Background Adenoid cystic carcinoma (ACC) of the salivary glands has a poor long-term prognosis. Independent prognostic factors of ACC include histological and clinicopathological features, while a validated gold-standard prognostic immunohistochemical markers are still lacking. Functions of cell adhesion molecule E-cadherin which maintain epithelial integrity, and cell cycle and function regulators nuclear protein Cyclin D1 and transmembrane heparan sulfate proteoglycan syndecan-2 in ACC have not been studied. Objective The aim of this study was to investigate the immunohistochemical expression of E-cadherin, syndecan-2, and cyclin D1 in ACC of the minor salivary glands. Our objective was to evaluate the prognostic relevance of these markers in relation to disease progression and patient outcomes. Methods This retrospective study included 46 patients with minor salivary gland ACC treated at the Department of Otorhinolaryngology–Head and Neck Surgery, Helsinki University Hospital, Finland, between 1974 and 2012. Formalin-fixed paraffin-embedded tumor tissue samples were used for immunohistochemical analysis. Staining intensity was scored and associated with clinicopathological parameters and survival data. Results Immunopositivity varied among tumors, sometimes exhibiting heterogeneous expression within the same tumor. We found moderate to high E-cadherin expression to significantly associate with improved overall ( p = 0,024) and disease-specific survival ( p = 0.005). Additionally in multivariate analysis, moderate to high E-cadherin associated with better disease-specific survival with hazard ratio of 0.219 (95% CI 0.065–0.734, p = 0.014). Notably, all four patients with neck recurrences demonstrated low syndecan-2 positivity ( p = 0.023). Cyclin D1 did not associate significantly with survival. Conclusions In conclusion, all the studied markers were expressed in the minor salivary gland ACC. E-cadherin showed potentiality as a prognostic immunohistochemical biomarker for survival analysis. Low syndecan-2 expression may be indicative for regional recurrence. Validation in larger multicenter cohorts is warranted to confirm these observations.
Background Measurement of the circulating protein-based tumour markers by immunoassay is used in the routine clinical care of cancer patients, from aiding diagnosis to monitoring disease progression, response to therapy and detecting recurrence. The standardisation of these immunoassays is of critical importance, where inter-method variability and a lack of harmonisation can impact the comparability of results and affect clinical utility. World Health Organisation (WHO) International Standards (IS) are available for many of these protein tumour markers. Objective To provide an overview of how these WHO IS are prepared, characterised and established, and introduce the IS that are available for the calibration of tumour marker immunoassays. Results and conclusion Although WHO IS are available for many protein tumour markers, there remains a need for improvement in the harmonisation of some of these assays to enable more widespread and optimum utilisation in clinical practice. It will remain important to maintain these WHO International Standards, to achieve harmonisation through consistent global calibration of these assays, in addition to supporting the development of new technologies as they arise.
Background Serum tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and prostate-specific antigen (PSA) are crucial to clinical decision-making based on defined medical thresholds. However, significant inter-method variability and lack of harmonization limit result comparability and hinder consistent application of international guidelines. Objective This letter proposes an expanded role for External Quality Assessment (EQA) programs as active drivers of assay harmonization beyond conventional proficiency testing. Methods This proposal draws on recent studies evaluating the commutability of frozen human serum pools (FSPs) from the Korean Association of External Quality Assessment Service (KEQAS) and findings from EQA-based harmonization simulations. It demonstrated that harmonization of tumor markers such as CA 15-3 and CEA, is achievable. Results KEQAS FSPs demonstrated commutability for AFP, CEA, and total PSA across major diagnostic platforms. Simulation results indicated that “in silico” recalibration substantially reduced inter-method variability; for example, the bias range for CA 15-3 was reduced from [−29.28%, 9.86%] to [−0.09%, 0.12%], and recalibrating outlier methods for CEA improved the alignment also. Conclusions EQA programs can serve as practical harmonization hubs by leveraging commutable materials and implementing EQA-driven recalibration. Such approaches can help that medical decision points, retain consistent clinical significance across diverse analytical systems.
BackgroundTriple-negative breast cancer (TNBC) remains clinically challenging due to its aggressive nature, high recurrence rate, and lack of targeted therapies. To address these limitations, combination chemotherapies that synergistically enhance antitumor efficacy while permitting dose reduction and supporting dose-sparing strategies are urgently needed. Cisplatin has a broad spectrum of anticancer activity. However, its resistance and dose-limiting toxicities constrain clinical benefit. Digitoxin is a cardiac glycoside that has anticancer activity.ObjectiveWe aimed to assess the nature of interaction between digitoxin and cisplatin in TNBC cells, define the most synergistic area (MSA), and estimate dose-sparing potential.MethodsWe profiled digitoxin-cisplatin effects in MDA-MB-231 TNBC cell line by checkerboard and fixed-ratio designs, quantifying interaction with Chou-Talalay combination index/dose-reduction index by CompuSyn, and multiple matrix models by SynergyFinder.ResultsThe CI analysis demonstrated synergy across all tested ratios, with the strongest synergistic interaction at a digitoxin/cisplatin ratio of 1:200 (CI = 0.30 at ED97). Dose-reduction analysis showed up to 27-fold cisplatin sparing (ratio 1:25, ED97). Matrix-based models confirmed synergy (Bliss 6.9, Loewe 18.6, ZIP 7.1, and HSA 14), converging on MSA at 31.25 nM digitoxin and 6.25 µM cisplatin.ConclusionOur results highlight a robust synergistic interaction between digitoxin and cisplatin in MDA-MB-231 cells with a dosing window that maximizes cytotoxic effect while potentially reducing cisplatin exposure.
Background Tumour biomarkers have become increasingly important in oncology, shaping cancer diagnostics, classification, and patient management. Despite their potential, the use of cancer biomarkers in clinical settings remains limited. Objective This paper aims to outline biomarker development, from classical, serum protein markers to emerging tumour biomarkers, including meta-biomarkers, to show their diversity and point out the challenges in their development, reporting, and implementation in clinical practice as well as their relevance in evidence-based pathology and cancer classification. Methods A literature-based analysis, incorporating insights from our ongoing research, is presented. Results Although numerous potential biomarkers, biomarker signatures, and meta-biomarkers, are being discovered, existing innovations are often not supported by sufficiently rigorous research methodologies and standardised reporting practices to enable their translation into clinical practice. Conclusions To ensure that biomarker discoveries are both scientifically sound and clinically useful, improved research and validation methods, along with adherence to established reporting standards, are essential. We propose the use of the Hierarchy of Evidence for Tumour Pathology as a framework to evaluate and map existing evidence and identify knowledge gaps and research priorities.
