Prognostic value of HER2, PD-L1 and RET mRNA expression in salivary gland tumor.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18534-e18534 ◽  
Author(s):  
Svetlana Kutukova ◽  
Evgeny Imyanitov ◽  
Grigory Raskin ◽  
Julia V. Ivaskova ◽  
Natalia P. Beliak ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Mrna Expression ◽  
Immune Cell ◽  
Salivary Gland Tumor ◽  
Salivary Gland Cancer ◽  
Low Grade ◽  
High Grade ◽  
Naive Patient ◽  
Morphological Studies ◽  
Mrna Gene

e18534 Background: The objective of our study was to evaluate the cytologically, morphologically and IGH detection of salivary gland (SGT), expression of HER2 and PD-L1, CPS and determine these associations with patient survival. Methods: The study included 59 patients with a confirmed diagnosis of salivary gland cancer (stage II-IVA) by cytology, morphology and IGH analyses. After that HER2, in tumor and tumor infiltrating immune cell PD-L1 expression (with CPS) was determined using IHC-testing. RET mRNA gene expression calculated with using real-time PCR. Results: Aspiration biopsies results: only in 22 (37.29%) cases the malignant tumor was cytologically confirmed. An IHC study showed the proportion of high-grade tumors significantly exceeded 3.82 times the proportion of low-grade tumors (p < 0.00001). Low grade SGT were 2 times more often recorded by morphological studies (p = 0.0172), high grade SGT - 1.37 times more often by IHC study (p = 0.0176). HER2 expression: (0) – 29(60.42%), (1+) – 11(22.92%), (2+) – 4(8.33%), (3+) – 4(8.33%). Median OS HER2-neg pp was 170.25±24.49 mo (95% CI 125.25-218.26), median OS of 8 pp (16.33%) with HER2 (2+,3+) was 41,00 mo (95%CI 4.50-72.00) (HR 0,07; 95% CI 0,01-0,38; p = 0.00715). Median PFS HER2-neg pp was 168.00 mo (95% CI 75.00-168.00), median PFS of 8 pp (16.33%) with HER2 (2+,3+) was 19,00 mo (95%CI 1.00-31.00) (HR 0,23; 95% CI 0.04-1.22; p = 0.01641). PD-L1 expression was: in tumor cells 0-90% in 11/49 pp (22.45%), in immune cells 0-50% in 26/49 pp (53.06%) (p = 0.0006). CPS was 0-100, median CPS 5 (95% CI 0.03-10.00). Median OS pp with CPS > 1 was 72.00 mo (95% CI 19.5-72.00); with CPS < 1 hasn’t yet been achieved (OR 0.26; 95% CI 0.09-0.75; p = 0.0124). RET mRNA expression was detected in 13 of 48 cases (27.08%). The expression level ranged from 0 to 0.205. The median PFS in the RET mRNA-positive pp was 168.00 mo (95% CI 16.00-168.00) and tended to exceed the median TTP in the RET mRNA-naive patient group. Conclusions: The results suggest that the understanding the receptor status of salivary gland cancer can be effective prognostic factors.

scholarly journals Secretory Carcinoma of Salivary Gland with High-Grade Histology Arising in Hard Palate: A Case Report

Reports ◽  
2020 ◽  
Vol 3 (2) ◽  
pp. 6
Author(s):  
Kiyofumi Takabatake ◽  
Keisuke Nakano ◽  
Hotaka Kawai ◽  
Saori Yoshida ◽  
Haruka Omori ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Hard Palate ◽  
Relevant Literature ◽  
Salivary Gland Tumor ◽  
World Health ◽  
Fusion Product ◽  
Low Grade ◽  
High Grade ◽  
Secretory Carcinoma ◽  
High Grade Transformation

Secretory carcinoma (SC) is a recently described salivary gland tumor reported in the fourth edition of World Health Organization classification of head and neck tumors. SC is characterized by strong S-100 protein, mammaglobin, and vimentin immunoexpression, and harbors a t(12;15)(p13;q25) translocation which leads to ETV6-NTRK3 fusion product. Histologically, SC displays a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogenous or bubbly secretion. SC is generally recognized as low-grade malignancy with low-grade histopathologic features, and metastasis is relatively uncommon. In this case, we described a SC of hard palate that underwent high grade transformation and metastasis to the cervical lymph node in a 54-year-old patient. In addition, this case showed different histological findings between primary lesion and metastasis lesion. Therefore, the diagnosis was confirmed by the presence of ETV6 translocation. Here, we report a case that occurred SC with high-grade transformation in the palate, and a review of the relevant literature is also presented.

scholarly journals Dedifferentiated Acinic Cell Carcinoma of the Parotid Gland With Myoepithelial Features

2002 ◽  
Vol 126 (9) ◽  
pp. 1104-1105 ◽  
Author(s):  
Simonetta Piana ◽  
Alberto Cavazza ◽  
Corrado Pedroni ◽  
Rosa Scotti ◽  
Luigi Serra ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Parotid Gland ◽  
Cell Carcinoma ◽  
Clinical Course ◽  
Acinic Cell Carcinoma ◽  
Low Grade ◽  
High Grade ◽  
Epithelial Proliferation ◽  
Acinic Cell

Abstract Dedifferentiated acinic cell carcinoma of the salivary gland is an uncommon variant of acinic cell carcinoma, characterized by the coexistence of both an usual low-grade acinic cell carcinoma and a high-grade dedifferentiated component, as well as by an accelerated clinical course. We describe a case of acinic cell carcinoma of the parotid gland in a 67-year-old woman, which recurred 4 times after surgery and radiotherapy. The recurrences consisted of residual foci of acinic cell carcinoma intermingled with a high-grade epithelial proliferation; the latter was focally constituted by cells with morphologic and immunohistochemical features of myoepithelium.

scholarly journals Single-cell RNA Sequencing Reveals Immunosuppressive Myeloid Cell Diversity and Restricted Cytotoxic Effector Cell Trafficking and Activation During Malignant Progression in Glioma

2021 ◽  
Author(s):  
Sakthi Rajendran ◽  
Clayton Peterson ◽  
Alessandro Canella ◽  
Yang Hu ◽  
Amy Gross ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Immune Cell ◽  
Myeloid Cell ◽  
Malignant Progression ◽  
Low Grade ◽  
Cell Trafficking ◽  
High Grade ◽  
Single Cell Rna Sequencing

Low grade gliomas (LGG) account for about two-thirds of all glioma diagnoses in adolescents and young adults (AYA) and malignant progression of these patients leads to dismal outcomes. Recent studies have shown the importance of the dynamic tumor microenvironment in high-grade gliomas (HGG), yet its role is still poorly understood in low-grade glioma malignant progression. Here, we investigated the heterogeneity of the immune microenvironment using a platelet-derived growth factor (PDGF)-driven RCAS (replication-competent ASLV long terminal repeat with a splice acceptor) glioma model that recapitulates the malignant progression of low to high-grade glioma in humans and also provides a model system to characterize immune cell trafficking and evolution. To illuminate changes in the immune cell landscape during tumor progression, we performed single-cell RNA sequencing on immune cells isolated from animals bearing no tumor (NT), LGG and HGG, with a particular focus on the myeloid cell compartment, which is known to mediate glioma immunosuppression. LGGs demonstrated significantly increased infiltrating T cells, CD4 T cells, CD8 T cells, B cells, and natural killer cells in the tumor microenvironment, whereas HGGs significantly abrogated this infiltration. Our study identified two distinct macrophage clusters in the tumor microenvironment; one cluster appeared to be bone marrow-derived while another was defined by overexpression of Trem2, a marker of tumor associated macrophages. Our data demonstrates that these two distinct macrophage clusters show an immune-activated phenotype (Stat1, Tnf, Cxcl9 and Cxcl10) in LGG which evolves to an immunosuppressive state (Lgals3, Apoc1 and Id2) in HGG that restricts T cell recruitment and activation. We identified CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Interestingly, these results were mirrored by our analysis of the TCGA dataset, which demonstrated a statistically significant association between CD74 overexpression and decreased overall survival in AYA patients with grade II gliomas. Targeting immunosuppressive myeloid cells and intra-tumoral macrophages within this therapeutic window may ameliorate mechanisms associated with immunosuppression before and during malignant progression.

scholarly journals Mammary analogue secretory carcinoma: a rare salivary gland tumor

2020 ◽  
Vol 6 (5) ◽  
pp. 998
Author(s):  
Shashikant Anil Pol ◽  
Surinder K. Singhal ◽  
Nitin Gupta ◽  
Himanshu Bayad
Keyword(s):  
Salivary Gland ◽  
Salivary Gland Tumor ◽  
Needle Aspiration ◽  
Good Prognosis ◽  
Low Grade ◽  
Secretory Carcinoma ◽  
Mammary Analogue Secretory Carcinoma ◽  
Grade Malignancy ◽  
Enhanced Computed Tomography ◽  
Slow Growing

<p>Mammary analogue secretary carcinoma are salivary gland tumors similar to secretary carcinoma of breast histologically. It usually affects adults with mean age group of 45 years. Clinically it is usually slow growing, low grade malignancy with favorable prognosis. We are reporting a case of 47 years old female presented with complaints of swelling behind left ear for last 7 years. It was slow growing, painless and persistent. On examination, 4 x 3 cm swelling was present just below left ear lobule. It was nontender, firm, irregular in shape with smooth surface with slight mobility and overlying skin pinchable. Fine needle aspiration cytology suggested benign tumor with cystic change. On contrast enhanced computed tomography scan, there was a lobulated hypodense lesion measuring 24×35×32 mm with internal septations and enhancement of wall in expected location of superficial as well as deep lobe of left parotid gland. Patient underwent left total conservative parotidectomy and histopathology came out to be secretory analogue mammary carcinoma. Subsequently she received post-operative radiotherapy. Patient is on regular follow up and disease free till date. Usually mammary analogue secretory carcinoma is a low-grade malignancy with good prognosis. Immunohistochemistry is confirmatory which shows positivity for S-100 protein and mammaglobin.</p>

scholarly journals Expression of FOXP3 in Canine Gliomas: Immunohistochemical Study of Tumor-Infiltrating Regulatory Lymphocytes

2019 ◽  
Vol 79 (2) ◽  
pp. 184-193 ◽  
Author(s):  
Dolors Pi Castro ◽  
Roberto José-López ◽  
Francisco Fernández Flores ◽  
Rosa M Rabanal Prados ◽  
Maria Teresa Mandara ◽  
...  
Keyword(s):  
Immune Cell ◽  
Low Grade ◽  
Similar Distribution ◽  
High Grade ◽  
Human Gliomas ◽  
Forkhead Box ◽  
Astrocytic Gliomas ◽  
The Difference ◽  
Regulatory Lymphocytes ◽  
The Brain

Abstract Dogs develop gliomas with similar histopathological features to human gliomas and share with them the limited success of current therapeutic regimens such as surgery and radiation. The tumor microenvironment in gliomas is influenced by immune cell infiltrates. The present study aims to immunohistochemically characterize the tumor-infiltrating lymphocyte (TIL) population of naturally occurring canine gliomas, focusing on the expression of Forkhead box P3-positive (FOXP3+) regulatory T-cells (Tregs). Forty-three canine gliomas were evaluated immunohistochemically for the presence of CD3+, FOXP3+, and CD20+ TILs. In low-grade gliomas, CD3+ TILs were found exclusively within the tumor tissue. In high-grade gliomas, they were present in significantly higher numbers throughout the tumor and in the brain-tumor junction. CD20+ TILs were rarely found in comparison to CD3+ TILs. FOXP3+ TILs shared a similar distribution with CD3+ TILs. The accumulation of FOXP3+ Tregs within the tumor was more pronounced in astrocytic gliomas than in tumors of oligodendroglial lineage and the difference in expression was significant when comparing low-grade oligodendrogliomas and high-grade astrocytomas. Only high-grade astrocytomas presented FOXP3+ cells with tumoral morphology. In spontaneous canine gliomas, TILs display similar characteristics (density and distribution) as described for human gliomas, supporting the use of the dog as an animal model for translational immunotherapeutic studies.

Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma: evidence of distinct immunological microenvironments that reflect tumor biology

2011 ◽  
Vol 115 (3) ◽  
pp. 505-511 ◽  
Author(s):  
Isaac Yang ◽  
Seunggu J. Han ◽  
Michael E. Sughrue ◽  
Tarik Tihan ◽  
Andrew T. Parsa
Keyword(s):  
Pilocytic Astrocytoma ◽  
Immune Cell ◽  
Tumor Biology ◽  
Human Leukocyte ◽  
Low Grade ◽  
High Grade ◽  
Cell Infiltrate ◽  
Leukocyte Antigen ◽  
Pilocytic Astrocytomas ◽  
Immune Cell Infiltrate

Object The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma. Methods Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tissue was collected at the time of the initial surgery prior to adjuvant treatment. Immune cell infiltrate not associated with necrosis or hemorrhage was analyzed on serial 4-μm sections. Analysis was performed for 10 consecutive hpfs and in 3 separate regions (total 30 × 0.237 mm2). Using immunohistochemistry for markers of infiltrating cytotoxic T cells (CD8), natural killer cells (CD56), and macrophages (CD68), the inflammatory infiltrates in these tumors were graded quantitatively and classified based on microanatomical location (perivascular vs intratumoral). Control markers included CD3, CD20, and human leukocyte antigen. Results Glioblastomas exhibited significantly higher perivascular (CD8) T-cell infiltration than pilocytic astrocytomas (62% vs 29%, p = 0.0005). Perivascular (49%) and intratumoral (89%; p = 0.004) CD56-positive cells were more commonly associated with glioblastoma. The CD68-positive cells also were more prevalent in the perivascular and intratumoral space in glioblastoma. In the intratumoral space, all glioblastomas exhibited CD68-positive cells compared with 86% of pilocytic astrocytomas (p = 0.0014). Perivascularly, CD68-positive infiltrate was also more prevalent in glioblastoma when compared with pilocytic astrocytoma (97% vs 86%, respectively; p = 0.0003). The CD3-positive, CD20-positive, and human leukocyte antigen-positive infiltrates did not differ between glioblastoma and pilocytic astrocytoma. Conclusions This analysis suggests a significantly distinct immune profile in the microenvironment of high-grade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.

scholarly journals Results of photon radiotherapy for unresectable salivary gland tumors: is neutron radiotherapy’s local control superior?

2014 ◽  
Vol 48 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Daniel E. Spratt ◽  
Lucas Resende Salgado ◽  
Nadeem Riaz ◽  
Michael G. Doran ◽  
Moses Tam ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Local Control ◽  
Late Complications ◽  
Salivary Gland Tumors ◽  
Salivary Gland Cancer ◽  
Low Grade ◽  
Severe Toxicity ◽  
Grade 3 ◽  
Photon Radiotherapy

Abstract Background. The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980’s reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution’s results of photon radiotherapy for unresectable salivary gland tumors. Patients and methods. From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. Local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed. Results. With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient’s experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients. Conclusions. Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.

scholarly journals CREB3L1 and PTN expressions correlate with prognosis of brain glioma patients

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Li-qiang Liu ◽  
Li-fei Feng ◽  
Cheng-rui Nan ◽  
Zong-mao Zhao
Keyword(s):  
Mrna Expression ◽  
Survival Time ◽  
Population Distribution ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Brain Glioma ◽  
Expression Levels ◽  
Cell Counts ◽  
High Grade Gliomas

The present study was conducted to investigate the clinical significance of cAMP responsive element binding protein 3 like 1 (CREB3L1) and pleiotrophin (PTN) expression in prognosis of patients with brain gliomas. Human brain tissue samples were collected from normal glial tissues (control), low- and high-grade glioma tissues. CREB3L1 and PTN expression levels in cells were assessed by immunohistochemistry (IHC), and population distribution of the CREB3L1- and PTN-presenting patients was examined. The CREB3L1 and PTN mRNA expression levels in three types of the brain cells was determined by RT-PCR. Survival rates for population of the CREB3L1- and PTN-presenting patients were examined. CREB3L1+ cell counts were decreased with increased PTN+ cells in the low-grade and high-grade glioma tissues as compared with the control. Population proportion of the CREB3L1+-presenting patients decreased from the control to the high-grade glioma and the population of the PTN+-presenting patients increased in low- and high-grade gliomas as compared with the control (both P<0.05). The decrease in the CREB3L1 mRNA expression was associated with the increase in the PTN mRNA expression in the low- and high-grade gliomas (P<0.05). Survival time for patients with CREB3L1− and PTN+ gliomas was shorter than patients with CREB3L1+ and PTN− gliomas in the investigated cohorts (both P<0.05). There was a relationship between the expression levels of both proteins and survival time. CREB3L1 and PTN expression levels serve as biomarkers with utility in grading gliomas. Absence of CREB3L1 and presence of PTN in brain glioma cells correlate with survival time of the glioma patients.

scholarly journals Immuno-Phenotyping of High-Grade Glioma Infiltrating Immune Cells Reveals Grade Specific Differences in Cells of Myeloid Origin

2020 ◽  
Author(s):  
Raksha A. Ganesh ◽  
Jayashree V. Raghavan ◽  
Pranali Sonpatki ◽  
Divya Naik ◽  
Priyanka Arunachalam ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
High Grade Gliomas ◽  
Cell Phenotypes ◽  
Grade Iii

AbstractGliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade III and IV) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, grade IV) or grade III gliomas. Our data show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade III glioma tissue. In addition, we observe that neutrophils are highly heterogeneous among individuals with glioma, and a greater proportion of granulocytic myeloid-derived suppressor cells are present in grade III gliomas when compared to GBM. Finally, we show that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor, and suggest that these may be used as possible markers for prognosis.

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