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CRC subtypes

Alan J Simmons, Cherié R Scurrah, Eliot T McKinley, Charles A Herring, Jonathan M Irish, M Kay Washington, Robert J Coffey, Ken S Lau
Cellular heterogeneity poses a substantial challenge to understanding tissue-level phenotypes and confounds conventional bulk analyses. To analyze signaling at the single-cell level in human tissues, we applied mass cytometry using cytometry time of flight to formalin-fixed, paraffin-embedded (FFPE) normal and diseased intestinal specimens. This technique, called FFPE-DISSECT (disaggregation for intracellular signaling in single epithelial cells from tissue), is a single-cell approach to characterizing signaling states in embedded tissue samples...
October 11, 2016: Science Signaling
Andreas U Lindner, Manuela Salvucci, Clare Morgan, Naser Monsefi, Alexa J Resler, Mattia Cremona, Sarah Curry, Sinead Toomey, Robert O'Byrne, Orna Bacon, Michael Stühler, Lorna Flanagan, Richard Wilson, Patrick G Johnston, Manuel Salto-Tellez, Sophie Camilleri-Broët, Deborah A McNamara, Elaine W Kay, Bryan T Hennessy, Pierre Laurent-Puig, Sandra Van Schaeybroeck, Jochen H M Prehn
OBJECTIVE: The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). DESIGN: Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC...
September 23, 2016: Gut
Catherine E Bond, Diane M McKeone, Murugan Kalimutho, Mark L Bettington, Sally-Ann Pearson, Troy D Dumenil, Leesa F Wockner, Matthew Burge, Barbara A Leggett, Vicki L J Whitehall
Serrated pathway colorectal cancers (CRCs) are characterised by a BRAF mutation and half display microsatellite instability (MSI). The Wnt pathway is commonly upregulated in conventional CRC through APC mutation. By contrast, serrated cancers do not mutate APC. We investigated mutation of the ubiquitin ligases RNF43 and ZNRF3 as alternate mechanism of altering the Wnt signal in serrated colorectal neoplasia. RNF43 was mutated in 47/54(87%) BRAF mutant/MSI and 8/33(24%) BRAF mutant/microsatellite stable cancers compared to only 3/79(4%) BRAF wildtype cancers (p<0...
September 20, 2016: Oncotarget
Noralane M Lindor, Melissa C Larson, Melissa S DeRycke, Shannon K McDonnell, Saurabh Baheti, Zachary C Fogarty, Aung Ko Win, John D Potter, Daniel D Buchanan, Mark Clendenning, Polly A Newcomb, Graham Casey, Steven Gallinger, Loïc Le Marchand, John L Hopper, Mark A Jenkins, Ellen L Goode, Stephen N Thibodeau
MicroRNAs (miRNAs) regulate up to one-third of all protein-coding genes including genes relevant to cancer. Variants within miRNAs have been reported to be associated with prognosis, survival, response to chemotherapy across cancer types, in vitro parameters of cell growth, and altered risks for development of cancer. Five miRNA variants have been reported to be associated with risk for development of colorectal cancer (CRC). In this study, we evaluated germline genetic variation in 1,123 miRNAs in 899 individuals with CRCs categorized by clinical subtypes and in 204 controls...
September 16, 2016: Genes, Chromosomes & Cancer
Melanie Maierthaler, Axel Benner, Michael Hoffmeister, Harald Surowy, Lina Jansen, Phillip Knebel, Jenny Chang-Claude, Hermann Brenner, Barbara Burwinkel
Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I-IV disease from a population-based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards...
September 15, 2016: International Journal of Cancer. Journal International du Cancer
Jinhua Piao, Paul Friedman, Sameer Siddiqui, Jula Veerapong, Jin-Ping Lai
Synchronous colorectal cancer (CRC) and renal cell carcinoma (RCC) is relatively rare, particularly when the synchronous RCC is of papillary subtype, which is exceedingly rare. We report a case of a 63-year-old Caucasian man with synchronous CRC and type 1 papillary RCC. After the patient presented with three episodes of melena, colonoscopy followed by biopsy confirmed rectal adenocarcinoma. The computed tomographic imaging also showed an incidental mass of the upper pole of the left kidney suspicious for RCC...
September 2016: Anticancer Research
Masakazu Sugiyama, Eiji Oki, Yu Nakaji, Satoshi Tsutsumi, Naomi Ono, Ryota Nakanishi, Masahiko Sugiyama, Yuichiro Nakashima, Hideto Sonoda, Kippei Ohgaki, Nami Yamashita, Hiroshi Saeki, Shinji Okano, Hiroyuki Kitao, Masaru Morita, Yoshinao Oda, Yoshihiko Maehara
: The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged-1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E-cadherin and their associations with clinicopathologic characteristics, overall survival (OS), and relapse-free survival (RFS) were evaluated...
September 2, 2016: Cancer Science
Kiyoko Takane, Keisuke Matsusaka, Satoshi Ota, Masaki Fukuyo, Yao Yue, Motoi Nishimura, Eiji Sakai, Kazuyuki Matsushita, Hideaki Miyauchi, Hiroyuki Aburatani, Yukio Nakatani, Tadatoshi Takayama, Hisahiro Matsubara, Kiwamu Akagi, Atsushi Kaneda
While sporadic colorectal cancer (CRC) is classified into several molecular subtypes, stratification of familial colorectal tumors is yet to be well investigated. We previously established two groups of methylation markers through genome-wide DNA methylation analysis, which classified sporadic CRC and adenoma into three distinct subgroups: high-, intermediate-, and low-methylation epigenotypes. Here, we investigated familial adenomatous polyposis (FAP), through quantitative methylation analysis of 127 samples (16 cancers, 96 adenomas, and 15 benign mucosa from 14 patients with FAP) using six Group-1 and 14 Group-2 methylation markers, APC, BRAF, and KRAS mutation analysis, and CTNNB1 and TP53 immunohistochemical analysis...
August 22, 2016: Oncotarget
Sajid A Khan, Melinda Morris, Kamran Idrees, Mark I Gimbel, Shoshana Rosenberg, Zhaoshi Zeng, Fangyong Li, Geliang Gan, Jinru Shia, Michael P LaQuaglia, Philip B Paty
INTRODUCTION: Colorectal cancer (CRC) diagnosed before age 30 years is a fatal disease whose biology remains poorly understood. To understand its pathogenesis, we compared molecular and clinical data in surgically treated early-age onset and adult onset patients. MATERIALS AND METHODS: Clinical data and tumor tissue were collected retrospectively for 94 patients with early-age onset CRC (age ≤30 years) and compared to 275 adult CRC patients (age ≥50 years). Tumor morphology, microsatellite instability (MSI) and stability (MSS), KRAS and BRAF mutations, and mismatch repair (MMR) expression (MSH2, MLH1, MSH6, PMS2) were assessed...
November 2016: Journal of Pediatric Surgery
Anne Trinh, Kari Trumpi, Felipe de Sousa E Melo, Xin Wang, Joan H de Jong, Evelyn Fessler, Peter J K Kuppen, Marlies S Reimers, Marloes Swets, Miriam Koopman, Iris D Nagtegaal, Marnix Jansen, Gerrit K J Hooijer, G Johan Offerhaus, Onno Kranenburg, Cornelis J A Punt, Jan Paul Medema, Florian Markowetz, Louis Vermeulen
PURPOSE: Recent transcriptomic analyses have identified four distinct molecular subtypes of colorectal cancer (CRC) with evident clinical relevance. However, the requirement for sufficient quantities of bulk tumor and difficulties in obtaining high quality genome-wide transcriptome data from formalin-fixed paraffin-embedded tissue are obstacles towards widespread adoption of this taxonomy. Here, we develop an immunohistochemistry-based classifier to validate the prognostic and predictive value of molecular CRC subtyping in a multi-center study...
July 26, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Dong Hoon Lee, NaNa Keum, Edward L Giovannucci
OBJECTIVES: To review the contribution of the Nurses' Health Study (NHS) to identifying risk and protective factors for colorectal adenomas and colorectal cancer (CRC). METHODS: We performed a narrative review of the publications using the NHS between 1976 and 2016. RESULTS: Existing epidemiological studies using the NHS have reported that red and processed meat, alcohol, smoking, and obesity were associated with an increased risk of CRC, whereas folate, calcium, vitamin D, aspirin, and physical activity were associated with decreased risk of CRC...
September 2016: American Journal of Public Health
Erin M Bertino, Elizabeth L McMichael, Xiaokui Mo, Prashant Trikha, Melanie Davis, Bonnie Paul, Michael Grever, William E Carson, Gregory A Otterson
mAbs can induce antibody-dependent cellular cytotoxicity (ADCC) via the innate immune system's ability to recognize mAb-coated cancer cells and activate immune effector cells. Lenalidomide is an immunomodulatory agent with the capacity to stimulate immune cell cytokine production and ADCC activity. This phase I trial evaluated the combination of cetuximab with lenalidomide for the treatment of advanced colorectal and head and neck squamous cell cancers (HNSCC). This trial included patients with advanced colorectal cancer or HNSCC...
September 2016: Molecular Cancer Therapeutics
Deborah Rotoli, Manuel Morales, María Del Carmen Maeso, María Del Pino García, Araceli Morales, Julio Ávila, Pablo Martín-Vasallo
The immunophilin FK506-binding protein 5 (FKBP51) is a scaffold protein that serves a pivotal role in the regulation of multiple signaling pathways, integrating external and internal stimuli into distinct signal outputs. In a previous study, we identified several genes that are significantly up- or downregulated in the peripheral white cells (PWCs) of colorectal adenocarcinoma (CRC) patients undergoing oxaliplatin-based chemotherapy. In our screening, FKBP51 gene expression was downregulated following chemotherapy...
August 2016: Oncology Letters
Emmanuel K Abudu, Oluyinka S Akinbami
Colorectal carcinomas (CRC) were initially thought to be rare in Africa including Nigeria, but recent studies have shown a reverse trend in our environment. This study is aimed to identify the clinical and pathological characteristics of CRC diagnosed between July 2006 and June 2015 in the University of Uyo Teaching Hospital, and a Private Specialist Laboratory, Uyo, Akwa Ibom State, Nigeria. All histological diagnosed cases of CRC seen in the two laboratories (University teaching and a private facility) in Uyo, Akwa-Ibom state, Nigeria during the study period were retrieved noting their bio-data, pathological and clinical variables...
June 28, 2016: Rare Tumors
M Tong, W Zheng, H Li, X Li, L Ao, Y Shen, Q Liang, J Li, G Hong, H Yan, H Cai, M Li, Q Guan, Z Guo
Until recently, few prognostic signatures for colorectal cancer (CRC) patients receiving 5-fluorouracil (5-FU)-based chemotherapy could be used in clinical practice. Here, using transcriptional profiles for a panel of cancer cell lines and three cohorts of CRC patients, we developed a prognostic signature based on within-sample relative expression orderings (REOs) of six gene pairs for stage II-III CRC patients receiving 5-FU-based chemotherapy. This REO-based signature had the unique advantage of being insensitive to experimental batch effects and free of the impractical data normalization requirement...
2016: Oncogenesis
Virginia E Duncan, Shuko Harada, Todd M Stevens
We report a case of a 53-year-old woman who presented with rectal bleeding and a 9.5 cm hemicircumferential ascending colon mass. Histology revealed adenosquamous carcinoma (ASC), a rare subtype comprised of malignant squamous and glandular elements. Immunohistochemistry revealed loss of MLH1/PMS2 expression and retained MSH2/MSH6 expression in squamous and glandular components, indicative of microsatellite instability (MSI). MSI is caused by loss-of-function defects in DNA mismatch repair genes, leading to increased susceptibility to a variety of neoplasms; the role of MSI in colorectal ASC is unknown...
October 2016: International Journal of Surgical Pathology
Anne Tuomisto, José García-Solano, Päivi Sirniö, Juha Väyrynen, Miguel Pérez-Guillermo, Markus J Mäkinen, Pablo Conesa-Zamora
Serrated colorectal adenocarcinoma (SAC) is a morphologically distinct subtype of colorectal cancer (CRC), in which increased HIF-1α mRNA expression and HIF-1α protein stabilization are typical features. Here we aimed to further elucidate HIF-1α protein expression in serrated and non-serrated colorectal carcinomas (CRCs) and their precursor lesions and its association with vascular endothelial growth factor (VEGF) and microvascular density (MVD). HIF-1α and VEGF expressions were determined immunohistochemically in 134 serrated polyps (SPs), 104 non-serrated adenomas (NSAs), 81 SACs, and 74 matched conventional adenocarcinomas (CCs) and were correlated with morphology, clinicopathological features, and MVD...
October 2016: Virchows Archiv: An International Journal of Pathology
Koichi Okamoto, Shinji Kitamura, Tetsuo Kimura, Tadahiko Nakagawa, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Tetsuji Takayama
Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers (CRCs). Accordingly, serrated polyps such as traditional serrated adenoma (TSA) and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into 3 subtypes, consisting of hyperplastic polyp (HP), SSA/P, and TSA, according to the World Health Organization (WHO) classification...
July 4, 2016: Journal of Gastroenterology and Hepatology
Natasja L de Vries, Marloes Swets, Alexander L Vahrmeijer, Marianne Hokland, Peter J K Kuppen
Although most cancer types have been viewed as immunologically silent until recently, it has become increasingly clear that the immune system plays key roles in the course of tumor development. Remarkable progress towards understanding cancer immunogenicity and tumor-immune system interactions has revealed important implications for the design of novel immune-based therapies. Natural immune responses, but also therapeutic interventions, can modulate the tumor phenotype due to selective outgrowth of resistant subtypes...
2016: International Journal of Molecular Sciences
David Barras, Edoardo Missiaglia, Pratyaksha Wirapati, Oliver M Sieber, Robert N Jorissen, Christopher Love, Peter L Molloy, Ian T Jones, Stephen McLaughlin, Peter Gibbs, Justin Guinney, Iris M Simon, Arnaud Roth, Fred T Bosman, Sabine Tejpar, Mauro Delorenzi
PURPOSE: Mutation of BRAF at the valine 600 residue occurs in ~10% of colorectal cancers (CRC), a group with particularly poor prognosis. The response of BRAF mutant CRC to recent targeted strategies such as anti-BRAF or combinations with MEK and EGFR inhibitors remains minimal and highly heterogeneous within BRAF V600E cohorts. There is clearly an unmet need in understanding the biology of BRAF V600E CRC and potential subgroups within this population. EXPERIMENTAL DESIGN: In the biggest yet reported cohort of 218 BRAF V600E with gene expression data, we performed unsupervised clustering using non-negative matrix factorization to identify gene expression based subgroups and characterized pathway activation...
June 27, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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