108 results found
Pinato DJ, Vallipuram A, Evans JS, et al., 2020, Programmed cell death ligands expression drives immune tolerogenesis across the diverse subtypes of neuroendocrine tumours, Neuroendocrinology: international journal for basic and clinical studies on neuroendocrine relationships, Vol: 111, Pages: 465-474, ISSN: 0028-3835
INTRODUCTION: A comprehensive characterisation of the tumour microenvironment is lacking in neuroendocrine tumours (NETs), where programmed cell death-1 receptor-ligand (PD-1/PD-L1) inhibitors are undergoing efficacy testing. OBJECTIVE: We investigated drivers of cancer-related immunosuppression across NETs of various sites and grade using multi-parameter immunohistochemistry and targeted transcriptomic profiling. METHODS: Tissue microarrays (n=102) were stained for PD-L1 & 2, Indoleamine-deoxygenase-1 (IDO-1) and evaluated in relationship to functional characteristics of tumor-infiltrating T-lymphocytes (TILs) and biomarkers of hypoxia/angiogenesis. PD-L1 expression was tested in circulating tumour cell (CTCs, n=12) to evaluate its relationship with metastatic dissemination. RESULTS: PD-L1 expression was highest in lung NETs (n=30, p=0.007), whereas PD-L2 was highest in pNETs (n=53, p<0.001) with no correlation with grade or hypoxia/angiogenesis. PD-L1+ NETs (n=26, 25%) had greater CD4+/FOXP3+ and CD8+/PD1+ TILs (p<0.001) and necrosis (p=0.02). CD4+/FOXP3+ infiltrate was highest PD-L1/IDO-1 co-expressing tumours (p=0.006). Grade 3 well-differentiated NETs had lower CD4+/FOXP3+ and CD8+/PD1+ TILs density (p<0.001) and Nanostring immune-profiling revealed enrichment of macrophage-related transcripts in cases with poorer prognosis. We identified PD-L1(+) CTC subpopulations in 75% of evaluated patients (n=12). CONCLUSIONS: PD-L1 expression correlates with T-cell exhaustion independent of tumour hypoxia and is enhanced in a subpopulation of CTCs, suggesting its relevance to the progression of NETs. These findings support a potential therapeutic role for PD-L1 inhibitors in a subset of NETs.
Marcus D, Savage A, Balog J, et al., 2019, ENDOMETRIAL CANCER: CAN THE IKNIFE DIAGNOSE ENDOMETRIAL CANCER?, Publisher: BMJ PUBLISHING GROUP, Pages: A100-A101, ISSN: 1048-891X
Mizamtsidi M, Nastos K, Palazzo F, et al., 2019, Association Between hsa-miR-30e Polymorphisms and Sporadic Primary Hyperparathyroidism Risk, IN VIVO, Vol: 33, Pages: 1263-1269, ISSN: 0258-851X
Pinato DJ, Vallipuram A, Evans J, et al., 2019, Molecular characterization of the tumour microenvironment in neuroendocrine malignancy., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Capitanio A, Dina RE, Treanor D, 2019, Reply to Van Es et al. Digital pathology: A constant evolution, CYTOPATHOLOGY, Vol: 30, Pages: 264-264, ISSN: 0956-5507
Dina R, 2019, Digital Technology: Its Advantages in the New Era, 19 Internationa Congres of Cytology, Publisher: Karger Publishers, ISSN: 0001-5547
Hariri AA, Tsagkovits A, McIntyre C, et al., 2019, Calcitonin-Negative Neuroendocrine Thyroid Tumours: A Diagnostic and Management Challenge, Annual Scientific Meeting of the British-Association-of-Endocrine-and-Thyroid-Surgeons (BAETS), Publisher: WILEY, Pages: 22-22, ISSN: 0007-1323
Elshiekh M, Dina R, 2018, Causes of discordance between cytology and histology in pancreatic lesions, Publisher: SPRINGER, Pages: S39-S39, ISSN: 0945-6317
Capitanio A, Dina RE, Treanor D, 2018, Digital cytology: A short review of technical and methodological approaches and applications, CYTOPATHOLOGY, Vol: 29, Pages: 317-325, ISSN: 0956-5507
Patel N, Lathouras K, Dina R, et al., 2018, Broad Ligament Endometriosis Presenting as a Solid Mass: A Diagnostic "Curveball", JOURNAL OF GYNECOLOGIC SURGERY, Vol: 34, Pages: 225-228, ISSN: 1042-4067
Mizamtsidi M, Nastos C, Mastorakos G, et al., 2018, Diagnosis, management, histology and genetics of sporadic primary hyperparathyroidism: old knowledge with new tricks, Endocrine Connections, Vol: 7, Pages: R56-R68, ISSN: 2049-3614
Primary hyperparathyroidism (pHPT) is a common endocrinopathy resulting from inappropriately high PTH secretion. It usually results from the presence of a single gland adenoma, multiple gland hyperplasia or rarely parathyroid carcinoma. All these conditions require different management and it is important to be able to differentiate the underlined pathology, in order for the clinicians to provide the best therapeutic approach. Elucidation of the genetic background of each of these clinical entities would be of great interest. However, the molecular factors that control parathyroid tumorigenesis are poorly understood. There are data implicating the existence of specific genetic pathways involved in the emergence of parathyroid tumorigenesis. The main focus of the present study is to present the current optimal diagnostic and management protocols for pHPT as well as to review the literature regarding all molecular and genetic pathways that are be involved in the pathophysiology of sporadic pHPT.
Khalil AB, Dina R, Meeran K, et al., 2018, Indeterminate Thyroid Nodules: A Pragmatic Approach, EUROPEAN THYROID JOURNAL, Vol: 7, Pages: 39-43, ISSN: 2235-0640
Plonczak AM, DiMarco AN, Dina R, et al., 2017, Correction to: Breast cancer metastases to the thyroid gland - An uncommon sentinel for diffuse metastatic disease: A case report and literature review., Journal of Medical Case Reports, Vol: 11, ISSN: 1752-1947
Plonczak A, DiMarco A, Gujral D, et al., 2017, Breast cancer metastases to the thyroid gland - An uncommon sentinel for diffuse metastatic disease: A case report and literature review., Journal of Medical Case Reports, Vol: 11, ISSN: 1752-1947
BackgroundMetastases to the thyroid are rare. The most common primary cancer to metastasize to the thyroid is renal cell carcinoma, followed by malignancies of the gastrointestinal tract, lungs, and skin, with breast cancer metastases to the thyroid being rare. Overall, the outcomes in malignancies that have metastasized to the thyroid are poor. There are no prospective studies addressing the role of surgery in metastatic disease of the thyroid. Isolated thyroidectomy has been proposed as a local disease control option to palliate and prevent the potential morbidity of tumor extension related to the airway. Here, we present a case of a patient with breast cancer metastases to the thyroid gland and discuss the role of thyroidectomy in the context of the current literature.Case presentationA 62-year-old Afro-Caribbean woman was diagnosed as having bilateral breast carcinoma in 2004, for which she underwent bilateral mastectomy. The pathology revealed multifocal disease on the right, T2N0(0/20)M0 grade 1 and 2 invasive ductal carcinoma, and on the left side, T3N1(2/18)M0 grade 1 invasive ductal carcinoma. Surgery was followed by adjuvant chemotherapy and regional radiotherapy. The disease was under control on hormonal therapy until 2016, when she developed cervical lymphadenopathy. The fine-needle aspiration cytology of the thyroid was reported as papillary thyroid cancer; and the fine-needle biopsy of the left lateral nodal disease was more suggestive of breast malignancy. She underwent a total thyroidectomy and a clearance of the central compartment lymph nodes and a biopsy of the lateral nodal disease. The histopathological analysis was consistent with metastatic breast cancer in the thyroid and lymph nodes with no evidence of a primary thyroid malignancy.ConclusionsA past history of a malignancy elsewhere should raise the index of suspicion of metastatic disease in patients presenting with thyroid lumps with or without cervical lymphadenopathy. Detection of metasta
Zhang YZ, Dina R, Wright C, et al., 2017, Adequacy, clinicopathological and service parameters of molecular testing on respiratory cytology specimens at a UK Tertiary Referral Centre: A review of 64 cases from 2013 to 2016, Publisher: SPRINGER, Pages: S102-S103, ISSN: 0945-6317
Fassina A, Cappellesso R, Toetsch M, et al., 2017, Next-Generation Learning and Training: The Cy-TEST Experience, CANCER CYTOPATHOLOGY, Vol: 125, Pages: 669-673, ISSN: 1934-662X
Pinato DJ, Black J, Trousil S, et al., 2017, Programmed cell death ligands expression in phaeochromocytomas and paragangliomas: relationship with the hypoxic response, immune evasion and malignant behaviour., OncoImmunology, Vol: 6, ISSN: 2162-4011
Background: The hypoxic response underlies the pathogenesis and malignant behaviour of PCC/PGL. Regulation of PD-1 receptor-ligand signalling, a therapeutically actionable driver of the anti-tumour immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Methods: Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 & 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A). We explored the biologic significance of PD ligands expression using gene set enrichment analysis (GSEA) on The Cancer Genome Atlas (TCGA) for PCC/PGL (n=184). Results: In total, 100 patients, 10% malignant, 64% PCC, 29% familial with a median tumour size of 4.7 cm (range 1-14) were included. Median follow-up was 4.7 years. We found PD-L1 expression in 18% of PCC/PGL, which was independent of adverse pathological features including capsular (CI), vascular invasion (VI), necrosis (N) and expression of biomarkers of hypoxia. PD-L2 expression (16%) strongly correlated with CI, VI, N and malignant behaviour (p<0.05) and was associated with stronger Hif-1a and CaIX immunolabeling (p<0.01). PD-L2 was predictive of shorter survival (162 versus 309 months, HR 3.1 95%CI 1.1-9.2, p=0.02). GSEA on TGCA samples confirmed enrichment of transcripts involved in hypoxia and anti-cancer immunity.Conclusions: We report for the first time PD ligands expression in PCC/PGL with a distinctive prognostic, clinico-pathologic and immuno-biologic role. These findings support a potential therapeutic role for PD-1/PD-L1 targeted checkpoint inhibitors in these tumours.
Pinato DJ, Black JM, Trousil S, et al., 2017, Programmed cell death ligands expression in pheochromocytomas (PCC) and paragangliomas (PGL): Relationship with the hypoxic response and malignant behaviour., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Patten DK, Ahmed A, Greaves O, et al., 2017, Anaplastic Spindle Cell Squamous Carcinoma Arising from Tall Cell Variant Papillary Carcinoma of the Thyroid Gland: A Case Report and Review of the Literature, Case Reports in Endocrinology, Vol: 2017, ISSN: 2090-6501
Tall cell variant (TCV) of papillary thyroid carcinoma (PTC), an aggressive form of thyroid cancer, is characterised by 50% of cells with height that is three times greater than the width. Very rarely, some of these cancers can progress to spindle cell squamous carcinoma (SCSC) resulting in cancers with elements of both SCSC and TCV PTC. Here we report a case of SCSC arising from TCV PTC. In addition to this case, we have performed a literature review and compiled all published reports of SCSC arising from TCV PTC, including the nature of treatment and the prognosis for each of the 20 patients recorded. This is intended for use as a guide for clinicians in what the most appropriate treatment options may be for a newly diagnosed patient. Due to the rarity coupled with diagnosis occurring at a very advanced stage of disease progression, performing clinical trials is difficult and therefore drawing conclusions on optimal treatment methods remains a challenge.
Kornasiewicz O, Clift AK, Drymousis P, et al., 2017, GOBLET CELL CARCINOMAS OF THE APPENDIX: RARE BUT AGGRESSIVE TUMOURS WITH CHALLENGING MANAGEMENT, Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S1280-S1280, ISSN: 0016-5085
Phelps DL, Borley J, Flower K, et al., 2017, Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multi-centre study, British Journal of Cancer, Vol: 116, Pages: 1287-1293, ISSN: 1532-1827
BackgroundSurvival benefit from surgical debulking of ovarian cancer (OC) is well established but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery.MethodsClinical data from women debulked for high-stage OC was analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium’s HumanMethylation27 array interrogated tumour-DNA for differentially-methylated CpG sites, correlated to survival, in patients with the least residual disease (RD) (Hammersmith Array). Validation was performed using bisulphite pyrosequencing (Charité Hospital, Berlin, Germany cohort) and The Cancer Genome Atlas’ (TCGA) methylation dataset. Kaplan-Meier curves and Cox models tested survival.ResultsAltogether 803 women with serous ovarian cancer were studied. No RD was associated with significantly improved overall- (OS) (hazard ratio [HR] 1.25, 95% CI 1.06-1.47; P=0.0076) and progression-free survival (PFS) (HR 1.23, 1.05-1.43; P=0.012) (Hammersmith database n=430). Differentially-methylated loci within FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE associated with survival. Patients with the least RD had significantly better OS with higher methylation of MYLK3 (Hammersmith (HR 0.51, 0.31-0.84; P=0.01), Charité (0.46, 0.21-1.01; P=0.05), TCGA (0.64, 0.44-0.93; P=0.02)). ConclusionMYLK3 methylation is associated with improved OS in patients with the least RD, which could potentially be used to determine response to surgery.
Chatterjee J, Dai W, Abd Aziz NH, et al., 2016, Clinical use of programmed cell death-1 (PD-1) and its ligand (PD-L1) expression as discriminatory and predictive markers in ovarian cancer, Clinical Cancer Research, Vol: 23, Pages: 3453-3460, ISSN: 1557-3265
Purpose We aimed to establish whether PD-1 and PD-L1 expression, in ovarian cancer (OC) tumour tissue and blood, could be used as biomarkers for discrimination of tumour histology and prognosis of OC. Experimental Design Immune cells were separated from blood, ascites and tumour tissue obtained from women with suspected OC and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumour associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses. Results Biomarkers from the discovery cohort that associated with PD-L1+ cells were found. PD-L1+ CD14+ cells and PD-L1+ CD11c+ cells in the monocyte gate showed a distinct expression pattern when comparing benign tumours and epithelial ovarian cancers (EOC) - confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1+ and PD-L1+ CD14+ cells in the monocyte gate performed better than the well-established tumour marker CA-125 alone. Plasma soluble PD-L1 was elevated in EOC patients compared to healthy women and patients with benign ovarian tumours. Low total PD-1+ expression on lymphocytes was associated with improved survival. Conclusions Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti PD-1/PD-L1 therapy in ovarian cancer.
Dina RE, Capitanio A, Wilbur D, 2016, Digital Cytology as a tool in E-training and e-learning, European Congress of Cytology, Publisher: Wiley: 12 months, ISSN: 1365-2303
Pinato DJ, Brown M, White SDT, et al., 2016, Programmed cell death (PD-1) ligands expression in gastro-entero-pancreatic neuroendocrine tumours (GEP-NETs): relationship with angiogenesis and clinical outcome., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Chatterjee J, Howden S, Saso S, et al., 2016, Metastatic low-grade fibromyxoid sarcoma of the broad ligament: A case report and literature review., Journal of Obstetrics and Gynaecology, Pages: 1-3, ISSN: 1364-6893
Shovlin CL, Gilson C, Busbridge M, et al., 2016, Can iron treatments aggravate epistaxis in some patients with hereditary hemorrhagic telangiectasia?, The Laryngoscope, Vol: 126, Pages: 2468-2474, ISSN: 1091-756X
Objectives/HypothesisTo examine whether there is a rationale for iron treatments precipitating nosebleeds (epistaxis) in a subgroup of patients with hereditary hemorrhagic telangiectasia (HHT).Study DesignSurvey evaluation of HHT patients, and a randomized control trial in healthy volunteers.MethodsNosebleed severity in response to iron treatments and standard investigations were evaluated by unbiased surveys in patients with HHT. Serial blood samples from a randomized controlled trial of 18 healthy volunteers were used to examine responses to a single iron tablet (ferrous sulfate, 200 mg).ResultsIron tablet users were more likely to have daily nosebleeds than non–iron-users as adults, but there was no difference in the proportions reporting childhood or trauma-induced nosebleeds. Although iron and blood transfusions were commonly reported to improve nosebleeds, 35 of 732 (4.8%) iron tablet users, in addition to 17 of 261 (6.5%) iron infusion users, reported that their nosebleeds were exacerbated by the respective treatments. These rates were significantly higher than those reported for control investigations. Serum iron rose sharply in four of the volunteers ingesting ferrous sulfate (by 19.3–33.1 μmol/L in 2 hours), but not in 12 dietary controls (2-hour iron increment ranged from −2.2 to +5.0 μmol/L). High iron absorbers demonstrated greater increments in serum ferritin at 48 hours, but transient rises in circulating endothelial cells, an accepted marker of endothelial damage.ConclusionsIron supplementation is essential to treat or prevent iron deficiency, particularly in patients with pathological hemorrhagic iron losses. However, in a small subgroup of individuals, rapid changes in serum iron may provoke endothelial changes and hemorrhage.
Barazeghi E, Gill AJ, Sidhu S, et al., 2016, 5-Hydroxymethylcytosine discriminates between parathyroid adenoma and carcinoma, Clinical Epigenetics, Vol: 8, ISSN: 1868-7083
BackgroundPrimary hyperparathyroidism is characterized by enlarged parathyroid glands due to an adenoma (80–85 %) or multiglandular disease (~15 %) causing hypersecretion of parathyroid hormone (PTH) and generally hypercalcemia. Parathyroid cancer is rare (<1–5 %). The epigenetic mark 5-hydroxymethylcytosine (5hmC) is reduced in various cancers, and this may involve reduced expression of the ten-eleven translocation 1 (TET1) enzyme. Here, we have performed novel experiments to determine the 5hmC level and TET1 protein expression in 43 parathyroid adenomas (PAs) and 17 parathyroid carcinomas (PCs) from patients who had local invasion or metastases and to address a potential growth regulatory role of TET1.ResultsThe global 5hmC level was determined by a semi-quantitative DNA immune-dot blot assay in a smaller number of tumors. The global 5hmC level was reduced in nine PCs and 15 PAs compared to four normal tissue samples (p < 0.05), and it was most severely reduced in the PCs. By immunohistochemistry, all 17 PCs stained negatively for 5hmC and TET1 showed negative or variably heterogeneous staining for the majority. All 43 PAs displayed positive 5hmC staining, and a similar aberrant staining pattern of 5hmC and TET1 was seen in about half of the PAs. Western blotting analysis of two PCs and nine PAs showed variable TET1 protein expression levels. A significantly higher tumor weight was associated to PAs displaying a more severe aberrant staining pattern of 5hmC and TET1. Overexpression of TET1 in a colony forming assay inhibited parathyroid tumor cell growth.Conclusions5hmC can discriminate between PAs and PCs. Whether 5hmC represents a novel marker for malignancy warrants further analysis in additional parathyroid tumor cohorts. The results support a growth regulatory role of TET1 in parathyroid tissue.
Dina RE, 2016, The British Classification of thyroid cytology: reproducibility, positive predictive value and impact of the MultiDisciplinary Team discussion, 19th International Congress of Cytology
Marchio C, Barroca H, Dina R, et al., 2016, CyTEST- A Pan European Project for Training & Testing in Cytopathology, 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology, Publisher: NATURE PUBLISHING GROUP, Pages: 142A-142A, ISSN: 0893-3952
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