• Biopsy
• Laparoscopic abdominoperineal resection
• Low rectal cancer
• Neuroendocrine differentiation
• Signet ring cell carcinoma

• Humans
• Carcinoma, Signet Ring Cell/surgery
• Carcinoma, Signet Ring Cell/diagnosis
• Carcinoma, Signet Ring Cell/pathology
• Carcinoma, Signet Ring Cell/complications
• Rectal Neoplasms/surgery
• Rectal Neoplasms/pathology
• Rectal Neoplasms/diagnosis
• Rectal Neoplasms/complications
• Male
• Aged

• Colorectal cancer
• Poorly cohesive cells
• Prognosis
• Risk factors
• Signet-ring cell histology
• Systematic review
• Therapeutic management

• biomarkers
• colorectal
• genomic
• multidisciplinary
• screening

• not available Sociedad Española de Oncología Médica (SEOM)
• not available Merck (Spain)

• acute appendicitis
• appendectomy
• appendix
• case report
• literature review
• signet ring cell carcinoma

• JP10/22 Faculty of Medical Sciences at the University of Kragujevac, Serbia

• appendiceal cancer
• colorectal cancer
• peritoneal metastases
• signet ring cells

• No specific number Bengt Ihre Research Fellowship
• No specific number Makarna Eriksson's fund at Uppsala University Hospital
• No specific number Lion's research fund in Uppsala
• 21 1719 Pj to TS and 22 2054 Pj 01H to BG Swedish Cancer Society

A large proportion of indigenous African (IA) colorectal cancer (CRC) patients in South Africa are young (< 50 years), with no unique histopathological or molecular characteristics. Anatomical site as well as microsatellite instability (MSI) status have shown to be associated with different clinicopathological and molecular features. This study aimed to ascertain key histopathological features in microsatellite stable (MSS) and low-frequency MSI (MSI-L) patients, to provide insight into the mechanism of the disease.

A retrospective cohort (2011–2015) of MSS/MSI-L CRC patient samples diagnosed at Charlotte Maxeke Johannesburg Academic Hospital was analyzed. Samples were categorized by site [right colon cancer (RCC) versus left (LCC)], ethnicity [IA versus other ethnic groups (OEG)] and MSI status (MSI-L vs MSS). T-test, Fischer’s exact and Chi-square tests were conducted.

IA patients with LCC demonstrated an increased prevalence in males, sigmoid colon, signet-ring-cell morphology, MSI-L with BAT25/26 marker instability and advanced disease association.

This study revealed distinct histopathological features for LCC, and suggests BAT25 and BAT26 as negative prognostic markers in African CRC patients. Larger confirmatory studies are recommended.

• African
• BAT25
• BAT26
• Colorectal cancer
• Low level microsatellite instability
• Microsatellite stable

• colorectal cancer
• meta-analysis
• signet ring cell carcinoma
• systematic review

• NGS
• colon
• genetics
• rare tumors
• rectum

Large pedunculated colorectal polyps are not frequent among colonic polyps. We present a clinical case of a large pedunculated colorectal polyp with signet ring cell cancer infiltrating the submucosa and lymph node invasion in a patient who ultimately underwent additional surgery. Clinicians should attach importance to pedunculated colorectal polyps and choose the most appropriate therapy.

A 52-year-old female farmer underwent routine screening colonoscopy and denied constipation, diarrhea, hematochezia, or other gastrointestinal symptoms. Her past medical history and general biochemical examination results were unremarkable. During the colonoscopy, a 25-mm pedunculated polyp in the sigmoid colon was identified. The superficial epithelium was macroscopically congestive, rough, and granular, showing characteristic features of adenoma. We first ligated the root of the pedunculated polyp using nylon loops as well as a titanium clip. Histopathological examination revealed high-grade intraepithelial neoplasia of the tumor surface and a negative margin with signet ring cell adenocarcinoma infiltrating the submucosal layer. The deepest infiltration was approximately 0.9 cm from the tumor surface and 0.55 cm from the stratum basale. We performed radical resection of the left colon with lymph node dissection after two weeks. The lesion was completely resected, and pathological assessment revealed signet ring cell adenocarcinoma infiltrating the submucosal layer as well as lymph node invasion (stage PT1N1M0 and grade IIIA in pathological grading, NRAS-, BRAF V600E-, KRAS-).

This case highlights the importance of paying attention to the malignancy of large pedunculated polyps. Polyps or adenomas removed via endoscopy must be evaluated histologically. Even if adenomas may be fragile, endoscopy doctors should still remove polyps as completely as possible and choose perpendicular sections through the stalk and base to fix by formaldehyde solution.

• Signet ring cell carcinoma
• Colorectal cancer
• Pedunculated colorectal polyp
• Surgery
• Pathology
• Case report

• Colon carcinoma
• Esophagus carcinoma
• Gastric carcinoma
• Rectal carcinoma
• Small bowel carcinoma

Colorectal signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC) with unique characteristics. Due to the limited researches on it, a comprehensive and in-depth understanding of this subtype is still lacking. In this article, we summarize the clinicopathological features and molecular characteristics of colorectal SRCC based on a literature review. Clinically, SRCC has been associated with young age, proximal site preference, advanced tumor stage, high histological grade, high rate of lymph node involvement, frequent peritoneal metastasis, and a significantly poor prognosis. Regarding molecular characteristics, in SRCC, the mutation burden of the classic signaling pathways that include WNT/β-catenin, RAS/RAF/MAPK, and PI3K/AKT/mTOR signaling pathways are generally reduced. In contrast, some genes related to the “epithelial-mesenchymal transition (EMT) process” and the “stem cell properties”, including RNF43, CDH1, and SMAD4, as well as the related TGF-β signaling pathway have been observed more frequently altered in SRCC than in conventional adenocarcinoma (AC). In many studies but not in others, SRCC showed a higher frequency of BRAF mutation, microsatellite instability-high (MSI-H) and CpG island methylator phenotype (CIMP) positive status compared to AC. It has been proposed that colorectal SRCC consists of two subtypes, in which the MSI⁺/CIMP⁺/BRAF⁺/CD3⁺/PD-L1⁺ hypermethylated genotype is more common in the proximal colon, and may represent the potential candidate for immunotherapy. Understanding the special molecular mechanisms related to the aggressive biology of SRCC is of great importance, which may provide a theoretical basis for the development of more targeted and effective treatments for this refractory disease.

• clinicopathology
• colorectal cancer
• molecular features
• review
• signet ring cell carcinoma

• Colorectal cancer
• Histopathological subtype
• Mucinous adenocarcinoma
• Non-predominant
• Signet-ring cell carcinoma

• Endoscopy
• Imaging studies
• Metastasis
• Rectal cancer
• Signet ring cell carcinoma

• Colorectal cancer
• Signet ring cell component
• Survival rate

• Colorectal cancer
• E-cadherin
• Early onset
• Microsatellite instability
• Signet ring cells

• Irinotecan
• Irinotecan-based regimens
• metastatic colorectal cancer

Signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC). The aim of this study was to characterise the genomic alterations and outcomes of SRCC.

Medical records of metastatic CRC (mCRC) patients whose tumours were evaluated by NGS analysis were reviewed. SC-mCRC were classified into two groups: SRCC (>50% signet ring cells) and adenocarcinoma (AC) with SC component (≤50% signet ring cells).

Six hundred and sixty-five mCRC patients were included. Of the 93 mCRC cases with SC features, 63 had slides for review. Of those 63 cases, 35 were confirmed SRCC, and 28 were AC with SC component. Compared with AC group, KRAS and PIK3CA mutations (mts) were found in only 11% (OR: 0.13) and 3% (OR: 0.15) of SRCC cases, respectively. In contrast to the 44% rate of APC mts in AC group, only 3% of SRCC patients had APC mts (OR = 0.04).

SRCC has distinct molecular features, including low rates of KRAS, PIK3CA and APC mts. Further study to identify activation pathways and potential therapeutic targets are needed.

• adenocarcinoma with osseous metaplasia
• clear cell carcinoma
• colorectal cancer histotypes
• cribriform/comedo-type carcinoma
• hepatoid carcinoma
• lymphoepitelioma-like carcinoma
• medullary carcinoma
• micropapillary carcinoma
• rhabdoid carcinoma
• signet ring cell carcinoma

• colorectal adenocarcinoma
• mucinous
• prognosis
• signet ring
• stage

• Cytoreductive surgery
• HIPEC
• IBD
• Peritoneal Metastases

• adenomatous polyp
• cancer stem cells
• colorectal cancer
• gene expression profiling
• gene sequencing
• serrated polyp
• tumor xenotrasplantation assay

The prognostic role of the V600E mutation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in metastatic colorectal cancer (mCRC) is well established, but the therapeutic regimen targeting this disease is lacking. This study aimed to analyze the clinicopathologic features of and treatment efficacy of commonly used regimens on BRAF-mutated mCRCs.

We collected and reviewed the medical records of mCRC patients treated at Peking University Cancer Hospital & Institute (Beijing, China) between July 2011 and July 2016. Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and BRAF mutational status was assayed using direct sequencing. The details of clinicopathologic characteristics of patients and their responses to FOLFOXIRI regimen or standard therapy were obtained by reviewing the medical records. The progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier analysis and compared using the log-rank test.

Of 1694 patients studied, 75 had BRAF exon 15 mutations. Of these 75 patients, 71 had V600E mutation, 1 had D594G mutation, 2 had K601E mutation, and 1 had a novel T599_V600insAGA alteration. No patients had KRAS or NRAS mutations. Of 63 patients with BRAF V600E-mutated mCRC and sufficient clinical data, 27 (42.9%) had right-sided colon tumors, 19 (30.2%) had left-sided colon tumors, and 17 (26.9%) had rectal tumors; 26 (41.3%) had peritoneal metastases, and 50 (79.4%) had distant lymph node metastases. The patients with BRAF K601E- and T599_V600insAGA-mutated tumors had similar clinicopathologic features to those with BRAF V600E-mutated tumors. Patients with the BRAF V600E mutation benefited more from FOLFOXIRI regimen compared with patients who underwent standard therapy (overall response rate 83.3% vs. 14.0%; median PFS 6.4 months vs. 2.8 months, P = 0.220; median OS 11.0 months vs. 6.9 months, P = 0.048).

BRAF V600E mutations were commonly identified in right-sided tumors and showed a high incidence of peritoneal and distant lymph nodes metastases. This subtype of mCRC was characterized by short OS and unique patterns of metastasis. Compared with standard treatment regimens, the FOLFOXIRI regimen had acceptable and manageable toxicities and favorable efficacy on patients with BRAF-mutated mCRC.

• BRAF
• Chemotherapy
• Colorectal cancer
• Prognosis

The aim of this study was to analyze the clinicopathological features and prognosis of esophageal signet ring cell (SRC) carcinoma in China.

Patients with poorly differentiated adenocarcinoma were identified in two hospitals from January 2006 to June 2016. The patients were divided into three groups according to component of SRCs: SRC≥50% group, SRC < 50% group and non-SRC poorly differentiated adenocarcinoma group.

Fifty-seven patients had carcinoma (SRC≥50%), and 79 patients had tumors containing <50% SRCs, and 535 patients was in non-SRC poorly differentiated adenocarcinoma group. There were no significant differences among the three groups in clinicopathological characteristics. Patients in SRC≥50% group had a lower overall survival rate (at 3-year 37.6%versus71.1%; at 5-year 0% versus 43.3%; p<0.001) compared with the control group. Even survival outcome of patients in SRC < 50%was inferior to that of in control group (at 3-year 53.0%versus71.1%; at 5-year 25.9% versus 43.3%; p<0.001). Female sex, large tumor size and increasing TNM stage were independent prognostic factors for SRC ≥50% esophageal carcinoma patients.

The incidence of esophageal SRC carcinoma is relatively rare and the worst outcome is observed in the SRC≥ 50% group. It is necessary to explore new therapeutic modalities to achieve further improvements in the clinical outcome of these patients.

• Aged
• Carcinoma, Signet Ring Cell/pathology
• Carcinoma, Signet Ring Cell/surgery
• Cell Differentiation
• China
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/surgery
• Female
• Humans
• Male
• Middle Aged
• Retrospective Studies
• Survival Analysis

The microRNA, miR-196b, serves a role in normal cell differentiation, proliferation and tumorigenesis of different types of cancer. The aim of the present study was to explore the serum expression of miR-196b in colorectal cancer (CRC) and its correlation with clinicopathological features. Sera samples were obtained from 103 patients with CRC, 51 patients with colorectal adenoma (Ad) and 100 healthy individuals for the present study. The serum expression of miR-196b in sera samples of the three cohorts was detected using reverse transcription-quantitative polymerase chain reaction. The diagnostic value of miR-196b in the serum of the patients with CRC was evaluated by receiver operating characteristic (ROC) curve and survival analysis, using the Kaplan-Meier method, which was performed with the data from a 5-year follow-up. The expression of miR-196b in the serum of patients with CRC was significantly higher compared with that in Ad patients or healthy individuals (all P<0.001), and the overexpression of serum miR-196b was clearly associated with lymph node invasion, differentiation, and the tumor-lymph nodes-metastasis stage (all P<0.05). ROC curve analysis demonstrated that, comparing patients with CRC with healthy individuals, the area under the curve of serum miR-196b was 0.8135, and its specificity and sensitivity were 63 and 87.38%, respectively, at a diagnostic threshold of −4.785. Patients with CRC of miR-196b-high status had shorter overall survival and disease-free survival rates compared with those of miR-196b-low status. In conclusion, the results of the present study demonstrated that serum miR-196b is upregulated in CRC, and may have an application as a diagnostic and prognostic biomarker for patients with CRC.

• biomarker
• colorectal cancer
• diagnosis
• miR-196b
• prognosis