Clinicopathological Characteristics and Survival Outcomes of Primary Signet Ring Cell Carcinoma in the Stomach: Retrospective Analysis of Single Center Database

Background: Gastric signet ring cell carcinoma (SRCC) appears to have clinical features and survival rates particularly different from other histological types. The aim of this study was to investigate clinicopathological features and survival outcomes of SRCC and to compare them with non-signet ring cell carcinoma (NSRCC). Methods: We retrospectively studied 145 patients with non-metastatic gastric carcinoma who underwent gastrectomy in our institute from 2005 to 2015. Among them, 36 patients (9.4%) with SRCC were compared to 109 patients (90.6%) with NSRCC. Results: Patients with SRCC presented at a younger age (p=0.001) with more advanced stage III-IV disease (p=0.005) and advanced N stages with a higher rate of pN3 (p=0.0001), a higher number of invaded lymph nodes (p=0.002) and a higher rate of patients with a lymph node ratio exceeding 25% (63.9% vs 36.7, p=0.004). After a median follow up of 35.30 months, there was no significant difference in the 5 years overall (OS) survival between SRCC and NSRCC ((36.7% vs 45.7%, p=0.206).However, the 5 years progressive free survival (PFS) was significantly decreased in case of SRCC (38.7% vs 50.9%, p=0.038) with a higher rate of metastasis in (52.9% vs 29.5%, p=0.013) and peritoneal recurrence (35.3% vs 9.5%, p<0.0001). The main prognostic factors of PFS and OS in SRCC were tumoral stenosis, hypoprotidemia, tumor size, depth of invasion (p=0.001), perineural and lymphovascular invasion, the UICC stage and complete surgical resection. Conclusion: Gastric SRCC have a particular clinicopathological behavior compared to NSRCC suggesting its more aggressive character.

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Clinicopathological Characteristics and Survival Outcomes of Primary Signet Ring Cell Carcinoma of the Prostate: A SEER-Based Study

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2017.06.1168 ◽

2017 ◽

Vol 99 (2) ◽

pp. E236

Author(s):

X. Gu ◽

X.S. Gao

Keyword(s):

Cell Carcinoma ◽

Clinicopathological Characteristics ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Survival Outcomes ◽

Carcinoma Of The Prostate ◽

Signet Ring ◽

Ring Cell

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The Clinicopathological Characteristics And Genetic Alterations of Signet-ring Cell Carcinoma in Gastric Cancer

Cancers ◽

10.3390/cancers12082318 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2318

Author(s):

Kuo-Hung Huang ◽

Ming-Huang Chen ◽

Wen-Liang Fang ◽

Chien-Hsing Lin ◽

Yee Chao ◽

...

Keyword(s):

Gastric Cancer ◽

Liver Metastasis ◽

Cell Carcinoma ◽

Genetic Alterations ◽

Clinicopathological Characteristics ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Akt Pathway ◽

Signet Ring ◽

Ring Cell

Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more PIK3CA amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have PD-L1 expression. For advanced GC without SRC, patients with liver metastasis tended to have PD-L1 expression, PI3K/AKT pathway mutations, TP53 mutations and MSI-H tumors. For advanced GC, PD-L1 expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have PI3K/AKT pathway mutations, TP53 mutations and PD-L1 expression; immunotherapy and targeted therapy may be beneficial for these patients.

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Sa1657 Endoscopic Findings and Clinicopathological Characteristics of Signet Ring Cell Carcinoma in Early Gastric Cancer

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2011.03.392 ◽

2011 ◽

Vol 73 (4) ◽

pp. AB237

Author(s):

Sam Ryong Jee ◽

Sang Young Seol ◽

Jung Sik Choi ◽

Ji Hyun Kim ◽

Sang Heon Lee

Keyword(s):

Gastric Cancer ◽

Early Gastric Cancer ◽

Cell Carcinoma ◽

Clinicopathological Characteristics ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Endoscopic Findings ◽

Signet Ring ◽

Ring Cell

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Metastatic patterns and prognostic significance of signet ring cell carcinoma of the colon: Retrospective analysis of SEER database.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e15594 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e15594-e15594

Author(s):

John Khoury ◽

Rebecca Chacko ◽

David Macari ◽

Bolanle Gbadamosi ◽

Daniel Ezekwudo ◽

...

Keyword(s):

Cell Carcinoma ◽

Retrospective Analysis ◽

Prognostic Significance ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Seer Database ◽

Carcinoma Of The Colon ◽

Signet Ring ◽

Metastatic Patterns ◽

Ring Cell

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Prognostic value of tumor-infiltrating lymphocytes in signet-ring cell carcinoma of the rectum and sigmoid colon.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15079 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15079-e15079

Author(s):

Jiaolin Zhou ◽

Jia Wang ◽

Yaping Xu ◽

Guole Lin ◽

Huanwen Wu ◽

...

Keyword(s):

Cell Carcinoma ◽

Sigmoid Colon ◽

Tumor Infiltrating Lymphocytes ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Stage Ii ◽

Survival Outcomes ◽

Signet Ring ◽

Ring Cell ◽

Infiltrating Lymphocytes

e15079 Background: Signet-ring cell carcinoma (SRCC) of rectum and sigmoid colon is an extremely rare subtype of colorectal cancer (CRC) with very poor prognosis. Tumor-infiltrating lymphocytes (TILs) signify the host immune response to tumors, which were reported to predict survival outcomes of patients with various cancer types. In this study, we aimed to characterize TILs and mutational features of SRCC of rectum and sigmoid colon as well as their correlations with the clinicopathological parameters and survival outcomes. Methods: 28 patients with stage II-IV SRCC of rectum and sigmoid colon were included, in which 12 patients had tumors with ≥50% signet-ring cells (SRCs) and 16 had tumors with <50% SRCs. Targeted next generation sequencing using a 1,021-gene panel was used to investigate the genetic alterations of tumor tissue. Multiplex immunofluorescence assays were performed to visualize TILs. TILs within cancer cell nests (iTILs) and in cancer stroma (sTILs) were counted separately. The correlations of TILs with survival outcomes were analyzed in stage II/III patients who underwent the radical resection. Results: Somatic alterations were detected in all the 28 cases. The most frequently mutated genes included TP53, APC and SMAD4, occurring in 68%, 36% and 36% of cases, respectively. BRAF mutation were detected in only one patient (3.6%). The median tumor mutational burden (TMB) was 4.80 (range, 0.96-42.24) muts/Mb. Three patients (10.7%) were with microsatellite instability-high (MSI-H) status and a high TMB of more than 10 muts/Mb. Patients with stage IV tumors have significantly lower PD-1+ CD8+ iTILs and sTILs (p=0.018 for both), CD8+ iTILs (p=0.022), and PD-1+ iTILs (p=0.013) levels than those with stage II/III tumors. Tumors with ≥ 50% SRCs showed lower levels of CD8+ sTILs than those with < 50% SRCs (p=0.046). Patients with CEA>5.0 ng/ml showed significantly lower levels of PD-1+ CD8+ iTILs than those with CEA≤5.0 ng/ml (p=0.015). Moreover, significantly lower levels of PD-1+ CD8+ sTILs (p=0.036) were observed in tumors that appeared as long circumferential thickening of the bowel wall with stenosis compared to those did not. Multivariate analysis indicated that patients with high PD-1+ CD8+ iTILs and sTILs levels had significantly better disease-free survival (DFS) than those with low PD-1+ CD8+ iTILs and sTILs levels (not reached vs. 22 months for both; p=0.008 and 0.003, respectively). High PD-1+ CD3+ sTILs levels were associated with significantly longer overall survival (OS) compared to low levels (not reached vs. 39 months, p=0.034). No correlation between MSI or TMB and DFS or OS was observed in this small cohort. Conclusions: Our results demonstrated that PD-1+ CD8+ iTILs and sTILs are powerful independent predictors of survival outcomes in patients with resectable SRCC of rectum and sigmoid colon. Further investigations in larger cohorts are needed to validate our findings.

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Differences in clinicopathological characteristics and computed tomography findings between signet ring cell carcinoma and nonsignet ring cell carcinoma in early and advanced gastric cancer

Cancer Medicine ◽

10.1002/cam4.1417 ◽

2018 ◽

Vol 7 (4) ◽

pp. 1160-1169 ◽

Cited By ~ 6

Author(s):

Jian Chen ◽

Rong Cai ◽

Gang Ren ◽

Jianxi Zhao ◽

Huali Li ◽

...

Keyword(s):

Gastric Cancer ◽

Computed Tomography ◽

Cell Carcinoma ◽

Advanced Gastric Cancer ◽

Clinicopathological Characteristics ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Signet Ring ◽

Ring Cell

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

10.21203/rs.3.rs-26608/v1 ◽

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.

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