Diagnosis Of Precancerous Lesions Research Articles

Diagnostic endoscopique des lésions précoces

Summary The diagnosis of precancerous lesions of the bronchial tree remains a challenge for WKHFKHVWSK\VLFLDQV,QWKHODVW\HDUVWKHGHYHORSPHQWRIDXWRAXRUHVFHQFHEDVHGtechniques greatly impacted the detection of precancerous lesions compared with white light endoscopy. New techniques have been recently developed to get over the limitations RIDXWRAXRUHVFHQFHDOORZLQJWKHOXQJH[SORUDWLRQERWKGLVWDOO\DQGDWWKHPLFURVFRSLFlevel in vivo. 7KHVHPHWKRGVLQFOXGHDXWRAXRUHVFHQFHYLGHRHQGRVFRS\QDUURZEDQGimaging (NBI), endobronchial ultrasonography (EBUS), optical coherence tomography (OCT) and probe based confocal laser endomicroscopy (MCFF). The histopathologic analysis is still currently the gold standard, however these new techniques could allow optical biopsies, then improving the diagnosis and the therapeutic management.© 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved. Diagnostic endoscopique des lesions precoces Endoscopic diagnosis of early lesions

Analysis of the depolarizing properties of normal and adenomatous polyps in colon mucosa for the early diagnosis of precancerous lesions

Optical characterization of biological tissues by means of polarimetric techniques is an area of growing interest. Polarized light can be used for malignant neoplasms detection. To our knowledge, few studies have so far focused on lesions that are prone to result in cancer. In this work we present a polarimetric study of depolarization in prepathological tissues. Specifically, we will focus on premalignant lesions in human colon due to their clinical relevance. Colonic adenoma, the potential precursor of malignant adenocarcinoma, provokes significant structural modifications in colon mucosa that affect light depolarization. The depolarizing properties of normal and adenomatous polyps mucosa are compared. The average linear degree of polarization is shown to present a strong dependence with the precancerous state of the colonic tissue. This method has the potential to enable an early diagnosis of colon cancer.

Sa1619 Chromoendoscopy With Indigo Carmine Dye Added to Acetic Acid in the Diagnosis of Early Gastric Cancer and Precancerous Lesion

Sa1619 Chromoendoscopy With Indigo Carmine Dye Added to Acetic Acid in the Diagnosis of Early Gastric Cancer and Precancerous Lesion

Connective tissue growth factor expression in precancerous lesions of human esophageal epithelium and prognostic significance in esophageal squamous cell carcinoma

Connective tissue growth factor (CTGF, CCN2), a secreted protein, is involved in the development and progression of esophageal squamous cell carcinoma (ESCC). However, it remains unclear how CTGF expression affects the progression of ESCC. Our study implicated differences of CTGF protein status in precancerous lesions, and retrospectively examined the associations of CTGF mRNA and protein levels with clinical prognosis in ESCC patients. Here immunohistochemistry and the quantitative real-time real-time reverse transcription polymerase were performed for predicting the CTGF protein status and mRNA levels in ESCC patients, respectively. Different degrees of CTGF protein status presented in normal human esophageal epithelium and precancerous lesions, and CTGF protein was highly expressed in ESCCs. Survival analysis showed that CTGF protein status was significantly related to poor survival of ESCC patients (P= 0.024), while no significant difference was observed between CTGF mRNA levels and the survival of ESCC patients (P= 0.196). Multivariate Cox analysis demonstrated that CTGF protein status was the independent factor in prognosis of ESCC patients. In that way, CTGF protein status might elevate the progression of ESCC, and would be significant for the diagnosis of precancerous lesions or early ESCC.

Robust multi-tissue gene panel for cancer detection

BackgroundWe have identified a set of genes whose relative mRNA expression levels in various solid tumors can be used to robustly distinguish cancer from matching normal tissue. Our current feature set consists of 113 gene probes for 104 unique genes, originally identified as differentially expressed in solid primary tumors in microarray data on Affymetrix HG-U133A platform in five tissue types: breast, colon, lung, prostate and ovary. For each dataset, we first identified a set of genes significantly differentially expressed in tumor vs. normal tissue at p-value = 0.05 using an experimentally derived error model. Our common cancer gene panel is the intersection of these sets of significantly dysregulated genes and can distinguish tumors from normal tissue on all these five tissue types.MethodsFrozen tumor specimens were obtained from two commercial vendors Clinomics (Pittsfield, MA) and Asterand (Detroit, MI). Biotinylated targets were prepared using published methods (Affymetrix, CA) and hybridized to Affymetrix U133A GeneChips (Affymetrix, CA). Expression values for each gene were calculated using Affymetrix GeneChip analysis software MAS 5.0. We then used a software package called Genes@Work for differential expression discovery, and SVM light linear kernel for building classification models.ResultsWe validate the predictability of this gene list on several publicly available data sets generated on the same platform. Of note, when analysing the lung cancer data set of Spira et al, using an SVM linear kernel classifier, our gene panel had 94.7% leave-one-out accuracy compared to 87.8% using the gene panel in the original paper. In addition, we performed high-throughput validation on the Dana Farber Cancer Institute GCOD database and several GEO datasets.ConclusionsOur result showed the potential for this panel as a robust classification tool for multiple tumor types on the Affymetrix platform, as well as other whole genome arrays. Apart from possible use in diagnosis of early tumorigenesis, some other potential uses of our methodology and gene panel would be in assisting pathologists in diagnosis of pre-cancerous lesions, determining tumor boundaries, assessing levels of contamination in cell populations in vitro and identifying transformations in cell cultures after multiple passages. Moreover, based on the robustness of this gene panel in identifying normal vs. tumor, mislabelled or misinterpreted samples can be pinpointed with high confidence.

The value of methylene blue staining in diagnosis of precancerous lesions and early gastric cancer

Objective To evaluate the value of methylene blue staining in diagnosis of precancerous lesions and early gastric cancer.Methods There are 224 paients with abnormal gastric mucous membrance,104 cases were biopsy after stain by Methylene blue and 120 cases were taken biopsy simplicity.Results One hundred and four suspected early careinonm of stomach cases were stain by Methylene blue and 81 eases were found dyeing.There are 75 patients with atypical hyperplasia or intestinal metaplasi,6 with early gastric cancers,4 with preinvasive carcinoma.One hundred and twenty patients were taken biopsy simplicity.There are 14 patients with mild to moderate atypical hyperplasia,36 cases of chronic gastritis with focal intestinal metaplasia.Conclusions The early diagnosis rate of precancerous lesions and early gastric cancer are very well improved by methylene blue staining. Key words: Early gastric cancer; Precancerous lesions; Mucous membrane dyeing

Image-Guided Raman Endoscopic Probe for In Vivo Early Detection of High Grade Dysplasia

Objective: Raman spectroscopy is a molecular vibrational spectroscopic technique that is capable of optically detecting the biomolecular changes associated with diseased transformation. We have designed a rapid-acquisition dispersive-type near infrared (NIR) Raman system equipped with a specially designed Raman endoscopic probe which can be passed through the instrument channel of conventional endoscopes to acquire tissue Raman spectroscopic measurements at 785 nm laser excitation during endoscopy. The purpose of this study was to investigate the feasibility of applying this prototype for distinguishing high grade dysplasia from normal gastric mucosa tissues in vivo at endoscopy. Materials and Methods: A total of 24 in vivo tissue Raman spectra were acquired from different sites of the gastric antrum, in which 17 were from 4 patients who underwent endoscopic inspection for gastric cancer surveillance and 7 were from 1 patient who underwent endoscopic submucosal dissection (ESD). Histopathogical examinations of biopsy specimens obtained from the scanned sites of the 4 surveillance patients showed normal findings, while the dissected specimen from the ESD confirmed high grade dysplasia. Results: High-quality Raman spectra in the range of 800-1800 cm-1 were collected from in vivo gastric tissues in less than 1 second, together with the simultaneous utilization of white-light reflectance imaging modality for guiding the Raman endoscopic probe to the suspicious tissue sites. Raman spectral shapes were significantly different between normal and dysplasia, particularly in the spectral ranges of 850-900 cm-, 1000-1090 cm-, 1200-1305 cm- and 1600-1800 cm-, which contain signals related to hydroxyproline for collagen, phenylalanine, amide III, amide I and C=C stretching of lipids. The ratio of Raman intensities at 1450 to 1655 cm- provided a diagnostic sensitivity of 100%, specificity of 82.4% for identifying dysplasia from normal gastric tissues. The intensity ratio-based diagnostic algorithm achieved an integration area under the receiver operating characteristics curve of 0.9, confirming the diagnostic potential of near-infrared Raman spectroscopy for in vivo gastric dysplasia detection. Conclusion: This is the first in vivo Raman endoscopic spectroscopy in conjunction with white-light reflectance imaging to be used for distinguishing dysplasia from normal gastric mucosal tissues in real-time. This study suggests that near-infrared Raman technique may be a clinically useful endoscopic tool for in vivo detection and diagnosis of precancerous lesions in human stomach.

Activation of PI3K-AKT Pathway in Oral Epithelial Dysplasia and Early Cancer of Tongue

Increasingly, cancers are being diagnosed at an early stage. Leukoplakia, a precancerous lesion, progresses to cancer in 5-10% of cases. We performed genetic analysis using cDNA microarray and immunohistochemistry in 6 patients, 3 with precancerous lesions and 3 with early tongue cancer, to evaluate the usefulness of these methods in the diagnosis of precancerous lesions and early cancer. Samples of normal epithelium, epithelial dysplasia, and cancer tissues were collected by laser microdissection, RNA was extracted, and the signals converted to numerical values. Immunohistochemical analysis was performed using antibody against phospho AKT (p-AKT), a component of the phosphoinositide 3-kinase (PI3K) signal pathway. Five genes showed a 2 times or greater level of increase in expression in epithelial tissue in comparison with in normal tissue, while 4 genes showed a 2 times or greater increase in early cancer tissues. In cancer tissues and epithelial dysplasia tissues, PI3K class III was expressed at 2.5 times and 11 times the level of that found in normal tissue, respectively. Histochemistry using p-AKT antibody revealed no positive cells in normal tissue. Positive cells were noted in the basal and parabasal cell layers, and partially in the spinous layer of epithelial dysplasia tissues, and in the spinous layer of early cancer tissues. These findings suggest that activation of the PI3K-AKT signal pathway is associated with oral carcinogenesis.

Review: Optical Micrometer Resolution Scanning for Non-invasive Grading of Precancer in the Human Uterine Cervix

Management of cervical precancer is archetypal for other cancer prevention programmes but has to consider diagnostic and logistic challenges. Numerous optical tools are emerging for non-destructive near real-time early diagnosis of precancerous lesions of the cervix. Non-destructive, real-time imaging modalities have reached pre-commercial status, but high resolution mapping tools are not yet introduced in clinical settings. The NCBI PubMed web page was searched using the keywords 'CIN diagnosis' and the combinations of 'cervix {confocal, optical coherence tomography, ftir, infrared, Raman, vibrational, spectroscopy}'. Suitable titles were identified and their relevant references followed. Challenges in precancer management are discussed. The following tools capable of non-destructive high resolution mapping in a clinical environment were selected: confocal microscopy, optical coherence tomography, IR spectroscopy, and Raman spectroscopy. Findings on the clinical performance of these techniques are put into context in order to assist the reader in judging the likely performance of these methods as diagnostic tools. Rationale for carrying out research under the prospect of the HPV vaccine is given.

Influence of years of professional experience in relation to the diagnostic skill of general dental practitioners (GDPs) in identifying oral cancer and precancerous lesions

To evaluate skill in diagnosing cancer and oral precancerous lesions among general dentists in the Autonomous Community of Murcia (Spain). Twenty randomly distributed clinical images were used, of which 45% corresponded to benign lesions, 35% to oral precancerous lesions, and 20% to oral cancer. Each case was accompanied by a summarised clinical history. The study sample comprised 150 general dentists divided into two groups: group I (60 recently graduated dentists without professional experience) and group II (90 dentists with established professional activity). In group I, the sensitivity of oral cancer diagnosis was 61.3% versus 85.5% in group II (p < 0.001), while the sensitivity of precancerous lesion diagnosis was 71.7% in group I versus 80.7% in group II (p = 0.004). The results obtained show that junior dentists and general dentists with public or private practice need more training and more experience in diagnosing cancer and oral precancerous lesions.

Expression of ornithine decarboxylase in precancerous and cancerous gastric lesions.

To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. We studied the expression of ODC in gastric mucosa from patients with chronic superficial gastritis (CSG, n=32), chronic atrophic gastritis [CAG, n=43; 15 with and 28 without intestinal metaplasia (IM)], gastric dysplasia (DYS, n=11) and gastric cancer (GC, n=48) tissues using immunohistochemical staining. All 134 biopsy specimens of gastric mucosa were collected by gastroscopy. The positive rate of ODC expression was 34.4%, 42.9%, 73.3%, 81.8% and 91.7% in cases with CSG, CAG without IM, CAG with IM, DYS and GC, respectively (P<0.01), The positive rate of ODC expression increased in the order of CSG < CAG (without IM) < CAG (with IM) < DYS and finally, GC. In addition, ODC positive immunostaining rate was lower in well-differentiated GC than in poorly-differentiated GC (P<0.05). The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions.

Signification de l'évaluation de la qualité des frottis selon le système de Bethesda

The principal objective of this article is an analysis of the effectiveness of the diagnosis of precancerous lesions of the cervix, as well as of invasive cancer, compared to the quality of the smear test, according to the Bethesda system. Among the 202 345 smears there were 1406 squamous intra-epithelial lesions (SIL) and as well as 41 invasive cancers. The analysis of the quality of the smear was carried out according to the gynaecologists by comparing the results of the years 2001 and 2002. The quality of smears was better the smears carried out during the year 2002 compared with those of the year 2001 (53,2 % vs 36,9 % if AI). The percentage of pathological cases among ⪡satisfactory smears (AI)⪢ was higher compared to detection among the smears ⪡satisfactory but limited by… (AII)⪢ (0,91 % vs 0,59 %). The unsatisfactory smears are classified AIII. The results of this experiment underscore the importance of informing persons who perform the gynaecological smears about quality of the smear. Such information may help them to improve the quality of the smear.

Direct Correlation between Proliferative Activity and Dysplasia in Pancreatic Intraepithelial Neoplasia (PanIN): Additional Evidence for a Recently Proposed Model of Progression

A growing body of morphological, clinical, and genetic observations suggests a progression model for pancreatic ductal adenocarcinoma. In this model, pancreatic ducts progress through a series of architectural and cytological changes that define degrees of pancreatic intraepithelial neoplasia (PanIN). Expressed in dividing cells, Ki-67 has been extensively used as a proliferation marker. Its expression in different grades of PanIN has not been well studied. A total of 76 PanINs from 41 patients were histologically graded according to recently established criteria. These PanINs were then immunolabeled with a monoclonal antibody against Ki-67 (Mib-1). Normal ducts and invasive ductal adenocarcinomas were also labeled with the antibody. In 15 normal ducts, only 0.41% of the epithelial cells expressed Ki-67. Ki-67–labeling indices in the increasing grades of PanIN were as follows: PanIN-1A, 0.69%; PanIN-1B, 2.33%; PanIN-2, 14.08%; and PanIN-3, 22.01%. Fifteen invasive ductal adenonocarcinomas showed an average labeling index of 36.99%. The difference in Ki-67 labeling among these groups was statistically significant (P < .0005, Kruskal-Wallis test). This pattern of proliferation provides additional evidence supporting the recently proposed pancreatic progression model. It also correlates well with known molecular changes, such as activating point mutations in the K-ras oncogene and the loss of DPC4 and p16 gene expression. Ki-67 staining may be useful as an adjunct in the diagnosis of precancerous lesions in the pancreas and may provide a reliable way to identify lesions at high risk for the subsequent development of infiltrating carcinoma.

Immunohistochemical detection of p53 protein in neoplastic, preneoplastic and normal bronchial mucosa specimens obtained during diagnostic bronchoscopy.

The expression of p53 protein was evaluated immunochemically in cancer tissue, preneoplastic lesions and normal bronchial mucosa obtained during diagnostic bronchoscopy from 53 patients with lung cancer and 12 patients with benign lung diseases. In lung cancer patients, positive p53 staining was detected in 26/53 (49%) of the tumour specimens. In preneoplastic lesions p53 positive staining was found in 8 of 24 (33.3%) squamous metaplasia, 1 of 4 hyperplasia and 1 of 3 dysplasia lesions. In the same group of patients, 12 cases were found with positive p53 cells in normal bronchial mucosa. In patients with benign diseases, positive p53 staining was found in 1 of 4 cases with squamous metaplasia and in one normal mucosa. Our results provide evidence that somatic genetic alterations may occur in early stages of lung tumorigenesis, raising the possibility that molecular analyses is useful in the early diagnosis of precancerous lesions of the bronchial mucosa, and results indicate that p53 expression can be studied in small tissue specimens obtained during bronchoscopy.

Side effects of 5-amino levulinic acid photosensitization in photodynamic diagnosis of precancerous lesions in the gastrointestinal tract

Side effects of 5-amino levulinic acid photosensitization in photodynamic diagnosis of precancerous lesions in the gastrointestinal tract

Histological diagnosis of precancerous lesions of the stomach: a reliability study.

Within the framework of a chemoprevention trial on stomach cancer, two substudies based on repeat measurement were undertaken to evaluate reliability of histological diagnoses of gastric precancerous lesions. A subgroup of 45 subjects received two endoscopies separated by a period of one month. The two biopsies were reviewed by a single pathologist. A second subsample of 50 subjects had a single endoscopy and the biopsy results were reviewed by two pathologists. Agreement between the two diagnoses was assessed by Cohen's Kappa and by repeat frequency. When the same samples were reviewed by the pathologists involved in the trial, agreement was very high for advanced lesions (repeat frequency = 0.96 for intestinal metaplasia and 1.00 for dysplasia) but lower for less advanced lesions (repeat frequency = 0.73 for superficial gastritis and chronic gastritis, 0.65 for atrophic gastritis). When the same pathologist reviewed two sets of biopsies taken less than 2 months apart, the combination of random observer error and biopsy sampling error gave rise to quite low agreement, especially for early lesions, mainly attributable to biopsy sampling error. Comparison of diagnoses made at routine reading and at review by the same pathologist and by different pathologists showed substantial overall agreement with the exception of one pathologist for whom agreement was moderate. These results confirm that misclassification of histological diagnosis may be a relevant problem in chemoprevention trials of stomach cancer, more so when baseline diagnosis is taken into account in the analysis to estimate progression and regression rates of precancerous lesions. Further, the results suggest that misclassification is limited to early lesions, while diagnostic reliability of severe lesions is quite high.

Microsatellite alterations in bronchial and sputum specimens of lung cancer patients: Miozzo M, Sozzi G, Musso K et al. Division of Experimental Oncology A, Istituto Nazionale Tumori, Via G, Venezian 1, 20133 Milano. Cancer Res 1996;56:2285–2288

Early diagnosis of lung cancer based on conventional screening procedures has been unable thus far to decrease lung cancer mortality. We explored the possibility of using microsatellite instability in the detection and screening of early phases of lung carcinogenesis. We studied tumor, histopathologically normal bronchial mucosa, and cytological specimens of 51 lung cancer patients for the presence of clonal variations at microsatellite polymorphisms. Microsatellite alterations were found in tumor, normal bronchial mucosa and cytological specimens of 25 of 51 (49%) of the patients. The detection of microsatellite alterations in histopathologically normal bronchial specimens and cytological clinical samples with minimal atypia suggests a possible application of this genetic marker in early diagnosis of precancerous lesions and lung cancer.

Recent advances in the study of hepatocellular carcinoma.

Among the known causes for the occurrence of hepatocellular carcinoma (HCC), chemical carcinogens, chronic alcoholic intake and hepatitis B virus (HBV), especially in Asia, has been emphasized. HBV has been industriously studied and many queries about the relationship between HBV infection and hepatocarcinogenesis have been clarified. Recent discovery of hepatitis C virus (HCV) revealed that there may be the participation of this virus in hepatocarcinogenesis. However, a precise mechanism in such a viral infection has not been known. Host immunological defence mechanisms including the role of cytokines should be also taken into consideration. Cellular gene abnormalities have been noted in the late period of cancer cell progression. The technical development in the clinically available diagnostic procedures have enabled us to detect early phase of HCC. Some new concepts in the pathological diagnosis of precancerous lesions of HCC and also early HCC have been reported recently. We gave an outline of the recent advances and references in the study of HCC.

Breast cancer: Early diagnosis of precursor lesions and clinically inapparent carcinoma by fine needle aspiration

Breast cancer death rate has remained stable at 26 per 100,000 for over 50 years. This control failure is due in large part to difficulty in early diagnosis. Combined clinical evaluation, mammography and fine needle aspiration (FNA) offer the best opportunity for early diagnosis. Non-directed FNA is a useful adjunctive technique and three illustrative cases are presented. Cancer evolves from proliferative epithelial disease of ducts and lobules. Atypical duct hyperplasia in association with family history is a pertinent marker for development of cancer. Identification of hyperplastic lesions traditionally occurs after surgical biopsy and histopathologic review. FNA demonstrates patterns of both duct hyperplasia and atypical duct hyperplasia. Ploidy studies of such smears offer the possibility of selecting precancerous lesions for extirpation. A combination of directed and undirected punctures and ploidy studies may yield early diagnosis of precancerous lesions.