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https://www.readbyqxmd.com/read/28210747/extent-of-field-change-in-colorectal-cancers-with-braf-mutation
#1
Aaron Poh, Heidi Sian Ying Chang, Kok Yang Tan, Xin Xiu Sam, Avery Khoo, Shoa Nian Choo, Min En Nga, Wei Keat Wan
INTRODUCTION: Sporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours. METHODS: Eight microsatellite instability-high (MSI-H) tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis...
February 17, 2017: Singapore Medical Journal
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#2
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28165633/back-to-the-future-routine-morphological-assessment-of-the-tumour-microenvironment-is-prognostic-in-stage-ii-iii-colon-cancer-in-a-large-population-based-study
#3
Seán O Hynes, Helen G Coleman, Paul J Kelly, Steven Irwin, Roisin F O'Neill, Ronan T Gray, Claire McGready, Philip D Dunne, Stephen McQuaid, Jacqueline A James, Manuel Salto-Tellez, Maurice B Loughrey
AIMS: Both morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of tumour microenvironment has not been adopted into routine practice. METHODS AND RESULTS: Based on existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative H&E-stained whole tumour sections, from a population-based cohort of 445 stage II/III colon cancer cases...
February 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28160106/variable-levels-of-long-noncoding-rna-expression-in-dna-mismatch-repair-proficient-early-stage-colon-cancer
#4
Qian Li, Nanshan Li, Yueqiong Lao, Wu Lin, Guojun Jiang, Nan Wei, Canghai Wang, Kuiliang Liu, Jing Wu
BACKGROUND: Long noncoding RNAs (lncRNAs) have been suggested to be biomarkers for diagnosis and prognosis of sporadic colorectal cancer. AIMS: This study aimed to characterize the expression profile of lncRNAs in DNA mismatch repair-proficient (pMMR) early-stage colon cancer (CC). METHODS: The microsatellite instability (MSI) status was examined by a multiplex PCR. The expression of lncRNA and mRNA was analyzed by microarrays. The differentially expressed lncRNAs and mRNAs were determined by bioinformatic analyses and validated in 44 CC samples and 32 non-tumor colonic specimens by quantitative real-time polymerase chain reaction (qRT-PCR)...
February 3, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28133101/-evaluation-of-braf-v600e-mutations-in-high-level-microsatellite-instability-msi-h-colon-cancer-comparison-between-genetic-testing-and-immunohistochemical-staining
#5
Takehiko Sakimoto, Noriyasu Chika, Okihide Suzuki, Keiichiro Ishibashi, Tetsuhiko Tachikawa, Kiwamu Akagi, Hidetaka Eguchi, Yasushi Okazaki, Hideyuki Ishida
BRAF V600E mutation plays an important role in the serrated neoplasia pathway of colorectal tumorigenesis and is a negative predictive factor for chemotherapy response as well as a prognostic factor in patients with colorectal cancer. To evaluate BRAF V600E mutations, a conventional polymerase chain reaction(PCR)is performed but recently immunohistochemistry (IHC)with a BRAF antibody has been used. Although similarities between the PCR and IHC methods have been reported, some investigators have doubts about the usefulness of IHC for BRAF mutation analysis...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28106826/colorectal-carcinoma-a-general-overview-and-future-perspectives-in-colorectal-cancer
#6
REVIEW
Inés Mármol, Cristina Sánchez-de-Diego, Alberto Pradilla Dieste, Elena Cerrada, María Jesús Rodriguez Yoldi
Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28104993/synchronous-quintuple-primary-gastrointestinal-tract-malignancies-case-report
#7
Soo-Hong Kim, Byung-Soo Park, Hyun Sung Kim, Jae Hun Kim
Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and intermittent blood-tinged stool was diagnosed with malignancies in the stomach, jejunum, ascending colon, transverse colon and rectum. He underwent a subtotal gastrectomy, segmental resection of the jejunum and total protocolectomy with end ileostomy. The postoperative pathologic findings were moderate differentiated gastric adenocarcinoma (pT1bN0M0, pStageIA), combined adenocarcinoma and neuroendocrine carcinoma of the jejunum (pT3N0M0, pStageIIA), three mucinous adenocarcinoma of the ascending colon (pT3N0M0, pStageIIA), transverse colon (pT1N0M0, pStageI) and rectum (pT3N1aM0, pStageIIIB)...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28093453/interactions-between-microsatellite-instability-and-human-gut-colonization-by-escherichia-coli-in-colorectal-cancer
#8
Johan Gagnière, Virginie Bonnin, Anne-Sophie Jarrousse, Emilie Cardamone, Allison Agus, Nancy Uhrhammer, Pierre Sauvanet, Pierre Déchelotte, Nicolas Barnich, Richard Bonnet, Denis Pezet, Mathilde Bonnet
Recent studies suggest that colonization of colonic mucosa by pathogenic Escherichia coli (E. coli) could be involved in the development of colorectal cancer (CRC), especially through the production of genotoxins such as colibactin and/or by interfering with the DNA mismatch repair (MMR) pathway which leads to microsatellite instability (MSI). This work, performed on 88 CRC patients, revealed a significant increase in E. coli colonization in the MSI CRC phenotype. In the same way, E. coli persistence and internalization were increased in vitro in MMR-deficient cells...
16, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28087988/cpg-island-methylator-phenotype-is-an-independent-predictor-of-survival-after-curative-resection-for-colorectal-cancer-a-prospective-cohort-study
#9
Chang Hyun Kim, Jung Wook Huh, Hyeong Rok Kim, Young Jin Kim
BACKGROUND AND AIMS: The CpG island methylator phenotype (CIMP) is found in approximately 30% of colorectal cancer (CRC) cases. However, the role of CIMP status in predicting oncologic outcomes in curatively resected CRC is still unclear. STUDY: Between January 2006 and December 2006, we retrospectively reviewed 157 consecutive patients who underwent curative surgery for CRC. Prognostic significance of CIMP status was evaluated using reverse transcriptase-polymerase chain reaction...
January 14, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28040692/prognostic-value-of-braf%C3%A2-and%C3%A2-kras%C3%A2-mutations-in-msi-and-mss-stage-iii-colon-cancer
#10
Julien Taieb, Karine Le Malicot, Qian Shi, Frédérique Penault Lorca, Olivier Bouché, Josep Tabernero, Enrico Mini, Richard M Goldberg, Gunnar Folprecht, Jean Luc Van Laethem, Daniel J Sargent, Steven R Alberts, Jean Francois Emile, Pierre Laurent Puig, Frank A Sinicrope
BACKGROUND: The prognostic value of BRAF and KRAS mutations within microsatellite-unstable (MSI) and microsatellite-stable (MSS) subgroups of resected colon carcinoma patients remains controversial. We examined this question in prospectively collected biospecimens from stage III colon cancer with separate analysis of MSI and MSS tumors from patients receiving adjuvant FOLFOX +/- cetuximab in two adjuvant therapy trials. METHODS: Three groups were defined: BRAF Mutant, KRAS Mutant, and double wild-type...
May 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28000726/heterogeneity-of-paclitaxel-distribution-in-different-tumor-models-assessed-by-maldi-mass-spectrometry-imaging
#11
Silvia Giordano, Massimo Zucchetti, Alessandra Decio, Marta Cesca, Ilaria Fuso Nerini, Marika Maiezza, Mariella Ferrari, Simonetta Andrea Licandro, Roberta Frapolli, Raffaella Giavazzi, D'Incalci Maurizio, Enrico Davoli, Lavinia Morosi
The penetration of anticancer drugs in solid tumors is important to ensure the therapeutic effect, so methods are needed to understand drug distribution in different parts of the tumor. Mass spectrometry imaging (MSI) has great potential in this field to visualize drug distribution in organs and tumor tissues with good spatial resolution and superior specificity. We present an accurate and reproducible imaging method to investigate the variation of drug distribution in different parts of solid tumors. The method was applied to study the distribution of paclitaxel in three ovarian cancer models with different histopathological characteristics and in colon cancer (HCT116), breast cancer (MDA-MB-231) and malignant pleural mesothelioma (MPM487)...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27979806/cytotoxic-t-cells-and-granzyme-b-associated-with-improved-colorectal-cancer-survival-in-a-prospective-cohort-of-older-women
#12
Anna E Prizment, Robert A Vierkant, Thomas C Smyrk, Lori S Tillmans, Heather H Nelson, Charles F Lynch, Thomas Pengo, Stephen N Thibodeau, Timothy R Church, James R Cerhan, Kristin E Anderson, Paul J Limburg
BACKGROUND: Host immune response may predict the course of colorectal cancer (CRC). We examined the survival of 468 CRC patients associated with two tumor-infiltrating immune biomarkers - the number of cytotoxic T lymphocytes (CTL) and the activated CTLs, as reflected by the number of cells expressing granzyme B (GZMB) in the prospective Iowa Women's Health Study. METHODS: Using paraffin-embedded tissue samples, we constructed and immunostained tumor microarrays with CD8 (for CTL) and GZMB antibodies...
December 15, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27938333/pseudomyxoma-peritonei-of-a-mature-ovarian-teratoma-caused-by-mismatch-repair-deficiency-in-a-patient-with-lynch-syndrome-a-case-report
#13
Yoshimasa Gohda, Rei Noguchi, Tomoko Horie, Toru Igari, Harumi Nakamura, Yasunori Ohta, Kiyoshi Yamaguchi, Tsuneo Ikenoue, Seira Hatakeyama, Nozomi Yusa, Yoichi Furukawa, Hideaki Yano
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1-2 cases per million individuals per year. PMP is characterized by the accumulation of abundant mucinous or gelatinous fluid derived from disseminated tumorous cells. Most of the tumorous cells are originated from rupture of appendiceal neoplasms, but some are from the metastasis of cancer of the colon, ovary, fallopian tube, urachus, colorectum, gallbladder, stomach, pancreas, lung and breast. Although frequent mutations in KRAS and/or GNAS genes have been reported, precise molecular mechanism underlying PMP remains to be elucidated...
December 9, 2016: BMC Medical Genetics
https://www.readbyqxmd.com/read/27925331/the-mirna-landscape-of-colorectal-polyps
#14
Martha L Slattery, Jennifer S Herrick, Roger K Wolff, Lila E Mullany, John R Stevens, Wade Samowitz
The genomic landscape of adenomas and polyps may help define disease pathways. Expression of miRNAs in adenomas and polyps may importantly contribute to these pathways. We evaluated miRNA expression in 293 polyp-normal colorectal mucosa pairs. Polyps were classified as either adenomatous polyp (AD), hyperplastic polyp (HP), or sessile serrated polyp (SSP). We compared these miRNA expression profiles in polyps to miRNA expression in microsatellite unstable (MSI) and stable (MSS) tumors. A False Discovery Rate of 0...
December 7, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27889996/elevated-microsatellite-alterations-at-selected-tetranucleotide-repeats-emast-and-microsatellite-instability-in-patients-with-colorectal-cancer-and-its-clinical-features
#15
H S Lee, K U Park, D-W Kim, M H Ihn, W H Kim, A N Seo, H E Chang, S K Nam, S Y Lee, H-K Oh, S-B Kang
PURPOSE: Recently, a different type of microsatellite instability (MSI) instability designated 'elevated microsatellite alterations at selected tetranucleotide repeats' (EMAST) has been reported in several neoplasms, but its clinical implications remain unclear. We aimed to determine the relationships among EMAST, MSI and clinicopathologic characteristics, including oncologic outcomes, in colorectal cancer (CRC). MATERIALS AND METHODS: We evaluated 100 sporadic CRC cases subjected to surgery using five markers (MYCL1, D9S242, D20S85, D8S321, and D20S82) for EMAST and the Bethesda panel for MSI status...
November 23, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27859935/single-nucleotide-polymorphisms-within-micrornas-microrna-targets-and-microrna-biogenesis-genes-and-their-impact-on-colorectal-cancer-survival
#16
Lila E Mullany, Jennifer S Herrick, Roger K Wolff, Martha L Slattery
We have shown that single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes, miRNA target genes, and miRNA biogenesis genes minimally contribute to colon cancer risk. It is possible that these SNPs alter survival. We analyzed 565 SNPs in or adjacent to microRNAs, target genes, or biogenesis genes, using 1,115 cases and 1,173 controls; 837 cases had survival information. We tested SNPs for associations with colorectal cancer (CRC) survival using a Cox proportional hazard model adjusting for age, study center, gender, AJCC disease stage, and MSI tumor status...
November 18, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27853901/microsatellite-instability-was-not-associated-with-survival-in-stage-iii-colon-cancer-treated-with-adjuvant-chemotherapy-of-oxaliplatin-and-infusional-5-fluorouracil-and-leucovorin-folfox
#17
Jeong Eun Kim, Yong Sang Hong, Hwa Jung Kim, Kyu-Pyo Kim, Sun Young Kim, Seok-Byung Lim, In Ja Park, Chan Wook Kim, Yong Sik Yoon, Chang Sik Yu, Jin Cheon Kim, Ji Hun Kim, Tae Won Kim
BACKGROUND: The impact of microsatellite instability (MSI) on survival in stage III colon cancer treated with adjuvant 5-fluorouracil-oxaliplatin combination (FOLFOX) chemotherapy is not clear. We evaluated the association between MSI and survival in this population. METHODS: We analyzed 598 patients with curatively resected stage III colon cancer treated with adjuvant FOLFOX chemotherapy. We determined MSI status using polymerase chain reaction amplification; tumors were classified as high MSI (MSI-H, ≥2 unstable markers), low MSI (MSI-L, 1 unstable marker), or microsatellite stable (MSS, no unstable marker)...
November 16, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27836416/associations-of-defect-mismatch-repair-genes-with-prognosis-and-heredity-in-sporadic-colorectal-cancer
#18
L Ghanipour, K Jirström, M Sundström, B Glimelius, H Birgisson
BACKGROUND: Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives. MATERIAL AND METHODS: Tumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases...
February 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27835699/gasdermin-c-is-upregulated-by-inactivation-of-transforming-growth-factor-%C3%AE-receptor-type-ii-in-the-presence-of-mutated-apc-promoting-colorectal-cancer-proliferation
#19
Masashi Miguchi, Takao Hinoi, Manabu Shimomura, Tomohiro Adachi, Yasufumi Saito, Hiroaki Niitsu, Masatoshi Kochi, Haruki Sada, Yusuke Sotomaru, Tsuneo Ikenoue, Kunitoshi Shigeyasu, Kohji Tanakaya, Yasuhiko Kitadai, Kazuhiro Sentani, Naohide Oue, Wataru Yasui, Hideki Ohdan
Mutations in TGFBR2, a component of the transforming growth factor (TGF)-β signaling pathway, occur in high-frequency microsatellite instability (MSI-H) colorectal cancer (CRC). In mouse models, Tgfbr2 inactivation in the intestinal epithelium accelerates the development of malignant intestinal tumors in combination with disruption of the Wnt-β-catenin pathway. However, no studies have further identified the genes influenced by TGFBR2 inactivation following disruption of the Wnt-β-catenin pathway. We previously described CDX2P-G19Cre;Apcflox/flox mice, which is stochastically null for Apc in the colon epithelium...
2016: PloS One
https://www.readbyqxmd.com/read/27819670/hsp110-promotes-colorectal-cancer-growth-through-stat3-activation
#20
K Berthenet, A'dem Bokhari, A Lagrange, G Marcion, C Boudesco, S Causse, A De Thonel, M Svrcek, A R Goloudina, S Dumont, A Hammann, D S Biard, O N Demidov, R Seigneuric, A Duval, A Collura, G Jego, C Garrido
Heat shock protein 110 (HSP110) is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps cells survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently shown that colorectal cancer patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110-inactivating mutation (HSP110DE9). In this work, we used patient biopsies, human colorectal cancer cells grown in vitro and in vivo (xenografts), and intestinal crypts to demonstrate that HSP110 is also involved in colon cancer growth...
November 7, 2016: Oncogene
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