Analysis of microsatellite instability and loss of heterozygosity in uterine endometrial adenocarcinoma

Microsatellite instability (MSI) and loss of heterozygosity (LOH) were examined in 60 cases of uterine endometrial adenocarcinoma, using 13 microsatellite markers. In non-Smad-related regions, MSI and LOH were noted in 13 of 60 (21.7%) and in 20 of 60 (33.3%) cases, respectively. Genetic alternation of TGF-beta RII was noted in 1 of 60 cases (1.7%). The frequency of MSI and LOH was highest in Stages III and IV, respectively. Cases with G2 carcinoma showed the highest frequency, but LOH frequency did not differ among G1, G2, and G3 carcinoma cases. In Smad-related microsatellite regions, MSI and LOH were noted in 10 of 60 (16.7%) and in 12 of 60 (20.0%) cases, respectively. The frequency of MSI and LOH was highest in Stages III and IV, respectively. LOH was seen only in the Smad2 gene but not in the Smad4 gene. Our results suggest that the alterations in MSI and LOH were associated with middle and late stages of carcinogenesis of endometrial carcinoma. Both MSI and LOH tended to show an association with moderate to severe atypia of carcinoma. Our results also suggest that genetic alteration of the Smad2 gene is more responsible for endometrial carcinogenesis than that of the Smad4 gene. However, the TGF-beta type II receptor gene was considered a minor target of genetic instability in endometrial carcinogenesis.     

肝细胞癌肿瘤抑制基因的杂合性缺失和微卫星不稳定性研究

目的　了解肿瘤抑制基因(TSG)杂合性缺失(LOH)与微卫星不稳定性(MSI)在肝细胞癌发生机制中的作用,并探讨其临床病理学意义。方法　采用显微组织切割基础上的DNA直接测序法,从92例手术切除肝细胞癌中筛选出36例信息性肝细胞癌进行6种TSG(APC、DCC、MCC、OGG1、p53和RB1)的LOH检测,对其中15例肝细胞癌进行13个多态性微卫星位点的LOH和MSI检测,并与临床病理学参数的相关性进行统计学分析。结果　TSG的LOH总发生率为41 .7% (15 /36),仅MCC基因未出现LOH。15例肝细胞癌中有9例(60% )发生微卫星LOH,占检测微卫星的46 .2% (6 /13),但无1例肝细胞癌出现MSI。若将APC、OGG1和DCC基因LOH作为Ⅰ型(n=7 ),将p53和RB1基因LOH作为Ⅱ型(n=8)进行统计学处理,则两组肝细胞癌的平均瘤体直径分别为( 2. 9 ±1 .7)cm和(7 .2 ±3 .4)cm (P<0 .01),两组患者术后平均生存期分别为( 72. 0 ±38 6 )个月和(51 .0±30. 4)个月(P<0 .05 )。肝细胞癌基因变异型与患者的年龄、性别、血清甲胎蛋白水平、HBsAg阳性率、合并肝炎/肝硬化、肝细胞癌分化程度和组织学类型之间无明显相关性。结论　在肝细胞癌发生的多阶段演进与多基因变异过程中,LOH路径所起的作用要比MSI路径更大。Ⅰ型基因变异(APC、OGG1和DCC)主要在肝细胞癌早期阶段起作     

beta-Catenin expression pattern, beta-catenin gene mutations, and microsatellite instability in endometrioid ovarian carcinomas and synchronous endometrial carcinomas.

beta-Catenin gene mutations and microsatellite instability (MI) have been reported in endometrioid ovarian carcinomas. In colon but not endometrial cancer, beta-catenin gene mutations are associated with a replication error phenotype and MI. In this study the authors investigate whether beta-catenin mutations and MI are two independent oncogenic pathways in endometrioid ovarian carcinomas. They also evaluate the usefulness of these molecular markers in determining the primary origin of simultaneous tumors in the ovary and endometrium. This study was performed on 26 patients diagnosed with primary endometrioid ovarian carcinoma, five of whom also had pathologically diagnosed primary synchronous endometrioid endometrial carcinoma. Immunohistochemical and molecular analyses indicated that there were 25 primary ovarian tumors with four primary synchronous endometrial cancers and one ovarian metastasis of a primary endometrial carcinoma. All studies were performed on formalin-fixed, paraffin-embedded tissue samples. The beta-catenin expression pattern (nuclear vs. membranous) was analyzed immunohistochemically. Mutations in exon 3 of the beta-catenin gene were studied by polymerase chain reaction, single-strand conformational polymorphism, and direct sequencing. MI status was established by studying BAT-26 and BAT-25 mononucleotide repeats. In the group with 21 single ovarian tumors, 18 (85%) had beta-catenin nuclear expression, eight (38%) had beta-catenin gene mutations (always associated with beta-catenin nuclear expression), and four (19%) had MI. Only one case (5%) had both beta-catenin gene mutations and MI. The mutations affected one of the serine/threonine residues targeted for phosphorylation by glycogen synthase kinase-3beta or adjacent residues. At codon 32, a GAC-to-TAC (D32Y) change was found; at codon 33, two TCT-to-TGT (S33C) changes were found; at codon 37, three TCT-to-TTT (S37F) changes and one TCT-to-TGT (S37C) change were found; and, lastly, one ACC-to-GCC change at codon 41 (T41A) was detected. Four of the 25 endometrioid ovarian carcinomas (16%) had an associated synchronous endometrial carcinoma. There was a higher percentage of beta-catenin mutations (n = 3, 75%) in synchronous ovarian carcinomas than in single ones, although with a similar percentage of MI (n = 1, 25%). beta-catenin mutations were S37C in two cases and D32G in one. One of the four endometrial carcinomas showed an S33C beta-catenin mutation, and two carcinomas had MI. None of the four tumors had both beta-catenin gene mutation and MI. beta-catenin gene mutations were always associated with a nuclear beta-catenin expression pattern, whereas MI was associated with a membranous pattern. In one patient both the ovarian and the endometrial carcinomas had beta-catenin gene mutations, in another patient both tumors showed MI, whereas in the remaining two patients the ovarian carcinomas showed beta-catenin gene mutations and the endometrial carcinomas showed MI. To summarize, the results of this study suggest that beta-catenin mutations and MI could represent two independent pathways in endometrioid ovarian carcinomas because they occur simultaneously very infrequently (in 5% of these cases). beta-catenin mutations are always associated with a nuclear beta-catenin expression pattern, whereas cases with a replication error -plus phenotype showed no abnormal beta-catenin subcellular localization. The study of the beta-catenin expression pattern, beta-catenin mutations, and MI, together with conventional clinicopathologic findings, could aid in distinguishing between the metastatic or independent origin of simultaneous endometrioid ovarian and endometrial carcinomas. Tumors with identical immunohistochemical and molecular features should therefore be considered to have a common origin.     

Screening for loss of heterozygosity and microsatellite instability in oligodendrogliomas

To assess the frequency of loss of heterozygosity (LOH) and microsatellite instability (MI) in oligodendrogliomas, we performed an extensive screening of 16 oligodendrogliomas and nine anaplastic oligodendrogliomas by using 132 microsatellite markers on chromosomes 1 through 12 and 15 through 21. In total, 3,135 loci were examined in 25 tumor samples. Only 33/1,965 (1.7%) of oligodendroglioma (low-grade) and 11/1,070 (1.0%) of anaplastic oligodendroglioma (high-grade) loci exhibited MI. High-frequency LOH regions were identified on chromosome arms 1p (31–73% for oligodendrogliomas and 60–100% for anaplastic oligodendrogliomas) and 19q (23–69% for oligodendrogliomas and 100% for anaplastic oligodendrogliomas). In addition, regions on chromosomes 4, 6, and 11 were found to be lost in 30–80% of both oligodendrogliomas and anaplastic oligodendrogliomas. Increased LOH frequency of chromosome 17 (38–40%) was found only in high-grade oligodendrogliomas. The differences in LOH frequencies between low-grade and high-grade oligodendrogliomas in all loci combined and at three loci (D1S447, D1S226, and D1S252) on chromosome arm 1p were determined to be statistically significant [χ²(1) = 20.2, P < 0.0001, and Fisher's exact test respective P values: 0.01, 0.03, and 0.02]. Our results provide evidence that microsatellite instability does not play an important role in the development of oligodendrogliomas. Furthermore, high LOH frequency on chromosomes 6 and 11 in addition to that identified previously on chromosomes 1, 19, and 4 suggests that multiple candidate tumor suppressor genes on these chromosomes may underlie the processes of initiation and/or progression in oligodendroglioma tumorigenesis. Genes Chromosomes Cancer 21:207–216, 1998. © 1998 Wiley-Liss, Inc.     

Molecular genetic alterations in endometrioid carcinomas of the ovary: similar frequency of beta-catenin abnormalities but lower rate of microsatellite instability and PTEN alterations than in uterine endometrioid carcinomas

Endometrioid carcinomas of the ovary closely resemble their uterine counterparts. It has been suggested that the former tumors have the same molecular alterations (microsatellite instability [MSI], PTEN, and beta-catenin) described in endometrioid carcinomas of the uterus. We analyzed 55 ovarian carcinomas, including 22 endometrioid, 18 clear cell, and 15 mixed types. MSI was detected in 5 of 39 cases (13%). MLH1 promoter hypermethylation was identified in 2 of the 5 MSI-positive tumors. PTEN was mutated in 5 of 54 cases (9%); of these, 3 had MSI and exhibited frameshift mutations in short-coding mononucleotide repeats. Beta-catenin nuclear expression was detected in 11 of 54 cases (20%) by immunostaining; of these, 7 exhibited CTNNB1 gene mutations. These alterations were found more frequently in endometrioid carcinomas than in tumors of the other 2 groups. Among the former tumors, MSI was detected in 3 of 17 cases (17.5%); PTEN mutations, in 3 of 21 (14%); and beta-catenin, in 8 of 21 (38%). The molecular alterations were found more often in tumors associated with endometriosis than in tumors without endometriosis. Six endometrioid tumors demonstrating matrix metalloproteinase-7 (MMP-7) immunoreactivity with nuclear accumulation of beta-catenin had good outcomes, in contrast to poor outcomes in 7 of 9 predominantly nonendometrioid tumors demonstrating expression of MMP-7 only. We found a similar frequency of beta-catenin abnormalities but lower rates of MSI and PTEN alterations than in uterine endometrioid carcinomas. Alterations in beta-catenin and PTEN genes, as well as MSI, are frequent in low-stage ovarian carcinomas of endometrioid type that have a favorable prognosis.     

Analysis of microsatellite instability and loss of heterozygosity in human aortic atherosclerotic lesions

The aim of the present study is to investigate whether microsatellite instability (MSI) and loss of heterozygosity (LOH) are involved in atherogenesis. Paraffin-embedded tissues of thoracic and abdominal aortas were collected from 29 non-neoplastic autopsied cases. We selected two types of atherosclerotic lesions including fibrocellular intimal thickening and uncomplicated atheromatous lesions, and analyzed two sites such as the aortic tunica intima and tunica media in each case. The frequencies of MSI and LOH were highest in the aortic tunica intima of atheromatous lesions and lowest in the aortic tunica media of fibrocellular intimal thickening lesions. Our results suggest that genetic instabilities such as MSI and LOH may be involved in the development of atherosclerotic lesions.     

头颈部鳞癌的微卫星不稳定性和杂合性丢失的初步研究

目的:探讨头颈部鳞癌的微卫星不稳定性(MSI)及杂合性丢失(LOH)。方法:选择来自3、5、6、8、9、13、17和18号染色体的15个微卫星标志对36例头颈部鳞癌标本和相应的外周血进行微卫星分析。结果:36例头颈部鳞癌中,27.8%(10/36)分别有1-8个位点存在MSI,MSI发生率较高的位点为:D17S520(22.9%)、D6S105(16.7%)和D8S264(13.9%)。在9p21-p22和3p14等处存在一定的LOH。微卫星异常的检出率与肿瘤分期、分级无相关性。结论:提示MSI是头颈部鳞癌中较为常见的遗传学变化,染色体9p21-p22和3p14区域可能存在与头颈部鳞癌有关的抑癌基因。     

喉癌p16区域的杂合性丢失和微卫星序列不稳定性分析

目的 缩小喉癌抑癌基因的寻找范围,探讨Ｐ１６基因在喉癌发生中的作用。方法 选择Ｐ１６基因附近５个微卫星多态标记对６０例喉癌进行杂合性丢失和微卫星序列不稳定性分析。结果 ５个标记在喉癌中杂合性丢失频率均不高,最高仅达２３．１％,但２个标记的微卫星序列不稳定性的频率较高,其中示记微卫星序列恶性循环频率高达４６．１％。结论 提示Ｐ１６基因在喉癌的发生中不以缺失为主,在Ｄ９Ｓ１７５２附近可能存在参与喉癌演     

WT-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma

AIMS: It has been suggested that WT-1 is helpful in distinguishing a primary ovarian serous carcinoma (OSC) from a primary uterine serous carcinoma (USC). Since both neoplasms are often disseminated at diagnosis and since USC often spreads to the ovary and vice versa, it may be difficult to ascertain the primary site. This is important, since adjuvant therapies for OSC and USC may differ. WT-1 staining patterns also differ between OSC and ovarian endometrioid carcinoma and so it is possible that WT-1 may assist in the distinction of these two neoplasms, which is sometimes problematic, especially with poorly differentiated tumours. This study aims to document the value of WT-1 in these settings. Cases of ovarian borderline serous tumour, primary peritoneal serous carcinoma (PPSC) and uterine endometrioid carcinoma were also studied. METHODS AND RESULTS: Cases of OSC (n = 38), USC (n = 25) (in five of these cases there was also a component of endometrioid adenocarcinoma), ovarian endometrioid carcinoma (n = 13), uterine endometrioid carcinoma (n = 7), ovarian borderline serous tumour (n = 16) and PPSC (n = 6) were stained with WT-1. Cases were scored on a scale of 0-3, depending on the percentage of positive cells. The intensity of staining was scored as weak, moderate or strong. There was positive nuclear staining of 36 of 38 (94.7%) OSC with WT-1. In most OSC (68.4%), >50% of cells stained positively and staining was usually strong. Five of 25 (20%) USC were positive with only two cases exhibiting staining of >50% of cells. All primary ovarian and uterine endometrioid carcinomas were negative. All PPSC were positive, usually with diffuse strong immunoreactivity. Fourteen of 16 borderline serous tumours exhibited positivity with WT-1. CONCLUSIONS: WT-1 is useful in distinguishing OSC (characteristically diffuse strong nuclear positivity) from USC (characteristically negative). However, rarely OSC is negative and occasional cases of USC are positive. WT-1 may also be helpful in differentiating poorly differentiated OSC from poorly differentiated ovarian endometrioid carcinoma.     

Microsatellite instability, loss of heterozygosity, and loss of hMLH1 and hMSH2 protein expression in endometrial carcinoma

Microsatellite instability (MSI) due to replication errors occurs frequently in hereditary tumors. Association with functional inactivation of the mismatch repair (MMR) genes and lack of protein expression has been described. In endometrial carcinoma (EC), the prevalence and clinical significance of these phenomena are not well known. Therefore, DNA samples from 89 EC and 5 metachronous tumors were analyzed with polymerase chain reaction, using 5 microsatellite markers and a DNA sequencer for amplicon detection. The results were correlated with immunohistochemistry of hMLH1 and hMSH2. MSI at >or=2 loci (MSI-H) was detected in 10/89 EC (11%); 1 of 10 showed loss of both hMLH1 and hMSH2, and 5 of 10 showed loss of hMLH1 (P < 0.0001). MSI-H was observed frequently in tumors with mucinous differentiation (P = 0.048), >10% of solid-cribriform pattern (P = 0.037), International Federation of Obstetrics and Gynecology (FIGO) stage III to IV (4 of 13; P = 0.016), and necrosis >5% (P = 0.07). Loss of heterozygosity (LOH) in >or=1 loci was found in 17 of 156 (11%). Survival (Kaplan-Meier) was longer for patients with endometrioid tumors with predominant glandular pattern, <5% necrosis, low FIGO stage and grade, superficial myometrial infiltration, no lymph-vascular invasion (LVI), and loss of hMLH1 expression (all P 相似文献   

No evidence of microsatellite instability but frequent loss of heterozygosity in primary resected lung cancer

We examined microsatellite instability and loss of heterozygosity (LOH) in primary lung tumors from 93 cancer patients, using 16 microsatellite markers. The cases studied included 87 non-small-cell lung cancers (NSCLC) and six small-cell lung cancers (SCLC). All the patients except two were current or former smokers. The microsatellite markers were all dinucleotide repeat sequences from chromosomal locations 1p, 3p, 5q, 8p, 9p, 10p, 11p, 13q, and 17q. None of the tumors showed microsatellite instability (0/93). In NSCLC, 28% (24/87) of the cases showed LOH in at least one locus, whereas, in SCLC, 67% (4/6) had allelic losses. The frequency of LOH differed between the various cell types of NSCLC. The highest frequency was seen in large cell carcinoma (3/6, 50%) followed by squamous cell carcinoma (16/43, 37%) and adenocarcinoma (5/35, 14%). The most common site of LOH was 3p, where markers D3S1284, D3S659, D3S1289, D3S966, D3S647, and D3S1038 were studied. LOH, studied with 9p markers (D9S126, D9S171, D9S162), was less common. The present results, together with earlier reports, suggest that smoking-related primary lung cancers seldom show microsatellite instability but are characterized by frequent LOH. Environ. Mol. Mutagen. 30:217–223, 1997. © 1997 Wiley-Liss, Inc.     

Frequent microsatellite instability in synchronous ovarian and endometrial adenocarcinoma and its usefulness for differential diagnosis

Synchronous tumors of the ovary and endometrium are a well-known phenomenon. There are histological criteria for defining double primary tumors or metastasis from one organ to another, but in some cases a precise diagnosis is difficult. In this study we reviewed 17 cases of synchronous ovarian and endometrial adenocarcinoma by previously reported histological criteria and performed a microsatellite analysis, combined with X-linked clonality analysis. We also analyzed 8 cases of endometrial adenocarcinoma with pelvic lymph node metastasis as a control. Five dinucleotide microsatellite markers were selected, and microsatellite analysis was performed by a high-resolution method using fluorescence-labeled polymerase chain reaction and laser scanning. In synchronous tumors, 11 ovarian carcinomas (65%) and 10 endometrial carcinomas (59%)demonstrated microsatellite instability (MSI). In total, 13 of the 17 patients demonstrated MSI in the ovarian tumor, the endometrial tumor, or both. Four cases of endometrial carcinoma with pelvic lymph nodes metastases displayed MSI, and MSI findings of the endometrial tumor and lymph node metastasis were same in all cases. Based on these findings, we considered that similar MSI findings indicate metastatic tumors. According to the MSI findings, 13 of the 17 patients (76%) had single or double clonal tumors, 11 (67%) with double primary tumors and 2 (13%) with metastatic tumors. Using X-linked clonality analysis, 3 patients were diagnosed with double primary tumors. The molecular diagnosis corresponded with the histological criteria in all but 1 case. In conclusion, using both MSI and X-linked clonality analysis, most patients (82%) could be diagnosed as having single or double clonal tumors. The histological criteria are accurate and useful in most cases; however, in some cases where the relationship between the 2 tumors is difficult to determine, high-resolution MSI analysis may be helpful.     

Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach

Adenocarcinoma of the gastroesophageal junction is rapidly rising in incidence. It has been proposed that these tumors be classified as three different types: distal esophageal (AEG I), cardia (AEG II), and subcardia (AEG III). Using comparative genomic hybridization (CGH) analysis, one recent study reported that the 14q chromosomal arm showed a significantly higher rate of deletion in esophageal than in cardia adenocarcinoma. Using a microsatellite analysis technique, we analyzed this area and regions in the vicinity of the APC, DCC, and p53 genes. Tumor and normal tissues were microdissected from 54 cases (27 AEG I and 27 AEG III). DNA was extracted and then amplified using seven fluorescent-labeled microsatellite markers, one pair each on 5q, 18q, and 17p and four on 14q. The results were analyzed for loss of heterozygosity (LOH) and microsatellite instability (MSI). LOH varied from 20% to 30% at each locus except for the 17p locus, where it was slightly above 50% in both groups. No significant differences in LOH or MSI were found between the esophageal and gastric tumors, including the 14q chromosomal arm. These results fail to confirm the finding that abnormalities on the 14q chromosomal arm distinguish between distal esophageal and proximal gastric tumors.     

胃癌p53基因突变与微卫星DNA不稳定性关系的研究

目的 探讨术前不同分期的胃癌ｐ５３基因突变与微卫星ＤＮＡ不稳定性（ｍｉｃｒｏｓａｔｅｌｌｉｔｅ ｉｎｓｔａｂｉｌｉｔｙ,ＭＳＩ）的变化及其相互关系。方法 应用超声内境（ｅｎｄｏｓｃｏｐｉｃ ｕｌｔｒａｓｏｎｏｇｒａｐｈｙ,ＥＵＳ）对７３例胃癌患者行术前分期,同时采用银染ＰＣＲ－ＳＳＣＰ方法检测仙镜活检组织标本ｐ５３基因突变及ＭＳＩ。结果 ｐ５３基因总突变率为５４．８％;Ｔ３期（６４．３％）和Ｔ４期     

Infrequent loss of heterozygosity of APC/MCC and DCC genes in gastric cancer showing DNA microsatellite instability

AIM: To investigate the role of DNA microsatellite instability (MSI) in gastric carcinogenesis by studying associations between MSI status, clinicopathological features, and loss of genetic loci. METHODS: Six microsatellite loci and loss of heterozygosity at APC, DCC, and MCC were analysed by polymerase chain reaction based methods in 53 cases of advanced gastric cancer. RESULTS: MSI was observed in 32.1% of gastric carcinomas (17/53) and 20% of foci of intestinal metaplasia (3/15). Seven gastric carcinomas (13.7%) were MSI-high (MSI-H) (three loci or more) and 10 (18.9%) were MSI-low (MSI-L) (one or two loci). The frequency of MSI-H was higher in intestinal (25.0%) than in diffuse carcinomas (3.7%) (p < 0.05). None of the MSI-H tumours showed loss of heterozygosity at APC, MCC, or DCC loci. CONCLUSIONS: MSI may have an important and early role in a subset of gastric cancers, particularly the intestinal type. The MSI-H subset of gastric cancer has features in common with its colorectal counterpart, whereas MSI-L and microsatellite stable cancers appear to develop through the loss of heterozygosity pathway.     

Independent endometrial and ovarian carcinomas: two cases of synchronous and metachronous endometrioid carcinomas

Simultaneous carcinomas involving both the ovary and the endometrium may cause diagnostic difficulties, particularly if the tumors have a similar histology. We report two cases of independent endometrioid carcinomas of the endometrium and the ovary. Tumor development was synchronous in one case and metachronous in the other. These cases illustrate the morphological criteria helpful in distinguishing independent primaries from metastatic carcinomas which have a different therapeutic implication. Endometrial tumors were intra-mucosal without myometrial or vascular invasion, or tubal involvement and were associated with atypical complex hyperplasia (case 2). The ovarian tumors were uninodular, unilateral, without hilar invasion and were associated with endometriosis (case 2). The prognosis of endometrioid type carcinomas is better than for other histological types of carcinoma. Both our patients are well and disease free at 27 and 24 months.     

The loss of heterozygosity and microsatellite instability analysis in differential diagnostics of leiomyosarcoma and proliferative leiomyoma of the uterus

Uterine leiomyosarcoma (ULMS) is rare and highly malignant smooth muscle tumor. The different diagnosis between uterine leiomyoma with high proliferative index (ULM) and ULMS is one of the basic problems in the pathology for nowadays. We had investigated the loss of heterozygosity (LOH) and microsatellite instability (MI) to find out a genetic differences between ULM and ULMS. The inicrosatellite analysis was evaluated by PCR using 6 polymorphic markers for chromosomal regions 10q22.1 (D10S1146, D010S218), 10q26.13 (D10S1213), 10p13 (D10S24), 9p21.3 (D9S942), 3p14.3 (D3S1295) in 20 patients with ULMS. 38 patients with ULM were suggested as control group. Our results have demonstrated high frequency allelic imbalance in ULMS samples (average frequency 40%). The comparative analysis between 2 studied groups of patients has been shown higher frequencies of genetic changes for ULMS. Specificity and sensitivity of the LOH and/or MI markers scores 92 and 95% accordingly.     

Low microsatellite instability and high loss of heterozygosity rates indicate dominant role of the suppressor pathway in squamous cell carcinoma of head and neck and loss of heterozygosity of 11q14.3 correlates with tumor grade

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been recognized as important events in squamous cell carcinoma of the head and neck (HNSCC), suggesting involvement of both suppressor and mutator pathways. We analyzed 153 HNSCC with 8 Bethesda reference panel markers and 14 microsatellite markers selected from chromosomal regions known to harbor either tumor-suppressor genes or oncogenes. A combination of multiplex fluorescence-based polymerase chain reaction and automatic fragment analysis was performed. LOH was observed in 78% of all tumors. 2% to 17% LOH frequency was observed with Bethesda reference panel markers comparing to higher 8% to 48% LOH in chromosomal areas 3p, 9p, 11q, and 17p. LOH of 11q14.3 correlated with tumor grade. The proportions of high- and low-MSI tumors were 3% and 10%, respectively, but no mutation was identified in MLH1 and MSH2 mismatch repair genes. These results indicate the dominant role of the suppressor in comparison with the mutator pathway in HNSCC carcinogenesis.