Signet ring cell percentage in poorly cohesive gastric cancer patients: A potential novel predictor of survival

Roviello, Franco; Marano, Luigi; Ambrosio, Maria Raffaella; Resca, Luca; D’Ignazio, Alessia; Petrelli, Federica; Petrioli, Roberto; Costantini, Maurizio; Połom, Karol; Macchiarelli, Raffaele; Biviano, Ivano; Marrelli, Daniele

doi:10.1016/j.ejso.2021.09.003

Cited by 22 publications

(16 citation statements)

References 31 publications

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“…Our group previously reported that the percentage of SRCs is inversely related to tumor aggressiveness in poorly cohesive GCs confirming the role of SRC pattern as an independent predictor of survival (8). By extending the concept of this new evidence to mixed histology, we can postulate that the inconsistent findings of previous studies (23-28) could be explained by the heterogeneity of SRC components.…”

Section: Discussionsupporting

confidence: 67%

“…The latter account for 6%-27% of all GCs and are characterized by the coexistence of two or more distinct histological components: glandular (tubular/papillary) and signet ring cell (SRC)/poorly cohesive. Recently, the percentage of SRC was proposed as an independent prognostic factor of cancer-related survival in a poorly cohesive histotype, and high amounts of SRC were related to lower recurrence and mortality rates, better prognosis, and most advantageous clinicopathological features (6)(7)(8). Surprisingly, clinicopathological and prognostic aspects of mixed histotype have not been deeply investigated.…”

Section: Introductionmentioning

confidence: 99%

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The Percentage of Signet Ring Cells Is Inversely Related to Aggressive Behavior and Poor Prognosis in Mixed-Type Gastric Cancer

et al. 2022

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Background and ObjectivesOnly recently the percentage of signet ring cells (SRCs) in gastric cancer (GC) has been proposed as an independent predictor of survival. High amounts of SRCs have been related to lower recurrence and mortality rates, better prognosis, and favorable clinicopathological features in a poorly cohesive histotype. It is not known what the effect of SRC percentage in mixed-type GC is. We investigate the role of SRCs as a prognostic marker in mixed-histotype GC.MethodsA retrospective analysis was performed through a prospectively maintained database of patients with diagnosed “mixed-type” gastric carcinoma, defined according to 2019 WHO classification. These patients underwent surgery between 1995 and 2016, and their tissue samples were stored in a tissue bank. All slides were analyzed, and patients were divided into three groups according to the percentage of SRCs: “Group 1” (displaying ≤10% of SRCs), “Group 2” (displaying <90% but >10% of SRCs), and “Group 3” (displaying ≥90% of SRCs). We compared clinical and pathological features as well as prognostic factors between the different groups.ResultsAmong 164 enrolled patients, 68.9% were male and 31.1% were female (p = 0.612). The mean (±SD) age at diagnosis was 71.4 ± 9.6 years. Ninety-eight (59.7%) patients were classified as “Group 1”, 66 (40.3%) as “Group 2”, and none as “Group 3”. Five-year overall survival was remarkably higher in Group 2 (73.8%) in comparison to Group 1 (35.4%), p < 0.001. Mortality risk was three times higher in patients with ≤10% SRC pattern compared to those with >10% [HR 2.70 (95% CI 1.72–4.24)]. After adjusting according to potential confounding factors, SRC percentage was still an independent predictor of survival.ConclusionsThe proportion of SRCs is inversely related to aggressive behavior and poor prognosis in mixed-type GCs, highlighting the role of SRC amount as an independent predictor of survival.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

The Percentage of Signet Ring Cells Is Inversely Related to Aggressive Behavior and Poor Prognosis in Mixed-Type Gastric Cancer

et al. 2022

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“…Among PCC tumors, the prognostic impact of the relative percentages of an SRC component within the tumors remains controversial[ 40 ]. Two studies evaluated the prognostic role of the Verona consensus with marked differences between the distribution of the three categories questioning the reproducibility of the classification (Table 1 )[ 40 , 47 , 48 ]. Bencivenga et al [ 47 ] showed that the percentage of SRC was associated with tumor stage and survival in PCC-GC: The percentage of SRC was inversely related to tumor aggressiveness, pT stage ( P < 0.001) and the number of positive nodes coded as a continuous variable ( P = 0.009).…”

Section: Overview and Update On Histological And Molecular Classifica...mentioning

confidence: 99%

“…Long-term survival was significantly higher in SRC-type (> 90% SRC) compared with PCC with SRC component (< 90% but > 10% of SRC) and PCC-NOS (< 10% of SRC) tumors[ 47 ]. In the other study, on pathological revision no patients with SRC-type (> 90% SRC) were identified[ 48 ]. The 5-year overall survival (OS) was significantly higher in PCC with an SRC component (< 90% but > 10% of SRC) compared with PCC-NOS (< 10% of SRC) (63.3% vs 12.7%)[ 48 ].…”

Section: Overview and Update On Histological And Molecular Classifica...mentioning

confidence: 99%

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Poorly cohesive cells gastric carcinoma including signet-ring cell cancer: Updated review of definition, classification and therapeutic management

Drubay¹,

Nuytens²,

Renaud³

et al. 2022

WJGO

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While the incidence of gastric cancer (GC) in general has decreased worldwide in recent decades, the incidence of diffuse cancer historically comprising poorly cohesive cells-GC (PCC-GC) and including signet ring cell cancer is rising. Literature concerning PCC-GC is scarce and unclear, mostly due to a large variety of historically used definitions and classifications. Compared to other histological subtypes of GC, PCC-GC is nevertheless characterized by a distinct set of epidemiological, histological and clinical features which require a specific diagnostic and therapeutic approach. The aim of this review was to provide an update on the definition, classification and therapeutic strategies of PCC-GC. We focus on the updated histological definition of PCC-GC, along with its implications on future treatment strategies and study design. Also, specific considerations in the diagnostic management are discussed. Finally, the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens (5-Fluorouracil, leucovorin, oxaliplatin and docetaxel), the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.

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Clinicopathological features and cancer transcriptomic profiling of poorly cohesive gastric carcinoma subtypes

Yen,

Chen,

Huang

et al. 2024

The Journal of Pathology CR

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Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet‐ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC‐NOS) and signet‐ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced‐stage PCCs, consisting of 43 PCC‐NOS and 12 SRCC cases. Subsequently, 12 PCC‐NOS and 5 SRCC cases were randomly selected for initial cancer‐related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC‐NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC‐NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1‐year progression‐free survival rate compared to SRCC cases. Clustering of PCC‐NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC‐NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC‐NOS related to vesicle‐mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC‐NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.

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Signet ring cell percentage in poorly cohesive gastric cancer patients: A potential novel predictor of survival

Cited by 22 publications

References 31 publications

The Percentage of Signet Ring Cells Is Inversely Related to Aggressive Behavior and Poor Prognosis in Mixed-Type Gastric Cancer

The Percentage of Signet Ring Cells Is Inversely Related to Aggressive Behavior and Poor Prognosis in Mixed-Type Gastric Cancer

Poorly cohesive cells gastric carcinoma including signet-ring cell cancer: Updated review of definition, classification and therapeutic management

Clinicopathological features and cancer transcriptomic profiling of poorly cohesive gastric carcinoma subtypes

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