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PubMed2006

Analysis of gene expression identifies candidate molecular markers in nasopharyngeal carcinoma using microdissection and cDNA microarray.

PURPOSE: Microarray analysis was used to bring a comprehensive insight into underlying molecular mechanisms and obtain a whole assessment of aberrant gene expression in nasopharyngeal carcinoma (NPC). METHODS: Combined with microdissection, gene expression profiles in 23 NPCs and 10 nontumor nasopharyngeal epithelial tissue samples were analyzed. RESULTS: Gene expression patterns suggested the dysregulation of the GTP/GDP-bound Ras cycle and an abnormal hyperactivity of cell cycle in NPC. Alterations in the WNT pathway suggest that this pathway may be activated in NPC. A 6-feature weighted-voting model was chosen because it represented the main characteristics of NPCs and predicted NPCs most accurately from the nontumor tissues (33 of 34 correct calls; 97.1% accuracy, Fisher's exact test, P value = 8.389 x 10(-8)). CONCLUSIONS: The data generated in this study represent a comprehensive list of genes aberrantly regulated in NPC. The 6-feature weighted-voting model may provide an extensive list of potential molecular markers for early diagnosis.

Biomarkers, Tumor↗
PubMed1999

Nerve growth factor (NGF) supports tooth morphogenesis in mouse first branchial arch explants.

Posterior midbrain and anterior hindbrain neuroectoderm trans-differentiate into cranial neural crest cells (CNCC), emigrate from the neural folds, and become crest-derived ectomesenchyme within the mandibular and maxillary processes. To investigate the growth factor requirement specific for the initiation of tooth morphogenesis, we designed studies to test whether nerve growth factor (NGF) can support odontogenesis in a first branchial arch (FBA) explant culture system. FBA explants containing neural-fold tissues before CNCC emigration and the anlagen of the FBA were microdissected from embryonic day 8 (E8) mouse embryos, and cultured for 8 days in medium supplemented with 10% fetal calf serum only, or serum-containing medium further supplemented with either NGF or epidermal growth factor (EGF) at three different concentrations: 50, 100, or 200 ng/ml. Morphological, morphometric, and total protein analyses indicated that growth and development in all groups were comparable. Meckel's cartilage and tongue formation were also observed in all groups. However, odontogenesis was only detected in explants cultured in the presence of exogenous NGF. NGF-supplemented cultures were permissive for bud stage (50 ng/ml) as well as cap stage of tooth morphogenesis (100 and 200 ng/ml). Morphometric analyses of the volume of tooth organs showed a significant dose-dependent increase in tooth volume as the concentration of NGF increased. Whole-mount in situ hybridization and semiquantitative reverse transcription-polymerase chain reaction for Pax9, a molecular marker of dental mesenchyme, further supported and confirmed the morphological data of the specificity and dose dependency of NGF on odontogenesis. We conclude that (1) E8 FBA explants contain premigratory CNCC that are capable of emigration, proliferation, and differentiation in vitro; (2) serum-supplemented medium is permissive for CNCC differentiation into tongue myoblasts and chondrocytes in FBA explants; and (3) NGF controls CNCC cell fate specification and differentiation into tooth organs.

Animals↗
PubMed1978

Quantitative determination of G6Pase activity in histochemically defined zones of the liver acinus.

Qualitative histochemical G6Pase distribution patterns obtained with an improved method (Teutsch, 1978) served as the basis for a zonal microdissection of the liver acinus. G6Pase activity was determined quantitatively in tissue samples of zones 1 and 3 by a microfluorometric method (Burch et al., 1978). Using a correlation system it could be demonstrated that the histochemical distribution pattern obtained with the improved method was in better agreement with quantitatively estimated zonal differences of G6Pase activity, both in fed and starved female rats, than with the Wachstein and Meisel medium (1956). From a total of 50 tissue samples analyzed the following average G6Pase activities were calculated: in fed animals 15.36 +/- 3.48 U/g dry weight in zone 1, and 9.28 +/- 2.15 U/g dry weight in zone 3; in starved female rats 42.50 +/- 8.20 U/g dry weight in zone 1, and 29.25 +/- 5.68 U/g dry weight in zone 3. The qualitative histochemical as well as quantitative zonal differences of G6Pase activities are taken as further support for the hypothesis of metabolic zonation of liver parenchyma.

Animals↗
PubMed1984

A procedure for small-volume brain grafting; vasopressin cells in neonatal and adult Brattleboro rats.

A simple and reliable technique is described for the transplantation of fetal vasopressin (VP) neurons in the third ventricle of the brain of homozygous Brattleboro neonates. Small-volume grafting is introduced by microdissection of paraventricular and supraoptic areas and by pelleting the minced tissue for insertion into the transplantation cannula. Morphological and immunocytochemical evaluation yielded results in both neonatal and adult host brain that were similar to those described for anterior hypothalamic grafts in adult Brattleboro brain. The present protocol circumvents some of the general problems encountered when the use of small grafts is imperative, and is also applicable to the implantation of pelleted cell suspensions.

Animals↗
PubMed2003

Identical allelic losses in mature teratoma and other histologic components of malignant mixed germ cell tumors of the testis.

Teratomas of the testis in post-pubertal patients are histologically diverse tumors that often coexist with other types of germ cell tumors. Using laser capture microdissection and loss of heterozygosity analysis, we investigated the clonality of mature teratoma and its relationship to other components of malignant mixed germ cell tumors to gain potential insight into the histogenetic relationship of teratoma with other germ cell tumor components. All 16 patients had mature teratoma as one component of their mixed germ cell tumors. The other histological subtypes included immature teratoma, seminoma, embryonal carcinoma, yolk sac tumor, and choriocarcinoma. Laser-assisted microdissection was performed on the formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 1p36.2 (D1S508), 2q22-32 (D2S156), 9p21-22 (D9S162), 11p13 (D11S903), 12q22-23 (D12S1051), and 18q21 (D18S46). Fourteen of 16 (88%) cases showed allelic loss in one or more components of the mixed germ cell tumors. Fourteen of 16 mature teratomas showed allelic loss in at least one of six microsatellite polymorphic markers analyzed. The frequency of allelic loss in mature teratoma was 50% (7 of 14) with D1S508, 33% (5 of 15) with D2S156, 58% (7 of 12) with D9S162, 43% (6 of 14) with D11S903, 20% (3 of 15) with D12S1051, and 33% (5 of 15) with D18S46. Completely concordant allelic loss patterns between mature teratoma and all of the other germ cell tumor components were seen in 10 of 14 tumors in which mature teratoma showed loss of heterozygosity. Our data support the common clonal origin of mature teratoma with other components of malignant mixed germ cell tumors of the testis.

Adolescent↗
PubMed2001

Mutational analysis of the 5' noncoding region of the bcl-6 gene in primary gastric lymphomas.

Bcl-6 mRNA and protein are frequently expressed in the transformed counterparts of the germinal center B-cells, diffuse large B-cell lymphoma and follicular lymphoma, irrespective of the gene rearrangements. Most of the primary gastric lymphomas are thought to be of mucosa-associated lymphoid tissue (MALT) origin, and neither bcl-6 gene rearrangement nor protein expression is found in low-grade gastric lymphomas of the MALT type as in normal marginal zone cells. However, bcl-6 protein expression was identified in high-grade gastric lymphomas, suggesting its role in high-grade transformation. In this study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis for bcl-6 primer was performed in order to ascertain the molecular mechanisms of bcl-6 protein expression in primary gastric lymphomas. A total 31 cases of gastric lymphoma were classified into low-grade gastric lymphomas of MALT type (n = 13), high-grade gastric lymphomas of MALT type (n = 6) and gastric diffuse large B-cell lymphomas (n = 12). Bcl-6 mutations were observed in 11 of 13 (84.6%) low-grade gastric lymphomas of the MALT type and in 8 of 12 (66.7%) diffuse large B-cell gastric lymphomas. In 6 cases of the high-grade gastric lymphomas of the MALT type, both the low- and high-grade components demonstrated the same frequency (3/6, 50%) of mutations. The tissue obtained from the marginal zone of Peyer's patch by microdissection technique revealed no bcl-6 mutations by the PCR-SSCP analysis. These findings suggest that the acquisition process of bcl-6 mutations by the marginal zone cells may be involved in the lymphomagenesis of the stomach, but our data does not explain the reason why bcl-6 protein is expressed only in high-grade gastric lymphomas.

DNA Mutational Analysis↗
PubMed2003

Genetic and epigenetic alterations in tumor progression in a dedifferentiated chondrosarcoma.

In this case of a dedifferentiated chondrosarcoma, we searched for genetic or epigenetic alterations in both components of the tumor, the low grade chondroblastic component, and the high grade osteosacomatouscomponent. To date, only little is known about aberrant patterns of DNA methylation in chondrosarcomas. Microdissection was used as a valuable method for clearly separating the tissues. We examined CpG island methylation of 8 tumor suppressor genes and candidate tumor suppressor genes, which are involved in different pathways: cell cycle (p21WAF1, p16INK4, p14ARF), apoptosis (DAPK, FHIT), DNA repair (hMLH1), and cell adherence (E-Cadherin). We found p16INK4 and E-cadherin promotor methylation in the low grade chondroid compartment of the dedifferentiated chondrosarcoma. P16INK4, FHIT, and E-cadherin were methylated in the highly malignant osteosarcomatous compartment of the tumor. Earlier investigations of this chondrosarcoma showed p53 mutation and p53-LOH in the anaplastic component. As shown in this case, it was accompanied by Rb-LOH. Early methylation of p16IK4 and E-cadherin in the chondroid compartment could point to the monoclonal origin of demonstrated dedifferentiated chondrosarcoma. Further alterations, as shown in p53, Rb and FHIT, are responsible for the "switch" to a high grade anaplastic sarcoma.

Cadherins↗
PubMed2002

A microdissected thin tensor fasciae latae perforator flap.

A new method, named "microdissection," has been introduced to create a thin flap by elevating the tensor fasciae latae perforator flap to serve as microdissected thin tensor fasciae latae perforator flap. In microdissection, perforators that run in the posterolateral direction in the adipose tissue after penetrating the deep fascia are dissected meticulously using an operative microscope, and a thin flap is elevated in a single process. The caliber of the perforator artery and vein in the tensor fasciae latae muscle measures approximately 0.7 mm and 0.9 mm, respectively. When transplanting the flap, an end-to-side anastomosis to the main artery measuring 1 to 2 mm is preferable to avoid the risk of arterial thrombosis. In contrast, an end-to-end anastomosis of the perforator vein to the comitans vein of the main artery can be performed safely. In the present study, 11 flaps were transplanted to the sites of skin defects of the neck, hand, axilla, knee, and foot. The author considers that the first clinical indication of this flap is reconstruction of hand skin defects.

Adult↗
PubMed2003

Real-time analysis of beta- and gamma-catenin mRNA expression in ret/PTC-1 activated and nonactivated thyroid tissues.

Our group has previously demonstrated an association between ret/PTC-1 activation and decreased E-cadherin mRNA levels in papillary thyroid carcinoma. We also observed similarities in the E-cadherin expression profiles of Hashimoto thyroiditis and ret/PTC-1-positive papillary thyroid carcinomas and have hypothesized that ret/PTC-1 activation might cause not only the structural and nuclear peculiarities of PTC but also an immune reaction to thyroid epithelium. The objective of this study was to examine the expression of E-cadherin's ligands, beta- and gamma-catenin, in various thyroid tissue types in the context of ret/PTC-1 positivity using laser capture microdissection and TaqMan (Applied Biosystems, Foster City, CA). One-Step RT-PCR. Beta-catenin mRNA levels were found to be consistently decreased in both papillary and anaplastic carcinomas when compared with a normal/follicular adenoma group. A significant difference in expression levels was observed between papillary and follicular thyroid carcinomas with the latter having elevated mRNA levels of beta-catenin. Gamma-catenin mRNA was decreased in anaplastic carcinomas compared with normal/follicular adenoma groups. A similar expression profile of gamma-catenin as beta-catenin was observed in papillary and follicular carcinomas with the latter once again having higher mRNA levels. These results therefore suggest that although beta- and gamma-catenin may play a role in the progression of thyroid cancer in general, they do not appear to be associated with ret/PTC-1-modulated pathways.

Cytoskeletal Proteins↗
PubMed2006

Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach.

To identify specific markers for the diagnosis of choroid plexus tumors, gene expression profiles of choroid plexus epithelial cells (n = 8) and ependymal cells (n = 6) microdissected from human autopsy brains as well as choroid plexus papilloma tissue were investigated using DNA microarrays. Protein expression of genes overexpressed in choroid plexus was evaluated in normal choroid plexus, choroid plexus papilloma, choroid plexus carcinoma, other primary brain tumors, and cerebral metastases. Forty-six genes found to be overexpressed in normal choroid plexus epithelial cells were also present in choroid plexus papilloma. Among those, 11 were further analyzed by immunohistochemistry. Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases. Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases. Transthyretin stained choroid plexus (33 of 35), choroid plexus papilloma (14 of 18), and plexus carcinoma (2 of 5), but its specificity was significantly lower. Antibodies directed against coagulation factor V, glutathione peroxidase 3, pigment epithelium derived factor, serotonin receptor 5-HTR2C, lumican, fibulin-1, plastin-1, and cytokeratin 18 revealed varying degrees of specificity and sensitivity. Our data suggest that antibodies directed against Kir7.1 and stanniocalcin-1 might serve as sensitive and specific diagnostic markers for choroid plexus tumors.

Adult↗
PubMed1988

The brown protein of Drosophila melanogaster is similar to the white protein and to components of active transport complexes.

The brown gene of Drosophila melanogaster is required for deposition of pteridine pigments in the compound eye and other tissues. We isolated a ca. 150-kilobase region including brown by microdissection and chromosome walking using cosmids. Among the cDNAs identified by hybridization to the cosmids, one class hybridized to a genomic region that is interrupted in two brown mutants, bw and In(2LR)CK, and to 2.8- and 3.0-kilobase poly(A)+ RNAs which are altered in the mutants. Nucleotide sequencing of these cDNAs revealed that the two transcripts differ as a consequence of alternative poly(A) addition and that both encode the same predicted protein of 675 amino acids. Searches of available databases for amino acid sequence similarities detected a striking overall similarity of this predicted protein to that of the D. melanogaster white gene. The N-terminal portion aligned with the HisP family of membrane-associated ATP-binding proteins, most of which are subunits of active transport complexes in bacteria, and to two regions of the multidrug resistance P-glycoprotein. The C-terminal portion showed a structural similarity to integral membrane components of the same complexes. Taken together with earlier biochemical evidence that brown and white gene products are necessary for uptake of a pteridine precursor and genetic evidence that brown and white proteins interact, our results are consistent with suggestions that these proteins are subunits of a pteridine precursor permease.

ATP-Binding Cassette Transporters↗
PubMed2001

Genomic homogeneity in fibrolamellar carcinomas.

BACKGROUND: Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC) with distinctive clinical and histological features. To date there have been few studies on the genotypic aspects of FLC and no previous attempts have been made to use the arbitrarily primed-polymerase chain reaction (AP-PCR) technique to detect genetic alterations in this disease. AIM: The aim of this study was to assess the degree of genomic heterogeneity of FLC using the AP-PCR technique. METHODS: A total of 50 tissue samples of primary and metastatic FLCs from seven patients were microdissected. AP-PCR amplification of each genomic DNA sample was carried out using two arbitrary primers. RESULTS: DNA fingerprints of the primary FLCs and all their metastatic lesions (both synchronous and metachronous disease) were identical in an individual patient. The fingerprints were different between tumours of different patients. No evidence of intratumour heterogeneity was observed. CONCLUSIONS: Such genomic homogeneity in FLCs may explain their indolent growth. The absence of clonal evolution, which is present in other tumours (particularly HCCs), may explain the distinct behaviour in this tumour. The tumorigenic pathway and degree of somatic genomic changes in this disease may be less complex than in HCC.

Carcinoma, Hepatocellular↗
PubMed2002

INK4a-ARF alterations in liver cell adenoma.

BACKGROUND: The INK4a-ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16(INK4a) and p14(ARF), whose functions are inactivated in many human cancers. AIMS: To evaluate p14(ARF) and p16(INK4a) alterations in liver cell adenoma. METHODS: After microdissection, DNA from 25 liver cell adenomas and corresponding normal liver tissue were analysed for INK4-ARF inactivation by DNA sequence analysis, methylation specific polymerase chain reaction, restriction enzyme related-polymerase chain reaction (RE-PCR), mRNA expression, microsatellite analysis, and immunohistochemistry. In addition, microdeletion of p14(ARF) and p16(INK4a) were assessed by differential PCR. RESULTS: Methylation of p14(ARF) was found in 3/25 cases (12%) and alterations in p16(INK4a) occurred in 6/25 liver cell adenomas (24%) which correlated with loss of mRNA transcription. We failed to detect microdeletions or specific mutations of both exons. p16(INK4a) methylation appeared in the context of an unmethylated p14(ARF) promoter in six cases. In normal liver tissue, p14(ARF) or p16(INK4a) alterations were not observed. CONCLUSIONS: Our data suggest that p14(ARF) methylation occurs independently of p16(INK4a) alterations in liver cell adenomas. Furthermore, methylation of p14(ARF) and p16(INK4a) may be a result of cell cycle deregulation and does not seem to be a prerequisite of malignancy.

Adenoma, Liver Cell↗
PubMedDate not supplied

In vitro analysis of alpha-adrenoceptor interactions with the myogenic response in resistance vessels.

The interaction of alpha 1- and alpha 2-adrenoceptor constriction of isolated rat cremaster small arteries (mean diameter +/- SEM, 114 +/- 5 microns) with the myogenic mechanism was examined with in vitro videomicroscopy. Microdissected vessels were double-cannulated with glass micropipets in a tissue bath, and intraluminal pressure was set at 65 mm Hg baseline pressure. Norepinephrine (NE) concentration-response curves were obtained alone and in the presence of prazosin or rauwolscine to establish the concentration of NE required to selectively stimulate alpha 1- or alpha 2-adrenoceptors. A bimodal response was produced by NE alone, indicating interaction with more than one receptor population. Rauwolscine and prazosin each produced dextral displacement at low (< 0.1 microM) NE concentrations. However, while prazosin exhibited competitive antagonism, rauwolscine did not antagonize NE at concentrations > or = EC50 value. Thus, both alpha 1- and alpha 2-adrenoceptors mediate constriction at low NE concentrations, but only alpha 1-receptors contributed to constriction at intermediate and high concentrations. These data are in contrast to previous findings for the same vessels studied in vivo. Diameter responses to increases and decreases in transmural pressure from baseline were examined in the relaxed (passive) state with nitroprusside present, during spontaneous intrinsic tone, and during induced alpha 1- or alpha 2-tone (EC20 concentration of NE plus rauwolscine or prazosin). Myogenic constriction during increases in lumen pressure and myogenic inhibition of tone during decreases in pressure were greatest during alpha 2-tone, less during intrinsic tone and least during alpha 1-tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Differential transcription of Eomes and T-bet during maturation of mouse uterine natural killer cells.

During human and rodent uterine decidualization, transient but abundant numbers of uterine natural killer (uNK) cells appear, proliferate, and differentiate. uNK cells share features with peripheral NK cells but are specialized to promote interferon-gamma (IFN-gamma)-mediated, pregnancy-associated, structural changes in maternal placental arteries. In CD8+ T cells and NK cells, the transcription factors T-bet and eomesodermin (Eomes) regulate maturation and effector functions, including IFN-gamma production. No studies are reported for uNK cells. Implantation sites in T-bet null mice, which have a defect in NK cell maturation, had uNK cells normal in morphology and number and normally modified spiral arteries. As Eomes null mice are not viable, real-time polymerase chain reaction comparisons between C57Bl/6J (B6) and alymphoid (Rag2(0/0)gammac0/0) mice were used to assess uNK cell expression of T-bet, Eomes, and the target genes IFN-gamma, granzyme A, and perforin. Gestation dated (gd) uterine tissues (mixed cell composition) and 200 morphologically homogeneous, laser-capture, microdissected uNK cells of different maturation stages were used. In uterus, Eomes transcripts greatly outnumbered those of T-bet, whether donors were nonpregnant or pregnant, and increased to gd10. In uNK cells, transcripts for T-bet, Eomes, and IFN-gamma were most abundant in mature stage cells, and transcripts for granzyme A and perforin were lower at this stage than in immature or senescent cells. Thus, Eomes dominance to T-bet discriminates regulation of the uNK cell subset from that observed for peripheral NK cells.

Animals↗
PubMed2001

T cell activation in rheumatoid synovium is B cell dependent.

Rheumatoid arthritis results from a T cell-driven inflammation in the synovial membrane that is frequently associated with the formation of tertiary lymphoid structures. The significance of this extranodal lymphoid neogenesis is unknown. Microdissection was used to isolate CD4 T cells residing in synovial tissue T cell/B cell follicles. CD4 T cells with identical TCR sequences were represented in independent, nonadjacent follicles, suggesting recognition of the same Ag in different germinal centers. When adoptively transferred into rheumatoid arthritis synovium-SCID mouse chimeras, these CD4 T cell clones enhanced the production of IFN-gamma, IL-1beta, and TNF-alpha. In vivo activity of adoptively transferred CD4 T cells required matching of HLA-DRB1 alleles and also the presence of T cell/B cell follicles. HLA-DRB1-matched synovial tissues that were infiltrated by T cells, macrophages, and dendritic cells, but that lacked B cells, did not support the activation of adoptively transferred CD4 T cell clones, raising the possibility that B cells provided a critical function in T cell activation or harbored the relevant Ag. Dependence of T cell activation on B cells was confirmed in B cell depletion studies. Treatment of chimeric mice with anti-CD20 mAb inhibited the production of IFN-gamma and IL-1beta, indicating that APCs other than B cells could not substitute in maintaining T cell activation. The central role of B cells in synovial inflammation identifies them as excellent targets for immunosuppressive therapy.

Adult↗
PubMed2000

Cervical cancer suppressor gene is within 1 cM on 6p23.

We previously showed loss of heterozygosity at 6p to be a common genetic alteration in cervical cancer and cervical intraepithelial neoplasia. To characterize this critical area of deletion in chromosome 6, we evaluated 107 invasive cervical cancers, using 23 polymorphic markers. Genomic DNA from microdissected frozen or paraffin-embedded cervical tumors and corresponding normal tissue was analyzed. Fifty-three percent (57/107) of the cervical tumors showed loss in 6p. Deletions were found in all stages and histologic types. Ninety-one percent (52/57) of these tumors had a loss at 6p23. One tumor defined the distal area of deletion at marker D6S429. Two tumors defined the proximal area of deletion at marker D6S1578. Genotyping of parental DNA was done on 16 cases to evaluate the origin of chromosomal loss. The deletion occurred in the paternal chromosome in 10 tumors and in the maternal in six. Within each tumor, the same parental chromosome was lost at all tested heterozygous 6p markers. The order of the polymorphic markers and estimate of distances in the critical region were confirmed by generation of a yeast artificial chromosome (YAC) contig and pulse-field gel electrophoresis. Our data strongly suggest that a gene important in cervical cancer tumorigenesis is located within a 1-cM region of 6p23, and it is not imprinted.

Adult↗
PubMed2003

[Microsatellite instability and loss of heterozygosity in neoplastic and preneoplastic gastric lesions].

BACKGROUND: Gastric cancer is the leading cause of cancer deaths in the general population in Chile, with mortality rates as high as 33.7 per 105 in males in the IX region. A chain of genetic and morphological events precedes the intestinal type of gastric carcinoma. One of them is the called multifocal atrophic gastritis often associated with intestinal metaplasia. AIM: To study the frequency of microsatellite instability (MSI) and loss of heterocigozity (LOH) in neoplastic and preneoplastic lesions of gastric carcinoma, especially intestinal metaplasia. MATERIAL AND METHODS: Ninety four gastric cancer biopsies were studied using laser capture microdissection, to obtain well defined cell populations from paraffin-embedded tissues: lymphocytes (control DNA), intestinal metaplasia and gastric cancer areas. Primer flanking microsatellite 15 highly polymorphic regions were used to study MSI and LOH. Radioactive PCR products were electrophoresed and exposed for autoradiography. RESULTS: LOH was observed in 83% of gastric carcinomas and in 54% areas containing intestinal metaplasia. The most commonly altered regions were the CA repeat associated with the p53 gene and the 3p21 region. High grade MSI was observed in 11.7% of gastric cancer preparations and 17% of intestinal metaplasia associated to cancer with MSI-H phenotype. CONCLUSIONS: MSI and LOH were frequently observed in intestinal metaplasia glands in patients with gastric carcinoma. The frequency of MSI-H phenotype in gastric patients was slightly lower than the one described in sporadic colorectal cancer not associated to HNPCC. The high incidence of genetic lesions in intestinal metaplasia area, support the idea that intestinal metaplasia is a genetically highly unstable cell population.

Adenocarcinoma↗