The Transmembrane Receptor TIRC7 Identifies a Distinct Subset of Immune Cells with Prognostic Implications in Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a heterogeneous malignancy with a dismal prognosis. Therapeutic options are largely limited to surgery and conventional chemotherapy offers limited benefit. As immunotherapy has proven highly effective in various cancer types, we have undertaken a quantitative immunohistopathological assessment of immune cells expressing the immunoinhibitory T cell immune response cDNA 7 receptor (TIRC7), an emerging immunoinhibitory receptor, in a cohort of 135 CCA patients. TIRC7+ immune cells were present in both the tumor epithelia and stroma in the majority of CCA cases with the highest levels found in intrahepatic CCA. While intraepithelial density of TIRC7+ immune cells was decreased compared to matched non-neoplastic bile ducts, stromal quantity was higher in the tumor samples. Tumors exhibiting signet ring cell or adenosquamous morphology were exclusively associated with an intraepithelial TIRC7+ phenotype. Survival analysis showed intraepithelial TIRC7+ immune cell density to be a highly significant favorable prognosticator in intrahepatic but not proximal or distal CCA. Furthermore, intraepithelial TIRC7+ immune cell density correlated with the number of intraepithelial CD8+ immune cells and with the total number of CD4+ immune cells. Our results suggest the presence and prognostic relevance of TIRC7+ immune cells in CCA and warrant further functional studies on its pharmacological modulation.

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Anatomic Subsites and Prognosis of Gastric Signet Ring Cell Carcinoma: A SEER Population-based 1:1 Propensity-matched Study

10.21203/rs.3.rs-403278/v1 ◽

2021 ◽

Author(s):

Yangyang Xie ◽

Xue Song ◽

Haimin Jin ◽

Zhongkai Ni ◽

Xiaowen Li ◽

...

Keyword(s):

Cell Carcinoma ◽

Mortality Risk ◽

Cox Regression ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Survival Prediction ◽

Cancer Specific Survival ◽

Dismal Prognosis ◽

Signet Ring ◽

Ring Cell

Abstract Background: The dismal prognosis of gastric signet ring cell carcinoma (GSRC) is a global problem. The current study is conducted to comprehensively evaluate clinicopathological features and survival outcomes in GSRC patients stratified by anatomic subsites. Then predictive nomograms are constructed and validated to improve the effectiveness of personalized management.Method: The patients diagnosed with GSRC were recruited from the online SEER database. The influence of anatomic subsites on overall survival (OS) and cancer-specific survival (CSS) was evaluated using multivariate Cox regression and Kaplan-Meier analysis. Then we employed propensity score matching (PSM) technique to decrease selection bias and balance patients’ epidemiological factors. Predictive nomograms were constructed and validated.Results: Multivariate Cox regression demonstrated that the patients with overlapping gastric cancer (OGC) suffered the highest mortality risk for OS (HR, 1.29; 95%CI, 1.23-1.36; P<0.001) and CSS (HR, 1.33; 95%CI, 1.28-1.37; P<0.001). Age, TNM stage, tumor localization, tumor size, surgery and chemotherapy presented a highly significant relationship with OS and CSS. Following subgroup and PSM analysis, OGC patients were confirmed to have the worst OS and CSS. Then nomograms predicting 6 months, 12 months and 36 months OS and CSS were constructed. The calibration curves and reveiver operating characteristic curves demonstrated the great performance of the nomograms.Conclusion: We identified anatomic subsites as a predictor of survival in those with GSRC. Patients with OGC suffered the highest mortality risk. The proposed nomograms allowed a relatively accurate survival prediction for GSRC patients.

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Outcomes of Surgical Treatment of Primary Signet Ring Cell Carcinoma of the Colon and Rectum: 22 Cases Reviewed With Literature

International Surgery ◽

10.9738/intsurg-d-14-00067.1 ◽

2014 ◽

Vol 99 (6) ◽

pp. 691-698 ◽

Cited By ~ 19

Author(s):

Sedat Belli ◽

Huseyin Ozgur Aytac ◽

Erdal Karagulle ◽

Hakan Yabanoglu ◽

Fazilet Kayaselcuk ◽

...

Keyword(s):

Confidence Interval ◽

Cell Carcinoma ◽

Negative Impact ◽

Lung Metastases ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Survival Times ◽

Dismal Prognosis ◽

Signet Ring ◽

Ring Cell

Abstract Colorectal primary signet ring cell carcinoma (PSRCCR) is a rare entity with a dismal prognosis, mainly because of delayed diagnosis. The objective of this study was to investigate the clinicopathologic features and prognostic factors for PSRCCR. This is a retrospective study including the data of 22 patients with PSRCCR who underwent surgery. Patients were categorized by age, sex, tumor site, and stage. Fifteen patients were male. Median age was 40 years. Sites for metastases were lymph nodes (86.4%), peritoneum (40.9%), and liver (9.1%). Most of the patients (91%) had stage III or IV tumors. The rates of curative and palliative resections performed were equal. Mean overall survival and mean progression-free survival times were found to be 33.3 ± 7.1 months (95% confidence interval, 19.4–47.2 months) and 11.8 ± 3.5 months (95% confidence interval, 4.9–18.7 months), respectively. It was concluded that site of the tumor, presence of bowel obstruction, peritoneum and lung metastases, adjacent organ infiltration, TNM stage, and efficiency of surgery have significant effects on survival. All in all, these aggressive tumors are generally diagnosed at advanced stages. Depending on the situation, survival is shorter. A high degree of vigilance is required for these patients to avoid the negative impact of late diagnosis on survival.

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The importance of sPD-1, sOX40L and sGITR in terms of clinicopathology and histopathology in gastric cancer

Turkish Journal of Biochemistry ◽

10.1515/tjb-2020-0075 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Cem Horozoglu ◽

Dilara Sonmez ◽

Ozlem Kucukhuseyin ◽

Seyda Demirkol ◽

Mehmet Tolgahan Hakan ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Microenvironment ◽

Active Role ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Control Group ◽

Serum Samples ◽

Signet Ring ◽

Cancer Types ◽

Ring Cell

Abstract Objectives Immunoregulatory GITR, OX40L and PD-1 molecules play an active role in the regulation of tumor microenvironment and have been shown in many cancer types. However, there are limited studies of these molecules in terms of gastric cancer. In our study, we aimed to determine the histopathological significance of sPD-1, sOX40L and sGITR levels in gastric cancer cases. Methods Serum samples were obtained from peripheral blood samples of 20 gastric cancer and 34 healthy controls and candidate biomarker levels were determined by ELISA. Results sGITR level was found to be 48.28 ± 2.66 pg/mL in the gastric cancers and 39.19 ± 2.01 pg/mL in the controls (p=0.014). sOX40L level was 6.13 ± 0.64 pg/mL in the patients and 8.68 ± 0.99 pg/mL in the control, and the sOX40L level was found to be 1.41 times higher in the control group compared to the patients (p=0.033). sGITR levels of signet-ring cell carcinoma were found to be higher than other adenocarcinomas (p=0.04). There was no difference between groups in sPD-1 (p=0.490). Conclusions We suggest that sGITR, sOX40L and molecules may play a role in tumor microenvironment regulation and histological type in gastric cancer.

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Clinicopathological Characteristics and Prognosis of Signet Ring Cell Carcinoma of the Gallbladder

10.21203/rs.3.rs-154548/v1 ◽

2021 ◽

Author(s):

Jiayi Li ◽

Jun You ◽

Yanming Zhou ◽

Shijie Wang

Keyword(s):

Cell Carcinoma ◽

Cox Regression ◽

Multivariable Analysis ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Advanced Tumor Stage ◽

Dismal Prognosis ◽

Advanced Tumor ◽

Signet Ring ◽

Ring Cell

Abstract Background Signet ring cell carcinoma (SRC) is a rare histological subtype of gallbladder adenocarcinoma. The current study evaluates the clinicopathologic features and prognosis of SRC.Methods Patients with adenocarcinoma of the gallbladder were identified in the Surveillance, Epidemiology, and End Results database from 1973 to 2016. Overall survival (OS) was assessed using Cox regression method.Results Of 22,781 gallbladder adenocarcinomas retrieved, 377 (1.7%) were SRC and the other 22,404 were non-SRC. SRC was more significantly associated with older age, female gender, poor differentiation, advanced tumor stage, lymph node metastasis, distant metastasis, and advanced AJCC stage. The 1-, 2- and 5-year OS was 28.1%, 16.8% and 7.2% for SRC vs. 34.9%, 23.1% and 13.2% for non-SRC, respectively (P = 0.002). Multivariable analysis showed that the SRC histology was independently associated with a dismal prognosis (hazard ratio [HR] 1.256, P = 0.021). Surgery in combination with chemotherapy improved OS of gallbladder SRC patients compared with surgery alone (HR 0.726, P = 0.036) or chemotherapy alone (HR 0.433, P < 0.001). Conclusion Patients with SRC of the gallbladder have distinct clinicopathological features with poor prognosis. Surgery in combination with chemotherapy can improve survival.

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SIGNET RING CELL CARCINOMA PADA PAYUDARA

Majalah Kedokteran Andalas ◽

10.22338/mka.v37.i2.p162-166.2014 ◽

2015 ◽

Vol 37 (2) ◽

pp. 162

Author(s):

Muhartono Muhartono

Keyword(s):

Cell Carcinoma ◽

Needle Aspiration ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Architectural Distortion ◽

Signet Ring ◽

Cancer Types ◽

Ring Cell ◽

Needle Aspiration Cytology ◽

Common Malignancy

AbstrakKanker payudara merupakan keganasan yang paling sering ditemukan pada wanita. Kanker payudara jenis signet ring cell carcinoma (SRCC) sangat jarang ditemukan. Kasus SRCC paling banyak ditemukan pada saluran cerna (GIT). Dilaporkan kasus, wanita 46 tahun, terdapat benjolan di payudara. Pemeriksaan ultrasonografi payudara menunjukkan area hypoechoik. Mamografi menunjukkan payudara heterogen padat, distorsi arsitektur atau mikrokalsifikasi. Aspirasi jarum halus sitologi dari jaringan payudara menunjukkan bahwa tumor adalah ganas. Pada pemeriksaan endoskopi gastrointestinal normal. Pemeriksaan Patologi menunjukkan sel-sel neoplastik bentuk bulat, tersebar atau distribusi disertai musin intrasitoplasmik besar menekan inti menuju salah satu kutub sel. Secara klinis, usg, maupun endoskopi tidak ditemukan massa tumor pada GIT. Pada pemeriksaan imunohistokimia SRCC payudara GCDFP15+, ER+, CK7+, MUC1+, CK20-, MUC2- dan SRCC GIT CK20+, MUC2+, GCDFP15-, ER-, CK7-, MUC1-, Simpulan, SRCC payudara adalah tumor ganas yang sangat langka dan harus dibedakan dari metastasis GIT.AbstractBreast cancer is the most common malignancy in women. Breast cancer types signet ring cell carcinoma (SRCC) is very rare. SRCC case most commonly found in the saluran cerna (GIT). Reported cases, female 46 years, there is a lump in the breast. Breast ultrasound examination showed hypoechoic area. Mammography showed heterogeneous dense breasts, architectural distortion or microcalcifications. Fine-needle aspiration cytology (FNAC) of the breast tissue showed that the tumor was malignant. In normal gastrointestinal endoscopy. Pathologic examination menunjukkan neoplastic cells rounded shape, spread or distribution with large intracytoplasmik mucin core pressing toward one pole of the cell. Clinically, ultrasound, and endoscopy was not found in the GIT tumor mass. On immunohistochemical examination breast SRCC on ER+, CK7+, MUC1+, MUC2-, CK20-; GIT SRCC CK20+, MUC2+, ER-, CK7-, MUC1-. Conclusion, breast SRCC is a malignant tumor that is very rare and should be differentiated from metastatic GIT.

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