ABSTRACT
BACKGROUND: The influence of Helicobacter-pylori (H. pylori) infection and the characteristics of gastric cancer (GC) on tumor-infiltrating lymphocyte (TIL) levels has not been extensively studied. Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information. AIM: To determine the rates of deficient mismatch-repair (dMMR), HER2-status and H. pylori infection and their association with TIL levels in GC. METHODS: Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral (IT), stromal (ST) and invasive-border (IB) compartments. The density of CD3, CD8 and CD163 immune cells, and dMMR and HER2-status were determined by immunohistochemistry (IHC). H. pylori infection was evaluated by routine histology and quantitative PCR (qPCR) in a subset of samples. RESULTS: dMMR was found in 34.4%, HER2+ in 5% and H. pylori-positive in 55.7% of samples. High IT-TIL was associated with grade-3 (P = 0.038), while ST-TIL with grade-1 (P < 0.001), intestinal-histology (P < 0.001) and no-recurrence (P = 0.003). dMMR was associated with high TIL levels in the ST (P = 0.019) and IB (P = 0.01) compartments, and ST-CD3 (P = 0.049) and ST-CD8 (P = 0.05) densities. HER2- was associated with high IT-CD8 (P = 0.009). H. pylori-negative was associated with high IT-TIL levels (P = 0.009) when assessed by routine-histology, and with high TIL levels in the 3 compartments (P = 0.002-0.047) and CD8 density in the IT and ST compartments (P = 0.001) when assessed by qPCR. A longer overall survival was associated with low IT-CD163 (P = 0.003) and CD8/CD3 (P = 0.001 in IT and P = 0.002 in ST) and high IT-CD3 (P = 0.021), ST-CD3 (P = 0.003) and CD3/CD163 (P = 0.002). CONCLUSION: TIL levels were related to dMMR and H. pylori-negativity. Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.
ABSTRACT
OBJECTIVE: To evaluate the relationship between circulating tumor DNA (ctDNA) presence and tumor features including tumor-infiltrating lymphocyte (TIL) levels in Peruvian breast cancer patients. MATERIALS AND METHODS: This was a prospective study conducted at the Instituto Nacional de Enfemedades Neoplasicas, Peru. We evaluated level of TIL and PIK3CA mutations in ctDNA. Clinical characteristics, including outcome data, were collected from the patient file. Survival was calculated from the date of blood sample drawn to the event time. Data collected were analyzed using SPSS software version 25. RESULTS: We analyzed plasma samples from 183 breast cancer patients. most cases were of Luminal-B (44.8%) phenotype and stage II (41.5%), and median stromal TIL was 30%. PIK3CA mutation in ctDNA was detected in 35% cases (most with E545K) and was associated with lower TIL level (p=0.04). PIK3CA in ctDNA tended to be associated with advanced stages (p=0.09) in the whole series and with higher recurrence rates (p=0.053) in the non-metastatic setting. Patients with presence of PIK3CA in ctDNA tended to have shorter survival (p=0.083). CONCLUSION: Presence of PIK3CA mutation in ctDNA was frequently found in our Peruvian breast cancer series, was associated with lower TIL levels and tended to predict poor outcomes.
Subject(s)
Circulating Tumor DNA , Neoplasms , Lymphocytes, Tumor-Infiltrating/pathology , Peru , Prospective Studies , Class I Phosphatidylinositol 3-Kinases/genetics , Circulating Tumor DNA/genetics , Mutation , Biomarkers, Tumor/genetics , Neoplasms/pathologyABSTRACT
BACKGROUND: Breast cancer (BC) frequency in males is extremely low and tumor features vary from its female counterpart. Breast cancer clinical and pathological features differ by race in women. Tumor infiltrating lymphocyte (TIL) levels, mismatch repair (MMR) protein loss, androgen receptor (AR) expression, and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC. There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC. AIM: To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population. METHODS: This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018. Standard pathological features, TIL levels, MMR proteins, AR immunohistochemistry staining, and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material. Percentage of AR and estrogen receptor (ER) positive cells was additionally calculated by software after slide scanning. Statistical analyses included association tests, intraclass correlation test and Kaplan Meier overall survival curves. RESULTS: The median age was 63 years and most cases were ER-positive (85.7%), HER2 negative (87.2%), Luminal-A phenotype (60%) and clinical stage II (41.5%) among our male breast tumors. Median TIL was 10% and higher levels tended to be associated with Luminal-B phenotype and higher grade. AR-positive was found in 85.3% and was correlated with ER (intraclass index of 0.835, P < 0.001). Loss of MMR proteins was found in 15.4% and PIK3CA mutation (H1047R) in 14.3% (belonged to the Luminal-A phenotype). Loss of MMR proteins was associated with AR-negative (P = 0.018) but not with ER (P = 0.43) or TIL (P = 0.84). Early stages (P < 0.001) and lower grade (P = 0.006) were associated with longer overall survival. ER status, phenotype, AR status, TIL level, MMR protein loss nor PIK3CA mutation was not associated with survival (P > 0.05). CONCLUSION: Male BC is usually ER and AR positive, and Luminal-A. MMR loss and PIK3CA mutations are infrequent. Stage and grade predicted overall survival in our South American country population.
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Aim: To correlate levels of tumor-infiltrating lymphocytes (TIL) evaluated using the International Immuno-Oncology Biomarker Working Group methodology, and both density of tumor-infiltrating immune cell and clinicopathological features in different malignancies. Methods: 209 pathological samples from gastric cancer, cervical cancer (CC), non-small-lung cancer, cutaneous melanoma (CM) and glioblastoma were tested for TIL in hematoxylin eosin, and density of CD3+, CD4+, CD8+, CD20+, CD68+ and CD163+ cells by digital analysis. Results: TIL levels were higher in invasive margin compartments (IMC). TIL in IMC, intratumoral and stromal compartments predicted survival. CC and gastric cancer had higher TIL in intratumoral; CC and CM had higher TIL in stromal compartment and IMC. CM had the highest density of lymphocyte and macrophage populations. CD20 density was associated with survival in the whole series. Conclusion: Standardized evaluation of TIL levels may provide valuable prognostic information in a spectrum of different malignancies.
Subject(s)
Lymphocytes, Tumor-Infiltrating/cytology , Neoplasms/blood , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Leukocyte Count , Macrophages/cytology , Male , Middle Aged , Young AdultABSTRACT
PURPOSE: Helicobacter pylori (HP) and Epstein Barr virus (EBV) infections induce chronic gastritis (CG) and are accepted carcinogenics of gastric cancer (GC). Our objective for this study was to determine the prevalence of these agents and clinicopathological features of GC and CG associated with the infection. PATIENTS AND METHODS: A single-center cohort of 375 Peruvian patients with GC and 165 control subjects with CG were analyzed. Evaluation of HP and EBV genes was performed through quantitative polymerase chain reaction. RESULTS: Prevalence of HP was 62.9% in the whole population and 60.8% in the GC subset. The cagA gene was detected in 79.9%; vacAs1 and vacAm1 alleles in 41.6% and 60.7%, respectively; and concurrent expression of vacAs1 and vacAm1 in 30.4% of infected patients in the whole series. The prevalence of EBV was 14.1% in the whole population and was higher in GC (P < .001). Coinfection of HP and EBV was found in 7.8% and was also higher in GC in univariate (P < .001) and multivariate (P = .011) analyses. Infection rates of HP and EBV were not associated with a geographic location in the whole series. Few clinicopathological features have been associated with infectious status. CONCLUSION: Prevalence of HP infection and virulent strains are high in the Peruvian population. Infection by EBV was more frequent in patients with GC.
Subject(s)
Epstein-Barr Virus Infections/epidemiology , Gastritis/complications , Helicobacter pylori/pathogenicity , Stomach Neoplasms/complications , Chronic Disease , Female , Genotype , Humans , Male , Middle Aged , Peru , PrevalenceSubject(s)
Antigens, CD/analysis , CD8 Antigens/analysis , Cell Adhesion Molecules, Neuronal/analysis , Fetal Proteins/analysis , Lymphocytes, Tumor-Infiltrating/immunology , Receptors, Androgen/analysis , Triple Negative Breast Neoplasms , Biomarkers, Tumor/analysis , Cell Adhesion , Cell Proliferation , Epithelial-Mesenchymal Transition , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Prognosis , Ribonucleoproteins, Small Nucleolar/analysis , Survival Analysis , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathologyABSTRACT
AIM: Evaluation of features related to infiltrating immune cell level in glioblastoma. METHODS: Tumor-infiltrating lymphocytes (TILs) through H&E staining, and TILs (CD3, CD4, CD8 and CD20) and macrophage (CD68 and CD163) levels through immunohistochemistry were evaluated through digital analysis. RESULTS: CD68 (9.1%), CD163 (2.2%), CD3 (1.6%) and CD8 (1.6%) had the highest density. Higher CD4+ was associated with unmethylated MGMT (p = 0.016). Higher CD8+ was associated with larger tumoral size (p = 0.027). Higher CD163+ was associated with higher age (p = 0.044) and recursive partitioning analysis = 4. Women (p < 0.05), total resection (p < 0.05), MGMT-methylation (p < 0.001), radiotherapy (p < 0.001), chemotherapy (p < 0.001) and lower CD4+ (p < 0.05) were associated with longer overall survival. CONCLUSION: Macrophages are more frequent than TILs. Some subsets are associated with clinical features.
Subject(s)
Brain Neoplasms/pathology , Glioblastoma/pathology , Lymphocytes, Tumor-Infiltrating/pathology , Macrophages/pathology , Adolescent , Adult , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Brain Neoplasms/therapy , Child , Cohort Studies , DNA Methylation , DNA Modification Methylases/genetics , DNA Modification Methylases/metabolism , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism , Female , Glioblastoma/genetics , Glioblastoma/immunology , Glioblastoma/therapy , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Macrophages/immunology , Male , Middle Aged , Promoter Regions, Genetic , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Young AdultABSTRACT
AIM: To evaluate the prognostic value of tumor-infiltrating lymphocytes (TILs) and Ki67 in brain metastasis lesions, and the effect of adding them to variables of graded prognostic assessment score. PATIENTS & METHODS: Clinicopathological information from 111 medical charts of brain metastasis patients was obtained, and TIL distribution (n = 84), Ki67 index (n = 79) and CD3 TIL (n = 64) were prospectively evaluated. RESULTS: Most frequent TIL pattern was perivascular (67.8%), and median Ki67 and CD3 TIL percents were 30 and 4.8%, respectively. Ki67 ≥15 was associated with shorter survival (p = 0.018) but CD3 TIL was not (p = 0.870). The highest graded prognostic assessment score was not associated with survival (p = 0.648), however, those with low Ki67 and high score was associated with better outcome (p = 0.007). CONCLUSION: High Ki67 index in brain metastasis carries a worse prognosis.