Simultaneous assessment of DNA ploidy and biomarker expression in paraffin‐embedded tissue sections

Fleskens, Stijn J H M; Takes, Robert P.; Otte-Höller, Irene; Doesburg, Lisanne Van; Smeets, Annemieke; Speel, Ernst‐Jan M.; Slootweg, Pieter J.; Laak, Jeroen van der

doi:10.1111/j.1365-2559.2010.03599.x

Cited by 20 publications

(15 citation statements)

References 35 publications

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“…We used FISH analysis to determine chromosome 1 and 7 copy number imbalances and/or polysomy, which is often associated with a more general chromosome instability. 9,10 Our data show that chromosome stability was significantly associated with HPV-positivity. In contrast, chromosome instability was shown to correlate strongly with tobacco-and alcohol consumption, a higher T-stage and an unfavorable prognosis.…”

Section: Discussionmentioning

confidence: 60%

“…7,8 On the basis of imbalances in chromosome 1 and 7 copy number ratios, we were able to reliably predict malignant progression and tumor recurrence. [8][9][10] In these cases, the chromosome 1 copy number most often equalled the average copy number of all chromosomes (ploidy) in the lesions, whereas generally higher copy numbers for chromosome 7 were detected. The latter finding is also reflected by data of Benchekroun et al reporting increased epidermal growth factor receptor (EGFR) gene copy numbers on chromosome 7 in premalignant oral leukoplakia that progressed to carcinoma.…”

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confidence: 90%

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Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

Mooren

Kremer

Claessen

et al. 2012

Intl Journal of Cancer

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Tonsillar squamous cell carcinoma (TSCC) is frequently associated with human papillomavirus (HPV) and chromosome instability. Data from cellular model systems are, however, controversial concerning a relation between HPV and chromosome instability development. Here we studied this association in 77 primary TSCC with known clinical outcome and cell cycle protein expression profiles. Thirty‐two tumors (42%) showed HPV16‐integration. All 77 cases were analyzed by fluorescence in situ hybridization using chromosome 1‐ and 7‐specific centromere DNA probes to detect chromosome instability, indicated by the presence of chromosome imbalances and/or polyploidization for these chromosomes. In addition, eight HPV‐positive dysplasias, seven of which were adjacent to a carcinoma, were analyzed. Disomy for chromosome 1 and 7 was present in 29 out of 77 TSCC (38%), of which 19 were HPV16‐positive (p = 0.002). Aneusomy was observed in the remaining 48 TSCC, of which 13 were HPV‐positive. Aneusomies correlated significantly with tobacco‐ and alcohol consumption (p = 0.001 and p = 0.016, respectively) and a higher T‐stage (p = 0.018). Both HPV‐positivity and chromosome disomy were significantly associated with a favorable disease‐free survival (p = 0.001 and p = 0.025, respectively). Particularly in the HPV16‐positive group chromosome instability is a very strong indicator for an unfavorable prognosis (p = 0.032). In the dysplasias an identical HPV and chromosome copy number status was identified as in the adjacent tumors. We conclude that HPV‐positive TSCC and their precursor lesions are more often genetically stable than HPV‐negative lesions and that these tumors are associated with a favorable prognosis. Chromosome instability is an indicator for unfavorable prognosis, particularly in the HPV‐positive patient group.

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Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 90%

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

Mooren

Kremer

Claessen

et al. 2012

Intl Journal of Cancer

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“…Compared with manual histological review, the proposed method has the potential to be more objective. Compared with flow cytometry and cytology-preparation image cytometry, WSI cytometry is simple to use and only 27 has discussed the advantages of selective sampling that permits crossreferencing between DNA content histogram with the original tissue context. WSI cytometry extended this cross-referencing ability with the use of CellMap where DNA content histogram is visually associated with individual cell profile.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, biased sampling error could happen where smaller and isolated nuclei are preferred. 27,65 To avoid nuclear oversegmentation, this study used ∼ 1 μm thin tissue sections. When a thin tissue section is applied (e.g., 1-5 μm), the IOD of a segment of a nucleus rather than the entire nucleus is measured.…”

Section: Discussionmentioning

confidence: 99%

“…It uses two or more thick sections of FFPE (formalin fixed and paraffin embedded, e.g., 50 μm) and disaggregates cells into a monolayer preparation, followed by Feulgen staining. 26,27 Using digital image processing techniques, the integrated optical density for each nucleus is obtained followed by the construction and interpretation of DNA content histograms, similar to that of flow cytometry. This technology consumes valuable tissue samples, requires complex sample preparation, and is labor intensive, and hence not widely available for the frontline health care.…”

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confidence: 99%

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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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Pathological Aspects of Oral Precancer

Sloan¹

2012

Oral Precancer

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Simultaneous assessment of DNA ploidy and biomarker expression in paraffin‐embedded tissue sections

Abstract: The analysis model proposed in this study enables the combined analysis of histology, genotypic and phenotypic information.

Cited by 20 publications

References 35 publications

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

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

Pathological Aspects of Oral Precancer

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