A clinicopathological study of non-functioning pituitary neuroendocrine tumours using the World Health Organization 2022 classification

BackgroundThe 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET).MethodsA total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses.ResultsBased on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease.ConclusionThe 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis

Clinical patterns of melanoma in Asians: 11-year experience in a tertiary referral center

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.Background: Malignant melanoma is a relatively common malignancy in the West, but has a significantly lower incidence in Asians. Stark contrast in clinicopathological characteristics and prognosis has been observed between the 2 populations, yet data are limited. Here, we evaluate 106 Asian patients from a tertiary referral center in Hong Kong during an 11-year period. The purpose of this study was to collectively review all types of melanomas to analyze the clinico-pathological characteristics of this poorly understood condition in an Asian population. Methods: Atotal of 106 patients diagnosed with malignant melanoma from 2002 to 2012 were retrospectively reviewed. Demographics, clinical presentations, pathological subtypes, treatments, and survival outcomes were evaluated. Results: Cutaneous melanomas dominated with 46 (43.4%) cases, followed by mucosal (39.6%), ocular (9.4%), and melanomas of unknown primary (7.5%); 43.3%patients presented in stage I, 36.7%in stage II, 18.9%in stage III, and 1.1%in stage IV. Acral lentiginous melanoma was the commonest subtype of cutaneous melanomas (60.9%).When types of melanomas were reviewed collectively, the median overall survival, disease-specific survival, and recurrence-free survival were 37, 45, and 48 months, respectively. Cutaneous melanoma had the best median overall survival of 59 months, followed by ocular melanoma (58 months), mucosal melanoma (18 months), and melanoma of unknown primary (2 months). Similar patterns were observed for disease-specific survival and recurrence-free survival. Conclusions: Melanoma among Asians remains poorly understood. There is a clear distinction in the clinical patterns between Asians and whites and the difference is not solely accounted for by the lower incidence of cutaneous melanoma. Certain subtypes, such as mucosal melanoma and is acral lentiginous melanoma, seemed to have disproportionately high incidences. Further studies are warranted to elucidate these observations. The poor survival outcomes reflected the need for better awareness and understanding of the condition by both the general public and the physicians.Link_to_subscribed_fulltex

DataSheet_1_A clinicopathological study of non-functioning pituitary neuroendocrine tumours using the World Health Organization 2022 classification.docx

BackgroundThe 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET).MethodsA total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses.ResultsBased on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test pConclusionThe 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis.</p

The Mulhall State Journal

Weekly newspaper from Mulhall, Oklahoma that includes local, state, and national news along with advertising. Established December 19, 1902

Molecular modifications induced by mud-bath therapy in patients with osteoarthritis

Background Mud-bath therapy (MBT) is a non-pharmacological approach commonly used to treat osteoarthritis (OA). Several data indicate that MBT improve patient's symptoms (1), exerting a beneficial effect on pain and joint function, although the biological mechanisms involved in the therapeutic response are poorly defined. Objectives This study aimed to find molecular changes (proteins and mRNA variations) in patients with OA after MBT treatment. Methods The study included 39 patients whit primary diffuse osteoarthritis, assigned to receive a cycle of mud-bath therapy over a period of 2 weeks added to usual pharmacologic treatment. Whole blood and serum were collected before and after standard MBT treatment: for each time points two pools of patients sera were analyzed by the direct antigen-labeling technology (RayBio® Biotin Label-based Antibody Array, RayBiotech) obtaining a broad, panoramic view of protein expression. Using this semi-quantitative technique up to 1000 target proteins was simultaneously detected, making this approach ideally suited for proteomic studies. Again, pooled samples of mRNA were used to investigate genes expression and to perform the transcriptomic analysis using an high-resolution array design that contains >6.0 million distinct probes, covering coding and non-coding transcripts (GeneChip® HTA 2.0, Affymetrix). Results At the end of mud-bath therapy, using first a semi-quantitative approach, we observed in both biological replicates increased levels (>1.5 fold change) of: inhibin beta A subunit (INHBA), activin A receptor type 2B (ACVR2B), angiopoietin-1 (ANGPT1), beta-2-microglobulin (B2M), growth differentiation factor 10 (BMP-3b/GDF10), C-X-C motif chemokine ligand 5 (CXCL5), fibroblast growth factor 2 (FGF2), fibroblast growth factor 12 (FGF12), oxidized low density lipoprotein receptor 1 (OLR1), matrix metallopeptidase 13 (MMP13). We observed that some increased proteins belongs to the same family or pathway: INHBA, ACVR2B and BMP-3b are members of TGF-Beta superfamily; CXCL5 and MMP13 participate into IL-17 signaling pathway; FGF2 and FGF12 are proteins of FGF family. We are currently performing the transcriptome analysis, and the next step will be to correlate detected proteins with mRNA levels considering also post-transcriptional or epigenetic modifications. Finally we will validate these findings with other quantitative techniques (like ELISA and RT-PCR). Conclusions Our first proteomic and broad spectrum analysis suggest the implication of molecular pathways involved in a wide variety of cellular functions such as gene expression modulation, differentiation, angiogenesis, tissue repair, acute and chronic inflammatory response which may explain the beneficial effects of MBT observed in osteoarthritis. This “omic” approach (proteomic and transcriptomic), generated a huge amount of data that is currently under statistical and bioinformatic analysis. References Forestier R, Desfour H, Tessier JM, et al. Spa therapy in the treatment of knee osteoarthritis: a large randomised multicentre trial. Ann Rheum Dis. 2010;69:660–5

Functional effects of OPN on CRC cell migration.

<p>(<i>A</i>) Comparison of relative secretory OPN levels of two DLD1-OPN stable clones (DLD1-OPN#1 and #3) with that of DLD1-vector control (One way ANOVA). (<i>B</i>) Comparison of number of DLD1-OPN stable clones (DLD1-OPN#1 and #3) cells migrated with that of DLD1-vector control cells (One way ANOVA). (<i>C</i>) Comparison of number of DLD1 cells migrated using culture medium from DLD1-OPN stable clones (DLD1-OPN#1 and #3) or DLD1-vector control as chemoattractant (One way ANOVA). (<i>D</i>) Comparison of relative secretory OPN levels of DLD1-OPN#1 stable clone transfected with siRNA control (siCTL) or OPN siRNA (siOPN) (Student’s t-test). (<i>E</i>) Effect of siCTL or OPN siRNA transfection on migration of DLD1-OPN#1 stable cells (Student’s t-test). (<i>F</i>) Comparison of number of DLD1 cells migrated using culture medium from DLD1-OPN stable clones transfected with siCTL or siOPN as chemoattractant (Student’s t-test). All data are representative of three independent experiments.</p

Univariate and multivariate analyses of prognostic factors for disease-free survival of CRC patients.

<p>Note:</p><p>* indicates the difference is statistically significant</p><p>Univariate and multivariate analyses of prognostic factors for disease-free survival of CRC patients.</p