Signet Ring Cell Histology Confers Worse Overall Survival in Treated Esophageal Adenocarcinoma

Tang, Andrew; Rappaport, Jesse; Raja, Siva; Bribriesco, Alejandro; Sudarshan, Monisha; Siddiqui, Hafiz Umair; Raymond, Daniel P.; Murthy, Sudish C.; Ahmad, Usman

doi:10.1016/j.athoracsur.2020.04.134

Cited by 7 publications

(7 citation statements)

References 16 publications

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“…It is important to note that, although no information on surgical margins was available in this study, previous studies have shown that SRC has a higher R1/R2 resection rate, a higher number of positive lymph nodes, and is independently associated with a poorer prognosis (6,9,(11)(12)(13)22). Our study corroborates these findings and seems to be consistent with the early trend of SRC requiring surgery combined with adjuvant therapy.…”

Section: Discussionsupporting

confidence: 91%

“…Notably, the SRC type does not seem to respond significantly to neoadjuvant therapy (12)(13)(14), as 88.2% of patients with SRC showed minimal or no pathological response and only 27.8% were downstaged (10). However, other studies have shown that neoadjuvant chemoradiotherapy has a better prognosis than neoadjuvant chemotherapy, with no statistically significant difference in complete response rates (9,11,22). A study that also used the SEER database to discuss the effect of treatment modality on SRC outcomes showed that the addition of radiotherapy to the surgical cohort was beneficial for survival (17).…”

Section: Discussionmentioning

confidence: 97%

“…Although SRC has been found in a variety of organs in the human body, including the breast, lung, and bladder (6), the upper digestive tract is still a common site of occurrence, with the incidence of esophageal SRC reported to be less than 10% (7,8). Through many small-scale studies, it has been found that esophageal SRC has poor pathomorphological characteristics, and is often staged late, is insensitive to neoadjuvant therapy, has a high positive surgical margin rate, and has a poor prognosis (6,(8)(9)(10)(11)(12)(13)(14), and endoscopic resection for early esophageal SRC appears to be less effective (15). These characteristics have brought great challenges to treatment.…”

Section: Introductionmentioning

confidence: 99%

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Comparative analysis of clinical, treatment, and survival characteristics of signet ring cell and adenocarcinoma of esophagus

Zhang¹,

Li²,

Zeng³

et al. 2021

J Gastrointest Oncol

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Background: Signet ring cell carcinoma (SRC) is a rare pathological subtype of mucinous adenocarcinoma (AC). Clinical features, prognosis, and especially treatment methods between SRC and AC of the esophagus remain controversial. Thus, we conducted this study to explore the differences in clinicopathological characteristics and treatment modalities between SRC and AC of the esophagus.Methods: A retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) program database was conducted. Patients diagnosed with SRC or AC not otherwise specified (NOS) were selected between 2004 and 2018. We investigated the prognosis of SRC and AC in terms of overall survival (OS). A subgroup analysis was performed according to the stage and different treatment methods.Results: A total of 24,987 patients were enrolled, including 1,147 with SRC and 23,840 with AC. In the multivariate Cox analysis of the whole cohort, SRC, tumor site, differentiation, metastases, American Joint Committee on Cancer (AJCC) 6th edition staging, treatment, tumor size, lymph nodes examined, and positive lymph nodes were independent risk factors. The results of the subgroup analysis showed that surgery alone was associated with better OS for AC at the early stage, but was not significantly different for SRC (P=0.896). Surgery plus adjuvant therapy was the best treatment for SRC and AC at the late stage. In the multivariate Cox analysis, the treatment of surgery plus adjuvant therapy had a tendency towards better OS at the early stage [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.39-1.1, P=0.08].Conclusions: SRC is an independent risk factor, with a higher grade of differentiation, later stage, larger tumor size, more positive lymph nodes, and poorer prognosis compared with AC. Surgery plus adjuvant therapy seems to be useful for SRC at the early stage, but further research is needed.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Comparative analysis of clinical, treatment, and survival characteristics of signet ring cell and adenocarcinoma of esophagus

Zhang¹,

Li²,

Zeng³

et al. 2021

J Gastrointest Oncol

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“…The prevalence of SRCs in 13% of tumours at diagnosis confirms previous findings of 13 and 16% in two other cohorts of OAC patients treated with CROSS nCRT [8,12]. Our finding that SRCs in biopsies pre‐treatment are unrelated to pathological outcome and prognosis after nCRT is in line with one study examining both extracellular mucin plus SRCs [7], but is contradictory to other studies [12,23,24]. The best comparable publication to the present study is the paper by Corsini et al , describing 819 patients treated with CROSS nCRT and resection [12].…”

Section: Discussionsupporting

confidence: 77%

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet‐ring cells, and/or poorly cohesive cells

Valkema

Vos

Post

et al. 2023

The Journal of Pathology CR

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Oesophageal adenocarcinomas may show different histopathological patterns, including excessive acellular mucin pools, signet‐ring cells (SRCs), and poorly cohesive cells (PCCs). These components have been suggested to correlate with poor outcomes after neoadjuvant chemoradiotherapy (nCRT), which might influence patient management. However, these factors have not been studied independently of each other with adjustment for tumour differentiation grade (i.e. the presence of well‐formed glands), which is a possible confounder. We studied the pre‐ and post‐treatment presence of extracellular mucin, SRCs, and/or PCCs in relation to pathological response and prognosis after nCRT in patients with oesophageal or oesophagogastric junction adenocarcinoma. A total of 325 patients were retrospectively identified from institutional databases of two university hospitals. All patients were scheduled for ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) nCRT and oesophagectomy between 2001 and 2019. Percentages of well‐formed glands, extracellular mucin, SRCs, and PCCs were scored in pre‐treatment biopsies and post‐treatment resection specimens. The association between histopathological factors (≥1 and >10%) and tumour regression grade 3–4 (i.e. >10% residual tumour), overall survival, and disease‐free survival (DFS) was evaluated, adjusted for tumour differentiation grade amongst other clinicopathological variables. In pre‐treatment biopsies, ≥1% extracellular mucin was present in 66 of 325 patients (20%); ≥1% SRCs in 43 of 325 (13%), and ≥1% PCCs in 126 of 325 (39%). We show that pre‐treatment histopathological factors were unrelated to tumour regression grade. Pre‐treatment presence of >10% PCCs was associated with lower DFS (hazard ratio [HR] 1.73, 95% CI 1.19–2.53). Patients with post‐treatment presence of ≥1% SRCs had higher risk of death (HR 1.81, 95% CI 1.10–2.99). In conclusion, pre‐treatment presence of extracellular mucin, SRCs, and/or PCCs is unrelated to pathological response. The presence of these factors should not be an argument to refrain from CROSS. At least 10% PCCs pre‐treatment and any SRCs post‐treatment, irrespective of the tumour differentiation grade, seem indicative of inferior prognosis, but require further validation in larger cohorts.

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“…Several studies have demonstrated that patients with signet ring cell histology have worse response to chemoradiation, greater likelihood of positive surgical margins, and ultimately worse survival. [2][3][4][5][6] However, this is the first study to evaluate survival by breaking down the percentage of signet ring cell histology. Although the tumors with signet ring features had worse complete tumor response, the authors did not find that the degree of signet ring percentage correlated with the degree of tumor response.…”

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confidence: 99%

Commentary: Signet ring cell: One bad apple spoils the bunch!

Tang

Raja

2021

The Journal of Thoracic and Cardiovascular Surgery

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Signet Ring Cell Histology Confers Worse Overall Survival in Treated Esophageal Adenocarcinoma

Cited by 7 publications

References 16 publications

Comparative analysis of clinical, treatment, and survival characteristics of signet ring cell and adenocarcinoma of esophagus

Comparative analysis of clinical, treatment, and survival characteristics of signet ring cell and adenocarcinoma of esophagus

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet‐ring cells, and/or poorly cohesive cells

Commentary: Signet ring cell: One bad apple spoils the bunch!

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