Comprehensive molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and colon.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 63-63
Author(s):  
Alberto Puccini ◽  
Kelsey Poorman ◽  
Mohamed E. Salem ◽  
Richard M. Goldberg ◽  
Anthony Frank Shields ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Tumor Location ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Molecular Profile ◽  
Molecular Characteristics ◽  
Molecular Features ◽  
Signet Ring ◽  
Ring Cell ◽  
The Impact

63 Background: Signet ring cell carcinoma (SRCC) is a rare variant of adenocarcinoma, accounting for about 10% of gastric cancer (GC) and 1% of colorectal cancer (CRC). SRCC is associated with poor prognosis, however little is known about the underlying molecular characteristics. Herein, we aimed to characterize the molecular features of SRCCs, and to compare the molecular profile of SRCC to adenocarcinoma; further, we assessed the impact of tumor location on the molecular profile of SRCC. Methods: SRCCs were analyzed using NGS (MiSeq on 47 genes, NextSeq on 592 genes), immunohistochemistry, and in-situ hybridization. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. Chi-square and t-tests were used for comparative analyses. Results: A total of 8,500 CRC and 1,100 GC were screened for SRCC histology. Seventy-six SRCC were identified from the CRC cohort (<1%) and 98 from the GC cohort (9%). The most frequently mutated genes in CRC-SRCC were TP53 (47%), ARID1A (26%), APC (25%), KRAS (22%), RFN43 (16%), KMT2D (12%), KMT2C (11%), SMAD4 (10%) and BRAF (10%), while in GC-SRCC were TP53 (42%), ARID1A (27%), CDH1 (11%), BAP1 (7%), PIK3CA (7%), ERBB2 (5%). When compared to non-SRCC histology (N=3522), CRC-SRCC (N=37) showed more frequently mutation in BRCA1 (11% vs 1%, P < .001) and less mutation in APC (19% vs 78%, P < .001), KRAS (22% vs 51%, P = .001) and TP53 (47% vs 73%, P = .001). Among GC cohort, SRCC (N=54) had a higher frequency of mutations in CDH1, BAP1, and ERBB2, and higher rate of amplification MYB compared to non-SRCC (N=540), although none of these differences were statistically significance. When we compared GC-SRCC vs. CRC-SRCC, only the mutation rate in APC (0% vs 25%) and KRAS (2% vs 22%) genes were significantly different (P < .001). Conclusions: Our research is the first to comprehensively characterize the molecular features of SRCC. Our data suggest that SRCCs harbor similar molecular profile, regardless the tumor location. On the other hand, significant differences were observed between SRCCs and non-SRCC tumors, therefore tailored therapy should be provided to these patients.

scholarly journals Clinical and molecular characteristics of mucosal signet-ring cell carcinoma in Helicobacter pylori-uninfected stomach

2020 ◽  
Author(s):  
Mariko Kiso ◽  
Yuji Urabe ◽  
Masanori Ito ◽  
Kazuhiko Masuda ◽  
Tomoyuki Boda ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Cell Carcinoma ◽  
Clinicopathological Characteristics ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Control Group ◽  
Molecular Characteristics ◽  
Signet Ring ◽  
Mucosal Layer ◽  
Ring Cell

Abstract Background: Gastric cancer develops even in Helicobacter pylori-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in Helicobacter pylori -uninfected patients.Methods: Seventeen Helicobacter pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of Helicobacter pylori-infected patients with mucosal SRCCs. Seven SRCCs without Helicobacter pylori infection, including two invasive SRCCs, and seven Helicobacter pylori-positive SRCCs were subjected to a genetic analysis using next-generation sequencing. Results: Helicobacter pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the Helicobacter pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one Helicobacter pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without Helicobacter pylori infection. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smoking-induced mutation, was not found in any of the samples.Conclusions: Some SRCCs in Helicobacter pylori-uninfected patients may have a malignant potential similar to that of SRCCs in Helicobacter pylori-infected patients. Smoking is not a main carcinogenic factor for the development of SRCCs.

scholarly journals Clinicopathological and Molecular Characteristics of Colorectal Signet Ring Cell Carcinoma: A Review

2021 ◽  
Vol 27 ◽  
Author(s):  
Yang An ◽  
Jiaolin Zhou ◽  
Guole Lin ◽  
Huanwen Wu ◽  
Lin Cong ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Molecular Characteristics ◽  
Potential Candidate ◽  
Advanced Tumor Stage ◽  
Proximal Site ◽  
Signet Ring ◽  
Ring Cell

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.

scholarly journals Primary signet‐ring cell carcinoma of the lung in an HIV‐positive patient

2021 ◽  
Vol 12 (7) ◽  
pp. 1122-1125
Author(s):  
Alberto Testori ◽  
Gianluca Perroni ◽  
Camilla De Carlo ◽  
Alessandro Crepaldi ◽  
Marco Alloisio ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Positive Patient ◽  
Hiv Positive ◽  
Signet Ring ◽  
Ring Cell

scholarly journals Primary Signet Ring Cell/Histiocytoid Carcinoma of the Eyelid: Somatic Mutations in CDH1 and Other Clinically Actionable Mutations Imply Early Use of Targeted Agents

2021 ◽  
Vol 28 (1) ◽  
pp. 918-927
Author(s):  
Lei-Chi Wang ◽  
Tai-Chi Lin ◽  
Yi-Chen Yeh ◽  
Hsiang-Ling Ho ◽  
Chieh-Chih Tsai ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Cell Carcinoma ◽  
Tumor Tissue ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Next Generation ◽  
Signet Ring ◽  
Ring Cell ◽  
Generation Sequencing ◽  
E Cadherin

Primary signet ring cell/histiocytoid carcinoma of the eyelid is a rare ocular malignancy and its diagnosis is often delayed. This neoplasm presents as an insidious, diffusely infiltrative mass in the periocular area that later infiltrates the orbit. An exenteration is usually indicated; however, nearly one-third of patients develop local recurrence or metastasis. Morphologically, it resembles signet ring cell carcinoma of the stomach and breast, raising the possibility of mutations in CDH1, the gene encoding E-cadherin. To determine whether primary signet ring cell/histiocytoid carcinoma harbors the CDH1 mutation or other actionable mutations, we analyzed the tumor tissue via next-generation sequencing. We identified only one case of primary signet ring cell carcinoma of the eyelid with adequate DNA quality for sequencing from the pathological archive during the period 2000 to 2020. A comprehensive evaluation including histopathology, immunohistochemistry, and next-generation sequencing assay was performed on tumor tissue. Immunohistochemically, the tumor exhibited E-cadherin membranous staining with the aberrant cytoplasmic staining of β-catenin. Using next-generation sequencing, we demonstrated the mutation in the CDH1 gene. In addition, other clinically actionable mutations including ERBB2 and PIK3CA were also detected. The alterations in other actionable genes indicate a need for larger studies to evaluate the pathogenesis and potential therapies for primary signet ring cell/histiocytoid carcinoma of the eyelid.

Fundic Gland Polyp With Parietal Cell Vacuolation Mimicking Signet Ring Cell Carcinoma

2021 ◽  
pp. 106689692199418
Author(s):  
John D. Coyne ◽  
S. Thampy
Keyword(s):  
Proton Pump Inhibitor ◽  
Cell Carcinoma ◽  
Parietal Cell ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Fundic Gland ◽  
Fundic Gland Polyp ◽  
Signet Ring ◽  
Ring Cell

Pseudo-signet ring parietal cell vacuolation has been described as a mimic of invasive signet ring cell carcinoma. Moreover, signet ring cell carcinoma has been described in a fundic gland polyp. This case demonstrates parietal cell vacuolation in a fundic gland polyp in a patient on a long-term proton pump inhibitor.

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