Molecular characterization of sessile serrated adenoma/polyps with dysplasia/carcinoma based on immunohistochemistry, next-generation sequencing, and microsatellite instability testing: a case series study.

Published on Nov 20, 2018in Diagnostic Pathology2.335
· DOI :10.1186/S13000-018-0771-3
Takashi Murakami10
Estimated H-index: 10
(Juntendo University),
Yoichi Akazawa9
Estimated H-index: 9
(Juntendo University)
+ 6 AuthorsTakashi Yao63
Estimated H-index: 63
(Juntendo University)
Background Colorectal sessile serrated adenoma/polyps (SSA/Ps) are considered early precursor lesions in the serrated neoplasia pathway. Recent studies have shown associations of SSA/Ps with lost MLH1 expression, a CpG island methylator phenotype, and BRAF mutations. However, the molecular biological features of SSA/Ps with early neoplastic progression have not yet been fully elucidated, owing to the rarity of cases of SSA/P with advanced histology such as cytologic dysplasia or invasive carcinoma. In this study, we aimed to elucidate the molecular biological features of SSA/Ps with dysplasia/carcinoma, representing relatively early stages of the serrated neoplasia pathway.
📖 Papers frequently viewed together
42 Citations
37 Citations
15 Authors (Helen H.N. Yan, ..., Suet Yi Leung)
104 Citations
#1Mark Bettington (UQ: University of Queensland)H-Index: 19
#2Neal I. Walker (UQ: University of Queensland)H-Index: 36
Last. Vicki L. J. Whitehall (UQ: University of Queensland)H-Index: 34
view all 9 authors...
Objective Sessile serrated adenomas (SSAs) are the precursors of at least 15% of colorectal carcinomas, but their biology is incompletely understood. We performed a clinicopathological and molecular analysis of a large number of the rarely observed SSAs with dysplasia/carcinoma to better define their features and the pathways by which they progress to carcinoma. Design A cross-sectional analysis of 137 SSAs containing regions of dysplasia/carcinoma prospectively collected at a community GI patho...
116 CitationsSource
#1Magomed KhaidakovH-Index: 23
#2Keith Lai (University of Arkansas for Medical Sciences)H-Index: 13
Last. Curt H. HagedornH-Index: 42
view all 8 authors...
Objectives: A subset of colon cancers originates from sessile serrated adenomas/polyps (SSA/Ps). Our goal was to identify markers for SSA/Ps that could aid in distinguishing them from hyperplastic polyps (HPs). Methods: We performed immunostaining for gastric proteins MUC5AC and TFF1 in formalin-fixed, paraffin-embedded (FFPE) samples of HPs (n = 47), SSA/Ps (n = 37), and normal colon (n = 30). Results: Control mucosa expressed only trace amounts of MUC5AC and TFF1. HPs exhibited an 11.3- and 11...
11 CitationsSource
#1Umberto Malapelle (University of Naples Federico II)H-Index: 29
#2Pasquale Pisapia (University of Naples Federico II)H-Index: 17
Last. Giancarlo Troncone (University of Naples Federico II)H-Index: 55
view all 9 authors...
Aims The incidence of RAS/RAF/PI3KA and TP53 gene mutations in colorectal cancer (CRC) is well established. Less information, however, is available on other components of the CRC genomic landscape, which are potential CRC prognostic/predictive markers. Methods Following a previous validation study, ion-semiconductor next-generation sequencing (NGS) was employed to process 653 routine CRC samples by a multiplex PCR targeting 91 hotspot regions in 22 CRC significant genes. Results A total of 796 s...
54 CitationsSource
#1Jun CaoH-Index: 6
#2Minghua GeH-Index: 10
Last. Zhi-Qiang LingH-Index: 14
view all 3 authors...
Rapidly accumulating data indicate that F-box/WD repeat-containing protein 7 (Fbxw7) is one of the most frequently mutated genes in human cancers and regulates a network of crucial oncoproteins. These studies have generated important new insights into tumorigenesis and may soon enable therapies targeting the Fbxw7 pathway. We searched PubMed, Embase, and ISI Web of Science databases (1973–2015, especially recent 5 years) for articles published in the English language using the key words “Fbxw7,”...
53 CitationsSource
#1Chia-Chu Chang (TMU: Taipei Medical University)H-Index: 2
#2Hung-Hsin Lin (NYMU: National Yang-Ming University)H-Index: 11
Last. Shih-Ching Chang (NYMU: National Yang-Ming University)H-Index: 10
view all 11 authors...
Abstract This study aimed to determine the prognostic value of mutations in the tumor suppressor gene FBXW7 for clinical outcomes in colorectal cancer (CRC). Between January 2000 and December 2009, FBXW7 mutations in tumor tissues from 1,519 CRC patients at Taipei Veterans General Hospital were assessed using a MassArray system. We compared the clinicopathological variables and prognosis between the wild-type and mutant tumor tissue groups. FBXW7 mutations were present in 114/1,519 CRC patients ...
26 CitationsSource
#1Takashi Murakami (Juntendo University)H-Index: 10
#2Hiroyuki Mitomi (Dokkyo Medical University)H-Index: 31
Last. Sumio Watanabe (Juntendo University)H-Index: 63
view all 8 authors...
Distinct WNT/ β -catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum
41 CitationsSource
#1Michael J. O'Brien (BU: Boston University)H-Index: 92
#2Qing Zhao (BU: Boston University)H-Index: 1
Last. Shi Yang (BU: Boston University)H-Index: 16
view all 3 authors...
The serrated pathway (SP) can be viewed as two parallel, but partially overlapping, arrays of colorectal precursor lesions, and their respective endpoint carcinomas, that are distinct from those of the conventional adenoma–carcinoma sequence (APC-pathway). In this review we focus at the outset on the clinical impact, pathological features, molecular genetics and biological behaviours of the various SP cancers. Then we summarize the clinicopathological features, classification and molecular profi...
69 CitationsSource
#1Shinichi BanH-Index: 19
#2Hiroyuki Mitomi (Dokkyo Medical University)H-Index: 31
Last. Michio Shimizu (Saitama Medical University)H-Index: 40
view all 5 authors...
We reviewed the clinicopathological findings of eight cases of sessile serrated adenoma/polyps (SSA/Ps) with carcinoma, the largest diameter of which was 10 mm or less. All lesions were polyps located in the right side of the colon. Four lesions showed submucosal invasion and one lesion invaded the proper muscle layer. The depth of invasion, however, did not seem to be related to the carcinoma area size. Most carcinomas were well to moderately differentiated tubular adenocarcinomas focally showi...
19 CitationsSource
#1Zuanel DiazH-Index: 12
#2Adriana Aguilar-Mahecha (McGill University)H-Index: 16
Last. Gerald Batist (McGill University)H-Index: 64
view all 29 authors...
Next-generation biobanking of metastases to enable multidimensional molecular profiling in personalized medicine
29 CitationsSource
#1Michael Walsh (QIMR: QIMR Berghofer Medical Research Institute)H-Index: 113
#2Mark Clendenning (QIMR: QIMR Berghofer Medical Research Institute)H-Index: 40
Last. Daniel D. Buchanan (QIMR: QIMR Berghofer Medical Research Institute)H-Index: 66
view all 17 authors...
Mucinous differentiation is associated with both CpG island methylator phenotype and microsatellite instability in colorectal cancer. The mucinous phenotype derives from abundant expression of the colonic goblet cell mucin, MUC2, and de novo expression of gastric foveolar mucin, MUC5AC. We, therefore, investigated the protein expression levels of MUC2 and MUC5AC, as well as MUC5B and MUC6, in molecular subtypes of colorectal cancer. Seven-hundred and twenty-two incident colorectal carcinomas occ...
97 CitationsSource
Cited By13
#1Chiara Alquati (UNIBO: University of Bologna)H-Index: 2
#2Anna Prossomariti (UNIBO: University of Bologna)H-Index: 8
Last. Luigi Ricciardiello (UNIBO: University of Bologna)H-Index: 35
view all 7 authors...
Colorectal cancer (CRC) develops through a multi-step process characterized by the acquisition of multiple somatic mutations in oncogenes and tumor-suppressor genes, epigenetic alterations and genomic instability. These events lead to the progression from precancerous lesions to advanced carcinomas. This process requires several years in a sporadic setting, while occurring at an early age and or faster in patients affected by hereditary CRC-predisposing syndromes. Since advanced CRC is largely u...
1 CitationsSource
#2Hirokazu FukuiH-Index: 33
Last. Hiroto MiwaH-Index: 54
view all 9 authors...
Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma–carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the β-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. Fn was detecte...
#1Alexandra M Kane (UQ: University of Queensland)H-Index: 1
#2Cheng Liu (UQ: University of Queensland)H-Index: 9
Last. Vicki L. J. Whitehall (UQ: University of Queensland)H-Index: 34
view all 9 authors...
BACKGROUND Aspirin reduces the incidence of conventional adenomas driven by APC mutation and thus colorectal cancer. The effect of aspirin on the ~20% of colorectal cancers arising via BRAF mutation is yet to be established. METHODS BrafV637E/+;Villin-CreERT2/+ mice were allocated to a control (n = 86) or aspirin-supplemented (n = 83) diet. After 14 months the incidence of murine serrated lesions, carcinoma and distant metastases were measured by histological examination. RNA was extracted from ...
#1Giada MunariH-Index: 8
#2Gianluca Businello (UNIPD: University of Padua)H-Index: 3
Last. Matteo FassanH-Index: 62
view all 17 authors...
PURPOSE Non-neuroendocrine neoplasms of the appendix are a phenotypically heterogeneous group of lesions; a comprehensive molecular characterization of these tumors is still lacking. METHODS A total of 52 samples taken from 49 patients was evaluated: 18 sessile serrated lesions (SSL; 3 with dysplasia), 2 high-grade tubular adenomas, 1 tubulo-villous adenoma,1 hyperplastic polyp, 18 low-grade appendiceal mucinous neoplasms (LAMN), 3 high-grade appendiceal mucinous neoplasms (HAMN) and 9 mucinous ...
#1Iva Brcic (Medical University of Graz)H-Index: 10
#2Heather Dawson (University of Bern)H-Index: 21
Last. Karl Kashofer (Medical University of Graz)H-Index: 23
view all 5 authors...
BackgroundPatients with inflammatory bowel disease (IBD) and hyperplastic/serrated polyposis have an increased risk of colorectal cancer. The aim of our study was to elucidate the nature of serrate...
#1Enoch Kuo (UF: University of Florida)
#2Kai Wang (UF: University of Florida)
Last. Xiuli Liu (UF: University of Florida)H-Index: 9
view all 3 authors...
Colorectal cancer is the third most common cancer in both men and women in the United States, with most cases arising from precursor adenomatous polyps. Colorectal malignant polyps are defined as cancerous polyps that consist of tumor cells invading through the muscularis mucosae into the underlying submucosa (pT1 tumor). It has been reported that approximately 0.5-8.3% of colorectal polyps are malignant polyps, and the potential for lymph node metastasis in these polyps ranges from 8.5% to 16.1...
1 CitationsSource
#1Tomohiro Sugiyama (Hamamatsu University)H-Index: 1
#2Moriya Iwaizumi (Hamamatsu University)H-Index: 15
Last. Ken Sugimoto (Hamamatsu University)H-Index: 36
view all 12 authors...
The frequency of deficient mismatch repair (dMMR) or microsatellite instability-high colorectal cancer (CRC) is estimated to be ~15% of all patients with CRC; however, the patients reported are limited to surgical cases, and the frequency of patients exhibiting stage 0 disease is not considered, despite the currently increasing use of endoscopic techniques to cure a number of these patients. In the present study, the DNA MMR status for stage 0 patients with CRC treated using endoscopic submucosa...
#1Ryosuke Ota (Kanazawa University)H-Index: 6
#2Takeshi Sawada (Kanazawa University)H-Index: 15
Last. Toshinari Minamoto (Kanazawa University)H-Index: 51
view all 21 authors...
The molecular and clinical characteristics of non-ampullary duodenal adenomas and intramucosal adenocarcinomas are not fully understood because they are rare. To clarify these characteristics, we performed genetic and epigenetic analysis of cancer-related genes in these lesions. One-hundred seven non-ampullary duodenal adenomas and intramucosal adenocarcinomas, including 100 small intestinal type tumors (90 adenomas and 10 intramucosal adenocarcinomas) and 7 gastric type tumors (2 pyloric gland ...
5 CitationsSource
#1Rina Fujiwara-Tani (Nara Medical University)H-Index: 9
#2Kiyomu Fujii (Nara Medical University)H-Index: 24
Last. Hiroki Kuniyasu (Nara Medical University)H-Index: 63
view all 14 authors...
Sessile serrated adenoma/polyp with dysplasia (SSA/P-D) is an SSA/P with cellular dysplasia and has a higher risk of progressing to colon carcinogenesis. Previously, we reported that tight junction impairment by Clostridium perfringens enterotoxin (CPE) leads to activation of the transcriptional co-activator yes-associated protein (YAP) in oral squamous cell carcinoma. Here, we investigated whether CPE activates YAP to promote the malignant progression of SSA/P. E-cadherin expression was lower i...
4 CitationsSource
#1Wataru Sano (Yahoo!)H-Index: 1
#2Daizen HirataH-Index: 5
Last. Yasushi SanoH-Index: 35
view all 7 authors...
In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway. Colorectal serrated polyps are histopathologically classified into hyperplastic polyps (HPs), sessile serrated lesions, and traditional serrated adenomas; in the serrated neoplasia pathway, the latter two are considered to be premalignant. In western countries, all colorectal polyps, including serrated polyps, apart from diminutive re...
2 CitationsSource