Improving clinical diagnosis of early-stage cutaneous melanoma based on Raman spectroscopy

Dermatology-oncolog

Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus

Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical changes that distinguish between the different stages of disease. Our aim is to understand these changes through Raman mapping studies. Raman spectral mapping was used to analyse 20-μm sections of tissue from 29 snap-frozen oesophageal biopsies. Contiguous haematoxylin and eosin sections were reviewed by a consultant pathologist. Principal component analysis was used to identify the major differences between the spectra across each map. Pseudocolour score maps were generated and the peaks of corresponding loads identified enabling visualisation of the biochemical changes associated with malignancy. Changes were noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra obtained from selected regions demonstrate increased levels of glycogen in the squamous area compared with increased DNA levels in the abnormal region. Raman spectroscopy is a highly sensitive and specific technique for demonstration of biochemical changes in the carcinogenesis of Barrett's oesophagus. There is potential for in vivo application for real-time endoscopic optical diagnosis

Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines

Raman spectroscopy could offer non-invasive, rapid and an objective nature to cancer diagnostics. However, much work in this field has focused on resolving differences between cancerous and non-cancerous tissues, and lacks the reproducibility and interpretation to be put into clinical practice. Much work is needed on basic cellular differences between malignancy and normal. This would allow the establishment of a clinically relevant cellular based model to translate to tissue classification. Raman spectroscopy provides a very detailed biochemical analysis of the target material and to 'unlock' this potential requires sophisticated mathematical modelling such as neural networks as an adjunct to data interpretation. Commercially obtained cancerous and non-cancerous cells, cultured in the laboratory were used in Raman spectral measurements. Data trends were visualised through PCA and then subjected to neural network analysis based on self-organising maps; consisting of m maps, where m is the number of classes to be recognised. Each map approximates the statistical distribution of a given class. The neural network analysis provided a 95% accuracy for identification of the cancerous cell line and 92% accuracy for normal cell line. In this preliminay study we have demonstrated th ability to distinguish between "normal" and cancerous commercial cell lines. This encourages future work to establish the reasons underpinning these spectral differences and to move forward to more complex systems involving tissues. We have also shown that the use of sophisticated mathematical modelling allows a high degree of discrimination of 'raw' spectral data

Optical Imaging of Tumor Response to Hyperbaric Oxygen Treatment and Irradiation in an Orthotopic Mouse Model of Head and Neck Squamous Cell Carcinoma

PURPOSE: Hyperbaric oxygen therapy (HBOT) is used in the treatment of radiation-induced tissue injury but its effect on (residual) tumor tissue is indistinct and therefore investigated in this study. PROCEDURES: Orthotopic FaDu tumors were established in mice, and the response of the (irradiated) tumors to HBOT was monitored by bioluminescence imaging. Near infrared fluorescence imaging using AngioSense750 and Hypoxisense680 was applied to detect tumor vascular permeability and hypoxia. RESULTS: HBOT treatment resulted in accelerated growth of non-irradiated tumors, but mouse survival was improved. Tumor vascular leakiness and hypoxia were enhanced after HBOT, whereas histological characteristics, epithelial-to-mesenchymal transition markers, and metastatic incidence were not influenced. CONCLUSIONS: Squamous cell carcinoma responds to HBOT with respect to tumor growth, vascular permeability, and hypoxia, which may have implications for its use in cancer patients. The ability to longitudinally analyze tumor characteristics highlights the versatility and potential of optical imaging methods in oncological research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11307-015-0834-8) contains supplementary material, which is available to authorized users

Real-time fluorescence imaging for cancer surgery: a pathologist's perspective

Surgical oncolog

Next generation diagnostic molecular pathology: Critical appraisal of quality assurance in Europe

Contains fulltext : 136387.pdf (publisher's version ) (Open Access)Tumor evaluation in pathology is more and more based on a combination of traditional histopathology and molecular analysis. Due to the rapid development of new cancer treatments that specifically target aberrant proteins present in tumor cells, treatment decisions are increasingly based on the molecular features of the tumor. Not only the number of patients eligible for targeted precision medicine, but also the number of molecular targets per patient and tumor type is rising. Diagnostic molecular pathology, the discipline that determines the molecular aberrations present in tumors for diagnostic, prognostic or predictive purposes, is faced with true challenges. The laboratories have to meet the need of comprehensive molecular testing using only limited amount of tumor tissue, mostly fixed in formalin and embedded in paraffin (FFPE), in short turnaround time. Choices must be made for analytical methods that provide accurate, reliable and cost-effective results. Validation of the test procedures and results is essential. In addition, participation and good performance in internal (IQA) and external quality assurance (EQA) schemes is mandatory. In this review, we critically evaluate the validation procedure for comprehensive molecular tests as well as the organization of quality assurance and assessment of competence of diagnostic molecular pathology laboratories within Europe

Botryomycosis, responding well to antibiotics

A 49 year old man, presented to our department dermatology with a therapy resistant lesion on his right forearm. The lesion had been present for some months and treatment with different topical ointments and oral therapies was unsatisfactory. Examination revealed an erythematous, partially verrucous and erosive lesion. Histopathology showed a botryomycosis infection with the typical Splendore-Hoeppli phenomenon. Long term oral antibiotics were extremely effective.</p

Gene Expression Clustering and Selected Head and Neck Cancer Gene Signatures Highlight Risk Probability Differences in Oral Premalignant Lesions

BACKGROUND: Oral premalignant lesions (OPLs) represent the most common oral precancerous conditions. One of the major challenges in this field is the identification of OPLs at higher risk for oral squamous cell cancer (OSCC) development, by discovering molecular pathways deregulated in the early steps of malignant transformation. Analysis of deregulated levels of single genes and pathways has been successfully applied to head and neck squamous cell cancers (HNSCC) and OSCC with prognostic/predictive implications. Exploiting the availability of gene expression profile and clinical follow-up information of a well-characterized cohort of OPL patients, we aim to dissect tissue OPL gene expression to identify molecular clusters/signatures associated with oral cancer free survival (OCFS). MATERIALS AND METHODS: The gene expression data of 86 OPL patients were challenged with: an HNSCC specific 6 molecular subtypes model (Immune related: HPV related, Defense Response and Immunoreactive; Mesenchymal, Hypoxia and Classical); one OSCC-specific signature (13 genes); two metabolism-related signatures (3 genes and signatures raised from 6 metabolic pathways associated with prognosis in HNSCC and OSCC, respectively); a hypoxia gene signature. The molecular stratification and high versus low expression of the signatures were correlated with OCFS by Kaplan-Meier analyses. The association of gene expression profiles among the tested biological models and clinical covariates was tested through variance partition analysis. RESULTS: Patients with Mesenchymal, Hypoxia and Classical clusters showed an higher risk of malignant transformation in comparison with immune-related ones (log-rank test, p = 0.0052) and they expressed four enriched hallmarks: "TGF beta signaling" "angiogenesis", "unfolded protein response", "apical junction". Overall, 54 cases entered in the immune related clusters, while the remaining 32 cases belonged to the other clusters. No other signatures showed association with OCFS. Our variance partition analysis proved that clinical and molecular features are able to explain only 21% of gene expression data variability, while the remaining 79% refers to residuals independent of known parameters. CONCLUSIONS: Applying the existing signatures derived from HNSCC to OPL, we identified only a protective effect for immune-related signatures. Other gene expression profiles derived from overt cancers were not able to identify the risk of malignant transformation, possibly because they are linked to later stages of cancer progression. The availability of a new well-characterized set of OPL patients and further research is needed to improve the identification of adequate prognosticators in OPLs