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Stephanie M Wood, Anthony J Gill, Alexander S Brodsky, Shaolei Lu, Kenneth Friedman, Galina Karashchuk, Kara Lombardo, Dongfang Yang, Murray B Resnick
Fatty acid-binding protein 1 (FABP1) is an intracellular protein responsible for the transportation of long chain fatty acids. Aside from its functions in lipid metabolism and cellular differentiation, FABP1 also plays a role in inflammation through its interaction with peroxisome proliferator-activated receptors (PPARs). Previously, we compared expression of colonic epithelium genes in a subset of microsatellite instable (MSI) colorectal carcinomas (medullary carcinomas) to normal colonic mucosa and found that FABP1 expression was markedly decreased in the tumors...
September 30, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Ondřej Kubeček, Jindřich Kopecký
Microsatellite instability (MSI) and mismatch repair deficiency are an emerging issue in oncology and molecular pathology. Besides being associated with better clinical outcome in colon cancer, MSI also harbors the potential to predict response to chemotherapy and immunotherapy. MSI was also observed in other solid tumors, including endometrial cancer, ovarian cancer, and melanoma, besides colon cancer. Strong evidence shows that MSI is a frequent event in melanoma. However, the data on MSI prevalence, pathogenesis, and clinical consequences in melanoma are limited...
September 12, 2016: Melanoma Research
Kevin Berthenet, Christophe Boudesco, Ada Collura, Magali Svrcek, Sarah Richaud, Arlette Hammann, Sebastien Causse, Nadhir Yousfi, Kristell Wanherdrick, Laurence Duplomb, Alex Duval, Carmen Garrido, Gaetan Jego
HSP110 is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps the cells to survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently showed that colorectal cancer (CRC) patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110 inactivating mutation (HSP110DE9). In this work, we have used patients' biopsies and human CRC cells grown in vitro and in vivo (xenografts) to demonstrate that (1) HSP110 is secreted by CRC cells and that the amount of this extracellular HSP110 is strongly decreased by the expression of the mutant HSP110DE9, (2) Supernatants from CRC cells overexpressing HSP110 or purified recombinant human HSP110 (LPS-free) affect macrophage differentiation/polarization by favoring a pro-tumor, anti-inflammatory profile, (3) Conversely, inhibition of HSP110 (expression of siRNA, HSP110DE9 or immunodepletion) induced the formation of macrophages with a cytotoxic, pro-inflammatory profile...
July 2016: Oncoimmunology
María Arriba, Ricardo Sánchez, Daniel Rueda, Laura Gómez, Juan L García, Yolanda Rodríguez, José Antonio Pajares, Jessica Pérez, Miguel Urioste, Rogelio González Sarmiento, José Perea
BACKGROUND: Two or more primary colorectal tumors coexisting at the time of diagnosis are considered to be synchronous tumors. It is estimated that synchronous colorectal cancer (SCRC) only accounts for 1.1% to 8.1% of all colorectal cancers (CRCs), and its molecular basis is still poorly understood. PATIENTS AND METHODS: We evaluated the microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) statuses in a series of 49 patients (98 tumors) diagnosed with sporadic SCRC at the 12 de Octubre University Hospital with the aim of improving the molecular characterization of this type of tumor...
August 9, 2016: Clinical Colorectal Cancer
Bo Young Oh, So-Young Kim, Yeo Song Lee, Hye Kyung Hong, Tae Won Kim, Seok Hyung Kim, Woo Yong Lee, Yong Beom Cho
Colorectal cancer (CRC) with microsatellite instability (MSI) may exhibit impaired epithelial-mesenchymal transition (EMT), but little is known about the underlying mechanisms of this phenomenon. In this study, we investigated the role of Twist1 and its downstream signaling cascades in EMT induction according to MSI status. To investigate the effects of Twist1 on EMT induction according to MSI status, MSS LS513 and MSI LoVo colon cancer cell lines, which overexpress human Twist1, were generated. Twist1-induced EMT and its downstream signaling pathways were evaluated via in vitro and in vivo experiments...
August 1, 2016: Oncotarget
Patrícia Silva, Cristina Albuquerque, Pedro Lage, Vanessa Fontes, Ricardo Fonseca, Inês Vitoriano, Bruno Filipe, Paula Rodrigues, Susana Moita, Sara Ferreira, Rita Sousa, Isabel Claro, Carlos Nobre Leitão, Paula Chaves, António Dias Pereira
Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and/or polyps/CRC (SPP-FHP/CRC). Sixty-two lesions from 12 patients with SPP-FHP/CRC and 6 patients with sporadic SPP were included. The patients with SPP-FHP/CRC presented with an older mean age at diagnosis (p=0...
September 2016: International Journal of Molecular Medicine
Ehsan Nazemalhosseini Mojarad, Seyed Mohammad Hossein Kashfi, Hanieh Mirtalebi, Mohammad Yaghoob Taleghani, Pedram Azimzadeh, Sanaz Savabkar, Mohammad Amin Pourhoseingholi, Hasan Jalaeikhoo, Hamid Asadzadeh Aghdaei, Peter J K Kuppen, Mohammad Reza Zali
The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance...
2016: Journal of Oncology
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
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
H M Mohan, E Ryan, I Balasubramanian, R Kennelly, R Geraghty, F Sclafani, D Fennelly, R McDermott, E J Ryan, D O'Donoghue, J M P Hyland, S T Martin, P R O'Connell, D Gibbons, Des Winter, K Sheahan
BACKGROUND: Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. METHODS: Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St...
June 22, 2016: European Journal of Surgical Oncology
Amikar Sehdev, Harvey M Cramer, Ashley A M Ibrahim, Anne E Younger, Bert H O'Neil
IMPORTANCE: Mismatch repair (MMR) and BRAF mutation status are established independent prognostic factors for colorectal cancer (CRC). MMR deficient tumors are considered to have better prognosis whereas BRAF mutation is associated with poor prognosis. Studies evaluating the combined effect of BRAF and MMR status suggest MSI-high and BRAF mutant patients have a poorer prognosis as compared to MSI-high and BRAF wild type patients. Emerging evidence suggests MMR status predicts the immune response to anti-PD-1 therapy in CRC patients; however little is known about combined MMR and BRAF mutation status in this context...
May 2016: Discovery Medicine
Martin M Watson, Kjetil Søreide
The TNM-system fails to accurately predict disease recurrence in a considerate number of patients. While node-negative (stage II) colon cancer is considered to have an overall good prognosis, the 5-year cancer-specific survival is reported at 81-83% in patients who did not have adjuvant chemotherapy. Thus, reliance on node-status alone has lead to under-treatment in a subgroup of stage II patients with an unfavorable prognosis. The search for new and better prognosticators in stage II colon cancer has suggested several proposed biomarkers of better prognostication and prediction...
May 3, 2016: Molecular Medicine
Chang Gon Kim, Joong Bae Ahn, Minkyu Jung, Seung Hoon Beom, Chan Kim, Joo Hoon Kim, Su Jin Heo, Hyung Soon Park, Jee Hung Kim, Nam Kyu Kim, Byung Soh Min, Hoguen Kim, Woong Sub Koom, Sang Joon Shin
BACKGROUND: Among colorectal cancers (CRCs), high-frequency microsatellite instability (MSI-H) is associated with a better prognosis, compared with low-frequency MSI or microsatellite stability (MSI-L/MSS). However, it is unclear whether MSI affects the prognosis of recurrent CRCs. METHODS: This study included 2940 patients with stage I-III CRC who underwent complete resection. The associations of MSI status with recurrence patterns, disease-free survival (DFS), overall survival from diagnosis to death (OS1), and overall survival from recurrence to death (OS2) were analysed...
June 28, 2016: British Journal of Cancer
M Alizade Naini, P Mokarram, S Kavousipour, N Zare, A Atapour, M Hassan Zarin1, G Mehrabani, M Borji
BACKGROUND: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Martha L Slattery, Jennifer S Herrick, Lila E Mullany, Erica Wolff, Michael D Hoffman, Daniel F Pellatt, John R Stevens, Roger K Wolff
MiRNAs regulate gene expression by post-transcriptionally suppressing mRNA translation or by causing mRNA degradation. It has been proposed that unique miRNAs influence specific tumor molecular phenotype. In this paper, we test the hypotheses that miRNA expression differs by tumor molecular phenotype and that those differences may influence prognosis. Data come from population-based studies of colorectal cancer conducted in Utah and the Northern California Kaiser Permanente Medical Care Program. A total of 1893 carcinoma samples were run on the Agilent Human miRNA Microarray V19...
August 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Yohei Masugi, Reiko Nishihara, Juhong Yang, Kosuke Mima, Annacarolina da Silva, Yan Shi, Kentaro Inamura, Yin Cao, Mingyang Song, Jonathan A Nowak, Xiaoyun Liao, Katsuhiko Nosho, Andrew T Chan, Marios Giannakis, Adam J Bass, F Stephen Hodi, Gordon J Freeman, Scott Rodig, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
OBJECTIVE: Evidence suggests that CD274 (programmed death-ligand 1, B7-H1) immune checkpoint ligand repress antitumour immunity through its interaction with the PDCD1 (programmed cell death 1, PD-1) receptor of T lymphocytes in various tumours. We hypothesised that tumour CD274 expression levels might be inversely associated with T-cell densities in colorectal carcinoma tissue. DESIGN: We evaluated tumour CD274 expression by immunohistochemistry in 823 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study...
May 5, 2016: Gut
J M Xu
Previous studies have demonstrated that there are biological differences between colon and rectal cancers. Recently, some authors have proposed that colorectal cancer could be classified into several categories according to the primary sites of the tumor, proximal or distal. It is speculated that the differences are due to different embryologic origin and time to initial diagnosis. Further evidence supports that the molecular differences in the status of K-ras, BRAF, and microsatellite instability (MSI) based on primary sites in the bowel are the basis that impacts the response to therapeutic agents and patient prognosis...
May 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Renato Costi, Caterina Santi, Lorena Bottarelli, Cinzia Azzoni, Alban Zarzavadjian Le Bian, Matteo Riccó, Leopoldo Sarli, Enrico Maria Silini, Vincenzo Violi
BACKGROUND AND OBJECTIVES: Anastomotic recurrence (AR), whose etiopathogenesis is attributed to intraluminal implantation of cancerous cells or metachronous carcinogenesis, is a major issue for patients undergoing colon cancer (CC) resection. The objective of the study is to throw some light on AR etiopathogenesis and to identify risk factors of AR in selecting patients to undergo early endoscopy. METHODS: An analysis of clinical and histopathological parameters, including MSI and LOH of seven sites (Myc-L, BAT26, BAT40, D5S346, D18S452, D18S64, D16S402) was performed in primary CC and AR of 18 patients...
August 2016: Journal of Surgical Oncology
Philip D Dunne, Paul G O'Reilly, Helen G Coleman, Ronan T Gray, Daniel B Longley, Patrick G Johnston, Manuel Salto-Tellez, Mark Lawler, Darragh G McArt
The Colorectal Cancer (CRC) Subtyping Consortium (CRCSC) recently published four consensus molecular subtypes (CMS's) representing the underlying biology in CRC. The Microsatellite Instable (MSI) immune group, CMS1, has a favorable prognosis in early stage disease, but paradoxically has the worst prognosis following relapse, suggesting the presence of factors enabling neoplastic cells to circumvent this immune response. To identify the genes influencing subsequent poor prognosis in CMS1, we analyzed this subtype, centered on risk of relapse...
May 2, 2016: Oncotarget
Ju Hwa Lee, Sang Yong Song, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee
A transcription factor-encoding gene ZNF292 is considered a candidate tumor suppressor gene (TSG). Its mutations have been identified in cancers from liver, colon, and bone marrow. However, ZNF292 inactivating mutations that might suppress the TSG functions have not been reported in gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI). In a public database, we found that ZNF292 gene had mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with MSI...
July 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
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