We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Technopath Clinical Diagnostics - An LGC Company


  Gold Thermo Fisher Scientific provides analytical instruments, lab equipment, specialty diagnostics, reagents and integrat... read more Featured Products: More products

Download Mobile App


ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.

Melanoma Test Offers Reassurance of Low Risk of Cancer Spread

By LabMedica International staff writers
Posted on 25 Jan 2022
Print article
Image: The High Capacity RNA-to-cDNA Kit is a streamlined reverse transcription kit designed for optimum performance with TaqMan Gene Expression Master Mix, Power SYBR Green PCR Master Mix, and other PCR enzymes (Photo courtesy of Thermo Fisher Scientific)
Image: The High Capacity RNA-to-cDNA Kit is a streamlined reverse transcription kit designed for optimum performance with TaqMan Gene Expression Master Mix, Power SYBR Green PCR Master Mix, and other PCR enzymes (Photo courtesy of Thermo Fisher Scientific)
Cutaneous melanoma is an aggressive form of skin cancer with an increasing worldwide incidence, particularly in the younger population. Although treatment for patients with metastatic melanoma has improved remarkably in the last decade, principally with targeted therapies and immune checkpoint modulators, there are still no consistently beneficial treatments for patients with metastatic disease.

AMBRA1 is a scaffold protein with key roles in autophagy, cell survival and proliferation. AMBRA1 promotes autophagy through initiation of autophagosome formation, and mitophagy-mediated clearance of damaged mitochondria. Melanoma cells can influence the tumor microenvironment through secretion of growth factors, including transforming growth factors α and β (TGF-α, TGF-β).

Clinical Scientists at Newcastle University (Newcastle, UK) and AMLo Biosciences Limited (Newcastle upon Tyne, UK) and their colleagues evaluated the potential contribution of melanoma paracrine transforming growth factor (TGF)-β signaling to the loss of AMBRA1 in the epidermis overlying the primary tumor and disruption of epidermal integrity. Immunohistochemistry was used to analyze AMBRA1 and TGF-β2 in a cohort of 109 AJCC all-stage melanomas, and TGF-β2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analyzed in a cohort of 42 melanomas, with TGF-β2 signaling evaluated in primary keratinocytes.

The investigators performed semiquantitative immunohistochemistry for or AMBRA1, TGF-β2, TGF-β3, claudin-1 or AMLo expression. Claudin-1 expression was quantified by H-score using Aperio ImageScope (Leica Biosystems, Nussloch Germany). Western blotting was generated and visualized using enhanced chemiluminescence (Bio-Rad, Watford, UK). Total RNA was isolated from cell pellets and reverse transcribed using an AMV Reverse Transcriptase kit (Promega, Madison, WI, USA) or High Capacity Reverse Transcription Kit (Thermo Fisher Scientific, Waltham MA, USA).

The scientists reported that increased tumoral TGF-β2 was significantly associated with loss of peritumoral AMBRA1, ulceration, AMLo high-risk status and metastasis. TGF-β2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes. Importantly, they showed loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression, parakeratosis and cleft formation in the dermoepidermal junction.

Penny E. Lovat, PhD, Professor of Cellular Dermatology and senior author of the study, said, “Like mortar and bricks holding together a wall, AMBRA1, Loricrin and Claudin 1 are all proteins key to maintaining the integrity of the upper layer of the skin. When these proteins are lost gaps develop, like the mortar crumbling away in the wall. This allows the tumor to spread and ultimately ulcerate which we know is a process associated with higher risk tumors. Our new understanding of this biological mechanism underpins the test we have available.”

The authors concluded that their data suggested a paracrine mechanism whereby melanoma secretion of TGF-β2 causes peritumoral loss of AMBRA1 and reduced epidermal integrity facilitating erosion of the epidermis and tumor ulceration. Targeting TGF-β2 signaling may therefore represent a novel adjuvant treatment strategy for high-risk early-stage tumors with loss of epidermal AMBRA1. The study was published on January 13, 2022 in the British Journal of Dermatology.

Related Links:
Newcastle University
AMLo Biosciences Limited
Leica Biosystems
Thermo Fisher Scientific

Gold Supplier
SARS-CoV-2 Antigen Test
NG-Test SARS-NG-Test SARS-CoV-2 Ag Cassette
Automated R-AST Solution
Radian BC
Urine Analyzer
Silver Supplier
3-Part Diff Hematology Analyzer
Abacus Junior 30

Print article


Clinical Chem.

view channel
Image: The analysis pipeline used to investigate associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease (Photo courtesy of University College London)

Lipid Measurements Show Potential as Alzheimer’s Disease Biomarkers

Brain changes accompanying ageing are varied and can include pathologies that lead to cognitive impairment, the commonest of which is Alzheimer’s disease (AD). Identifying blood-based signatures of brain... Read more

Molecular Diagnostics

view channel
Image: Guidance UTI provides personalized results in less than one day from receipt at lab (Photo courtesy of Pathnostics)

Rapid Result Test for Complicated Urinary Tract Infections Proves Superior to Standard Urine Culture

Complicated urinary tract infections (cUTIs) are a significant burden on individual health and healthcare resources that must be diagnosed and treated early and accurately to reduce the risk of poor outcomes.... Read more


view channel
Image: The CS-2500 analyzer features pre-analytic sample checks and four detection methods simultaneously on a single platform – coagulation end-point, chromogenic kinetic analysis, turbidimetric immunoassay and automated platelet aggregation (Photo courtesy of Sysmex)

Microvascular/Endothelial Dysfunction Contributes to Post-COVID Syndrome Pathogenesis

Post-COVID syndrome (PCS) or Long-COVID is an increasingly recognized complication of acute SARS-CoV-2 infection, characterized by persistent fatigue, reduced exercise tolerance chest pain, shortness of... Read more


view channel
Image: Sales of lateral flow assays in clinical testing are expected to register a CAGR of 5% through 2032 (Photo courtesy of Pexels)

Global Lateral Flow Assays Market to Surpass USD 11.5 Billion by 2032 Due to Evolving Applications

The global lateral flow assays market was valued at USD 7.2 billion in 2021 and is projected to register a CAGR of 4.7% during 2022-2032 to surpass USD 11.7 billion by the end of 2032, driven by the growing... Read more
Copyright © 2000-2022 Globetech Media. All rights reserved.