CD4-positive Lymphocytes Research Articles

Expression of Death Receptor 3 (DR3) on Circulating CD4 Positive Lymphocytes on Patients with Vitiligo

Vitiligo is the most common depigmenting skin disorder with an estimated prevalence of 0.5–2% of the population in both adults and children worldwide. Death receptor 3 is a typical member of TNFRSF which play a role in apoptotic signalling and differentiation. DR3 is considered the primary activating receptor of TL1A and is predominantly expressed on leucocytes. DR3 expression is significantly upregulated on various activated cells in the immune system, including T lymphocytes, B lymphocytes, natural killer T (NKT) cells, dendritic cells and macrophages. The aim of this study was to study the expression of death receptor 3 (DR3) on CD4 positive lymphocytes on patients with vitiligo . This study was a case control study that included 50 patients with vitiligo in addition to 25 apparently healthy individuals of matched age and sex as a control group. All patients were recruited from the outpatient clinic of Dermatology, Venereology and Andrology Department of Benha University Hospitals. DR3 showed fair AUC (AUC=0.794). At cut off value of 23.8, sensitivity was72%, specificity was 80%, PPV was 87.8%, NPV was 58.8%, and accuracy was 74.7%. DR3 expression level was significantly higher in vitiligo cases when compared to control group. DR3 expression level was significantly correlated with BSA %. DR3 expression level was suggested to be independent predictor of vitiligo susceptibility and Extent.

Approaching the tumor microenvironment in patients with advanced hepatocellular carcinoma using needle biopsy samples.

334 Background: Currently, combined immunotherapy of atezolizumab (anti-PD-L1 antibody) plus bevacizumab (a humanized anti-VEGF monoclonal antibody) is the standard first-line treatment in patients with advanced hepatocellular carcinoma (HCC). At the threshold of this new era, there is limited information about tumor microenvironment (TME) in advanced HCC. Several studies on TME in HCC have analyzed samples obtained via hepatic resection. In general, hepatic resection is indicated for patients with limited size and number of intrahepatic nodules, i.e., early stage HCC. In contrast, most patients who have an indication for systemic therapy have developed macroscopic vascular invasion (MVI) or/and extrahepatic metastasis, namely in advanced stage HCC. Progression from an early stage HCC to an advanced stage HCC involves a lengthy clinical course, therefore, the TME at the time of initial diagnosis may differ from that at the time of systemic therapy indication. The present study was aimed to analyze the TME by using needle biopsy samples obtained prior to initiation of systemic therapy in patients with advanced HCC. Methods: Between March 2019 and May 2020, 80 patients underwent liver tumor biopsy at the time of indication for systemic chemotherapy. HCC was confirmed via pathological examination in 70 patients and their samples were analyzed. Microsatellite instability (MSI) was evaluated using polymerase chain reaction. Programed death-ligand 1 (PD-L1) expression and the levels of tumor-infiltrating lymphocytes (TIL) were evaluated using immunohistochemical staining. PD-L1 expression was defined as per the tumor proportion score (TPS; the number of PD-L1-positive cells/total number of tumor cells) and was classified as low (TPS < 1%) or high (TPS >1%). Levels of TIL were defined as the mean number of CD8-positive lymphocytes in the tumor per 1 mm2 and classified as low or high using the median value. Results: Out of the 70 tumors, one was MSI-high and 69 were MSI-negative. The PD-L1 expression was < 1% in 50 samples, 1%–10% in 12, 11%–20% in 7, and 21%–30% in 1. The median level of TIL was 266/mm2. PD-L1highTILhighwas present in 20.0%, PD-L1lowTILlowin 38.5%, PD-L1highTILlowin 8.6%, and PD-L1lowTILhighin 32.9%. In the MSI-high tumor, PD-L1 expression was < 1% and the level of TIL was 142/mm2. High PD-L1 expression and high levels of TIL were associated with hepatitis C virus infection, high alpha-fetoprotein levels, and presence of MVI respectively. We are currently performing RNA-sequencing in order to obtain more details about TME in patients with advanced HCC. Conclusions: MSI-high advanced HCC was detected in 1.4% patients and was not necessarily associated with a “hot” immune microenvironment. PD-L1 expression and levels of TIL were associated with some clinical parameters. In the present study, we also reported the changes in the TME over time.

Prognostic impact of the tumor immune microenvironment in pulmonary pleomorphic carcinoma

IntroductionPulmonary pleomorphic carcinoma (PC) is a rare non-small cell lung carcinoma (NSCLC) and is characterized by sarcomatoid and NSCLC components. This study aimed to characterize the association between immune microenvironmental factors and clinicopathological characteristics of PC. MethodsEighty consecutive PC patients who had undergone complete surgical resection were enrolled. We calculated the immunohistochemical staining scores for E-cadherin, vimentin, programmed death ligand 1 (PD-L1), and carbonic anhydrase IX in cancer cells and counted the numbers of CD204-positive tumor-associated macrophages (TAMs) and Foxp3-, CD8-, and CD20-positive tumor-infiltrating lymphocytes (TILs). We also examined the association between these scores and the prognostic outcomes. ResultsThe staining score for PD-L1 in cancer cells and the number of CD204-positive TAMs in the sarcomatoid component were significantly higher than those in the NSCLC component; E-cadherin score in the sarcomatoid component was significantly lower. Patients with high PD-L1 expression in the NSCLC component had significantly longer overall survival (OS) and recurrence-free survival (RFS) than those with low PD-L1 expression in the NSCLC component (OS: p = 0.001, RFS: p = 0.038). Multivariate analysis revealed that high PD-L1 expression in the NSCLC component was an independent favorable prognostic factor for OS (p = 0.018), whereas high PD-L1 expression in the sarcomatoid component was not. The number of CD8-positive TILs was significantly higher in the high PD-L1 expression group than in the low expression group (NSCLC components: p < 0.001). ConclusionHigh PD-L1 expression in the NSCLC component may be associated with a favorable prognostic value in pulmonary PC.

Colitis Nucleomigrans: A Proposal for The Third Type of Microscopic Colitis

Recently, we proposed the third entity of microscopic colitis (MC), termed colitis nucleomigrans (CN). The present review describes clinicopathological features of CN. CN shares clinical and endoscopic features of MC with collagenous colitis and lymphocytic colitis. We analyzed endoscopic biopsy specimens of nonspecific colitis clinically manifesting chronic watery diarrhea or inflammatory bowel disease (IBD)-like symptoms, but with minor endoscopic abnormality. The histopathological criteria of CN are as follows: a) chained nuclear migration to the middle part of the surface-lining columnar epithelia, b) apoptotic nuclear debris scattered below the nuclei, and c) mild to moderate chronic inflammation in the lamina propria. Thirty-three patients (M: F=20:13, median 63 years; range 17-88) fulfilled the above criteria. Seven cases accompanied MC-like clinical/endoscopic features. Mucosal reddening with or without erosions/aphthae was endoscopically observed in the remaining 26 cases with IBD-like clinical features: occult/gross hematochezia (n=19), abdominal pain (n=2) and mucin secretion (n=2). Apoptotic debris immunoreactive for cleaved caspase-3 appeared more frequently in IBD-like CN than in MC-like CN. CD8-positive intraepithelial lymphocytes were comparable in both types. Proton pump inhibitors (PPIs) were administered in five (71%) CN cases with MC-like features, and the diarrhea improved after cessation of PPIs in three. In IBD-like CN cases, eight (31%) received PPIs. Altered apoptotic processes in the colorectal surface-lining epithelia, predominantly with a debris pattern of apoptosis, may be involved in the pathogenesis. Mechanisms of nuclear migration to the unusual position and the impairment of nuclear anchoring to the basal situation in the surface-lining epithelia remain to be established.

Clinical Significance of PD-L1 Expression and CD8-Positive Tumor-Infiltrating Lymphocytes in Patients with Cavitary Lung Adenocarcinoma

Clinical Significance of PD-L1 Expression and CD8-Positive Tumor-Infiltrating Lymphocytes in Patients with Cavitary Lung Adenocarcinoma

GLI2/Hedgehog Signaling Contributes to the Induction of Malignant Phenotype of Gallbladder Cancer

Background: We have previously shown that Hedgehog (Hh) signaling is reactivated in GBC. However, which and how three GLI proteins; GLI1. GLI2 and GLI3 contribute to the induction of malignant phenotype of GBC is still unclear. To develop a new therapeutic strategy for refractory GBC, the biological significance of GLI1, GLI2 and GLI3 was investigated. Materials: 1) In vitro experiment; GLI proteins were inhibited using siRNA. GLI expressing 3 GBC cell lines (NOZ, TGBC2TKB, and TYGBK−1) were used for invasion assay and proliferation assay. 2) In vivo experiment; In xenograft mice model, tumorigenesis of GLI inhibited cells (NOZ) was analyzed. 3) Clinical experiment; 67 patients with GBC who underwent curative surgical resection were enrolled in this study. Correlation between GLI expression and clinicopathological findings was analyzed immunohistochemically. Results: 1) In vitro results; GLI2 siRNA but not GLI1/GLI3 siRNA transfection significantly inhibited the invasiveness and proliferation ability of GBC cells. 2) In vivo results; Tumor volume from mice injected with GLI2 siRNA transfected cells was significantly lower than that in control tumors. 3) Clinical results; The expression levels of GLI2 in human GBC specimens were higher than those in normal gallbladder tissue. GBC specimens with high GLI2 expression had significantly high level of PD-L1 expression and low number of infiltrated CD3 positive lymphocytes. Conclusion: GLI2 contributes to the induction of malignant phenotype of GBC and could be a potential therapeutic target for GBC.

Histopathological Analysis of Esophageal Mucosa in Patients with Achalasia.

Background/AimsAchalasia is an esophageal motor disorder that leads to functional esophageal obstruction. Food stasis and bacterial fermentation can predispose an individual to esophageal mucosal inflammation, causing multifocal dysplasia and increasing the risk of developing esophageal squamous cell carcinoma. We aimed to evaluate esophageal mucosal alterations in achalasia patients and determine clinical factors associated with the histopathological findings.MethodsFrom 2009 to 2013, we obtained endoscopic biopsies from the lower and middle esophagus of 22 patients with achalasia and 17 controls. Patients’ clinical data and histological severity of esophagitis were retrospectively analyzed. Additionally, immunohistochemical staining for CD3, CD20, Ki-67, and p53 was conducted.ResultsThe median age of achalasia patients was 49.5 years (range, 27 to 82 years), and there were nine males (40.9%). The median symptom duration was 5.8 years (range, 1 to 33.5 years), and 10 patients (45%) underwent previous treatment (nine, balloon dilation; one, botulinum toxin injection). Achalasia patients had significantly more severe esophagitis than did controls (p=0.001, lower esophagus; p=0.008, middle esophagus), and the number of CD3-positive lymphocytes exceeded that of CD20-positive lymphocytes (p<0.001). Achalasia patients also had a higher esophageal Ki-67 proliferation index (p=0.048). Although statistically nonsignificant, p53 expression was only observed in achalasia patients. There was no association between the histological severity of esophagitis and other clinicopathological findings.ConclusionsAchalasia patients showed significantly severe histological esophagitis and a high Ki-67 proliferation index, indicating an increased risk of neoplastic progression. Therefore, careful endoscopic inspection is necessary for the early detection of superficial neoplasia in these patients. (Gut Liver 2021;15-722)

GCT-51. IMMUNE CHECKPOINT MOLECULES AND TUMOR INFILTRATING LEUKOCYTES IN THE TUMOR MICROENVIRONMENT ARE ASSOCIATED WITH THE GROWTH OF INTRACRANIAL GERMINOMAS

The role of immune checkpoint molecules and the tumor immune microenvironment in the development of intracranial germ cell tumors remains unclear. In the present study, we investigated the expression of immune checkpoint molecules, as well as the number of tumor-infiltrating lymphocytes (TILs), in intracranial germinomas to determine whether there were any correlations between the statuses of these immune-related molecules/cells and clinical manifestations in patients with germinoma. The 8 patients were categorized based on the duration between symptom onset and pathological diagnosis into the long-term onset (LTO) group (> 1 year of symptoms, 3 patients) and the short-term onset (STO) group (< 1 year of symptoms, 5 patients). Compared with STO tumors, LTO tumors were significantly associated with a lower ratio of programed cell death ligand-1 (PD-L1)–positive tumor cells (p = 0.012), higher number of infiltrating CD3- and CD8-positive lymphocytes (p = 0.016, 0.003, respectively), and lower ratio of programed cell death-1 (PD-1)–positive cells per CD8–positive lymphocytes (p = 0.047). LTO germinomas were significantly smaller in size than STO tumors and tended to be present in patients with atypical tumor location. Our data suggest that the tumor immune microenvironment, including PD-1/PD-L1 signaling, is associated with the growth of intracranial germinomas. Immune checkpoint inhibitors might be a reasonable treatment option for recurrent germinomas or as replacement for radiotherapy in patients with intracranial germinomas.

Prognostic impact of peripheral blood neutrophil to lymphocyte ratio in advanced-stage pulmonary large cell neuroendocrine carcinoma and its association with the immune-related tumour microenvironment

BackgroundThe prognostic value of the neutrophil-to-lymphocyte ratio (NLR) with large cell neuroendocrine carcinoma (LCNEC) patients remains unclear. Thus, we performed a retrospective study to examine the relationship between the pretreatment NLR and clinical outcome in advanced LCNEC patients and the impact of the immune-related tumour microenvironment (TME).MethodsThis retrospective study included 63 advanced LCNEC patients who had received chemotherapy. We collected clinical data and investigated the TME status (CD4, CD8, CD20 and FOXP3).ResultsThe overall survival of the patients with a low NLR (<5) was significantly longer than those with a high NLR (≥5) (14.9 vs. 5.2 months; p < 0.001). A multivariate analysis identified a high NLR as a predictor of a poor prognosis (HR, 3.43; 95% CI, 1.73–6.79; p < 0.001). The NLR was inversely correlated with tumoural and stromal CD8-positive tumour-infiltrating lymphocytes (tumoural: r = −0.648, p = 0.005, stromal: r = −0.490, p = 0.046).ConclusionsA high NLR was associated with a poor prognosis in advanced LCNEC patients. Our study revealed that the NLR can reflect the TME, at least in part, suggesting that the NLR plays an important role not only as a clinical outcome predictor but also as a tumour immune status indicator.

The investigation of T-cell receptor subtypes in ovarian cancer: effects on survival and prognostic factors

The aim of this study was to investigate T-cell receptor (TCR) changes in ovarian carcinoma (OC). The study included 24 malignant and 23 benign adnexal masses. DNA was isolated from ovarian samples. Multiplex PCR was used to determine T-cell gene clonality. PCR products were loaded onto polyacrylamide gel electrophoresis and imaged. The relationship between prognostic parameters and T-cell rearrangement was evaluated. In the study group (SG), TCRB-B positivity was higher than control group (CG) and TCRD receptor positivity was higher in CG. In SG, TCRG-B levels were higher in patients with stage I–II tumours compared to stage III. TCRG-B receptor was higher in patients with overall survival of 36 months and above. In our study, subgroups of TCRs were analysed in OC. According to our findings, significant differences in TCRB-B and TCRD subgroups may be applied to immune therapies. Understanding of TCR pathways will provide new treatment approaches in OC. IMPACT STATEMENT What is already known on this subject? Ovarian cancer is the most challenging kind of gynaecologic cancer. Although the main route of spread is direct invasion and peritoneal spread in the abdominal cavity, lymphatic invasion is also very important. Recent studies put forward that immunological mechanisms play crucial role in ovarian cancer. CD3 and CD8 positive lymphocyte infiltration in ovarian tumour is related with better prognosis where, FoxP3 positive lymphocyte infiltration is a predictor of poor survival. Also, immune checkpoints and inhibitors are important topics in ovarian cancer. What the results of this study add? Despite all the improvements and studies regarding immune system and ovarian cancer, the role T-cell receptor (TCR) subtypes is not clear and there are very few number of studies in this area. This is one of the first studies that describe the rearrangement of TCR subtypes between normal ovarian tissue and ovarian cancer tissue. What the implications are of these findings for clinical practice and/or further research? Understanding the role of TCR subtypes has a key role because studies about lymphocyte infiltration in ovarian cancer varies from region to region in the world and same type of lymphocytes has different effects in different studies. Further studies on TCR subtypes may elucidate us about the behaviour of lymphocytes. Additionally, these receptor may be targeted if their roles are better understood.

An increase of CD8+\u2009T cell infiltration following recurrence is a good prognosticator in HNSCC

Programmed death-ligand 1 (PD-L1) expression and CD8-positive tumor-infiltrating lymphocyte (CD8+ TIL) infiltration are essential biomarkers for immune checkpoint inhibitor therapy. The objective of this study was to compare the expression of those biomarkers between initial and recurrent HNSCCs using paired analysis. Prognostic significance of those immunological changes was also investigated. Forty-two consecutive patients with locally recurrent HNSCCs were included. Immunohistochemical staining of CD8 and PD-L1 was done for both initial and recurrent tumor specimens. The IHC findings were verified with mRNA expression profiling. Also, the prognostic impact was analyzed based on overall survival (OS). Recurrent-to-initial (R/I) ratios of CD8+ TILs and PD-L1 were widely variable. CD8+ TIL density and PD-L1 expression decreased in 59.5% and 69% of patients, respectively (R/I ratio < 1). The R/I ratio of CD8A mRNA was significantly higher in patients with a CD8 R/I ratio > 1 (1.7 ± 1.5 vs. 0.6 ± 0.6, p = 0.042). CD8 R/I ratio (> 1) was a good prognosticator for OS (HR 0.293, 95% CI 0.091–0.945, p = 0.040). CD8+ TIL infiltration and PD-L1 expression changed variably following local recurrence of HNSCC. The increase of CD8+ TILs at recurrence was an excellent independent prognosticator.

Clinical Features and Short-Term Outcomes in COVID-19-Infected Patients with Cancer.

BackgroundCoronavirus disease 2019 (COVID-19) is an infectious disease that has been spreading very fast worldwide. Up to now, there is scarce information regarding the clinical features and short-term outcomes of infected patients with cancer.MethodsWe performed a retrospective study in Wuhan Union Hospital from Feb 14, 2020, to Mar 15, 2020, China. Data were retrieved including demographic and clinical features, laboratory findings, and outcome data. Patients were classified into the discharged group and undischarged group by the 4-week outcomes from admission. Difference analysis and correlation analysis were performed between the two groups.ResultsA total of 37 patients were enrolled in the study, including 27 cancer survivors in routine follow-up. Breast cancer (18.9%) was the most frequent cancer type, and common symptoms included cough (54.1%), fever (48.6%), and fatigue (27%). Lymphocytopenia and hypoproteinemia were much frequent in patients who had received chemotherapy, radiotherapy, or surgery within the past month. However, the concentration of D-dimer (median: 3.75 vs 0.43, P =0.010) and fibrin degradation products (median: 23.60 vs 1.80, P =0.002) were evidently increased in this population compared with cancer survivors. At the end of follow-up, 83.8% of the enrolled patients were discharged. Among the discharged, women (48.6%) and cancer survivors (67.6%) showed better short-term outcomes. The elevated level of FDP was significantly higher in the undischarged group (median: 21.85 vs 2.00, P =0.049). The proportion of CD3-positive lymphocyte cells and CD4-positive lymphocytes was correlated with short-term outcomes.ConclusionPeripheral lymphocyte subset (CD3-positive and CD4-positive) on admission as a novel biomarker had a potential association with early efficacy. Cancer survivors in routine follow-up would achieve better short-term outcomes. COVID-19 patients with cancer should gain more attention and close monitoring.

An Interesting Case Report of A Concurrent Classic Hodgkin Lymphoma and Gray Zone Lymphoma in the Mediastinum

Abstract Casestudy A 52-year-old female presented with night sweats, chills, anorexia, and weight loss. Computed tomography and positron emission tomography showed a soft tissue infiltration in the anterior mediastinum and hypermetabolic bilateral supraclavicular, mediastinal, right hilar, and left internal mammary lymph nodes. An anterior mediastinal mass resection and thymectomy was subsequently performed. Results Sections of the mediastinal mass showed Hodgkin/Reed-Sternberg cells (HRS) admixed with small lymphocytes, histiocytes, plasma cells, and eosinophils. The HRS cells are positive for CD30, CD15, and MUM1, faintly positive for PAX5, and negative for CD20, CD45, CD79a, and BCL6. The morphology and immunophenotype is diagnostic of nodular sclerosis classic Hodgkin lymphoma (CHL). Sections of the thymectomy specimen showed similar morphology, however, in an area that represents 10-20% of the specimen, there are nodular and diffuse lymphoid infiltrates consisting of small lymphocytes, histiocytes, and large atypical cells. The large atypical cells are positive for CD20, CD23, CD30, CD45, CD79a, BCL2, BCL6, MUM-1, and PAX5, and negative for CD1a, CD3, CD57, and Cyclin D1. The background small CD3-positive lymphocytes form a rosette around most of the large atypical cells. CD21 and CD23 stains highlight residual follicular structures. In situ hybridization for EBV-encoded RNA (EBER) is negative. The presence of residual follicular meshwork with an immunophenotype of large B cell lymphoma supports a diagnosis of a gray zone lymphoma (GZL). Overall, CHL is involving 80-90% and GZL is involving 10-20% of the thymic tissue. The patient was subsequently placed on ABVD chemotherapy and achieved remission. Conclusion An accurate diagnosis of GZL is challenging. GZL is a rare type of lymphoma with morphological features between CHL and diffuse large B-cell lymphoma (DLBCL). It is even rarer to encounter a CHL concurrently present with a GZL. The optimal therapeutic approach for cases with concurrent lymphoma diagnosed with CHL and GZL needs further investigation.

Correlative Analyses Between Immune Markers, Tumor Hypoxia And Outcomes Of Head-And-Neck Cancer Patients Undergoing Chemoradiation: Results From A Prospective Trial

Tumor-infiltrating lymphocytes (TILs) influence the response of patients with head-and-neck squamous cell carcinomas (HNSCCs) to chemoradiation and are modulated by the tumor microenvironment and tumor-associated hypoxia. This analysis aimed to assess the prognostic value of TILs and their association with the dynamic tumor hypoxia during chemoradiation in a prospective trial of HNSCC patients. 49 patients with locally advanced HNSCCs were enrolled in this prospective trial prior to undergoing definitive chemoradiation. Patients received tumor biopsies and [18F]-FDG-PET imaging at baseline and [18F]-FMISO hypoxia PET at baseline and in weeks 2 and 5 into treatment. Total lymphocytes, CD3-, CD4-, CD8-positive lymphocytes and expression of PD-1 and PD-L1 were quantified by immunohistochemistry in tumoral and stromal areas of the biopsies and correlated with the tissue hypoxia markers HIF1α, CAIX, CD34 and the longitudinal hypoxia PET/CT data. Potential correlations of immune markers with locoregional control and patient survival were assessed. Patients with high TIL numbers demonstrated increased locoregional control (p = 0.007) and progression-free survival (p = 0.003) compared to patients with lower levels in the biopsies. High numbers of CD3-positive T lymphocytes correlated with improved progression-free (p = 0.018) and overall survival (p = 0.037). In contrast, there was a trend towards impaired progression-free survival for high numbers of CD4-positive regulatory T lymphocytes (p = 0.091), while neither CD8-positive cytotoxic T lymphocytes nor PD-1 or PD-L1 expression correlated with patient outcomes. High levels of TILs were linked to an increased density of CD34-positive microvessels, but not increased levels of hypoxia markers HIF1α or CAIX. No significant correlations could be observed between TILs and dynamic hypoxia PET imaging parameters. In contrast, high expression of intratumoral and stromal PD-1 was associated with low initial tumor hypoxia levels (p = 0.023 for intratumoral PD-1, p = 0.004 for stromal PD-1) as well as a further decrease in the PET hypoxia signal between treatment initiation and week 5 (p = 0.033 for intratumoral PD-1, p = 0.001 for stromal PD-1). In this trial, infiltration of CD3-positive, but not CD4-positive or CD8-positive lymphocytes correlated with an improved locoregional control and increased survival of HNSCC patients after chemoradiation. While no clear associations were found between lymphocyte counts and tumor hypoxia, tumoral PD-1 expression was linked to low initial hypoxia levels and further reductions during treatment. The interplay between tumor hypoxia and tumor-associated immune patterns warrants further investigations to predict treatment response of HNSCC patients.

Role of CD4- and CD8-Positive T Cells in Breast Cancer Progression and Outcome: A Pilot Study of 47 Cases in Central India Region

Immune response plays an important role in cancer progression. In humans, the study of the inflammatory infiltrate in malignancies, mainly T lymphocytes, has been a subject of great interest. The study was conducted to correlate CD4- and CD8-positive lymphocyte expression with other prognostic factors in invasive breast cancer, such as clinical stage, histological grade, tumour size and clinical course. It was a retrospective cross-sectional study. In this study, 47 cases of breast carcinoma which were diagnosed at least 12 months back from the initiating point of study were included. The immunohistochemical expression of CD4 and CD8 in lymphocytes infiltrating the intratumoural, adjacent or distant stroma sites was studied and correlated with other prognostic factors. Less occurrence of adverse outcome was found with the presence of CD8+ T cells anywhere in the vicinity of tumour (only 27%, 7 out of 26 cases) as compared to the group in which both CD4+ and CD8+ T cells were absent where adverse outcome occurred in 78% (7 of 9 cases, p = 0.007). High histological grade was found to be associated with negative CD8+ T cells staining in 21 out of 30 cases with grade III tumours at distant stroma site (p = 0.026). Presence of CD8 cells at intratumoural site had reduced disease-free survival (DFS) (8 months) as compared to their absence at the same site (DFS = 31 months, log rank p = 0.001). CD4 and CD8 staining did not correlate with clinical staging (p > 0.05). Infiltration around the primary tumour by CD8+ T cells in carcinoma breast is a sign of good prognosis, while their absence indicates more adverse outcomes. On the other hand, intratumoural infiltration is associated with rapid advancement of disease. CD4+ cells did not correlate well with prognosis.

Descriptive study of the histopathological subtypes and programmed death-ligand 1 in metaplastic breast carcinoma.

Metaplastic Breast Carcinoma (MBC) is a rare heterogeneous group of tumors, the incidence of which is less than 1% of breast tumors. These are a unique set of tumors with varying subtypes, poor prognosis, and an increased chance of distant metastasis. We aimed to study the clinical, histomorphological, and immunohistochemical (IHC) features of Metaplastic Breast Carcinoma (MBC). This was a descriptive study of cases diagnosed as MBC at a tertiary care center in Southern India from January 2015 to December 2019. A total of 20 cases were diagnosed whose clinical, histomorphological, and IHC features were studied. PD-L1and CD8 IHC were performed and analyzed in 12 cases. The median age of presentation was 50years. Seventy percent (14/20) patients were postmenopausal women. On excision, 75% (15/20) showed mixed typed MBC, the remainder showing epithelial type MBC. Metastasis to axillary lymph node was seen only in 20% (4/20) of the cases. Thirty percent (6/20) of the cases belonged to stage 3 disease and 5% (1/20) of the cases belonged to stage 4 disease with liver metastasis. Estrogen receptor (ER), Progesterone receptor (PR) were negative in all the cases, Her2neu was positive in three cases. Ki67 labeling index was greater than 14% in all the cases. PD-L1was positive in 41.5% of the cases and intratumoral CD8 positive lymphocytes were increased in 83.3% of the cases. MBCs are tumors occurring in elderly postmenopausal women, presenting with large tumor size, have lesser chances of lymph node metastasis, and a higher chance of recurrence and hematogenous spread. They are negative for ER, PR, Her-2 neu, with a high Ki67 index and a strong PDL-1 expression.

125P Association of tumour CD4 positive lymphocytes with prognosis in non-small cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitor

125P Association of tumour CD4 positive lymphocytes with prognosis in non-small cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitor

Expression of Death Receptor 3 (DR3) on Circulating CD4 Positive Lymphocytes in Patients with Alopecia Areata

Alopecia areata (AA) is an autoimmune disorder characterized by transient hair loss and preservation of the hair follicle that affect both sexes.There is scarcity in the published data that discuss the role of DR3 in pathogenesis and prognosis of AA. Therefore, our study was conducted to study this role by assessment of DR3 expression on circulating CD4 positive lymphocytes in AA patients. This study was a case control study that included 50 patients with AA in addition to 50 apparently healthy individuals of matched age and sex as a control group. Assessment of DR3 expression on circulating CD4 positive lymphocytes on both groups was done by flow cytometric analysis. Results of the present study demonstrated a significant difference in DR3 expression level between AA patients and control group. DR3 expression level was considered as risk predictor of AA occurrence. In addition, it was considered as risk predictor of active and severe (higher SALT score) cases.

Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease

Background and Objective: Weakly acidic reflux reaching to the proximal esophagus is closely related to the perception of gastroesophageal reflux in patients with nonerosive reflux disease despite treatment with a proton pump inhibitor (PPI). However, little is known about the involvement of the patients’ mucosal integrity of the proximal esophagus. Methods: We recruited 15 symptomatic nonerosive gastroesophageal reflux disease (GERD) patients with a positive symptom index despite PPI treatment and 11 healthy asymptomatic volunteers as controls. The biopsy specimens obtained from the proximal and distal esophagus were applied to a mini-Ussing chamber system to measure transepithelial electrical resistance (TEER) against a pH 4 weak acid. The esophageal biopsy samples were subjected to quantitative real-time PCR and immunohistochemical analysis. Results: In the proximal esophagus, the weak acid exposure reduced the TEER in the PPI-refractory patients compared to that in the controls. The frequency of the reflux extending to the proximal esophagus had a significant correlation with the reduction in the proximal esophageal TEER in the patients. The reduced TEER in the proximal esophagus was accompanied by an increase in IL-8 and IL-1β mRNA and a decrease in occludin mRNA levels. The proximal esophageal mucosa in the patients presented infiltration of CD3-positive lymphocytes and an increased expression of solute carrier organic anion transporter family member 2A1 (SLCO2A1), a passage gate of reflux symptom-evoking molecules. Conclusions: The reflux perception is related to an impairment of the proximal esophageal mucosal integrity in patients with nonerosive reflux disease despite PPI.

Colitis nucleomigrans: The third type of microscopic colitis (part 1).

Microscopic colitis (MC), encompassing collagenous colitis and lymphocytic colitis, is featured by chronic diarrhea, normal‐looking endoscopic findings and unique microscopic appearance. After reviewing biopsied nonspecific colitis, we propose the third type of MC: colitis nucleomigrans (CN). Histopathological criteria of CN included: (i) chained nuclear migration to the middle part of the surface‐lining columnar epithelium; (ii) apoptotic nuclear debris scattered below the nuclei; and (iii) mild/moderate chronic inflammation in the lamina propria. Thirty‐three patients (M:F = 20:13; median age 63 years, range 17–88) fulfilled our criteria. Seven cases demonstrated MC‐like clinical/endoscopic features. Mucosal reddening with or without erosion/aphtha was endoscopically observed in the remaining 26 cases with inflammatory bowel disease (IBD)‐like features: occult/gross hematochezia seen in 19, abdominal pain in two and mucin secretion in two. Cleaved caspase‐3‐immunoreactive apoptotic debris appeared more frequently in IBD‐like CN than in MC‐like CN, while CD8‐positive intraepithelial lymphocytes comparably appeared in both. Proton pump inhibitors (PPIs) were administered in five (71%) cases with MC‐like features, and in three diarrhea improved after drug cessation. In IBD‐like CN cases, eight (31%) received PPIs. Four patients received chemotherapy against malignancies. Four patients associated immune‐related disorders. Microscopic appearance of CN also appeared in a remission state of ulcerative colitis (12/20 lesions).