scholarly journals A study of immunohistochemical expression of PD-L1 in gastric carcinoma

Biomedicine ◽  
2021 ◽  
Vol 41 (3) ◽  
pp. 630-637
Author(s):  
Srija Bodepudi ◽  
Susruthan Muralitharan ◽  
Barathi Gunabooshanam

Introduction and Aim: Aberrant over expression of PD L1 by tumours and tumour infiltrating lymphocytes provide an immune shield to the tumours. The present study aims to evaluate the effect of over expression of PD L1 in tumour cells and tumour infiltrating lymphocytes on various clinicopathological aspects of gastric carcinoma including the follow up and survival analysis.   Materials and Methods: Paraffin blocks were retrieved from 100 cases of primary gastric carcinoma who underwent curative resection. Immunostaining was done using a qualitative immunohistochemical assay from Ventana Roche with rabbit monoclonal anti PD-L1 clone SP142 intended for use in the assessment of the PD-L1 protein in formalin -fixed, paraffin -embedded (FFPE) tissue.   Results:    Out of 100 cases 65 were males and 35 were females. PD-L1 expression is observed in tumour cells in 17 cases and tumour infiltrating immune cells in 44 cases. Statistically significant correlation of expression of PD-L1 was observed with the clinicopathological characteristics like, larger tumour size (p value 0.03), lymphovascular invasion (p value 0.01), lymph node metastasis (p value 0.01) and higher tumour stage (p value 0.02). Two years follow up did not show any statistically significant correlation between PD-L1 expression in tumour cells and tumour infiltrating immune cells and survival (p value 0.27).   Conclusion:   Present study shows a substantial expression of PD-L1 in patients with gastric carcinoma. Hence PD-L1 immunohistochemistry can be potentially helpful in screening candidates for anti PD-L1 therapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 559-559
Author(s):  
Jae Myung PARK ◽  
Seung Bae Yoon ◽  
Kyo Young Song ◽  
Chun-Hyun Lim ◽  
Yu Kyung Cho ◽  
...  

559 Background: Metachronous recurrence after endoscopic resection (ER) of gastric cancer is known to be high. However, recurrence rate of metachrous lesions after ER of gastric adenoma has not been studied well. The aim of the study was to compare the metachronous recurrence between gastric carcinoma and adenoma patients. Methods: Four hundred eight carcinoma and 539 adenoma patients were enrolled in this study, and median follow-up period was 27 months (IQR: 16-45 months). Clinicopathological characteristics were assessed. At the follow-up endoscopy, the whole gastric mucosa was examined thoroughly to detect any gastric neoplasia. All suspicious lesions were evaluated histologically on endoscopic biopsies. Surveillance endoscopic schedule was as follows: every 3–6 months within 1 year, then once every year. Results: Forty three metachronous recurrence was diagnosed in in carcinoma patients and 45 in adenoma patients. There was no significant difference in the incidence of recurrent metachronous neoplasm between carcinoma and adenoma patients (p=0.728, log-rank test). After excluding metachronous adenoma, cancer recurrence was not different either between two groups (p=0.943). After adjusting for age, sex, multiplicity, and Helicobacter pylori status, the risk of the metachronous development of gastric cancer in adenoma patients was similar with that in carcinoma patients (HR, 0.96; 95% CI, 0.63-1.45). Conclusions: Metachronous gastric cancer after ER of gastric adenoma was as high as that of gastric carcinoma. Similar endoscopic surveillance program should be applied for both gastric carcinoma and adenoma patients after ER.


2020 ◽  
Author(s):  
Xiangmei Qiao ◽  
Lin Li ◽  
Zhengliang Li ◽  
Changfeng Ji ◽  
Hui Li ◽  
...  

Abstract Background To explore CT radiomics and morphologic characteristics for predicting programmed cell death ligand 1 on tumour cells (PD-L1) and tumour infiltrating lymphocytes (PD-L1-TILs) status in gastric cancer (GC). Methods From March 2019 to October 2019, 101 patients identified with GCs who underwent surgery at our hospital were enrolled in this study retrospectively. Radiomic features were extracted from regions of interest manually drawn on venous CT images. Besides, 13 morphologic characteristics were evaluated. The signatures based on radiomics and morphologic characteristics were built using multiple classifiers (Support Vector Machine [SVM], Naive Bayes [NB], Decision Trees [DT], and Random Forest [RF]). Receiver operating characteristic (ROC) curve was performed to assess diagnostic efficiency. Results The adjacent adipose tissue (P = 0.009) and numerous radiomic features (all P < 0.05) differed significantly between GCs with different PD-L1 status. Six radiomic features showed significant differences between different PD-L1-TILs status (all P < 0.05). The highest areas under the ROC curves (AUCs) of signatures generated by classifiers were 0.807 (SVM) and 0.729 (NB) for the prediction of PD-L1 and PD-L1-TILs status, respectively. Conclusions It was promising to predict PD-L1 status in GCs noninvasively using CT radiomics combined with morphologic characteristics. It might help to improve clinical decision making with regard to immunotherapy. However, the prediction for PD-L1-TILs needs to be explored further.


2021 ◽  
Author(s):  
Xinyue Li ◽  
Jing Yang

Abstract Background: To investigate the relationship between tumour deposits(TDs) with the clinicopathological characteristics,prognosis of gastric cancer and tumour-infiltrating lymphocytes( TILs).Methods: The pathological findings of 369 patients with gastric cancer were retrospectively analysed to observe the expression of TDs, and the levels of stromal TILs . The relationships between TDs status, clinicopathological characteristics, and TILs infiltration level were compared using the chi-square test, and rank data were tested using the rank sum test. Kaplan-Meier was used for survival analysis, and the log-rank test was used to determine the differences in survival curves between groups. The prognostic value of TDs was assessed using multivariate Cox proportional hazards regression analysis.Results: TDs were significantly associated with sex, Lymphovascular invasion, Perineural invasion, pathological TNM stage, and clinical stage (all P<0.05). TILs levels were lower in TDs(+) group and higher in TDs(-) group. TDs(+) group had poor Disease-free survival, cancer-specific survival , and overall survival as compared with TDs(-) groups.Conclusions: TDs is negatively correlated with TILs , and TDs+ was an Independent predictors of the prognosis of gastric cancer.


2020 ◽  
Author(s):  
Jie Wang ◽  
Shu Tian ◽  
Ji Sun ◽  
Jiahao Zhang ◽  
Lan Lin ◽  
...  

Abstract Background: Cancer cells induce the infiltration of various immune cells that are located or distributed in different sites and play multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance of the presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC). Methods: We retrospectively analysed 132 consecutive patients diagnosed with advanced HPSCC in 2013-2017. Tumoural parenchyma was immunohistochemically counted manually for the number of CD8, CD4 and Foxp3 cells. The ratios of CD8/Foxp3 and CD8/CD4 ratios were calculated for each specimen and analyzed with respect to patient clinicopathological variables and prognosis. Results: HPSCC patients with high levels of TILs showed evident correlations with well differentiated tumors (P < 0.05). Moreover, Foxp3+ TIL is also associated with overall staging group and T category (P =0.048 and P= 0.046, respectively). Kaplan-Meier analysis showed that high CD8 and FoxP3 infiltration correlated with favourable overall survival (OS, P = 0.019 and P = 0.001), disease-free survival (DFS, P = 0.045 and P = 0.028) and distant metastasis-free survival (DMFS, P = 0.034 and P = 0.009), respectively, but only Foxp3 displayed prognostic significance for DMFS in multivariate analysis (MVA). In the lymphocyte ratio analysis, CD8/Foxp3 appeared to play a pivotal role, and patients with a high CD8/Foxp3 ratio had a superior 3-year DFS and DMFS compared with those a low CD8/Foxp3 ratio in both univariate analysis (UVA) and MVA (P = 0.015 and P=0.011). A high CD8/CD4 ratio was associated with better DFS and local relapse-free survival (LRFS) in UVA, and was an independent prognostic factor for improved LRFS in MVA (P = 0.040).Conclusion: Although high TILs levels were determined to be prognostically significant in advanced HPSCC, the ratios of these subsets may be more informative. Particularly, a higher ratio of CD8/Foxp3 accurately predicts prognosis for improved DFS and DMFS, and an increased CD8/CD4 ratio is an independent predictor for favourable LRFS.


2019 ◽  
Author(s):  
Byeong-Joo Noh ◽  
Jae Young Kwak ◽  
Dae-Woon Eom

Abstract Background Colorectal adenocarcinoma is the third most common cancer worldwide and a leading cause of cancer-related death. The recent emergence of diverse immunotherapeutic agents has made it crucial to interpret a complex tumour microenvironment intermingled with tumour-infiltrating immune cells to predict the immunotherapeutic response rate. However, in colorectal adenocarcinoma, studies are lacking that provide detailed analyses of programmed death-ligand 1 (PD-L1) and tumour-infiltrating lymphocytes (TIL) to elucidate their prognostic values and to identify immunotherapy-targetable subgroups, preferably with multiple immune-related biomarkers. In the present study, we categorize colorectal adenocarcinomas into four types of tumour immune microenvironments according to PD-L1 expression and TIL, analyse their prognostic values, and propose an immunotherapy-targetable subgroup.Methods Formalin-fixed, paraffin-embedded tissue samples of surgically resected primary colorectal adenocarcinomas (n = 489) were obtained and arrayed on tissue microarray blocks. Immunohistochemical stains for PD-L1, programmed cell death protein 1 (PD-1), cluster of differentiation 8 (CD8), and microsatellite instability (MSI) were performed and evaluated.Results Tumour microenvironment immune type (TMIT) I (PD-L1-positive tumour cells and CD8-high TIL) and type II (PD-L1-negative tumour cells and CD8-low TIL) showed the best and worst prognoses, respectively. PD-L1 overexpression was significantly associated with MSI status. PD-L1 immunoreactivity was positively correlated with TIL having CD8 or PD-1 overexpression.Conclusions TMIT I subgroup showed stronger CD8/PD-L1/PD-1 signalling interaction compared to the other TMIT. Therefore, we propose that the TMIT I subgroup is a candidate TMIT to predict effective response rate for existing immune checkpoint inhibitors and determine targetable subgroups for emerging therapies.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11506-e11506
Author(s):  
Sanjay P Deshmukh ◽  
Anupama Dutt Mane

e11506 Background: The incidence of breast cancer is rising in India. It presents at a younger age in Indian population as compared to the western countries. Methods: This is a retrospective review of all breast cancer patients less than 40 years of age treated in single tertiary care center from June 2006 to June 2011. The aim was to assess the factors that may influence clinical outcome and prognosis including demographics, clinical characteristics, surgical and pathological findings and the treatment given. Clinical data was collected from medical records and histopathology reports. Independent variables like age, stage at presentation, surgery type, chemotherapy, radiation, tumour size, grade, nodal status, no. of positive nodes, perinodal extension, lymphovascular extension, ER, PR and Her2 neu were analysed. Results: Out of a total of 613 patients, 91 were under 40 years of age, corresponding to a prevalence of 14.8%. Median age was 35 years with the youngest being 23 years old. Maximum patients were in the age group of 36-40 years. Lymphovascular emboli was positive in 42 patients (48.8%) and perinodal extension was positive in 36 patients (41.8%). 30 patients(34.8%) had ER positivity, while 39 patients (45.3%) had PR positivity. Her 2 neu receptors were positive in 20 patients (23.2%). 39 patients were triple negative (45.3%). The median follow up period for all the patients was 28 months with the DFS being 76.1% and OS being 88.3%. In univariate analysis, factors significantly associated with survival were stage at presentation (p value- 0.026), presence of lymhovascular emboli (p value- 0.019) and presence of perinodal extension (p value- 0.007 ).Grade of the tumour also correlated with survival , however it was not statistically significant (p value- 0.086). Statistical analysis was done with SPSS 17. Conclusions: The incidence of breast cancer in younger women in India is high with increased number of triple negative patients. Overall survival is quite similar to that of the western population. Longer follow up and more studies are required to confirm this finding.


2007 ◽  
Vol 5 (4) ◽  
pp. 97
Author(s):  
A. Tamburini ◽  
V. Tomajer ◽  
E. Orsenigo ◽  
L. Albarello ◽  
C. Doglioni ◽  
...  

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Christine Lundgren ◽  
Pär-Ola Bendahl ◽  
Maria Ekholm ◽  
Mårten Fernö ◽  
Carina Forsare ◽  
...  

Abstract Background Tumour-infiltrating lymphocytes (TILs) are of important prognostic and predictive value in human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) and triple-negative breast cancer (TNBC), but their clinical relevance in oestrogen receptor-positive/HER2-negative (ER+/HER2−) remains unknown. The primary study aim was to analyse the prognostic effect of TILs on the BC-free interval (BCFi) in premenopausal patients stratified by BC subtypes. The secondary aim was to investigate if TILs are predictive of tamoxifen (TAM) benefit. Methods Archival tissues from primary breast tumours were collected from patients from the SBII:2pre trial, in which 564 premenopausal women were randomised to 2 years of adjuvant TAM or no systemic treatment, regardless of hormone receptor status. TILs were scored on whole tissue sections from 447 patients with available ER status. Tumours were divided into ER+/HER2−, HER2+ and TNBC subtypes by immunohistochemistry and in situ hybridisation. The prognostic value of TILs was analysed in systemically untreated patients (n = 221); the predictive information was investigated in the ER+ subgroup (n = 321) by cumulative incidence curves and Cox regression analyses. The median follow-up was 28 years. Results High (≥ 50%) infiltration of TILs was a favourable prognostic factor in terms of BCFi (univariable analysis: hazard ratioBCFi (HRBCFi) 0.40; 95% confidence interval (CI) 0.22–0.71; P = 0.002). Similar effects were observed across all BC subtypes. The effect of adjuvant TAM was stronger in patients with ER+ tumours and TILs < 50% (HRBCFi 0.63; 95% CI 0.47–0.84; P = 0.002) than in patients with high immune infiltration (≥ 50%) (HRBCFi 0.84; 95% CI (0.24–2.86); P = 0.77). However, evidence for differential effects of TAM in categories of TILs, i.e. interaction, was weak. Conclusions We demonstrate a long-term favourable prognostic value of high infiltration of TILs in a cohort of premenopausal BC patients and the positive prognostic effect was extended to the ER+/HER2− subgroup. A beneficial effect of TAM in ER+ patients was observed in patients with tumours of low TIL infiltration, but evidence for a treatment predictive effect was weak. Trial registration This trial is registered in the ISRCTN database, trial ID: ISRCTN12474687.


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