RESUMEN
Objective:To analyze the relationship between PD-L1 expression and the degree of infiltration of different types of TILs in triple-negative breast cancer, and the correlation with other pathological features to explore their clinical significance.Methods:Tumor tissues of 199 patients with triple-negative breast cancer in our hospital were selected, and the expression of PD-L1 and the distribution of TILs were analyzed using immunohistochemistry and counted using Image software. The relationship between CD8 +TILs, CD4 +TILs and PD-L1 expression was analyzed and compared, and survival analysis and correlation analysis between PD-L1 expression and pathological information were performed. Results:The density of CD4 + TILs ( χ2=8.75, P=0.003) and CD8 + TILs ( χ2=6.32, P=0.009) infiltration was higher in the PD-L1-positive group compared to that of the PD-L1-negative group. Among PD-L1-positive patients, patients with higher TILs infiltration compared to low infiltrating TILs could achieve longer overall survival time, and the difference was statistically significant ( P1=0.012, P2=0.023, P3=0.010). Patient PD-L1 expression was positively correlated with the number of positive lymph nodes, tumor stage, and ki-67 expression ( Pa=0.032, Pb=0.006, Pc=0.042), and was not related to age or tumor diameter ( Pd=1.031, Pe=0.672) . Conclusions:PD-L1 expression in triple negative breast cancer predicts higher infiltration of CD4 +TILs and CD8 +TILs, while higher infiltration of CD4 +TILs and CD8 +TILs predicts a relatively good survival prognosis.PD-L1 expression is associated with multiple pathological clinical factors and deserves further study to make PD-L1, TILs and other indicators better benefit triple-negative breast cancer patients.
RESUMEN
Objective To explore the expression of fibrinogen-like protein 1 (FGL1), the distribution of tumor-infiltrating lymphocytes (TILs), and their relationship with the prognosis of esophageal squamous-cell carcinoma (ESCC) patients. Methods We analyzed retrospectively the clinical data of 120 ESCC patients. The expression of FGL1 was detected through immunohistochemistry. The distributions of intratumoral TILs (iTILs) and stromal TILs (sTILs) were evaluated under a microscope. Survival analysis was used to evaluate the patient outcomes. Results The positive rate of FGL1 in ESCC was 18.3% (22/120), and it was connected to the TNM stage, lymph node status, and TILs. A total of 73 cases (60.8%) showed low levels of iTILs (iTILs≤10%), and 47 cases (39.2%) exhibited high iTIL levels (iTILs > 10%). Similarly, 82 cases (68.3%) presented low levels of sTILs (sTILs≤10%), and 38 cases (31.7%) manifested high sTIL levels (sTILs > 10%). The distribution of iTILs was associated with FGL1, tumor differentiation, and TNM stage, whereas the distribution of sTILs was associated with FGL1, tumor location, and TNM stage. The Kaplan–Meier survival analysis showed that tumor diameter, TNM stage, lymph node status, FGL1, and TILs were associated with the prognosis of patients with ESCC (P < 0.05). Multivariate Cox regression revealed that FGL1, TILs and TNM stage were the influencing factors of prognosis. Conclusion FGL1 expression is associated with the poor prognosis and may be a prognostic biomarker of ESCC. FGL1 combined with TILs can be used as a biomarker to predict ESCC.
RESUMEN
Objectives@#Known for their poor outcomes, triple negative breast cancers (TNBCs) have been investigated for immune checkpoint inhibitors that target Programmed death ligand 1 (PD-L1). In the recent decade, tumor-infiltrating lymphocytes (TILs) have also become potential biomarkers. The aim of the study is to determine the reproducibility of PD-L1 scoring system for TNBC (SP142 clone) and TILs interpretation in the local setting through intra- and interobserver agreement.@*Methodology@#Forty-three primary resection specimens TNBC were evaluated on two occasions with PD-L1 (Roche VENTANA SP142 assay) and TILs by two breast pathologists and one general pathologist on physical glass slides. PD-L1 expression was determined by at least 1% positivity among immune cells within the tumoral area and contiguous peritumoral stroma while TILs was assessed based on International Immuno-Oncology Biomarker Working Group on Breast Cancer. Kappa statistic for PD-L1 and TILs categories while intraclass correlation coefficient (ICC) were assessed, with cutoffs of 0.80 and 0.70, respectively.@*Results@#The overall interrater kappa statistic for PD-L1 on the first and second rounds were weak at 0.506 (95% CI: 0.334-0.679) and minimal at 0.314 (95% CI: 0.142-0.487), respectively. Intraobserver kappa statistic for PD-L1 were varied across the three readers while interobserver kappa values for PD-L1 showed none (0.181) to moderate (0.789) agreement. The TILs intraobserver reliability showed poor to good agreement, with the highest ICC of 0.889 (95% CI: 0.805-0.938).@*Conclusion@#This study demonstrated variable intra and interobserver agreement for both TILs and PD-L1 expression. Although it is desirable to have strong to almost perfect agreement, the kappa and ICC values suggest additional room for improvement. In light of the repercussions in management of patients who will undergo immune checkpoint inhibitor therapy, regular training sessions, concurrences of equivocal results, and possible use of digital pathology as a medium in interpreting TILs and PD-L1 stains to achieve consistent results.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , InmunohistoquímicaRESUMEN
Objective The prognostic role of PD-L1 expression in surgically resected lung adenocarcinoma(ADC)remains controversial. The aim of present study was to investigate the prognostic value of PD-L1 combined with CD8 +TILs expression in pa-tients with resectable lung adenocarcinoma. Methods A total of 104 patients with lung adenocarcinoma who underwent radical resec-tion were enrolled at the Affiliated Tumor Hospital of Harbin Medical University from January 2009 to December 2012. Immunohisto-chemistry was used to detect the expression of PD-L1 and CD8 +TILs in primary tumor specimens. Its clinical pathological factors and its relationship with prognosis were statistical analysis. Results The positive expression rate of PD -L1 in tumor cells was 38. 5% (40/104),and the positive rate of CD8 +TILs was 44. 2% (46/104). There was a significant correlation between the expres-sion of CD8 +TILs and TNM stages of patients with resectable ADC. The Kaplan-Meier survival analysis showed that low expression of PD-L1 and high expression of CD8 +TILs were significantly associated with disease -free survival ( DFS) and overall survival ( OS),and could be used as an independent predictors for predicting prognosis of patients with resectable ADC. Conclusion The ex-pression of PD-L1 and CD8 +TILs in the postoperative specimens can help to judge the prognosis of patients. This study has certain significance for immunotherapy of PD-1/PD-L1 pathway in patients with surgically resected ADC.
RESUMEN
Introducción Debido a su negatividad para los receptores hormonales y de her2, los cánceres de mama Triple Negativos (cmtn) no tienen tratamiento específico y es la quimioterapia la única modalidad de tratamiento sistémico. Objetivos El objetivo de este trabajo es, en primer lugar, evaluar en los cmtn la factibilidad de utilizar a la infiltración linfocitaria y a la expresión de la proteína p53 y de los receptores de andrógenos como marcadores pronósticos (sobrevida global y período libre de enfermedad), y, en segundo lugar, determinar su utilidad como elementos predictivos de respuesta a la quimioterapia. Material y método Analizamos un grupo de pacientes con diagnóstico de cmtn tratadas en el Hospital Alemán de Buenos de Aires y en el Sanatorio Mater Dei desde diciembre de 2000 a diciembre de 2012. Resultados Se analizaron 21 pacientes con cmtn. En nuestra población, la quimioterapia se asoció con menor riesgo de recaída y mortalidad. La prevalencia en la expresión de la proteína p53 fue del 61,9% en la población general, del 72,7% en las recaídas y del 66,6% en las pacientes fallecidas. El 23,8% de las pacientes estudiadas presentó expresión de receptores androgénicos. La infiltración linfocitaria tumoral (tils) promedio fue del 20,5% (5% - 60%), siendo menor cuando se evalúa exclusivamente la población de pacientes que recayeron (17,7%) y aún menor cuando se evalúa la población de pacientes fallecidas (11,7 %). Discusión La quimioterapia tuvo un rr de sobrevida de 0,15 (ic: 0,06 - 0,78) con una p: 0,0021. La expresión de la proteína p53 tuvo un rr de 1,2 como factor de riesgo de mortalidad o progresión (ic: 0,23 - 9,07; p: 0,6). La expresión de receptores androgénicos tiene un rr de 1,6 como factor de riesgo de mortalidad o progresión (ic: 0,21 - 6,24; p: 0,41). La presencia de tils mayor al 20% es predictora de mortalidad y recurrencia con una p: 0,023. Conclusiones La determinación de tils junto con la evaluación en la expresión de la proteína p53 son herramientas útiles a la hora de definir la conveniencia de un tratamiento quimioterápico ya que ambas se asocian con aumento de la sobrevida total y de la sobrevida libre de enfermedad, aunque en nuestra población esta asociación no haya sido estadísticamente significativa para la p53 y sí para la presencia de tils
Introduction Because of its negativity for hormonal and her2 receptors, Triple Negative tumors do not benefit from anti hormonal treatments or with anti her2. They have no specific treatment and chemotherapy being the only form of systemic treatment. Objectives The objective of this study is, first, to evaluate in Triple Negative tumors feasibility of using lymphocyte infiltration, the expression of p53 protein and androgen receptors as prognostic markers (overall survival and disease-free), and, second, evaluate their usefulness as predictors of response to chemotherapy. Materials and method We intend to analyze those patients diagnosed with tnbc treated at the German Hospital of Buenos Aires and at the Mater Dei Sanatorium from December 2000 to December 2012. Results Twenty-one patients with tnbc were analyzed. In our population, chemotherapy was associated with a lower risk of relapse and mortality. The prevalence in the p53 mutation was 61.9% in the general population, 72.7% in relapses and 66.6% in deceased patients. Tumor lymphocytic infiltration (tils) on average was 20.5% (5% - 60%), being lower when only the population of patients who relapsed were evaluated (17.7%), and even lower when evaluating the population of deceased patients (11.7%). Discussion Chemotherapy had a survival rr of 0.15 (ci: 0.06 - 0.78) with a p: 0.0021. The p53 protein mutation had a rr of 1.2 as a risk factor for mortality or progression (ci: 0.23 - 9.07; p: 0.6). The expression of androgen receptors has a rr of 1.6 as a risk factor for mortality or progression (ci: 0.21 - 6.24; p: 0.41). The presence of tils greater than 20% is a predictor of mortality and recurrence with a p: 0.023. Conclusions The determination of tils together with determination of the p53 protein mutation are useful tools in determining the suitability of a chemotherapeutic treatment since both are associated with increased total survival and disease-free survival, although in our population this association was not statistically significant for p53.
Asunto(s)
Humanos , Femenino , Pronóstico , Neoplasias de la Mama , Prevalencia , Neoplasias de la Mama Triple NegativasRESUMEN
Objective To identify clinicopathological features of high MSI (MSI-H).Methods We enrolled 150 patients,standard microsatellite loci (BA T25,BA T26,D2S123,D5S346,D17S250) were amplified by polymerase chain reaction(PCR) with fluorescent primers,and the PCR products were analyzed by GeneMapper software;age at diagnosis,gender and site were obtained;various pathological features were observed by light microscopy;the expression of tumor infiltrating lymphocytes (CD4~+ and CD8~+) was detected by immunohistochemistry.Using a stepwise logistic regression model,a formula was generated that could be used to calculate the probability of a colorectal carcinoma being MSI-H based on pathological features.Results Among 150 cancers,MSI-H was 13.33%.Independent identifiers inclucle poor differentiation,histologic heterogeneity,Crohn's-like reaction and tumor-infiltrating lymphocytes,logistic regression formula shows a sensitivity of 70.0% and a specificity of 99.2% and a accurate ratio of 95.3% for MSI-H.Conclusion MSI-H phenotype cancer is a type of nonfamilial colorectal cancer with specific pathological features,Clinicopathological features can efficiently identify MSI-H colorectal cancers.