The impact of signet-ring cell carcinoma histology on bladder cancer outcome

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.

Download Full-text

The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas

American Journal of Clinical Oncology ◽

10.1097/coc.0000000000000447 ◽

2018 ◽

Vol 41 (12) ◽

pp. 1176-1184 ◽

Cited By ~ 4

Author(s):

Mausam Patel ◽

Harliv S. Hans ◽

Kelsey Pan ◽

Humza Khan ◽

Elie Donath ◽

...

Keyword(s):

Cell Carcinoma ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Treatment Interventions ◽

Carcinoma Of The Pancreas ◽

Epidemiological Factors ◽

Signet Ring ◽

Ring Cell ◽

The Impact

Download Full-text

Signet ring cell carcinoma of the ampulla of Vater

10.26226/morressier.578f37fad462b8028d88fdf7 ◽

2016 ◽

Author(s):

Nihed Abdessayed

Keyword(s):

Cell Carcinoma ◽

Ampulla Of Vater ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Signet Ring ◽

Ring Cell

Download Full-text

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

Thoracic Cancer ◽

10.1111/1759-7714.13887 ◽

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

Download Full-text

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

Current Oncology ◽

10.3390/curroncol28010090 ◽

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.

Download Full-text

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

International Journal of Surgical Pathology ◽

10.1177/1066896921994183 ◽

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.

Download Full-text

Protein profiling reveals the characteristic changes of the complement cascade pathway in the tissues of gastric signet ring cell carcinoma

Molecular & Cellular Proteomics ◽

10.1016/j.mcpro.2021.100068 ◽

2021 ◽

pp. 100068

Author(s):

Yang Fan ◽

Bin Bai ◽

Yuting Liang ◽

Yan Ren ◽

Yanxia Liu ◽

...

Keyword(s):

Cell Carcinoma ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Protein Profiling ◽

Complement Cascade ◽

Signet Ring ◽

Ring Cell

Download Full-text

A Signet Ring Cell Carcinoma Presented as Refractory Acquired Thrombotic Thrombocytopenic Purpura

Case Reports in Oncology ◽

10.1159/000510745 ◽

2020 ◽

Vol 13 (3) ◽

pp. 1368-1372

Author(s):

Umit Yavuz Malkan ◽

Murat Albayrak ◽

Hacer Berna Ozturk ◽

Merih Reis Aras ◽

Bugra Saglam ◽

...

Keyword(s):

Cell Carcinoma ◽

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Unknown Origin ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Thrombocytopenic Purpura ◽

Signet Ring ◽

Gastric Endoscopy ◽

Ring Cell

Microangiopathic hemolytic anemia (MAHA) can be observed as a paraneoplastic syndrome (PS) in certain tumors. MAHA-related signet ring cell carcinoma (SRCC) of an unknown origin is very infrequent. Herein we present a SRCC case presented with refractory acquired thrombotic thrombocytopenic purpura (TTP). A 35-year-old man applied to the emergency service with fatigue and headache. His laboratory tests resulted as white blood cell 9,020/µL, hemoglobin 3.5 g/dL, platelet 18,000/µL. Schistocytes, micro-spherocytes, and thrombocytopenia were observed in his blood smear. MAHA was present and he was considered as having TTP. Plasma exchange treatment was initiated; however, he was refractory to this treatment. Thorax and abdomen computerized tomography revealed thickening of minor curvature in stomach corpus with hepatogastric and paraceliac lymphadenopathy. Bone marrow (BM) investigation by our clinic resulted as the metastasis of adenocarcinoma. Ulceration and necrosis were observed by gastric endoscopy procedure. Biopsy was taken during endoscopic intervention, which resulted as SRCC. MAHA may be seen as a PS in some tumors, especially gastric cancers. Tumor-related MAHA is generally accompanied by BM metastases. As a result, BM investigation may be used as the main diagnostic method to find the underlying cancer. The clinical course of cases with tumor-related MAHA is usually poor, and these cases are usually refractory to plasma exchange treatment. In conclusion, physicians should suspect a malignancy and BM involvement when faced with a case of refractory TTP.

Download Full-text