Colorectal Signet-ring Cell Carcinoma Research Articles

Reduced expression of SOX11 in colorectal adenocarcinoma is associated with mucinous and signet ring cell types, poor survival, and lower ALK expression

BackgroundMucinous and signet ring cell colorectal carcinoma (m/srCRC) are challenging colorectal adenocarcinoma (CRC) types with poor prognosis. This study aimed to investigate SOX11 and ALK immunohistochemical expression in the m/srCRC group, comparing the results to those of nonmucinous CRC (nmCRC) and studying their association with different clinicopathological CRC features to better understand their significance and role. Besides, the study assesses which marker has a better predictive value for clinical practice. MethodsTissue microarrays were prepared from 150 CRC blocks distributed equally between the m/srCRC and nmCRC groups. SOX11 and ALK immunohistochemical expressions were compared between both groups. In addition, their association with CRC clinicopathological data and survival was investigated. The Receiver Operating Characteristic (ROC) Curve analysis examined the predictive ability of SOX11 and ALK IHC expression for CRC mortality. ResultsBoth SOX11 and ALK expression were significantly reduced in m/srCRC compared to nmCRC. SOX11 is significantly associated with other prognostic clinicopathological factors (tumor size, lymph node status, overall TNM stage, grade, lymphovascular and perineural invasion) and overall survival. SOX11 significantly positively correlates with ALK expression. Using the ROC analysis, SOX11 is superior to ALK in survival prediction. ConclusionSOX11 can be used as a prognostic marker and is a suggested therapeutic target in mucinous and signet ring cell colorectal carcinoma through upregulation modulation.

Molecular characteristics of patients with colorectal signet-ring cell carcinoma with different ABO blood groups

BackgroundColorectal signet-ring cell carcinoma (SRCC) is a rare subtype of malignant adenocarcinoma, accounting for approximately 1 % of colorectal cancer (CRC) cases. Its biomarkers and molecular characteristics remain controversial, and there are no specific therapeutic targets or strategies for its clinical treatment. MethodsA retrospective study was conducted between January 2010 and December 2021. 1058 colorectal cancer cases from the Sun Yat-sen University Cancer Center and 489 cases from the Tumor Genome Atlas Project were included in the analysis, of which 64 were SRCC. Data extraction included patient demographics, blood types and risk factors, including clinical variables and genomics (either a 19-gene panel NGS or 1021-gene panel NGS). Univariate analyses were performed to identify factors significantly associated with overall survival. ResultsThe blood groups of 27 (42.2 %), 18 (28.1 %), 12 (18.8 %), and seven (10.9 %) patients were classified as O, A, B, and AB, respectively. We found that O was a unique blood group characterized by a low frequency of KRAS mutations, a high frequency of heterozygosity at each HLA class I locus, and a high tumor mutational burden (TMB). Patients in blood group A with high-frequency KRAS mutations and those in blood group B with anemia and metabolic abnormalities required targeted treatment. Furthermore, genetic alterations in SRCC differed from those in adenocarcinoma and mucinous adenocarcinoma. ConclusionsOur study revealed genomic changes in SRCC patients across different blood groups, which could advance the understanding and precise treatment of colorectal SRCC.

Impact of APC mutations on prognosis and tumor microenvironment in colorectal signet ring cell carcinoma.

e15500 Background: Colorectal signet ring cell carcinoma (CRC-SRC) is a malignant tumour characterized by its aggressive nature and unfavourable prognosis. In spite of the fact that numerous studies have examined the molecular profile and therapeutic targets of CRC-SRC, the prognostic biomarkers for this malignancy continue to be unknown. Methods: We conducted a comprehensive analysis of multi-omics in 35 cases of CRC-SRC and 10 cases of colorectal adenocarcinomas (CRC-AC). This analysis involved various techniques, including immunohistochemistry, DNA sequencing, and RNA sequencing. Results: In CRC-SRC, despite a lower frequency of APC mutations at the genomic level (P = 0.01), they rank as the second most prevalent mutations (40%), surpassed only by TP53 mutations (65.71%). The findings revealed that 13 genes associated with immunotherapy response were found to be upregulated in CRC-AC. Additionally, the levels of CD3+, CD8+, and CD3+ & CD8+ T cells were found to be similar in tumor regions in CRC-SRC. These results suggest that CRC-SRC is more likely to have an immunosuppressive tumor immune microenvironment (TiME) compared to CRC-AC. Multivariate Cox proportional hazard regression analysis (hazard ratio: 3.54, 95% confidence interval: 3.93-117.3; p-value = 0.0004), in particular, shows that the presence of APC mutations is associated with a worse prognosis. In contrast, APC-mutant cases of CRC-AC have the same overall survival (OS) rate as APC-wildtype patients in the TCGA cohort. On RNA level, APC-mutant tumors exhibited higher expression levels of VEGFA ( P = 0.028) and Mki67 (P = 0.014), which are implicated in tumour invasion and proliferation. In contrast, APC-mutant CRC-AC did not exhibit differential expression on these genes within the TCGA cohort. GSEA showed that only the E2F hallmark was significantly enriched in APC-mutant CRC-SRC patients ( P = 0.0072). On protein expression level, APC-mutant patients had a significantly lower CD3 or CD68 positive ratio in the tumour region (CD3: P = 0.035; CD68: P = 0.039). This indicated that lymphocyte infiltration is decreased in APC-mutant CRC-SRC. Conclusions: To summarize, APC mutations may have distinct functions in CRC-AC and CRC-SRC. Colorectal cancer (CRC) with APC mutations showed a more unfavourable prognosis and a distinct tumour immune microenvironment compared to CRC with normal APC. Clinical trial information: ChiCTR2300072881.

The tumor immune microenvironment features and their prognostic value in rectal and sigmoid colon signet-ring cell carcinoma.

3544 Background: Signet-ring cell carcinoma (SRCC) of the rectum and sigmoid colon is a rare and highly malignant challenge in clinical practice. Although high PD-1+CD8+ tumor-infiltrating lymphocyte (TIL) infiltration has been reported as a positive prognostic factor in gastric cancer, pancreatic cancer, etc., its role in colorectal SRCC remains unclear. This study aims to explore the immune landscape of colorectal SRCC and its prognostic implications. Methods: The study included 34 patients with stage II-IV SRCC of the rectum and sigmoid colon. The immune contextures of tumor tissues were characterized using multiplex immunofluorescence assays and compared with a cohort of 57 cases of stage II-IV AC. The ratio density and spatial distribution of CD3+, CD8+, PD-1+, PD-L1+ cells, M1/M2 macrophages, and NK cells were quantitively analyzed in both parenchymal (p) and interstitial (i) regions. Characteristics of immune cell infiltration and their prognostic value for long-term survival were investigated in SRCC cases. Results: Compared to AC, SRCC exhibited significantly higher infiltration of CD8+ and CD3+ iTILs in the interstitial region (P=0.00024; P=0.00321, respectively) and elevated CD8+ pTILs infiltration in tumor parenchyma (P=0.041). Conversely, parenchymal infiltration of TILs co-expressing PD-1 was significantly lower in SRCC than AC (PD-1+CD8+ pTILs: P=0.00035; PD-1+CD3+ pTILs: P=5.0e-05). SRCC showed significantly lower infiltration of M1 macrophages in both parenchyma and interstitium (P=0.0035; P=5.4e-09, respectively), lower interstitial infiltration of M2 macrophages (P=1.5e-05), and a borderline lower parenchymal infiltration of M2 macrophages (P=0.0522), compared to AC. Additionally, patients with high parenchymal or interstitial infiltration of PD-1+CD8+ TILs exhibited significantly longer DFS (P=0.00024; P=0.0041, respectively) and OS (P=0.011; P=0.0044, respectively) than those with low infiltration. Multivariate analysis indicated that the level of PD-1+CD8+ pTILs infiltration is an independent prognostic factor for DFS, being independent of CEA levels and TNM stage (P = 0.018; P = 0.02, respectively). Among patients with normal CEA level or of stage II-III, high level of PD-1+CD8+ pTILs infiltration was still associated with significantly improved DFS (P<0.0001; P=0.00018, respectively) and OS (P=0.00021; P<0.0001, respectively). Conclusions: SRCC of rectum and sigmoid colon exhibits distinct immune profiles compared to conventional AC, characterized by higher infiltration of CD8+ and CD3+ TILs, but lower infiltration of PD-1+CD8+ TILs. The unique immune landscape in SRCC, particularly the level of PD-1+CD8+ TILs infiltration and its positive predictive value for DFS and OS, provides new perspectives for immune-based stratification and therapeutic strategies for this clinically significant cancer subtype.

Systematic review of risk factors, prognosis, and management of colorectal signet-ring cell carcinoma.

Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC. To provide an updated overview of risk factors, prognosis, and management of CSRCC. A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: 'Signet ring cell carcinoma' and 'colorectal'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature. In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients. CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.

Prognostic and predictive value of tumor deposits in advanced signet ring cell colorectal cancer: SEER database analysis and multicenter validation.

Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P < 0.05). Compared to the TD-negative group, the TD-positive group showed significantly poorer CSS (the training cohort: HR, 1.87; 95% CI, 1.52-2.31; the validation cohort: HR, 2.43; 95% CI, 1.55-3.81; all P values < 0.001). This association was significant in stage III but not in stage IV. In the multivariate model, after adjusting for covariates, TD maintained an independent prognostic value (P < 0.05). A nomogram model including TD, N stage, T stage, TNM stage, CEA, and chemotherapy was constructed. Through internal and external validation, the model demonstrated good calibration and accuracy. Further survival curve analysis based on individual scores from the model showed good discrimination. TD positivity is an independent factor of poor prognosis in colorectal SRCC patients, and it is more effective to predict the prognosis of colorectal SRCC by building a model with TD and other clinically related variables.

Inherited KDM6AA649T facilitates tumor-immune escape and exacerbates colorectal signet-ring cell carcinoma outcomes.

Childhood onset of colorectal signet-ring cell carcinoma (CR-SRCC) is extremely rare and featured as highly malignant with poor prognosis. Here we reported a CR-SRCC case of 11-year-old boy with a novel inherited X-linked KDM6AA694T mutation. The H3K27me3 demethylase KDM6A was frequently mutated in varieties of tumors and acts as a tumor suppressor. In vivo H3K27me3 demethylation assay demonstrated that KDM6AA694T had dampened H3K27me3 demethylase activity. Overexpression of KDM6AA694T in SRCC cell line KATO3 promoted cell proliferation, invasion and migration, which were further confirmed in vivo by constructing orthotopic tumor growth and lung metastasis model. Besides, expression of KDM6AA694T in immune cells suppresses inflammatory macrophage response and effector T cell response. In conclusion, we characterized a novel inherited KDM6AA694T mutant from a childhood-onset SRCC case and demonstrated that the mutant with impaired H3K27me3 demethylase activity could potentiate tumor malignancy and suppress antitumor immunity.

A novel log odds of positive lymph nodes–based nomogram for predicting overall survival in patients with colorectal signet ring cell carcinoma: a SEER population-based study

PurposeConsidering the poor prognosis and high lymph node (LN) involvement rate of colorectal signet ring cell carcinoma (SRCC), this study aimed to construct a prognostic nomogram to predict overall survival (OS) with satisfactory accuracy and utility, based on LN status indicators with superior predictability.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we obtained cases of colorectal SRCC patients and employed univariate and multivariate Cox analyses to determine independent prognostic factors. Kaplan–Meier curves were utilized to visualize survival differences among these factors. Receiver operating characteristic curves were generated to assess predictive performances of models incorporating various LN status indicators. A novel nomogram, containing optimal LN status indicators and other prognostic factors, was developed to predict OS, whose discriminatory ability and accuracy were evaluated using calibration curves and decision curve analysis.ResultsA total of 1663 SRCC patients were screened from SEER database. Older patients and those with grades III–IV, tumor sizes > 39 mm, T3/T4 stage, N1/N2 stage, M1 stage, and higher log odds of positive lymph nodes (LODDS) values exhibited poorer prognoses. Age, grade, tumor size, TNM stage, and LODDS were independent prognostic factors. The model containing N stage and LODDS outperformed the one relying solely on N stage as LN status indicator, resulting in a validated nomogram for accurately predicting OS in SRCC patients.ConclusionThe integration of LODDS, N stage, and other risk factors into a nomogram offered precise OS predictions, enhancing therapeutic decision-making and tailored follow-up management for colorectal SRCC patients.

Individualized prediction of conditional survival for colorectal signet-ring cell carcinoma patients.

Conditional survival (CS) considers the time already survived after surgery and may provide additional survival information. The authors sought to construct and validate novel conditional survival nomograms for the prediction of conditional overall survival (OS) and cancer-specific survival (CSS) of colorectal signet-ring cell carcinoma (SRCC) patients. Patients diagnosed with stage I-III SRCC between 2010 and 2019 were identified from the Surveillance, Epidemiology, and End Results database. The formula calculating CS was: CS(x|y) = S(x+y)/S(x), where S(x) represents the survival at x years. CS nomograms were then constructed to predict the 5-year conditional OS and CSS, followed by internal validation. A total of 944 colorectal SRCC patients were finally identified in this study. The 5-year OS and CSS improved gradually with additional survival time. Univariate and multivariate Cox regression analysis conducted in training set revealed that age, race, T stage, LNR, and perineural invasion were independent risk factors for both OS and CSS. Two nomograms with considerable predictive ability were successfully constructed [area under the curve (AUC) for OS: 0.788; AUC for CSS: 0.847] and validated (AUC for OS: 0.773; AUC for CSS: 0.799) for the prediction of 5-year OS and CSS, based on the duration of 1-4 years post-surgery survival. The probability of achieving 5-year OS and 5-year CSS in colorectal SRCC patients improved gradually with additional time. Conditional nomograms considering survival time will be more reliable and informative for risk stratification and postoperative follow-up.

Spatial Epidemiology of Signet-ring Cell Colorectal Cancer in India.

Signet-ring cell colorectal carcinoma (SRCC) is an extremely aggressive yet uncommon histologic subtype of colorectal cancer (CRC) with an unknown etiology. There is a stark difference in the prevalence of signet cancers between Western countries and the Indian subcontinent; however, India itself is a vast and diverse country with variable cancer incidence. To study the spatial epidemiology of SRCC in India for identifying regions with high prevalence. This retrospective study included all patients diagnosed with colorectal adenocarcinoma at Tata Memorial Hospital, the largest colorectal cancer referral unit in India, between January 2020 and December 2022. Geocoding based on the location of the residence was done to map the incidences. Comparisons were performed between the proportion of signet cell and non-signet colorectal cancers. A total of 4100 patients with colon or rectal adenocarcinomas were included, of which signet cell histology was found in 624 (15%) patients. SRCC accounted for the highest proportions of CRCs in the Central (19%) and Northern (19%) regions, and the lowest in the North-Eastern (10%) and Western (12%) regions of India (P < 0.001), with non-overlapping confidence intervals. Compared with patients with non-signet CRCs, those with SRCC more commonly had colon cancers (22% vs. 17%; P = 0.003) and belonged to a lower socioeconomic background (67% vs. 59%; P < 0.001). This study found that SRCCs accounted for a significant proportion of CRC cases in India, but there was no substantial disparity in distribution across regions.

A nomogram for the prediction of survival for colorectal signet ring cell carcinoma after surgery: A population-based study.

The aim was to construct and verify a nomogram-based assessment of cancer-specific survival (CSS) in patients with colorectal signet ring cell carcinoma after surgery. Patients were collected from Surveillance, Epidemiology, and End Results program between 2004 and 2015. Independent prognostic indicators were determined in the training cohort by Cox regression model. We identified 2217 eligible patients, who were further categorized into the training set (n = 1693) as well as the validation set (n = 524). Multivariate analysis revealed that age at diagnosis, gender, grade, tumor size, T stage, N stage, and M stage were independent predictive indicators. Then, the above 7 predictive factors were incorporated into a nomogram model to assess CSS, which showed good calibration and discrimination capacities in both sets. Both internal and external calibration plot diagrams revealed that the actual results were consistent with the predicted outcomes. The time-independent area under the curves for 3-year and 5-year CSS in the nomogram were larger than American Joint Committee on Cancer and Surveillance, Epidemiology, and End Results summary stage system. Moreover, decision curve analysis indicated the clinical utility of the nomogram. The nomogram demonstrated favorable predictive accuracy of survival in colorectal signet ring cell carcinoma patients after surgery, which should be further confirmed before clinical implementation.

Early Images of Colorectal Signet Ring Cell Carcinoma.

Early Images of Colorectal Signet Ring Cell Carcinoma.

Clinicopathologic and prognostic factors of patients with T3/T4 colorectal signet ring cell carcinoma: a population-based study

BackgroundTo evaluate cancer-specific survival (CSS) and construct a nomogram to predict the CSS of patients with colorectal signet ring cell carcinoma (SRCC).MethodsThe data for patients with colorectal SRCC from 2000 to 2019 was identified from Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to minimize bias between SRCC and adenocarcinoma patients. Kaplan–Meier method and log-rank test were used to estimate the CSS. A nomogram was constructed based on the independent prognostic factors identified by univariate and multivariate Cox proportional hazards regression analyses. The model was evaluated by receiver operating characteristic (ROC) curves and calibration plots.ResultsPoor CSS was more common in patients with colorectal SRCC, especially in patients with T4/N2 stage, tumor size > 80 mm, grade III-IV, and chemotherapy. Age, T/N stage, and tumor size > 80 mm were identified as independent prognostic indicators. And a prognostic nomogram was constructed and validated as an accurate model for the CSS of patients with colorectal SRCC by ROC curves and calibration plots.ConclusionPatients with colorectal SRCC have a poor prognosis. And the nomogram was expected to be effective in predicting the survival of patients with colorectal SRCC.

Signet Ring Cell Colorectal and Appendiceal Cancer: A Small Signet Ring Cell Component Is Also Associated with Poor Outcome.

Colorectal signet ring cell (SRC) carcinoma with ≥50% SRCs (SRC ≥ 50) has a poor prognosis, but the prognostic role of SRCs < 50% (SRC < 50) is unclear. The aim of this study was to provide a clinicopathological characterization of SRC colorectal and appendiceal tumours and analyse the importance of the SRC component size. All patients in the Swedish Colorectal Cancer Registry diagnosed with colorectal or appendiceal cancer in 2009-2020 at Uppsala University Hospital, Sweden, were included. The SRCs were verified, and the components estimated by a gastrointestinal pathologist. Of the 2229 colorectal cancers, 51 (2.3%) had SRCs, with a median component size of 30% (interquartile range of 12.5-40) and 10 (0.45%) had SRC ≥ 50. The SRC tumours were primarily localized in the right colon (59%) and appendix (16%). No patients with SRCs had stage I disease, and 26 (51%) had stage IV, of whom, 18 (69%) had peritoneal metastases. The SRC tumours were often high grade with perineural and vascular invasion. The 5-year overall survival (OS) rate for patients with SRC ≥ 50 were 20% (95% confidence interval (CI) 6-70), for SRC < 50, 39% (95% CI 24-61); and for non-SRCs, 55% (95% CI 55-60). Among the patients with SRC < 50 and <50% extracellular mucin, the 5-year OS was 34% (95% CI 19-61), while those with ≥50% extracellular mucin had an OS of 50% (95% CI 25-99). The 5-year recurrence-free survival rates were 51% (95% CI 13-83) for patients with SRC tumours, as compared to 83% (95% CI 77-89) and 81% (95% CI 79-84) for mucinous and non-mucinous adenocarcinoma, respectively. The presence of SRCs was strongly associated with aggressive clinicopathological features, peritoneal metastases, and poor prognosis, also when they make up <50% of a tumour.

Diagnosis and Progression of Rectal Signet Ring Cell Carcinoma in a 15 Year Old Lebanese Boy: A Case Report

Introduction: Colorectal cancer (CRC) is a rare entity in children and adolescents compared to adults. In the young, it is mostly detected in the right and transverse parts of the colon. Among the variants of CRC are the uncommon Signet Ring Cell Carcinoma (SRCC) which has a late presentation and pessimistic prognosis. Patients are asymptomatic for a long time and suddenly develop changes in bowel habits or obstruction. Case Report: A 15-year-old boy with no known health issues presented with recent rectorrhagia and weight loss. He was stable but pale with abdominal tenderness and no rectal mass on digital rectal examination (DRE). Colonoscopy unveiled a 13 centimeters segment of circumferential ulcerated blackish mucosa extending from the upper rectum to the rectosigmoid junction. Pathology studies revealed SRCC of the rectum and sigmoid. Metastatic workup showed rectosigmoid wall thickening and denoted the tumor a stage IV with ascites and intraperitoneal implants. Palliative treatment with chemotherapy was initiated, and a follow-up CT was done later to assess disease progression and response to treatment. The disease had worsened and the patient deteriorated. Conclusion: In children, colorectal SRCC is scarce and usually presents at a late stage due to the lack of characteristic symptoms and findings. It is then usually missed by physicians and not considered in the differential thus delaying the diagnosis and rendering the prognosis poorer. To improve the outcome, pediatricians ought to keep CRC in mind when facing obstructive symptoms or refractory abdominal pain.

Prognostic value of log odds of positive lymph nodes, lymph node ratio, and N stage in patients with colorectal signet ring cell carcinoma: A retrospective cohort study.

Little attention has been paid in the prognosis of colorectal signet ring cell carcinoma (SRCC). This study aims to explore the predictive capacity of log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in the prognosis of patients with colorectal SRCC. A retrospective cohort study was designed, and data were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Data on demographic characteristics, clinicopathological features, and treatment were extracted. Outcomes were overall survival (OS) and cancer-specific survival (CSS). Association of LODDS, LNR, and pN stage with OS and CSS were explored using Cox proportional hazard model and Cox competing risk model, respectively, with results showing as hazard ratio and 95% confidence interval (CI). Predictive performance of LODDS, LNR, and pN stage in OS and CSS was assessed by calculating C-index. A total of 2,198 patients were included in this study. LODDS, LNR, and pN stage were associated with the OS and CSS of colorectal SRCC patients (all P < 0.05). LODDS showed a good performance in the OS (C-index: 0.704, 95% CI: 0.690-0.718), which was superior to LNR (C-index: 0.657, 95% CI: 0.643-0.671) and pN stage (C-index: 0.643, 95% CI: 0.629-0.657). The C-index of LODDS, LNR, and pN stage for CSS was 0.733 (95% CI: 0.719-0.747), 0.713 (95% CI: 0.697-0.729), and 0.667 (95% CI: 0.651-0.683), respectively. LODDS displayed a better predictive capacity in the OS and CSS than LNR and pN stage, indicating that LODDS may be effective to predict the prognosis of colorectal SRCC in the clinic.

Prognostic Impact of Lynch Syndrome in Signet-Ring Cell Carcinoma: A Case Report and Review

ABSTRACT Signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer with distinct molecular features and aggressive behavior compared to adenocarcinoma. Most cases are diagnosed at an advanced stage with poor prognosis. SRCC is often associated with CpG island methylation phenotype (CIMP)-high, high (Methylation) BRAF mutations, but their prognostic role is unclear. We report a 57-year-old male with locally advanced sigmoid SRCC and germline Lynch syndrome (pathogenic MLH1 mutation). Despite the advanced stage, he has shown excellent response to adjuvant 5-fluorouracil chemotherapy, unlike typical SRCC outcomes. This case highlights the need to determine the prognostic and predictive significance of lynch syndrome in colorectal SRCC. Identifying patients with improved chemotherapy sensitivity in lynch Syndrome could treatment and improve survival in this rare histological subtype.

S2190 A Case of Colorectal Signet Ring Cell Carcinoma Presenting as Ulcerative Recto-Sigmoiditis and Stricture

Introduction: Signet ring cell carcinoma accounts for about one percent of all colorectal cancers. It is an aggressive subtype of adenocarcinomas with the tendency for intramural spread and peritoneal carcinomatosis. Here, we reported a middle-aged male with circumferential colonic stenosis and inconclusive histology, found to have stage 4 colorectal signet ring cell carcinoma (SRCC). Case Description/Methods: A 41-year-old male without significant past medical history was referred to a gastroenterology clinic with bright red blood per rectum. Colonoscopy showed ulcerative recto-sigmoiditis with rectal bleeding, and there was stricture in the rectum, in the recto-sigmoid colon, and from anus to descending colon (Figure A). Biopsy was obtained from the stricture. The pathology revealed granulation tissue and abundant fibrinopurulent exudate showing small clusters, and individual atypical cells stained positive for CDX-2 immunostain. Unfortunately, the patient subsequently lost follow-up. Three months later, the patient was hospitalized for small bowel obstruction. CT showed markedly enlarged heterogeneous and edematous rectum, an abnormal mass within the posterior pelvis/rectum, retroperitoneal and pelvic lymphadenopathy with thickening and nodularity of the peritoneum. Biopsy was obtained from an inguinal lymph node with histological examination showing metastatic adenocarcinoma composed of poorly cohesive signet-ring cells (Figure B). Immunostains revealed that the neoplastic cells were strongly and diffusely positive for CDX2 and CK20 while negative for CK7, confirming a colorectal primary. Accordingly, the diagnosis of colorectal signet ring cell carcinoma was made. Discussion: The colonoscopic findings of colorectal SRCC could be nonspecific as diffuse circumferential thickening, stricture, or ulcerations. Typical pathological features may not appear on the initial biopsy sample. Immunohistochemical testing could help increase diagnostic yield and early identification of cancer cells. Our case hallmarked the importance of close follow-up for abnormal diffuse stricture and ulcerations in the colorectal area. These lesions may need to be rebiopsied, co-screened with abdominal imaging, and undergo an immunohistochemical investigation to characterize pathology further.Figure 1.: A: Colonoscopy: An intrinsic inflammatory circumferential fibrosis friable severe stenosis measuring 20cm (in length) * 9 mm (inner diameter) was found in the rectum, in the recto-sigmoid colon, and from anus to descending colon. B: Hematoxylin & eosin stain of tissue from lymph node showed metastatic adenocarcinoma composed of poorly cohesive signet-ring cells.

Predictors of Long-Time Survivors in Nonmetastatic Colorectal Signet Ring Cell Carcinoma: A Large Population-Based Study.

Background Colorectal signet ring cell carcinoma (SRCC) is a rare and distinct subtype of colorectal cancer (CRC), with extremely poor prognosis and aggressive tumor biological behavior. In this study, we aimed to analyze the clinicopathological characteristics and to identify the independent predictors of long-time survivors (LTSs) of nonmetastatic colorectal SRCC. Methods Patients diagnosed with nonmetastatic colorectal SRCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared and analyzed the clinicopathological characteristics between LTSs (patients survived over 5 years) and non-LTSs (patients survived of or less than 5 years). Afterwards, multivariate logistic regression analysis was used to identify independent predictors of LTSs, which were further used to construct a nomogram model to predict the probability of being LTSs. Results We enrolled 2050 patients with nonmetastatic colorectal SRCC, consisting of 1441 non-LTSs and 609 LTSs. Multivariate logistic regression analysis revealed that race, marital status, tumor infiltration, lymph node involvement, and primary tumor treatment were independent predictors of LTSs. In addition, these five parameters were incorporated into a nomogram model to predict the probability of being LTSs. In terms of the model performance, the calibration curve revealed good agreement between observed and predicted probability of LTSs, and receiving operator characteristic curve showed acceptable discriminative capacity in the training and validation cohorts. Conclusion Collectively, we analyzed and profiled the clinicopathological characteristics of LTSs in patients with nonmetastatic colorectal SRCC. Race, marital status, T stage, N stage, and primary tumor treatment were independent predictors of LTSs.

Colorectal signet-ring cell carcinoma treated with FOLFOX plus panitumumab.

Colorectal signet-ring cell carcinoma treated with FOLFOX plus panitumumab.