Angiogenic Squamous Dysplasia Research Articles

Detection of Angiogenic Squamous Dysplasia Using High Magnification Bronchovideoscopy Combined With Narrow Band Imaging

Detection of Angiogenic Squamous Dysplasia Using High Magnification Bronchovideoscopy Combined With Narrow Band Imaging

Persistence of Bronchial Dysplasia Is Associated with Development of Invasive Squamous Cell Carcinoma.

Bronchial dysplasia (BD), a presumed precursor of pulmonary squamous cell carcinoma (SCC), rarely progresses to invasive cancer. A high-risk cohort at the University of Colorado provided an opportunity to directly sample airway epithelium at mapped sites on successive bronchoscopies. We have hypothesized that persistent dysplastic lesions showing a similar or higher level of dysplasia on follow-up biopsy, are associated with increased risk for the development of SCC. Endoscopic biopsies from 188 high-risk subjects were histologically classified according to the current WHO classification for BD using a numeric histology score ranging from 1 to 8 representing normal bronchial mucosa through invasive lung cancer. Differences in follow-up histology scores were compared between sites classified by clinical, histologic, and immunohistochemical variables. Subjects with a higher frequency of sites that persist or progress to high-grade dysplasia (≥37.5% persist/progress, N = 35 versus <37.5% persist/progress, N = 114) show a significant association with development of incident invasive SCC (adjusted HR, 7.84; 95% confidence interval, 1.56-39.39), and those with incident lung SCC have adjusted mean follow-up histology scores 1.55 U higher than in subjects without lung cancer. Current smoking, elevated Ki67 growth fraction, histologic features of angiogenic squamous dysplasia (ASD) and higher histology score in baseline biopsies are significantly associated with increased follow-up histology scores. These results show that persistent BD is associated with the development of invasive SCC. Furthermore, increased expression of Ki67, the presence of angiogenic change and degree of baseline atypia are associated with persistence of BD.

Expression of Endoglin (CD-105) and Microvessel Density in Oral Dysplasia and Squamous Cell Carcinoma.

To assess the expression of Endoglin (CD-105) and Microvessel Density in clinically normal oral mucosa of non-tobacco and tobacco habituated patients & also histopathologically confirmed cases of oral squamous cell carcinoma (OSCC) patients. Twenty cases of clinically normal oral mucosa with tobacco habituation in the form of chewing or smoking, 20 histopathologically confirmed cases of OSCC and twelve normal healthy oral mucosal cases without tobacco habituation in any form, served as control group, were immunohistochemically analysed for expression of Endoglin (CD-105). Chi-square test is used to determine statistical analysis and significance. The finding of 65% of Endoglin CD - 105 positivity and microvessel density (MVD) in the mucosal specimens of tobacco users may be attributed as neoangiogenesis or angiogenic squamous dysplasia like phenomenon occurring as important pathological biomarker preceding oral cancer development, and may therefore be useful as a predictive marker of malignancy.

Relationship between Angiogenic Squamous Dysplasia and Bronchogenic Carcinoma in Patients Undergoing White Light Bronchoscopy

To better understand the characteristic morphology of angiogenic squamous dysplasia (ASD) and its association with different types of common bronchogenic carcinomas using routine white light bronchoscopy. Using a case-control design, 186 formalin-fixed paraffin-embedded blocks of bronchial tissue (136 cases, 50 controls) obtained from patients who underwent routine nonfluorescence bronchoscopy between 2004 and 2005 were studied. ASD occurred at a higher frequency in patients with neoplastic lesions compared with those without neoplastic lesions (28 of 136 versus one of 50). ASD was also more prevalent in patients with squamous cell carcinoma compared with other neoplasms. Seventy six per cent of the ASD patients (22 of 29) smoked cigarettes. The morphology of ASD on hematoxylin and eosin- and CD31-stained sections was characterized by prominent microvasculature and capillary projections closely juxtaposed to variable degrees of dysplasia in all of the bronchogenic carcinoma specimens, and to metaplasia in one case in the control group. ASD is a unique morphological entity that should be considered by pathologists even on bronchoscopic biopsies from patients who undergo white light bronchoscopy. The presence of ASD may represent a risk biomarker of bronchogenic carcinoma in screening programs and in chemoprevention of lung cancer.

Angiogenic squamous dysplasia-like phenomenon in oral epithelial precursor lesions

Statement of the problemDysplasia, the morphological yardstick of epithelial precursor lesions, is the collective term for a variety of architectural and cytological changes within the altered oral epithelium. Angiogenic squamous dysplasia (ASD), a distinct morphological characteristic in pre-invasive bronchial lesions, describes the presence of capillary tufts that are closely juxtaposed to and projecting into the dysplastic bronchial epithelium.ObjectiveTo determine whether ASD-like phenomenon occurs in oral epithelial precursor lesions, and to speculate on its relevance.MethodsTwenty cases each of mild, moderate and severe oral dysplasia (inclusive of carcinoma-in-situ), and 10 normal oral mucosa (normal controls) were serial sectioned for H and E staining, and for microvessel density (MVD) scoring with CD31, CD34 and CD105. Microcapillary pattern images were digitally captured for 3-D reconstruction.ResultsOral ASD foci consisting of CD31-and CD34-positive capillary loops abutting onto the overlying dysplastic oral epithelium (and causing it to assume an irregular or papillary surface configuration) were identified in moderate (3/20; 15%) and severe dysplasia (13/20; 65%), but not in normal oral mucosa and mild dysplasia. MVD score demonstrated increasing vascularity as epithelium progressed from normal to severe dysplasia (p < 0.05). CD105 demonstrated increase neovascularization in all dysplasia grades (p < 0.05).ConclusionsThese preliminary findings taken together suggest that: 1. ASD-like phenomenon may be an important intermediary biomarker in oral precursor lesions; and 2. architectural alterations of the entire disturbed mucosa may be a more useful pre-malignancy index.

PD2-2-6: Angiogenesis in bronchial dysplasia and angiogenic squamous dysplasia is associated with the development of immature vasculature

PD2-2-6: Angiogenesis in bronchial dysplasia and angiogenic squamous dysplasia is associated with the development of immature vasculature

Narrow Band Imaging in the Airway: Where Do We Stand?

Narrow Band Imaging in the Airway: Where Do We Stand?

Narrow Band Imaging: A New Diagnostic Approach to Visualize Angiogenesis in Superficial Neoplasia

Although numerous gastrointestinal endoscopes pass through the oropharynx and the hypopharynx, it is extremely difficult to detect an early cancer in these sites during routine endoscopic examination. Most patients with cancer in these sites are usually diagnosed in advanced stages. If effective screening methods can detect an earlier stage, such as carcinoma in situ, it would obviously be of great benefit. Narrow band imaging is an innovative optical technology that can clearly visualize the microvascular structure of the organ surface. Herein, we demonstrate that narrow band imaging combined with magnifying endoscopy can identify a carcinoma in situ in oropharyngeal and hypopharyngeal mucosal lesions. Scattered irregular foci of microvascular proliferation projecting to the dysplastic squamous epithelium are the typical features. These results indicate that an approach to visualize angiogenesis or morphologic changes of microvessels in the superficial neoplasm can be a new diagnostic method not only for the head and neck region but also for other sites in the gastrointestinal tract.

Angiogenic Squamous Dysplasia in Oral Epithelial Dysplastic Lesions

Statement of problem: Angiogenic squamous dysplasia (ASD), a qualitative distinct form of angiogenesis, was first described in pre-invasive bronchial mucosa of high-risk individuals. It is characterized histologically by the presence of capillary tufts that are closely juxtaposed to and projecting into the dysplastic bronchial epithelium. Objective: To determine whether ASD occurs in oral epithelial dysplastic lesions. Methods: Sixty cases of potentially malignant oral epithelial lesions comprising 20 mild epithelial dysplasia (ED), 20 moderate ED and 20 severe ED(inclusive of carcinoma-in-situ), and 10 normal oral mucosa (as normal controls) were retrieved from the archives of the Department of Oral Pathology, Oral Medicine & Periodontology, Faculty of Dentistry, University of Malaya, and the Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia. The grading of oral ED was in accordance with the recommendations of the World Health Organization. For all selected cases, new 5 micron thick sections were prepared for H&E staining, and for immunohistochemistry with three vascular markers, CD31, CD34 and CD105, with appropriate positive and negative controls. The established criteria for identification of ASD was applied. Results: ASD was identified in parts of severe oral ED, but was absent in normal oral epithelium, mild and moderate oral ED. About 65% of these severe oral ED cases were from individuals with high-risk habits. As with bronchial ASD, the capillaries typically formed CD31- and CD34-positive projections or loops that abut onto the overlying dysplastic oral epithelium causing the latter to assume a papillary surface configuration. Unlike bronchial ASD which occurs in respiratory-type epithelium, oral ASD was found in keratinzed stratified squamous epithelium. CD105 confirmed the presence of neoangiogenesis. Conclusions: Present findings confirm that ASD can occur in oral severe ED. It also demonstrates that this angiogenic abnormality is not unique to bronchial mucosal dysplastic lesions.

Angiogenic squamous dysplasia: Characteristics and implications

Objectives: Keith et al described angiogenic squamous dysplasia (ASD) in the lung epithelium of patients at high risk for the development of lung carcinoma. We have recently observed similar changes in the nasal epithelium of occasional patients undergoing routine sinus surgery. This retrospective study evalautes the demographic characteristics of this small group of patients and compares them to a control series of patients undergoing similar surgery to evaluate whether this lesion is premalignant. Methods: Consecutive sinus and nasal surgical pathological specimens were reviewed for the presence of ASD. Twelve patients with ASD were identified and studied in detail. Their demographic characteristics were compared to a control group found not to have ASD but undergoing similar sinus surgery for similar conditions, using a grid approach to allow consideration of clinical characteristics without violating patient confidentiality. Results: Clear demographic differences between the study and control groups were not identified, and no progression to carcinoma was observed in any patient with ASD. In 1 patient that was re-biopsied in view of other risk factors, the mucosa reverted to normal (absence of ASD). Conclusions: ASD is an identifiable histopathological change that occurs in the sinus epithelium. The presence of this lesion with chronic sinusitis suggests that these aberrent patterns of microvasculature may represent an inflammatory response in the sinus mucosa, rather than true neoplasia at risk to proceed to carcinoma, as occurs in the lung. Additional observations are indicated to evaluate this possibility in a larger group of patients.

Angiogenesis and cancer: from biopathology to therapy

Angiogenesis is an important factor in the development of epithelial neoplasias and is useful in the study of progression and metastasis. Neoplastic cells produce angiogenic factors that overtake the antiangiogenic capacity of autoimmune cells. The vascular endothelial growth factor (VEGF) is the most important factor in the neoplastic angiogenesis. In colo-rectal carcinoma the expression of VEGF is parallel with genetic alterations and Duke's grade. In non-small cell lung carcinoma it is possible to define the angiogenic squamous dysplasia that evolves to invasive epidermoid carcinoma. In invasive gastric and lung cancer, the stromal molecules: COX 2, metalloproteinasis and adhesion molecules develop angeogenesis and their validation is important either in and therapy. In breast cancer there is a correlation between the growing of microvessels density, VEGF expression and p53 alterations, pointing to prognosis. Serological values of VEGF may also be used to monitorise the follow up of sarcomas and its reccurrence but vascular metastatic process is not yet completely understood.

P-272 Angiogenic squamous dysplasia (ASD): A biomarker highly associated with squamous cell lung carcinoma

P-272 Angiogenic squamous dysplasia (ASD): A biomarker highly associated with squamous cell lung carcinoma

Is Autofluorescence Bronchoscopy Needed to Diagnose Early Bronchogenic Carcinoma?

Is Autofluorescence Bronchoscopy Needed to Diagnose Early Bronchogenic Carcinoma?

Role of biomarkers for early detection of lung cancer and chemoprevention.

Lung cancer is the leading cause of cancer deaths in developed countries. The poor prognosis associated with this disease is closely related to the fact that most lung cancer patients are not identified until their malignancy has reached an advanced stage. Recent advances have added to the understanding of the morphological and molecular characteristics of preinvasive bronchial lesions and early lung cancers. Such information is being used to provide new tests for the detection of lung cancer at early or preinvasive stages, and for identifying targets for therapeutic intervention that can prevent progression to advanced disease. Laser induced fluorescence endoscope bronchoscopy has improved the sensitivity with which preinvasive dysplastic bronchial lesions and early invasive malignancies can be detected. Morphological features of such lesions have been described and can be monitored by follow-up bronchoscopies in order to validate potential chemoprevention treatments. Distinct morphological characteristics such as angiogenic squamous dysplasia also suggest that processes like angiogenesis are present early in the development of lung cancer. Furthermore, tissue obtained from these early lesions has been used to describe alterations in the expression of a number of factors that distinguish these early lesions from normal bronchial epithelium. This could provide molecular markers and targets for the detection and treatment of early lung cancer. Studies to detect these alterations by polymerase chain reaction and/or immunhistochemical analyses of easily obtained specimens such as sputa are helping identifing molecular markers that could be utilized in effective screening programmes. The current article reviews new findings regarding the molecular biology of preinvasive bronchial lesions and early lung cancers, and describes new developments regarding their application in the early detection and chemoprevention of lung cancer.

Persistence of angiogenic squamous dysplasia for a year or more at the same bronchial sites in individuals at high risk for lung cancer

Persistence of angiogenic squamous dysplasia for a year or more at the same bronchial sites in individuals at high risk for lung cancer