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PubMed2000

Methacarn fixation: a novel tool for analysis of gene expressions in paraffin-embedded tissue specimens.

To establish a quantitative method for analysis of gene expressions in small areas of tissue after paraffin embedding, preliminary validation experiments with RT-PCR and Western blotting were performed using methacarn-fixed rodent tissues and a cultured PC12 cell line. A total RNA yield of 52 +/- 15 ng/mm2, sufficient for a quantitative RT-PCR of many genes, could be extracted from a deparaffinized 10-microm-thick rat-liver section by a simple, single-step extraction method. The low concentration of contaminating genomic DNA and the resolution of ribosomal RNAs in RNA gel proved the purity and integrity of the extracted RNA samples, allowing PCR amplification of a long mRNA sequence and mRNA species expressing low copy numbers. PCR amplification of mRNA-derived target gene fragments could be achieved by optimizing the amount of total RNA for reverse transcription and the number of subsequent PCR cycles for each gene. By this validation, organ- and sex-specific mRNA expression could be detected in methacarn-fixed paraffin-embedded tissues without additional DNase treatment of RNA samples. RT-PCR analysis could also be performed with total RNA extracted from deparaffinized tissue dissected with a laser capture microdissection system. In addition, extraction of protein yielded 4.9 +/- 2.1 microg/mm2 from a 10-microm-thick rat-liver section, allowing a quantitative expression analysis of protein by Western blotting. Thus, in addition to its advantages for immunohistochemistry, methacarn-fixed paraffin-embedded tissue has benefits for analysis of both RNAs and proteins in the cells of histologically defined areas.

Acetic Acid↗

PubMed2002

Toward efficient analysis of mutations in single cells from ethanol-fixed, paraffin-embedded, and immunohistochemically stained tissues.

Only a few studies have demonstrated successful molecular analysis after whole genome amplification using single cells dissected from paraffin-embedded tissues. The results in these studies were limited by low-amplification efficiency and high rates of allele dropout. In the present study, the amplification rate using a thoroughly modified primer extension and preamplification-PCR protocol was improved significantly for single cells microdissected from paraffin-embedded and immunohistochemically stained tissues. Tissue fixation with ethanol (85%) and the addition of 0.2 mmol/L EDTA helped to achieve an amplification rate between 67% (segments 200 to 400 bp) and 72% (segments <200 bp). Normal tissue sections were immunohistochemically double stained for overabundance of p53 protein and proliferating cell nuclear antigen. Microdissection of single cells was performed with a manual micromanipulator equipped with a Tungsten needle. Sequence analysis of the TP53 gene was performed after improved primer extension preamplification-PCR and multiplex PCR from single microdissected cells. The rate of allele dropout was at least 68%. These technical advances facilitate routine mutation analysis using a single cell or a few cells microdissected from routinely processed paraffin-embedded normal and tumor tissues. Allele dropout still represents a serious problem in single-cell mutation analysis, especially in samples with limited template DNA and prone to DNA damage.

Breast↗

PubMed1994

The use of the rigid endoscope in trans-sphenoidal pituitary surgery.

The use of the rigid endoscope has been evaluated during transsphenoidal microsurgery of 10 pituitary adenomas: three were prolactin-secreting adenomas; five growth hormone (GH)-secreting adenomas; and two without evidence of known endocrine activity. The use of the endoscope allowed close inspection and differentiation between tumour tissue and glandular remains. This resulted in microdissection of the tumour with maximum preservation of pituitary function. The angled view of the telescope helped total gross removal of tumour tissue from the less accessible supra- and para-sella extensions. More cases and a longer period of follow-up are necessary to provide long-term results.

Adenoma↗

PubMed2004

The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis.

AIM: Chemokines or chemotactic cytokines are known to be important in the directional migration or chemotaxis of leucocytes in conditions of homeostasis and in inflammatory or immunological responses. However, the role of chemokines is extending beyond their involvement in mediating leucocyte trafficking with an increasing body of evidence suggesting these proteins are intimately involved in many stages of tumour development and progression. Our aim was to study the role of the CXCL12:CXCR4 chemokine ligand:receptor complex in determining the organ-specific metastasis of prostate cancer. MATERIALS AND METHODS: CXCR4 mRNA expression was determined by RT-PCR in 3 metastatic prostate cancer cell lines DU145, LNCaP and PC3, the primary prostate cancer cell line 1542 CPT3X and the normal prostate epithelial cell lines 1542 NPTX and Pre 2.8. This was followed by Taqman quantitative PCR analysis of CXCR4 mRNA in these cell lines. Flow cytometry analysis was then used to measure the expression of the CXCR4 receptor protein on the cell surface. The influence of the receptor on cell migration was studied using Transwell, Migration Assays. Finally, Taqman quantitative PCR was performed on RNA obtained from laser microdissected fresh primary prostate tumour and benign tissue samples from patients. RESULTS: In DU145, LNCaP and PC3 CXCR4 mRNA expression was approximately 1000, 400 and 21 times respectively that of 1542 NPTX, Pre 2.8 and 1542 CPT3X. In patient primary tumour samples and patient benign tissue specimens CXCR4 mRNA expression was similar to that of the metastatic cell line DU145. Flow cytometry analysis showed that significantly higher levels of the CXCR4 receptor were present on the cell surface of the 3 metastatic cell lines. Migration studies revealed that chemotaxis of the metastatic cell lines PC3 and DU145 was enhanced by CXCL12 ligand and inhibited by antibody to CXCR4. CXCL12 did not influence the migration of the normal prostate epithelial cell line 1542 NPTX. CONCLUSIONS: We have demonstrated that human prostate cell lines derived from metastases express functional CXCR4 receptor and that CXCL12 ligand enhances their migratory capabilities. Also, laser microdissected primary patient tumours and patient benign tissue specimens express CXCR4 mRNA at high levels (it is suggested that post-transcriptional modification of the CXCR4 receptor plays a major role in regulating protein expression). These results suggest prostate cancers may be influenced by the CXCL12:CXCR4 pathway during metastasis. This pathway would provide a novel target for therapeutic intervention.

Cell Line, Tumor↗

PubMed2004

Quantitative, tissue-specific analysis of cyclooxygenase gene expression in the pathogenesis of Barrett's adenocarcinoma.

Cyclooxygenase (Cox-2) is implicated in the pathogenesis of many cancers including esophageal adenocarcinoma (EAC), whereas the role of the isoform Cox-1 in carcinogenesis is not well understood. To further elucidate the role of these factors in the development of EAC, we measured the gene expressions (mRNA levels) of Cox-2 and Cox-1 by real-time quantitative polymerase chain reaction (QRT-PCR) in tissues from normal esophagus with and without erosive gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), dysplasia, adenocarcinoma, and in healthy gastric antrum. All tissues were purified by laser capture microdissection from endoscopic or surgical resection specimens. Median Cox-2 gene expression did not differ significantly among the esophageal control groups but was elevated 5-fold in BE, 8-fold in dysplasia and 16-fold in EAC compared to normal esophageal controls with no erosive GERD. Erosive GERD tissue had slightly higher median Cox-2 expression but Cox-2 expression in normal antrum was much higher than that in a normal esophagus, close to that of dysplasia. In contrast to that of Cox-2, Cox-1 expression was significantly decreased in all neoplastic tissues compared to normal controls. Cox-1 and Cox-2 expression varied over a wide range in the neoplastic tissues but over a relatively narrow range in the esophageal normal tissues. The occurrence of substantial alterations in Cox-1 and Cox-2 expression at the BE stage indicates that these are early events in the development of EAC. These results confirm the important role of Cox-2 amplification in the pathogenesis of esophageal adenocarcinoma, but the unexpected down-regulation of Cox-1 raises questions about its role in carcinogenesis.

Adenocarcinoma↗

PubMed2005

Macrodissection versus microdissection of rectal carcinoma: minor influence of stroma cells to tumor cell gene expression profiles.

BACKGROUND: The molecular determinants of carcinogenesis, tumor progression and patient prognosis can be deduced from simultaneous comparison of thousands of genes by microarray analysis. However, the presence of stroma cells in surgically excised carcinoma tissues might obscure the tumor cell-specific gene expression profiles of these samples. To circumvent this complication, laser microdissection can be performed to separate tumor epithelium from the surrounding stroma and healthy tissue. In this report, we compared RNAs isolated from macrodissected, of which only surrounding healthy tissue had been removed, and microdissected rectal carcinoma samples by microarray analysis in order to determine the most reliable approach to detect the expression of tumor cell-derived genes by microarray analysis. RESULTS: As microdissection yielded low tissue and RNA quantities, extra rounds of mRNA amplification were necessary to obtain sufficient RNA for microarray experiments. These second rounds of amplification influenced the gene expression profiles. Moreover, the presence of stroma cells in macrodissected samples had a minor contribution to the tumor cell gene expression profiles, which can be explained by the observation that more RNA is extracted from tumor epithelial cells than from stroma. CONCLUSION: These data demonstrate that the more convenient procedure of macrodissection can be adequately used and yields reliable data regarding the identification of tumor cell-specific gene expression profiles.

Carcinoma↗

PubMed2003

Gene expression in the rhesus monkey endometrium: differential display and laser capture microdissection.

The primate endometrium is a complex heterogeneous tissue that requires proper maturation to achieve a hospitable environment for implantation. Endometrial differentiation and maturation is primarily controlled through the action of progesterone during the secretory phase. Many of the genes and gene networks that are involved in this process are likely to be induced or inhibited in a temporal, spatial, and cell-type specific context within the endometrium. We have used several approaches to address these latter issues in the rhesus monkey endometrium. The use of differential display with hormonally distinct endometrial cDNA populations prepared from artificially controlled menstrual cycles has allowed us to identify different P-dependent mRNA regulatory patterns during simulated secretory phases. In addition, we have coupled differential display with laser capture microdissection to further study region and cell-type specific changes in the primate endometrium.

Animals↗

PubMed2005

Advances in isolation and characterization of homogeneous cell populations using laser microdissection.

The isolation and characterization of homogeneous cell populations are of great importance for the analysis of gene expression, because normal tissues contain various types of cells, and the differences in the populations of isolated cells exert significant effects on gene expression analysis. Researchers have attempted to develop methods for the isolation of homogeneous cell populations, such as flow cytometry and mechanical dissection. However, the recent emergence of laser-assisted microdissection has revolutionized the isolation of single-cell populations from solid tissues. With the help of a cutting laser, laser microdissection can isolate tissues (cells) of interest without contamination from surrounding tissues with the microscopic visualization field. By combining laser microdissection and subsequent microarray technology, several studies have resulted in the identification of disease-related genes. In this review, we summarize the principle of laser microdissection and provide several successful examples of target-gene identification using the conventional method combining laser microdissection and microarray. Next, we discuss the practical drawbacks of the combinational method, such as the need for a large number of cells and the disturbance of the relative abundance of transcripts during RNA amplification. We introduce our modifications to combined laser microdissection and microarray for detection of disease-related genes; the technique is simple, yet practical and accurate. Finally, versatile applications of laser microdissection, not only to transcript expression analysis, but also to other genomics and proteomics analyses are, also presented.

Animals↗

PubMed1999

Evidence of focal genetic microheterogeneity in glioblastoma multiforme by area-specific CGH on microdissected tumor cells.

The term "multiforme" in glioblastoma multiforme (GBM) indicates the highly variable histomorphology that cannot be addressed by studies on homogenized tissue probes. In order to relate genetic findings with histomorphologically distinct areas we used microdissection to procure defined cell populations from microscopic tissue sections under direct visualization. Formalin-fixed and paraffin-embedded tissue sections of 10 GBM were evaluated for intratumoral genetic heterogeneity by microdissection of multiple areas of 20-50 tumor cells and DOP-PCR of DNA isolated from the dissected cell groups, followed by comparative genomic hybridization (CGH). Microdissected cells from histomorphologically normal extratumoral blood vessels from the same slides served as controls. The individual tumors showed variable combinations of primary chromosomal gains and losses common to all studied areas of a given case along with secondary, area-specific additional aberrations. CGH displayed a wider variety of chromosomal aberrations than metaphase cytogenetics of cell cultures from the same tumors. The most frequent aberrations observed were previously unperceived gains on chromosomes 4q (8/10) and 5q (5/10). Other nonrandom aberrations were gains on 12q (6/10), 13q (6/10), and 7 (5/10), and losses of 22 (5/10). Amplifications on 7p were intratumorally heterogeneous and only found in single areas of 2 tumors. In contrast to normal extratumoral vessels, vascular proliferates in most cases demonstrated chromosomal aberrations (CGH) which were partially different from the aberrations observed in the tumor itself. The described method gives evidence of considerable intratumoral genetic heterogeneity in GBM and provides a sensitive tool for the detection of quantitative chromosomal changes that are present only regionally within a given tumor.

Adult↗

PubMed2005

Somatic mosaicism and cancer: a micro-genetic examination into the role of the androgen receptor gene in prostate cancer.

Recent evidence has shown that the androgen receptor (AR) plays a major role in all prostate cancer stages, including both androgen-dependent and -independent tumors. A large number of studies have examined the possible effects of a functional polymorphism in the AR gene, a variable-length CAG repeat, on the development of prostate cancer, but the results to date have been inconclusive. We have considered the fact that the tissue heterogeneity present in almost all prostate cancer tumors has rarely been regarded as an indicator of AR genetic heterogeneity. To determine if genetic heterogeneity exists and is a significant event in prostate cancer development, we have examined prostate cancer tumors for somatic shortening of the AR gene CAG repeat. All 72 laser capture microdissected samples from archival prostate cancer tissues, as well as samples from freshly prepared prostate cancer tissues, showed some genetic heterogeneity (somatic mosaicism) for AR CAG repeat length. Cancerous tissues showed a much greater degree of genetic heterogeneity than adjacent benign tissues, as well as a very significant shortening of their CAG repeat lengths. However, CAG repeat length heterogeneity was not observed in normal prostate tissues. It is hypothesized that somatic mosaicism of the AR CAG repeat in prostate cancer tumors may be found to be an important genetic event in precancerous tissue, which may subsequently lead to the development of prostate cancer.

Aged↗

PubMed2001

PTEN expression is maintained in sporadic colorectal tumours.

Loss of PTEN (phosphatase and tensin homologue deleted from chromosome 10) function has been implicated in the progression of several types of cancer. Allele loss close to the PTEN locus occurs in sporadic colon cancer and germline PTEN mutations cause Cowden disease, an inherited cancer syndrome characterized by an increased incidence of gastrointestinal tract lesions that can progress to colorectal carcinoma. However, although PTEN is a good candidate for involvement in the pathogenesis of sporadic colon cancer, previous analyses have not revealed a high frequency of somatic mutations in colorectal tumours. Alternative mechanisms which could lead to a loss of PTEN expression in colon cancer have not been investigated. This study monitored PTEN mRNA and protein levels in a panel of 50 tumour tissues obtained from 35 patients with sporadic colon cancer. RT-PCR and immunohistochemistry were used to evaluate the expression of mRNA and protein, respectively, in normal, adenoma and adenocarcinoma colorectal tissues as well as in metastatic lesions. To overcome the problem of heterogeneity and normal stromal cell contamination in homogenized tissue specimens, specific cell types were isolated by microdissection prior to PCR analysis. No loss of PTEN expression was evident in any of the colon tissues examined. PTEN protein was localized exclusively in the cytoplasm of normal and tumour cells and no correlation of immunostaining intensity and tumour stage or grade was revealed. As with previous deletion and mutation analyses, the present study suggests that loss of PTEN expression is not prevalent in sporadic colon cancer.

Adenocarcinoma↗

PubMed1997

Presence of Human Herpesvirus 8 Is Specific to Kaposi's Sarcoma Lesion.

Background: Human herpesvirus 8(HHV8) has previously been shown to be associated with Kaposi's sarcoma (KS) skin lesions in HIV-positive and negative patients. This study was designed to test, on a microscopic level, using the microdissection technique in frozen and formalin-fixed tissue, whether HHV8 DNA is specific to the KS lesion. Methods and Results: Thirty-seven evaluable KS lesions were microdissected and DNA extracted, and HHV8-specific polymerase chain reaction (PCR) was performed. All of the KS lesions showed a PCR product; none of the microscopically adjacent normal tissue samples showed a PCR product. One of the PCR products was sequenced, confirming the presence of HHV8 DNA. Conclusions: HHV8 was shown to be specific to the KS lesion at the microscopic level.

Journal Article↗

PubMed1986

DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein: regional, tissue, and phylogenetic distribution.

Rabbit antisera and mouse monoclonal antibodies have been prepared to bovine DARPP-32 (dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein, Mr = 32,000), and used to study its regional, tissue, and phylogenetic distributions. The antibodies, none of which distinguished between dephospho-DARPP-32 and phospho-DARPP-32, were characterized and used to develop a sensitive and specific radioimmunoassay for DARPP-32. The radioimmunoassay, in conjunction with immunolabeling of SDS/PAGE transfers and immunoprecipitation of phosphorylated tissue extracts, was used to measure immunoreactive DARPP-32 in microdissected regions of rat CNS, in peripheral nervous and non-nervous tissues, and in CNS tissue from various animal species. The distribution of DARPP-32 was generally consistent with the interpretation that it is localized primarily to dopaminoceptive cells that possess dopamine-sensitive adenylate cyclase (D-1 dopamine receptors coupled to adenylate cyclase). Within the rat CNS, DARPP-32 was most highly concentrated in the basal ganglia. DARPP-32 was present in neostriatum from all six mammalian species tested (mouse, rat, guinea pig, rabbit, cow, and rhesus monkey) at concentrations of from 96 to 144 pmol/mg total protein, which constituted from 0.22 to 0.32% of the total protein. DARPP-32 was also identified at low levels in several peripheral tissues, including choroid plexus, parathyroid cells, adrenal chromaffin cells, posterior pituitary gland, pineal gland, and superior cervical sympathetic ganglion. A phylogenetic survey was carried out of proteins immunologically related to DARPP-32 in nervous tissue from nonmammalian species. DARPP-32-like proteins were identified in dopaminoceptive brain regions from representative members of the amniote vertebrate classes (birds and reptiles), while none was identified in dopaminoceptive brain regions from representative members of the anamniote vertebrate classes (bony fishes and amphibians) or in nervous tissue from representative members of several invertebrate classes.

Adenosine Monophosphate↗

PubMed1998

Correlation of histologic morphology and tumor stage with molecular genetic analysis using microdissection in gastric carcinomas.

Precise correlation of histomorphology with the results of molecular genetic analysis is difficult in gastric cancer tissue composed of intestinal and diffuse types. A novel microdissection procedure was applied to correlate p53 and APC allelic loss with histologic type and tumor stage (mucosal vs. invasive cancer) in formalin-fixed, paraffin-embedded specimens of 25 gastric cancers. In addition, mucosal and invasive lesions were dissected from each of 11 invasive gastric cancers to study progression, and allelic loss of the p53 and APC genes was assessed. The p53 gene underwent loss of heterozygosity (LOH) in 4 of 4 informative cases of intestinal-type gastric cancer with mucosal lesions associated with invasion. By contrast, no p53 LOH was found among 6 informative cases with mucosal cancer. LOH of the APC gene in both intestinal and diffuse types of cancer was detected in 4 of 7 and 5 of 6 informative cases, respectively. These data suggest that allelic deletion of the p53 gene in intestinal-type gastric carcinoma predicts the invasive potential of mucosal cancer, and that inactivation of the APC gene plays a role in the genetic tumorigenesis of both intestinal and diffuse types of gastric cancer. Microdissection can correlate genetic alterations with histologic morphology in gastric cancer.

Adenocarcinoma↗

PubMed2006

Breast cancer proteomics by laser capture microdissection, sample pooling, 54-cm IPG IEF, and differential iodine radioisotope detection.

The presence of progesterone receptor (PR) in estrogen receptor (ER)-positive breast cancer is associated with a good prognosis, and indicates that tumors are likely to respond to tamoxifen. However, ER+/PR- tumors respond less well. To reveal the potential molecular mechanism of this phenomenon, we sought to identify differential protein abundances between invasive ductal carcinoma cells from cryopreserved ER+/PR+ and ER+/PR- mammary tumor specimens. Because current proteomics methods are hampered in the examination of most primary human tumor samples by the extreme tissue heterogeneity, we used laser capture microdissection (LCM) to isolate tumor cells and developed a sample pooling strategy to analyze small sample protein lysates. Proteins from LCM-harvested tumors were pooled into four sub-pools from each condition of three tumors/sub-pool, and proteins from respective paired sub-pools were co-electrophoresed by 2-DE using 54-cm IEF over pH 4-9. Abundance ratios were accurately quantified by a differential multiplex radioactive ProteoTope method at low attomole levels ( approximately 3.6 microg protein per labeling reaction, <180 ng per multiplex protein sample per 54-cm gel). Applying this approach, differentially displayed proteins were identified by MS using comigrating non-radioactively labeled tumor proteins. They include decreased cytochrome b5 and transgelin, and more abundant CRABP-II, cyclophilin A, Neudesin, and hemoglobin in ER+/PR+ tumors versus ER+/PR- providing a possible explanation for differential susceptibility against tamoxifen as a result of deregulated cytochrome b5-dependent metabolism. This study demonstrates the potential of ProteoTope and LCM to enable extremely sensitive and precise differential analyses from well-defined primary clinical specimen.

Antineoplastic Agents, Hormonal↗

PubMed2004

[Laser microdissection in the molecular oncology of prostate cancer].

Nearly all diseases, including prostate cancer (PCA), occur in mixed tissues with different cell types interconnected by multiple interactions. Laser microdissection permits a separate analysis of specific cell types necessary to understand tumorigenesis. Microdissection can be combined with different molecular methods for analyses at the levels of the genome, the transcriptome or the proteome. With respect to the molecular pathogenesis of PCA, normal glands can be compared to preneoplasias, and these in turn to the carcinoma. Different malignancy grades, as well as intra- and extraprostatic tumor parts, can be specifically analysed and molecular markers of aggressiveness can be identified. The molecular signatures obtained provide the basis for functional studies. New prognostic markers and therapeutic targets can be expected from such approaches in the near future. A far reaching goal is the computer representation of multiple molecular components and their interactions, "E-cell in cyberspace", in which prognostic behaviour and therapeutic responsiveness can be approximately predicted.

Animals↗

PubMed2003

Automated sequencing of complete mitochondrial genomes from laser-capture microdissected samples.

Mitochondrial DNA mutations have been related to both aging and a variety of diseases such as cancer. Due to the relatively small size of the genome (16 kb) and with the use of automated DNA sequencing, the entire genome can be sequenced from clinical specimens in days. We present a reliable approach to complete mitochondrial genome sequencing from laser-capture microdissected human clinical cancer specimens that overcome the inherent limitations of relatively small tissue samples and partial DNA degradation, which are unavoidable when laser-capture microdissection is used to attain pure populations of cells from heterogeneous tissues obtained from surgical procedures. The acquisition of sufficient template combined with a standard set of 18 pairs of PCR primers allows for the efficient amplification of the genome. Subsequent single-stranded amplification is performed using 36 sequencing primers, and samples are run on an ABI PRISM 3100 Genetic Analyzer. The use of this procedure should allow even investigators with little experience sequencing from clinical specimens success in complete mitochondrial genome sequencing.

Base Sequence↗

PubMed2005

Comparative mutational analysis of pulmonary scar epithelium, bronchioloalveolar carcinomas, and invasive well-differentiated pulmonary adenocarcinomas: a molecular approach to diagnostically challenging cases.

Discrimination of invasive well-differentiated adenocarcinoma (IAD) from reactive bronchioloalveolar epithelium entrapped in pulmonary scars (PSE) may be difficult on routine histology, especially on small biopsies. Ancillary studies to help in this regard are desirable. Whereas IADs have been shown to harbor cumulative mutational damage of tumor suppressor genes, little is known about molecular changes in PSEs. In this study, we compared cumulative loss of heterozygosity (LOH) of tumor suppressor genes in PSEs (N = 12), bronchioloalveolar carcinomas (BACs, N = 15) and stage 1 IADs (N = 7). Unstained serial sections were microdissected to obtain lesional and normal tissue DNA. PCR was performed for up to 16 polymorphic markers. An allelic ratio of < 0.5 or >2.0 was designated as LOH. Fractional allelic loss (FAL) was calculated for each case as the number of markers with LOH divided by the total number of informative markers. Mean percentage of informative markers was 76.8%. PSEs showed significantly lower mean FAL compared with BACs and IADs (3.0% vs. 20.4% and 28.5%, respectively; P < 0.003). Only 1 case of PSE showed LOH of one marker in two different areas, whereas the majority of allelic losses in the neoplasms were present in two or more microdissected foci. Our study shows that PSEs harbor LOH of tumor suppressor genes at relatively low rates and in a random distribution compared with BACs and IADs, which show consistent allelic losses, and high FALs. These molecular differences may serve as an adjunct to histology in challenging glandular lesions of the lung.

Adenocarcinoma↗