A comparison of conventional cytology, DNA ploidy analysis, and fluorescence in situ hybridization for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus

Fritcher, Emily G. Barr; Brankley, Shannon M.; Kipp, Benjamin R.; Voss, Jesse S.; Campion, Michael B.; Morrison, Larry E.; Legator, Mona S.; Lutzke, Lori S.; Wang, Kenneth K.; Sebo, Thomas J.; Halling, Kevin C.

doi:10.1016/j.humpath.2008.02.003

Cited by 72 publications

(72 citation statements)

References 28 publications

(32 reference statements)

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“…13 Others report similar rates of ErbB2 positivity in oesophageal adenocarcinomas, highlighting the impact of ErbB2 amplification and ERBB2 overexpression during the malignant progression of Barrett's metaplasia to invasive cancer. [27][28][29] The relatively high number of ErbB2-positive cases in our study compared with other reports may be due to the definition of ErbB2 positivity, which was based on the guidelines of the ToGA study and the EMEA for trastuzumab (Herceptin r ) treatment for advanced gastric cancer. This recommendation requires a ErbB2 score of 3 þ by immunohistochemistry or an amplification level of Z2 (ErbB2/Chr17) even in small tumour cell clusters, 10 which is different from the breast carcinoma requirements, in which cases with a ErbB2/ Chr17 ratio between 1.8 and 2.2 are considered as equivocal and ErbB2 expression is less heterogeneous.…”

Section: Discussionmentioning

confidence: 63%

Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

et al. 2011

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Amplification and overexpression of ErbB2 (Her2) is a frequent event in oesophageal adenocarcinomas. Assessment of ErbB2 status is crucial for identifying patients who are likely to benefit from treatment with trastuzumab. In this study, we performed a comprehensive analysis of ErbB2 amplification and expression in 142 oesophageal adenocarcinomas by comparing the most commonly used methods for ErbB2 assessment: ErbB2 expression was determined by immunohistochemistry and was scored (0, 1 þ , 2 þ and 3 þ ) according to a recently described modified scoring system for gastric cancer. ErbB2 amplification was evaluated by bright field double in situ hybridisation. The results were compared with pathologic features, patients' survival and previously published data from fluorescence in situ hybridisation analysis. On the basis of immunohistochemistry, which was applicable in 110 cores of the cases, 83 tumours (75%) had a score of 0 or 1 þ (immunohistochemistry negative), 13 tumours (12%) were scored as 2 þ and 14 tumours (13%) were scored as 3 þ . In situ hybridisation data were obtained from 142 cases. There was a highly significant correlation of immunohistochemistry, bright field in situ hybridisation and fluorescent in situ hybridisation (Po0.001 each). In total, 41 tumours (29%) were categorised as ErbB2 positive, which was defined as immunohistochemistry 3 þ and/or an ErbB2/Chr17 quotient of Z2 as assessed by either bright field double in situ hybridisation or fluorescence in situ hybridisation. ErbB2 positivity was observed more frequently in tumours with lower differentiation grades (P ¼ 0.029). Patients with ErbB2-positive tumours had a significantly worse prognosis, both in univariate analysis (P ¼ 0.004) and in multivariate analysis (P ¼ 0.03).In conclusion, we demonstrate that a significant number of oesophageal adenocarcinomas are positive for ErbB2. Assessment of ErbB2 amplification can be equivalently performed by conventional fluorescence in situ hybridisation or other lightmicroscopy-based methods, such as the novel bright field double in situ hybridisation technique. Modern Pathology (2011) 24, 908-916;

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Section: Discussionmentioning

confidence: 63%

Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

et al. 2011

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“…It is a common molecular pathological characteristic in human carcinoma (7,15,16). A number of studies have suggested that using DNA probes for the detection of aneuploidy in cancer cells may be a superior technique to conventional pathological diagnosis (8)(9)(10)(11)(12)14). Han et al examined 113 EC patients using specific centromere DNA probes 3, 8, 10, 12, 17 and 20, and found that chromosomal signal numbers and all chromosomes were found to have abnormal copy numbers (12).…”

Section: Discussionmentioning

confidence: 99%

“…Malignant cells are therefore capable of being diagnosed by detecting aneuploidy, usually found in aneusomic nuclei. Fluorescence in situ hybridization (FISH) technology is a rapid and sensitive method for detecting aneusomy of a specific chromosome and is widely used in the diagnosis of hematological malignancies, lung, breast and kidney cancer, with high sensitivity and specificity (8)(9)(10)(11). The advantage of the FISH method has been considered to lie in its objective and quantitative evaluation of malignant cells.…”

Section: Introductionmentioning

confidence: 99%

Molecular pathological diagnosis for early esophageal cancer in Kazakh patients

Awut¹,

Niyaz²,

Biekemitoufu³

et al. 2011

Oncology Letters

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Abstract. Chromosome abnormalities in cancer cells occur early in carcinogenesis. We employed DNA probes for the detection of cancer cells in surgical specimens in Kazakh patients with suspected esophageal carcinoma, to analyze the application of this technique during the early diagnosis of esophageal cancer. Comparative analysis was used to compare the results of pathological diagnosis with the results of FISH. We performed esophagofiberscopic biopsy examinations in 50 Kazakh patients with suspected esophageal carcinoma, including 40 males and 10 females, with an average age of 56.8 years. The final diagnosis was esophageal squamous cell carcinoma in 47 patients, and adenocarcinoma, mucinous carcinoma and small cell carcinoma in one patient each. The pathological findings of the biopsy were positive in 45 cases, and false-negative in 5. The sensitivity and specificity of pathological diagnosis were 87.2 and 100%, respectively. Using FISH to examine the same tissues, we found that 48 cases showed aberrant copy numbers in either chromosome 3 or 17, and 2 cases were false-negative, with a sensitivity and specificity of 94.8 and 100%, respectively. The copy numbers of centromeres in chromosome 3 were significantly higher than the copy numbers of centromeres in chromosome 17 (P=0.0001). Compared with biopsy pathology, the FISH test was more sensitive. Being an objective and qualitative method, the technology of molecular pathological diagnosis may effectively increase the early diagnostic rate of esophageal cancer. In addition, the centromere probe in chromosome 3 may be the most sensitive probe for the diagnosis of esophageal cancer in Kazakh patients. IntroductionThe incidence of esophageal cancer (EC) has been high (68.88/100,000) among the Kazakh people living in the Xinjiang Uygur Autonomous Region (Northwest of China) during the past 30 years. Nevertheless, early detection and treatment rates of EC remain low, and it consequently has a poor prognosis. If early diagnosis and treatment were possible, the 5-year survival rate could be increased to above 90% as in other countries/regions that have early detection programs (1-3).Conventional pathological diagnosis plays a crucial role in the diagnosis of EC, and provides important information on tumor differentiation and the degree of morphological changes (4,5). However, due to the limitations of biopsy pathology, discrepancies between pathological diagnosis and actual diagnosis occasionally occur, making clinical diagnosis and treatment difficult. There is, therefore, a need to find a more objective and quantitative method to distinguish benign from malignant cells.A number of studies suggest that the incidence and evolution of EC involves a variety of chromosomal anomalies. During carcinogenesis, a cell goes through molecular cytogenetic changes prior to showing morphological changes. Nuclear chromosome abnormality, which can be observed in cancer cells, is an early event during the process of tumorigenesis, and it has become the determining objective index of c...

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“…The detection of high-grade dysplasia (HGD) in BE patients may lead to radical therapeutic interventions such as esophagectomy or endoscopic mucosal resection, and RFA treatment. [15][16][17] Some recent studies investigated the use of fluorescence in situ hybridization (FISH) for the detection of dysplasia, 18 and the potential molecular biomarkers for EAC progression, 19,20 including epigenetic phenomena. 21,22 Although these attempts may hold promise, the diagnostic interpretation and histological grading of key clinical decision points in BE, including negative for dysplasia (NFD), LGD, and HGD, remains problematic.…”

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confidence: 99%

“…[35][36][37] In tissue-based BE research, some researchers have investigated alternative computerized morphometry and texture measurements as indicators for disease progression. 18,38,39 Nonetheless, the majority of other studies are still focusing on the well-established DNA density measurements using tissue sections (e.g., 3-7 μm), especially the use of the commercially available ACIS system (Automated Cellular Imaging System, Dako, Denmark) from a field of view (FoV) of tissue sections. [40][41][42][43][44] Under a microscope at × 40 magnification, a FoV is digitally captured followed by image analysis to locate nuclei and to measure the integrated optical density (IOD) for each nucleus.…”

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confidence: 99%

Whole slide image cytometry: a novel method to detect abnormal DNA content in Barrett's esophagus

Wang

McManus

Arthur

et al. 2015

Laboratory Investigation

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Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Both low-grade dysplasia (LGD) and highgrade dysplasia (HGD) are associated with an increased risk of progression to EAC. However, histological interpretation and grading of dysplasia (particularly LGD) is subjective and poorly reproducible. This study has combined whole slide imaging with DNA image cytometry to provide a novel method for the detection of abnormal DNA content through image analysis of tissue sections. A total of 20 cases were evaluated, including 8 negative for dysplasia (NFD), 6 LGD, and 6 HGD. Feulgenstained esophageal sections were scanned in their entirety. Barrett's mucosa was interactively chosen for automatic nuclei segmentation where irrelevant cell types were ignored. The combined DNA content histogram for all nuclei within selected image regions was then obtained. In addition, three histogram measurements were computed, including xER-5C, 2cDI, and DNA-MG. Visual evaluation suggested the shape of DNA content histograms from NFD, LGD, and HGD cases exhibiting identifiable differences. The histogram measurements, xER-5C, 2cDI, and DNA-MG, were shown to be effective in differentiating metaplastic from dysplastic cases with statistical significance. Moreover, they also successfully separated NFD, LGD, and HGD patients with statistical significance. Whole slide image cytometry is a novel and effective method for the detection of abnormal DNA content in BE. Compared with histological review, it is more objective. Compared with flow cytometry and cytology-preparation image cytometry, it is low cost, simple to use, only requires a single 1 μm section, and facilitates selection of tissue and topographical correlation. Whole slide image cytometry can detect differences in DNA content between NFD, LGD, and HGD patients in this cross-sectional study. Abnormal DNA content detection by whole slide image cytometry is a promising biomarker of progression that could affect future diagnostics in BE.

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A comparison of conventional cytology, DNA ploidy analysis, and fluorescence in situ hybridization for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus

Cited by 72 publications

References 28 publications

Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

Molecular pathological diagnosis for early esophageal cancer in Kazakh patients

Whole slide image cytometry: a novel method to detect abnormal DNA content in Barrett's esophagus

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