effective means of FAP chemoprevention, with caution advised in the setting of IBD. Cancer Res; 77(9); 2424-38. ©2017 AACR.

Niclosamide is a potential therapeutic for familial adenomatosis polyposis by disrupting Axin-GSK3 interaction.

The epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and cancer progression, and canonical Wnt signaling tightly controls Snail, a key transcriptional repressor of EMT. While the suppression of canonical Wnt signaling and EMT comprises an attractive therapeutic strategy, molecular targets for small molecules reverting Wnt and EMT have not been widely studied. Meanwhile, the anti-helminthic niclosamide has been identified as a potent inhibitor of many oncogenic signaling pathways although its molecular targets have not yet been clearly identified. In this study, we show that niclosamide directly targets Axin-GSK3 interaction, at least in part, resulting in suppression of Wnt/Snail-mediated EMT. In vitro and in vivo, disruption of Axin-GSK3 complex by niclosamide induces mesenchymal to epithelial reversion at nM concentrations, accompanied with suppression of the tumorigenic potential of colon cancer. Niclosamide treatment successfully attenuates Snail abundance while increasing E-cadherin abundance in xenograft tumor. Notably, oral administration of niclosamide significantly suppressed adenoma formation in an APC-MIN mice model, indicating that niclosamide is an effective therapeutic for familial adenomatosis polyposis (FAP) patients. In this study, we identified a novel target to control the canonical Wnt pathway and Snail-mediated EMT program, and discovered a repositioned therapeutics for FAP patients.

Tekrarlayan Karın Ağrısı Olan Çocuk Hastada Menetrier Hastalığının Olağan Dışı Tutulumu

A 13 years old girl admitted due to epigastric pain. She had a history of osteoid osteoma operation and a cousin diagnosed as familial adenomatosis polyposis. She was found to have polypoid structures beginning from antrum to the end of the first part of duodenum at gastroduodenoscopy which are reported as parietal hyperplasia. Her complaints were increased with proton pump inhibitor treatment and two more gastroduodenoscopy were needed to be diagnosed as Menetrier's disease. No etiologic factor could be demonstrated. She's been followed for the last year.

Abstract 171: Comparative genomic analyses of synchronous colorectal cancers by exome sequencing

Abstract Colorectal cancer (CRC) is the third most common cancer type and the second leading cause for cancer deaths in the Western world. Around 3.5% of CRC patients have more than one primary colorectal carcinoma at the time of diagnosis. These so-called synchronous colorectal cancers (SCRC) are more common in men and have been associated with predisposing conditions, such as hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatosis polyposis (FAP) and inflammatory bowel disease. Such conditions account for slightly more than 10% of SCRC cases. The pathological and clinical features of the tumors have been widely studied. The underlying molecular mechanisms in SCRC have not been well described, though. The research has mainly focused on single factors such as microsatellite instability (MSI) status or APC-, KRAS-, and p53-mutations. By exome sequencing a tumor pair and corresponding normal sample from 23 patients, we aim to study the extent of genetic overlap between the synchronous tumors to assess if they derive from a common progenitor. The tumor data will be filtered against the normal tissue data to verify the somatic origin of the observed mutations. The comparison of the mutation profiles in each tumor pair will take into account the number of shared variants that occur in the exact same positions in the coding region. If the tumors share a high number of changes in exactly the same base it would suggest they have a common origin. Different mutation patterns, with possibly a few coincidental shared mutations, may support a stochastic process in the genesis of the two tumors. We will also identify commonly mutated genes - those that are mutated in both tumors of a synchronous pair or among synchronous pairs of different patients. The patient material derives mainly from a consecutive, population-based colorectal cancer collection “Suolisyöpä Keski-Suomi 2000-2010” from Jyväskylä, Finland. In addition three SCRC-cases were included from our in-house collections. Knowledge on the molecular basis of SCRC, which haven't been studied to this extent before, provides insight on how these tumors arise and allows for development of more personalized treatments. Citation Format: Ulrika A. Hänninen, Tomas Tanskanen, Riku Katainen, Jan Böhm, Minna Taipale, Jussi Taipale, Jukka-Pekka Mecklin, Netta Mäkinen, Lauri A. Aaltonen. Comparative genomic analyses of synchronous colorectal cancers by exome sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 171.