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Elena Trujillo-Arribas, Hada C Macher, Pilar Jiménez-Arriscado, Fernando de la Portilla, Patrocinio Molinero, Juan M Guerrero, Amalia Rubio
Genomic characterization of cell-free circulating tumour DNA (ctDNA) may offer an opportunity to assess clonal dynamics throughout the course of a patient's illness. The existence of KRAS driver mutations in colon cancer patients is determinant to decide their treatment and to predict their outcome. DNA is extracted automatically from 400 μL of serum using the MagNa Pure Compact with the Nucleic Acid Isolation Kit I. DNA amplification, COLD-PCR and HRM were performed in the same run in the Light Cycler 480...
2016: Advances in Experimental Medicine and Biology
Erina Takai, Yasushi Totoki, Hiromi Nakamura, Mamoru Kato, Tatsuhiro Shibata, Shinichi Yachida
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect molecular characteristics of tumors, supporting the concept of "liquid biopsy".We determined the mutational status of KRAS in plasma cfDNA using multiplex droplet digital PCR in 259 patients with PDAC, retrospectively...
2016: Advances in Experimental Medicine and Biology
Siavash Rahimi, Iolia Akaev, Costa Repanos, Peter A Brennan, Jean Daniel Dubois
Primary lingual intestinal-type adenocarcinomas are extremely rare with only a few cases described. A case with immunohistochemical expression of Androgen Receptor (AR) which was treated solely by chemo-radiotherapy is reported herein. A 54-year-old male was referred with symptoms of fullness in his tongue. Clinical examination showed an asymmetry of the tongue with a hard mass palpable within the middle of the tongue. Biopsy showed intestinal-type adenocarcinoma. The tumour showed positive staining with cytokeratin 7, cytokeratin 20, CDX2, AR, β-catenin and was mismatch repair proteins (MMR) proficient...
October 17, 2016: Head and Neck Pathology
Ji-Youn Han, Jae-Jin Choi, Jin Young Kim, You Lim Han, Geon Kook Lee
No abstract text is available yet for this article.
October 17, 2016: BMC Cancer
Taehwan Park, Chang-Ju Choi, Yeera Choi, Dong-Churl Suh
Cetuximab is a novel biological agent with superior therapeutic efficacy for colorectal cancer treatment. This study aimed to systematically review the existing evidence related to the cost-effectiveness of cetuximab. Areas covered: Using Medline and Cochrane Database of Systematic Reviews, a total of 12 articles were identified. Previous studies have shown mixed results on the cost-effectiveness of first-line cetuximab combined with FOLFIRI (5-Fluorouracil, leucovorin, irinotecan). However, cetuximab-irinotecan therapy as third-line treatment has consistently been found to be cost-ineffective compared to best supportive care or no third-line therapy...
October 18, 2016: Expert Review of Pharmacoeconomics & Outcomes Research
Yaser Atlasi, Rubina Noori, Ivana Marolin, Patrick Franken, Joana Brandao, Katharina Biermann, Paola Collini, Mariam Grigorian, Eugene Lukanidin, Noona Ambartsumian, Riccardo Fodde
INTRODUCTION: S100a4 is a calcium-binding protein belonging to the family of S100-proteins, highly expressed in different stromal cell types. S100A4 has been reported as a prognostic marker in colorectal cancer in association with tumour progression and metastasis. METHODS: In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models. RESULTS: We found that genetic ablation or overexpression of S100a4 in both Apc- and Smad4-mutant mice do not affect tumour initiation in the intestinal tract...
October 14, 2016: European Journal of Cancer
Carmine Pinto, Francesca Di Fabio, Gerardo Rosati, Ivan R Lolli, Enzo M Ruggeri, Libero Ciuffreda, Daris Ferrari, Giovanni Lo Re, Giovanni Rosti, Paolo Tralongo, Raimondo Ferrara, Oscar Alabiso, Silvana Chiara, Giovanni P Ianniello, Antonio Frassoldati, Domenico Bilancia, Giovanna A Campanella, Carlo Signorelli, Patrizia Racca, Elena Benincasa, Maria Elena Stroppolo, Francesco Di Costanzo
Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real-world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first-line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ-C30...
October 17, 2016: Cancer Medicine
Manojkumar Bupathi, Christina Wu
Colorectal cancer (CRC) is a heterogeneous disease for which the treatment backbone has primarily been cytotoxic chemotherapy. With better understanding of the involved molecular mechanisms, it is now known that there are a number of epigenetic and genetic events, which are involved in CRC pathogenesis. Specific biomarkers have been identified which can be used to determine the clinical outcome of patients beyond tumor staging and predict for treatment efficacy. Molecular testing is now routinely performed to select for patients that will benefit the most from targeted agents and immunotherapy...
October 2016: Journal of Gastrointestinal Oncology
Asha Bonney, Michael Christie, Anne Beaty, Sebastian Lunke, Graham Taylor, Louis Irving, Daniel Steinfort
BACKGROUND: With the rapid development of genotype-guided therapies, molecular testing is becoming important in the management of lung cancer. Bronchoscopy is one of the most common investigations performed to diagnose and investigate lung cancer. Given the limited samples often produced by bronchoscopy, this study aims to evaluate the feasibility of performing molecular testing on cell blocks created from bronchoscope cytology brush tip washings (BTW). METHODS: Patients with positive brush cytology for tumour cells had cell blocks created from the BTW...
September 2016: Journal of Thoracic Disease
Yoshiki Nando, Jiro Watari, Chiyomi Ito, Ken Hara, Takahisa Yamasaki, Takuya Okugawa, Takashi Kondo, Tomoaki Kono, Katsuyuki Tozawa, Toshihiko Tomita, Yoshio Ohda, Tadayuki Oshima, Hirokazu Fukui, Nagahide Matsubara, Naohiro Tomita, Seiichi Hirota, Hiroto Miwa
It is recommended that small (6-10 mm) lesions be treated with endoscopic resection (ER), while diminutive (≤ 5 mm) lesions are not currently an indication for ER according to the Japanese guidelines. The aim of this study was to evaluate the molecular alterations, and therefore treatment indications, in diminutive vs. small tubular adenoma (TA). We prospectively analyzed genetic instability, including microsatellite instability (MSI) and loss of heterozygosity, methylation status, KRAS/BRAF mutations, and Ki-67 staining in 96 TAs without a villous component...
October 13, 2016: Human Pathology
Pamela T Soliman, Qian Zhang, Russell R Broaddus, Shannon N Westin, David Iglesias, Mark F Munsell, Rosemarie Schmandt, Melinda Yates, Lois Ramondetta, Karen H Lu
OBJECTIVE: Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC. METHODS: In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery...
October 13, 2016: Gynecologic Oncology
Wen-Chih Huang, Chien-Chen Tsai, Chih-Chieh Chan
BACKGROUND/PURPOSE: Cholangiocarcinoma (CC) is a fatal malignancy originating from biliary tracts and constitutes approximately 10-20% of hepatobiliary cancers. CC is characterized by a very poor prognosis. The definite molecular mechanisms leading to oncogenesis remain unclear. This study aimed to perform mutation analysis and copy number changes of KRAS and BRAF genes of CC in Taiwan. METHODS: A total of 182 cases of biliary tact CC were studied for point mutation and quantitative real-time polymerase chain reaction analysis of KRAS and BRAF genes...
October 10, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Ottó Dócs, Katalin Hegyi, Attila Mokánszky, Anikó Mónusné, Lívia Beke, Csilla András, Judit Bedekovics, Gábor Méhes
Mutation rates determined by allele-specific PCR can be highly different in KRAS exon 2 mutant colorectal carcinoma (CRC) samples suggesting intratumoural heterogeneity. To address the effect of KRAS gene copy number on the relative mutant allele frequency the KRAS locus was individually quantified following FISH analysis in 36 cases. We observed, that mutant KRAS status was associated with an elevated KRAS locus number (2.36 ± 0.42 vs 2.63 ± 0.75; p = 0.037) reflecting an increased aneuploidy status but no true amplification of the locus...
October 15, 2016: Pathology Oncology Research: POR
Keisuke Goto, Daichi Maeda, Yukitsugu Kudo-Asabe, Takashi Hibiya, Akimasa Hayashi, Masashi Fukayama, Kenichi Ohashi, Akiteru Goto
AIMS: Hidradenoma papilliferum (HP) is a benign vulvar neoplasm that arises from anogenital mammary-like glands, and its morphology is similar to mammary intraductal papilloma. The aim of this study was to investigate oncogenic mutations involved in the tumourigenesis of HP. We focused specifically on PIK3CA and AKT1 mutations, which are both reported to be detected in 33% of mammary intraductal papillomas. METHODS: In total, seven HP cases were analysed. Clinicopathological analyses and immunohistochemistry for oestrogen receptor, p63, smooth muscle actin (SMA), p53 and β-catenin were performed...
October 14, 2016: Journal of Clinical Pathology
Kyuichi Kadota, Camelia S Sima, Maria E Arcila, Cyrus Hedvat, Mark G Kris, David R Jones, Prasad S Adusumilli, William D Travis
The potential clinical impact of KRAS and epidermal growth factor receptor (EGFR) mutations has been investigated in lung adenocarcinomas; however, their prognostic value remains controversial. In our study, we sought to investigate the prognostic significance of driver mutations using a large cohort of early-stage lung adenocarcinomas. We reviewed patients with pathologic early-stage, lymph node-negative, solitary lung adenocarcinoma who had undergone surgical resection (1995 to 2005; stage I/II=463/19). Tumors were classified according to the IASLC/ATS/ERS classification and genotyped by Sequenom MassARRAY system and polymerase chain reaction-based assays...
October 12, 2016: American Journal of Surgical Pathology
Alyssa M Krasinskas, Gerard J Oakley, Pelin Bagci, Kee-Taek Jang, Shih-Fan Kuan, Michelle D Reid, Ipek Erbarut, Volkan Adsay
Pancreatic cysts >1 cm lined by nonpapillary mucinous epithelium without ovarian-type stroma pose diagnostic challenges. The term "simple mucinous cyst" was recently proposed for this entity. Our goal was to determine the clinicopathologic characteristics of these cysts, as they have not been previously described. Of the 39 patients with pancreatic resections included in this study, the mean age was 65 years and the female-to-male ratio was 4:1. The characteristics of the cysts are as follows: 82% had elevated cyst fluid carcinoembryonic antigen levels, 67% were unilocular, 69% occurred in the body/tail, 92% did not communicate with pancreatic ducts, the mean size was 2...
October 12, 2016: American Journal of Surgical Pathology
Chenfei Zhou, Liangjun Zhu, Jun Ji, Fangmi Ding, Chao Wang, Qu Cai, Yingyan Yu, Zhenggang Zhu, Jun Zhang
Nimotuzumab, a monoclonal antibody against EGFR, has been shown to be efficacious in the treatment of advanced pancreatic cancer, but its predictive marker has not been established. The present study was designed to investigate the impact of EGFR and KRAS status on the antitumor efficacy of nimotuzumab and to explore its underlying mechanism of action. EGFR expression levels of pancreatic cancer cell lines, BxPC3, Panc-1, and Patu-8988, were analyzed by Western blot and immunocytochemistry, and their KRAS status was determined by gene sequencing...
October 13, 2016: Current Cancer Drug Targets
Ye Xu, Chen Zhu, Wenliang Qian, Min Zheng
PURPOSE: Although many studies have explored clinicopathologic characteristics and prognosis of lung adenocarcinoma, a few literatures reported the mutational status of lung adenocarcinomas with lepidic pattern and whether there is difference between adenocarcinomas with pure lepidic component and lepidic predominant adenocarcinomas remain unknown. METHODS: One hundred and thirty-three patients including 92 adenocarcinomas with pure lepidic component and 41 lepidic predominant adenocarcinomas were subjected to the study...
October 13, 2016: Journal of Cancer Research and Clinical Oncology
Timothy Chao, Emma E Furth, Robert H Vonderheide
Tumor-associated neutrophils are increasingly recognized for their ability to promote tumor progression, mediate resistance to therapy, and regulate immunosuppression. Evidence from various murine models has shown that the chemokine receptor CXCR2 attracts neutrophil into tumors and, therefore, represents a tractable therapeutic target. Here, we report prominent expression of a neutrophil gene signature in a subset of human pancreatic adenocarcinoma (PDA). CXCL5 was the most prominently expressed CXCR2 ligand in human PDA, and its expression was higher in PDA than in any other common tumor represented in The Cancer Genome Atlas...
October 13, 2016: Cancer Immunology Research
Ruoxu Dou, Reiko Nishihara, Yin Cao, Tsuyoshi Hamada, Kosuke Mima, Atsuhiro Masuda, Yohei Masugi, Yan Shi, Mancang Gu, Wanwan Li, Annacarolina da Silva, Katsuhiko Nosho, Xuehong Zhang, Jeffrey A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis...
October 13, 2016: Cancer Immunology Research
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