Tissue Microdissection and Processing

Maitra, Anirban; Gazdar, Adi F.

doi:10.1007/978-1-4615-1657-6_3

Cited by 12 publications

(10 citation statements)

References 94 publications

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“…The latter analyses do not preserve tissue histology and therefore may not detect topographically focal deletions of the p16 gene, as they rely on the microdissection of morphologically identifiable lesions. 22,23 These microdissections are likely to comingle cells having different p16 gene status in instances where the cells have an identical morphologic appearance. Microdissection can therefore obscure deletions that do not involve an entire morphologically defined lesion.…”

Section: Discussionmentioning

confidence: 99%

Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion

Leoni²,

et al. 2005

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The p16INK4A/CDKN2A (p16) gene on chromosome 9p21 is inactivated in 490% of invasive pancreatic cancers. In 40% of pancreatic cancers the p16 gene is inactivated by homozygous deletion, in 40% by an intragenic mutation coupled with loss of the second allele, and in 10-15% by hypermethylation of the p16 gene promoter. Immunohistochemical labeling for the p16 gene product parallels gene status, but does not provide information of the mechanism of p16 gene inactivation. The methylthioadenosine phosphorylase gene (MTAP) gene also resides on chromosome 9p21, approximately 100 kb telomeric to the p16 gene. The MTAP gene is frequently contained within p16 homozygous deletions, producing concordant loss of both p16 and MTAP gene expression. Concordant loss of both p16 and MTAP protein expression can therefore be used as a surrogate marker for p16 homozygous deletion. Here we immunolabeled a series of pancreatic intraepithelial neoplasia (PanIN) lesions of various histologic grades for the p16 and MTAP gene products using a high-throughput PanIN tissue microarray (TMA) format. We demonstrate concordant loss of p16 and MTAP protein expression in 6/73 (8%) PanINs, including five high-grade lesions and one low-grade lesion. Immunolabeling for both p16 and MTAP protein expression provides a tool to evaluate tissues with intact morphology for p16 gene homozygous deletions. The concordant loss of expression of both genes in PanIN lesions demonstrates that homozygous deletions of the p16 tumor suppressor gene can occur in noninvasive precursor lesions. Keywords: homozygous deletion; precursor lesion; pancreatic intraepithelial neoplasia; p16; MTAP Pancreatic intraepithelial neoplasia (PanIN) is a powerful system to study noninvasive precursors of an infiltrating cancer. First, the disease is important. The infiltrating cancer associated with PanINs, infiltrating adenocarcinoma of the pancreas, is the fourth leading cause of cancer death. 1 This year approximately 31,000 Americans will be diagnosed with PanINs infiltrating adenocarcinoma of the pancreas and 31 000 will die from it. Second, PanINs are histologically well-defined. An international consensus has been developed for the classification and grading of PanINs, allowing investigators at one institution to compare their results directly with findings from another institution. 2 Third, the genetics of PanINs are well described, and a progression model for the occurrence of genetic alterations in PanINs has been developed. 3 Telomere shortening and activating point mutations in the KRAS2 oncogene occur early in PanIN-1 lesions, the p16INK4A/CDKN2A (henceforth referred to as p16) gene is inactivated in intermediate and late lesions (PanINs 2 and 3), and the TP53, MADH4, and BRCA2 genes are inactivated late, in PanIN-3 lesions. [4][5][6][7][8][9][10]

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Section: Discussionmentioning

confidence: 99%

Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion

Leoni²,

et al. 2005

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“…The neoplastic epithelium was outlined and selectively microdissected as described previously22 (Suppl. Fig.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA miR-155 is a biomarker of early pancreatic neoplasia

Habbe¹,

Koorstra²,

Mendell³

et al. 2009

Cancer Biology & Therapy

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145

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“…Proteomic analysis of microdissected target (e.g. tumour) tissues is usually performed by gel-based or non-gel-based proteomics, which identifies an array of proteins present in that area and lacks the cell-type-specific information (Simone et al 2000;Maitra and Gazdar 2001;Monteoliva and Albar 2004). Proteomic analysis of single cells will provide a greater value in understanding particular function in specific cells or neurons.…”

Section: Lcm Coupled With Nanolc-ms/ms In Neurosciencementioning

confidence: 99%

Approaches for targeted proteomics and its potential applications in neuroscience

2015

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An extensive guide on practicable and significant quantitative proteomic approaches in neuroscience research is important not only because of the existing overwhelming limitations but also for gaining valuable understanding into brain function and deciphering proteomics from the workbench to the bedside. Early methodologies to understand the functioning of biological systems are now improving with high-throughput technologies, which allow analysis of various samples concurrently, or of thousand of analytes in a particular sample. Quantitative proteomic approaches include both gel-based and non-gel-based methods that can be further divided into different labelling approaches. This review will emphasize the role of existing technologies, their advantages and disadvantages, as well as their applications in neuroscience. This review will also discuss advanced approaches for targeted proteomics using isotope-coded affinity tag (ICAT) coupled with laser capture microdissection (LCM) followed by liquid chromatography tandem mass spectrometric (LC-MS/MS) analysis. This technology can further be extended to single cell proteomics in other areas of biological sciences and can be combined with other 'omics' approaches to reveal the mechanism of a cellular alterations. This approach may lead to further investigation in basic biology, disease analysis and surveillance, as well as drug discovery. Although numerous challenges still exist, we are confident that this approach will increase the understanding of pathological mechanisms involved in neuroendocrinology, neuropsychiatric and neurodegenerative disorders by delivering protein biomarker signatures for brain dysfunction.

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Tissue Microdissection and Processing

Cited by 12 publications

References 94 publications

Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion

Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion

MicroRNA miR-155 is a biomarker of early pancreatic neoplasia

Approaches for targeted proteomics and its potential applications in neuroscience

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