SEARCH · PubMed Health

Results for “DNA MICROSATELLITE INSTABILITY”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources

PubMed2004

Gastrointestinal cancers and neurofibromatosis type 1 features in children with a germline homozygous MLH1 mutation.

Heterozygous germline DNA mismatch repair gene mutations are typically associated with hereditary nonpolyposis colorectal cancer. The molecular hallmark of this syndrome is high-frequency microsatellite instability in the tumors. Rare childhood cases with homozygous or compound heterozygous DNA mismatch repair gene mutations have a described predisposition to leukemia, lymphoma, and brain tumors but not to gastrointestinal cancer. We have now characterized a family in which 2 children with a homozygous germline DNA mismatch repair gene mutation developed early-onset gastrointestinal cancers. The 11-year-old proband had café-au-lait macules and developed metastatic duodenal adenocarcinoma that arose in a tubulovillous adenoma. His 9-year-old sister with café-au-lait macules and axillary freckling presented with malignant colon polyps. A 6-year-old sister with café-au-lait macules, hairy nevi, and a plexiform neurofibroma of the tongue has no malignancies to date. The family history did not fulfill the Amsterdam criteria for hereditary nonpolyposis colorectal cancer, but 2 relatives in their 60s had gastric cancer and colorectal cancer, whereas the parents, who are first cousins, remain cancer free. The proband's metastatic duodenal cancer and his sister's malignant colon polyps had high-frequency microsatellite instability but had detectable MLH1, MSH2, and MSH6 proteins by immunohistochemistry. Because some germline DNA mismatch repair gene deficiencies are associated with apparently intact immunohistochemical DNA mismatch repair gene expression in tumors, we proceeded to DNA sequencing, which showed that all 3 children had a germline homozygous MLH1 missense mutation (exon 18, codon 687, CGG-->TGG), whereas both parents were heterozygous for this mutation.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Infrequent microsatellite instability in liver fluke infection-associated intrahepatic cholangiocarcinomas from Thailand.

The liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. The molecular basis of this ICC is poorly understood. To address possible roles of the DNA mismatch repair (MMR) system in ICC carcinogenesis, a fluorescence-labeling PCR/laser scanning technique with high sensitivity was employed to analyze genomic instability in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in 24 fresh and 13 formalin-fixed, paraffin-embedded tissues of ICC and their corresponding normal parts. Microsatellite instability (MSI) was assessed in nDNA, using 12 highly polymorphic loci including 5 Bethesda markers. These loci were mainly related to major MMR genes, hMSH2 and hMLH1. Also 3 (C)n and/or (C)n(A)n repeat instability at 1 noncoding region in the displacement-loop (D-loop) and 2 coding sequences in NADH dehydrogenase subunit 1 and subunit 5 gene in mtDNA were analyzed. MSI was only detected in 1 (2.7%), 6 (16.7%), 1 (2.9%), 1 (2.9%) or 2 (6.3%) out of 37, 36, 35, 35 or 32 cases at BAT-25, D2S123, D3S1611, D11S904 or D17S250, respectively. LOH was found at D3S1298, D3S1561, D5S346 and TP53 in 4 (18.2%) out of 22, 2 (18.2%) out of 11, 6 (33.3%) out of 18 and 3 (12.5%) out of 24 informative cases, respectively. In mtDNA, none except a single case out of the 37 (2.7%) exhibited repeat sequence instability in the D-loop. We conclude that the liver fluke infection-associated ICC in Thailand is classified as low frequency MSI or microsatellite stable type and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Microsatellite instability is rare in B-cell non-Hodgkin's lymphomas.

Microsatellite instability (MSI), a symptom of defect in DNA mismatch repair function, represents a type of genomic instability frequently detected in many types of cancers. However, the involvement of MSI in non-Hodgkin's lymphomas (NHL) has not been conclusively investigated. In this study, we have tested the presence of MSI in 69 cases of B-cell NHL (B-NHL) representative of the various histologic categories of the disease and including 17 cases of acquired immunodeficiency syndrome (AIDS)-related B-NHL (AIDS-NHL). In addition, for selected B-NHL cases, consecutive samples obtained before and after clinical progression (with and without concomitant histologic transformation) were also investigated. Five distinct microsatellite repeats (2 dinucleotide, 2 trinucleotide, and 1 tetranucleotide repeats) were analyzed by polymerase chain reaction in all cases. MSI, defined by the presence of microsatellite alterations in two or more of the five microsatellite loci tested, was not found in NHL. In contrast to a previous study reporting the frequent association between MSI and AIDS-NHL, we found this abnormality in only 1 of 17 cases of AIDS-NHL representative of the major subtypes. Overall, these data indicate that defects in DNA mismatch repair do not contribute significantly to the molecular pathogenesis of B-NHL.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Prevalence of minisatellite and microsatellite instability in radiation-induced post-Chernobyl pediatric thyroid carcinomas.

Exposure to ionizing radiation induces different forms of genomic instability in cultured cells and experimental animals. A higher rate of germline mutations at human hypervariable minisatellite loci was reported in children born from parents exposed to radiation after Chernobyl, implicating genome destabilization as a possible mechanism responsible for late radiation effects in humans. To test if radiation-induced carcinogenesis in the thyroid gland may be associated with somatic minisatellite instability or microsatellite instability, we utilized a PCR-based approach to study normal and tumor DNA from 17 pediatric post-Chernobyl papillary thyroid carcinomas for mutations at three different minisatellite loci (D1S80, D17S30, ApoB), and 27 microsatellite loci of di-, tri-, or tetranucleotide repeats. Minisatellite instability was found in three (18%) tumors, with one of them exhibiting mutations in all three minisatellite loci, whereas two others showed mutations in one of two informative markers. By contrast, none of 20 sporadic thyroid cancers from patients with no history of radiation exposure was positive for minisatellite instability. Microsatellite analysis of post-Chernobyl tumors revealed a mutation in one (6%) tumor only at the locus of D10S1412, whereas all other 26 microsatellite markers showed identical patterns in each normal/tumor pair. Our results suggest that somatic cell microsatellite instability does not contribute to radiation-induced thyroid carcinogenesis. However, somatic minisatellite mutation events are present in a subset of radiation-induced, but not sporadic, thyroid cancers, suggesting that this type of genomic instability may play a role in radiation-induced tumorigenesis in the thyroid gland.

Adolescent↗

PubMed2000

Low frequency of replication errors in primary nervous system tumours.

OBJECTIVES: Automated DNA technology was used to analyze the incidence of microsatellite instability (MIN) among the most frequent types of adult primary CNS tumours and to determine its relation with clinicopathological characteristics. METHODS: Fifty six gliomas, 32 meningiomas and 11 schwannomas were screened for size changes at eight microsatellite loci using fluorescent polymerase chain reaction (PCR) followed by fragment analysis in an automated sequencer. A tumour was considered as MIN+ when a different electrophoretic pattern between constitutional and tumour DNA was evidenced in one or more microsatellite markers and as replication error positive (RER+) when at least 25% of the markers analyzed (2/8) showed instability. The MIN phenotype was correlated with relevant clinical and pathological parameters. RESULTS: Globally, instability was found in 19/767 analyses (2.47%), with a higher rate among tetranuceotide than dinucleotide repeats (chi(2) test, p=0.018). Ten gliomas (17.9%), two meningiomas (6.3%), and two schwannomas (18.2%) were MIN+, whereas one glioma (1.8%), two meningiomas (6.3%), and one schwannoma (9.1%) were classified as RER+. A possible association between microsatellite instability and a shorter duration of clinical course was found in meningiomas. The MIN+ phenotype was more frequent in spinal than intracranial schwannomas (Fisher's exact test, p=0.018). No other significant association with clinical or histological features was detected. CONCLUSIONS: Although microsatellite instability can be demonstrated at a low rate in some primary CNS tumours, a true replication error phenotype (revealed by widespread microsatellite instability at numerous loci) is uncommon and unlikely to play an important part in the pathogenesis of these neoplasms. This form of instability was more frequent in tetranucleotide than in dinucleotide repeats. To our knowledge, this is the first report of MIN in schwannomas, where it was associated with the spinal localisation of the tumour.

Adult↗

PubMed2002

High level of microsatellite instability but not hypermethylation of mismatch repair genes in therapy-related and secondary acute myeloid leukaemia and myelodysplastic syndrome.

Microsatellite instability (MSI) is associated with defects in the DNA mismatch repair (MMR) system, such as mutation or epigenetic silencing of the genes by promoter hypermethylation. We investigated the presence of MSI and promoter hypermethylation of hMLH1 and hMSH2 genes in 82 patients (68 acute myeloid leukaemia, AML; 14 myelodysplastic syndromes, MDS). Twelve separate microsatellite loci, including three mononucleotide repeat markers, were used. Mutator phenotype (RER+) was detected in 20 AML (29.4%) and 3 MDS (21.4%) patients. RER+ rate was much higher in the therapy-related and secondary cases compared with the de novo cases. Three out of 7 (42.9%) secondary (s-AML) and 8 out of 17 (47.1%) therapy-related (t-AML) showed RER+ in comparison with 9 out of 44 (20.5%) de novo cases. Similar rates were detected in MDS patients (2/2 therapy-related and 1/12 de novo). The promoter hypermethylation was found in three hMLH1 (3.7%) and two hMSH2 (2.4%) genes. All these five patients had AML and were older than 60 years of age. Two of them had s-AML and one had t-AML. RER+ was detected in three of these five patients. Our data suggest that genetic instability is associated with AML and MDS, especially t-AML and s-AML. In addition, our results indicate that the hMSH2 and hMLH1 promoter hypermethylation is not a common event in these malignancies, but may play a role in the development of AML in elderly patients.

Acute Disease↗

PubMed2002

Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability.

The colorectum and uterine endometrium are the two most commonly affected organs in hereditary nonpolyposis colon cancer (HNPCC), but the genetic basis of organ selection is poorly understood. As tumorigenesis in HNPCC is driven by deficient DNA mismatch repair (MMR), we compared its typical consequence, instability at microsatellite sequences, in colorectal and endometrial cancers from patients with identical predisposing mutations in the MMR genes MLH1 or MSH2. Analysis of non-coding (BAT25, BAT26, and BAT40) and coding mononucleotide repeats (MSH6, MSH3, MLH3, BAX, IGF2R, TGF beta RII, and PTEN), as well as MLH1- and MSH2-linked dinucleotide repeats (D3S1611 and CA7) revealed significant differences, both quantitative and qualitative, between the two tumor types. Whereas colorectal cancers displayed a predominant pattern consisting of instability at the BAT loci (in 89% of tumors), TGF beta RII (73%), dinucleotide repeats (70%), MSH3 (43%), and BAX (30%), no such single pattern was discernible in endometrial cancers. Instead, the pattern was more heterogeneous and involved a lower proportion of unstable markers per tumor (mean 0.27 for endometrial cancers versus 0.45 for colorectal cancers, P < 0.001) and shorter allelic shifts for BAT markers (average 5.1 bp for unstable endometrial cancers versus 9.3 bp for colorectal cancers, P < 0.001). Among the individual putative "target" loci, PTEN instability was associated with endometrial cancers and TGF beta RII instability with colon cancers. The different instability profiles in endometrial and colorectal cancers despite identical genetic predisposition underlines organ-specific differences that may be important determinants of the HNPCC tumor spectrum.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Detection of microsatellite instability in sporadic cardiac myxomas.

OBJECTIVE: Microsatellite instability (MIN) is an early event in DNA repair-deficient associated diseases and reflects an elevated mutation rate in the genome of neoplastic cells. Sporadic cardiac myxomas are the most common primary heart tumours and their aetiopathology remains obscure. This study investigates the incidence of MIN in sporadic cardiac myxomas as a possible genetic mechanism of tumour pathogenesis. METHODS: Eleven surgically excised sporadic cardiac myxomas were assessed for MI using twenty-two highly polymorphic microsatellite markers, located on a wide range of chromosomal arms. DNA was extracted from myxoma tissue specimens as well as the respective normal tissue and subjected to polymerase chain reaction. RESULTS: The microsatellite analysis revealed that seven myxoma specimens (64%) exhibited MIN in at least one marker. One tumour specimen exhibited evidence of MIN in four microsatellite markers, while the most frequently affected marker was D17S855 (27%), located on chromosome 17q. DISCUSSION: We have detected a considerable incidence of MIN in sporadic cardiac myxomas indicating that decreased fidelity in DNA replication and repair is common in these tumours. To the best of our knowledge this is the first report describing MIN in sporadic cardiac myxomas, as a possible pathogenetic mechanism of these rare neoplasms.

Adult↗

PubMed1996

Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes.

To date, at least four genes involved in DNA mismatch repair (MMR) have been demonstrated to be altered in the germline of patients with hereditary nonpolyposis colon cancer: hMSH2, hMLH1, hPMS1, and hPMS2. Additionally, loss of MMR function has been demonstrated to lead to the phenomenon of microsatellite instability (MIN) in tumors from these patients. In this study, we have examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in paraffin-embedded tumors from 7 patients with MIN+ sporadic cancer, 13 patients with familial colorectal cancer, and 12 patients meeting the strict Amsterdam criteria for hereditary nonpolyposis colon cancer. The relationship between the expression of these two gene products, the presence of germline or somatic mutations, and the presence of tumor MIN was examined. Nineteen of the 28 tumors studied demonstrated MIN, whereas mutations in hMLH1 and hMSH2 were detected in 6 and 2 patients, respectively. Of the eight MIN+/mutation+ cases, the absence of protein expression was observed for the corresponding gene product in all but one case (missense mutation in hMLH1). However, seven MIN+/mutation- cases also showed no expression of either hMLH1 (n = 5), hMSH2 (n = 1), or both (n = 1), whereas four MIN+/mutation- cases demonstrated normal expression for both. None of the MIN-/mutation- cases (n = 9) demonstrated an altered expression pattern for either protein. These data suggest that examination of protein expression by immunohistochemistry may be a rapid method for prescreening tumors for mutations in the MMR genes.

Adaptor Proteins, Signal Transducing↗

PubMed1999

A case of multiple sebaceous epithelioma: analysis of microsatellite instability.

Sebaceous gland tumor is a rare disease that is a sign of Muir-Torre syndrome, an autosomal, dominantly inherited genodermatosis characterized by the presence of at least one sebaceous gland tumor and a minimum of one internal malignancy. Recent studies have indicated that defective DNA mismatch repair occurs in Muir-Torre syndrome. Cutaneous lesions may occur before diagnosis of the internal cancer. We describe a 64-year-old male patient with multiple sebaceous epitheliomas with no evident internal malignancy. Microsatellite instability, determined by examining dinucleotide CA repeats at the microsatellite loci, was observed in DNA from one sebaceous epithelioma but not from the other two sebaceous epitheliomas or from one basal cell epithelioma with sebaceous differentiation, suggesting that this condition is unlikely to be due to germ-line mutation of mismatch repair genes.

Adenocarcinoma, Sebaceous↗

PubMed2004

[Clinical analysis and molecular genetic study of hereditary nonpolyposis colorectal cancer kindreds].

OBJECTIVE: To study the clinicopathological and molecular genetic characteristics of hereditary nonpolyposis colorectal cancer (HNPCC), to enable the early diagnosis and to evaluate the treatment. METHODS: We analyzed 12 families of HNPCC from Wenzhou, Zhejiang province, China. Mismatch repair genes hMSH2 and hMLH1 expression and microsatellite instability of tumor tissue were studied using microdissection, microsatellite analysis, immunohistochemical staining and Gene Scan analysis. Direct DNA sequencing of hMSH2 and hMLH1 were performed subsequently. RESULTS: Altogether 32 patients with colorectal cancer were recognized in 12 HNPCC families, with the median age of 45.2 years (75.0% before the age of 50 years). The proximal tumors accounted for 51.1%, while multiple colorectal cancers accounted for 34.4%. Poor differentiation cancers occupied half of the patients (53.1%). And 68.8% of the patients had the tumor of Dukes A and B. Among 12 HNPCC families, 7 cases in 6 HNPCC families developed extracolonic cancer. 13 cases died during follow up of 1 - 23 years. The median survival time was 6.4 years. 19 alive cases followed up from 1 to 28 years. All tumors (9/9) displayed microsatellite instability, with the half losing hMSH2 or hMLH1 expression. In the 5 genetic analyzed kindreds 3 possessed germline mutation. Two of three mutations have not been reported in the worldwide database previously. CONCLUSION: HNPCC showed distinct clinicopathological characteristics. Microsatellite instability analysis and immunohistochemical staining might be the effective screening methods before direct DNA sequencing for the detection of mutation in mismatch repair genes. It is important to analyze the members of affected families.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Microsatellite instability is uncommon in breast cancer.

In some tumors, defects in mismatch repair enzymes lead to errors in the replication of simple nucleotide repeat segments. This condition is commonly known as microsatellite instability (MSI) because of the frequent mutations of microsatellite sequences. Although the MSI phenotype is well recognized in some colon, gastric, pancreatic, and endometrial cancers, reports of MSI in breast cancer are inconsistent. We report here our experience with >10,000 amplifications of simple nucleotide repeats in noncoding genomic regions using DNA from 267 cases of breast cancer, including cases that represent all major histological types of breast cancer. We rarely (10 reactions) found unexpected bands in amplifications of tumor DNA that were not present in amplifications of normal DNA. Moreover, repeats of these reactions did not confirm microsatellite instability in a single case. We also evaluated the simple nucleotide repeats in the transforming growth factor type II receptor, insulin-like growth factor type II receptor, BAX, and E2F-4 genes, which are frequently mutated in tumors with microsatellite instability. No mutations of these genes were found in any of the 30 breast cancer cell lines and 61 primary breast cancer samples examined. These results indicate that mismatch repair errors characteristic of the MSI phenotype are uncommon in human breast cancer.

Breast Neoplasms↗

PubMedDate not supplied

Testing tumors for microsatellite instability.

The methods for determining microsatellite instability in tumors are highly heterogeneous. Recently a 5-marker panel of microsatellites was suggested for this purpose. In this review attention is drawn to the fact that microsatellite instability can be assessed by analyzing tumor DNA with a single marker, BAT-26, and that normal tissue DNA from the same individual needs to be analyzed only when an aberrant allele is seen in the tumor. Whilst this simple procedure does not distinguish between different types and degrees of instability, it should be sufficient for many purposes, such as screening colorectal cancers for mismatch repair deficiency.

Base Pair Mismatch↗

PubMed2006

DNA mismatch repair and Lynch syndrome.

The evolutionary conserved mismatch repair proteins correct a wide range of DNA replication errors. Their importance as guardians of genetic integrity is reflected by the tremendous decrease of replication fidelity (two to three orders of magnitude) conferred by their loss. Germline mutations in mismatch repair genes, predominantly MSH2 and MLH1, have been found to underlie the Lynch syndrome (also called hereditary non-polyposis colorectal cancer, HNPCC), a hereditary predisposition for cancer. Lynch syndrome affects predominantly the colon and accounts for 2-5% of all colon cancer cases. During more than 30 years of biochemical, crystallographic and clinical research, deep insight has been achieved in the function of mismatch repair and the diseases that are associated with its loss. We review the biochemistry of mismatch repair and also introduce the clinical, diagnostic and genetic aspects of Lynch syndrome.

Adenosine Triphosphatases↗

PubMed1996

DNA alterations in sporadic colorectal tumors do not correlate with tumor staging diagnosed by the TNM system.

Blood normal and tumor tissue samples of 23 patients with sporadic colorectal tumors were screened for DNA alterations in the tumor relevant genes APC, K-ras, DCC and p53. Six different microsatellite regions were analyzed for instability by a new developed non-radioactive method. Somatic DNA alterations were found in 17 tumor samples: 13 carried single or multiple changes in single genes; six carried alterations in microsatellites; two tumors showed tumor suppressor gene mutations in addition to microsatellite changes. We found no indications of correlations between current genetic models of colorectal tumor progression and the established TNM system for histopathological tumor classification.

Aged↗

PubMed2000

Molecular profiling of sporadic colorectal tumors by microsatellite analysis.

To investigate the prognostic value of multiple genetic alterations, individual molecular tumor profiles were established in 79 sporadic colorectal carcinomas (41 stage II and 38 stage III). Tumors were analyzed for allelic loss (LOH) and genetic instability (MSI) using 14 microsatellites intragenic to or associated with tumor suppressor or DNA mismatch repair genes. Molecular profiling identified tumors with LOH at multiple loci without microsatellite instability (MSS), tumors with high levels of LOH and low level microsatellite marker instability (MSI-L), and tumors with high levels of MSI (MSI-H), but rare LOH. K-ras mutations occurred more frequently in MSS/MSI-L carcinomas (26%) than in MSI-H colorectal tumors (10%), the latter showing a high frequency of TGFbeta type II frameshift mutations (82%). Correlation of molecular and clinical data revealed a better prognosis for stage III tumor patients displaying 5q12 loss rather than retention of heterozygosity. Thus, molecular profiling allows the identification of new prognostic markers and might facilitate the stratification of colorectal cancer patients.

Adult↗

PubMed2001

Frequent alterations of the beta-catenin and TCF-4 genes, but not of the APC gene, in colon cancers with high-frequency microsatellite instability.

High-frequency microsatellite instability (MSI-H) due to defective DNA mismatch repair (MMR) is a characteristic of the majority of tumors from kindreds with hereditary nonpolyposis colorectal cancer (HNPCC) and a subset of sporadic cancers. To better understand the molecular characteristics of colon cancers with MSI-H, we analyzed these cancers for alterations of genes, such as APC, beta-catenin, and TCF-4 genes, involved in the Wnt signaling pathway. Following the National Cancer Institute (NCI) criteria, 385 unselected colon cancers were classified as follows: 50 (13%) MSI-H tumors, 36 (9%) low-frequency MSI (MSI-L) tumors, and 299 (78%) microsatellite stable (MSS) tumors. The frequency of APC mutations was significantly lower in MSI-H tumors (9 out of 50) than in MSI-L (12 out of 20) and MSS (66 out of 100) tumors (P = 0.0005 and P < 0.0001, respectively). In contrast, the frequency of exon 3 mutations in the beta-catenin gene was higher in MSI-H tumors (10 out of 50) than in MSI-L tumors (0 out of 30; P = 0.0110) and MSS tumors (3 out of 100; P = 0.0010). Frameshift mutations in a (A)9 tract of the TCF-4 gene were detected in 44% (22 out of 50) of MSI-H tumors, but not in any of the 20 MSI-L tumors or 40 MSS tumors. In total, 78% of MSI-H tumors and 84% of the remaining tumors had at least one alteration in APC, beta-catenin, or the TCF-4 genes. Although further analysis is needed to functionally characterize the consequences of each of these alterations on beta-catenin/TCF target gene expression, our results suggest that the activation of the Wnt signaling pathway plays a pivotal role in colon tumorigenesis, irrespective of MSI status.

Adenocarcinoma↗

PubMed1999

Allelic imbalance and microsatellite instability in chromosomes 2p, 3p, 5q, and 18q in esophageal squamous carcinoma in patients from South Africa.

Microsatellite polymerase chain reaction (PCR) and fluorescent DNA technology was used to assess allelic imbalance (AI) or loss of heterozygosity (LOH) and microsatellite instability (MSI) in chromosomes 2p, 3p, 5q, and 18q in esophagectomy specimens from 39 patients who had squamous carcinoma and who lived in a high-incidence geographic location in South Africa. The squamous carcinomas were graded by conventional light microscopy and staged using the tumor-node-metastasis (TNM)-Union Internationale Contre Le Cancer (UICC) criteria. The DNA was isolated using proteinase K digestion and standard phenol-chloroform extraction procedure. Microsatellite PCR was performed using fluorescent, CY5-labeled primers for the following markers: D2S123 (2p), D3S659 (3p), D3S1255 (3p), D5S346 (5q), DCC (18q), D18S34 (18q), and D18S58 (18q). These markers were chosen because they are the most frequently used and most informative markers for these particular gene loci. Results were analyzed using software attached to an automated DNA sequencer. Molecular changes obtained were correlated with clinicopathologic parameters. Molecular analysis did not correlate with clinicopathologic features, such as tumor grade, stage, or lymph node status. No correlation with patient outcome was seen, though only limited follow-ups were obtained. Rates of MSI and LOH on 3p and 18q in these specimens are similar to the range seen in studies from other geographic areas. However, a striking point of departure is the high LOH (30% of informative cases) seen on 2p.

Adult↗