散发性大肠癌的错配修复缺陷研究

目的探讨错配修复缺陷的散发性大肠癌的临床病理特征及错配修复缺陷检测手段的应用。方法对71例散发性大肠癌行hMLH1启动子甲基化检测、微卫星不稳定检测以及hMLH1和hMSH2的免疫组化检测,分析错配修复缺陷的散发性大肠癌的临床病理特征,探讨三种检测方法的应用价值。结果hMLH1基因启动子甲基化、微卫星不稳定和错配修复蛋白表达的阳性率分别为9.9%,9.9%和71.0%,三者密切相关。hMLH1启动子甲基化和微卫星不稳定的散发性大肠癌均具有结肠癌多发和低分化腺癌相对多见的特征。错配修复蛋白表达阴性的散发性大肠癌仅具有低分化腺癌相对多见的特征。结论错配修复缺陷的散发性大肠癌具有结肠癌和低分化腺癌多发的倾向,hMLH1启动子甲基化和微卫星不稳定以及错配修复蛋白的失表达三者密切相关。     

散发性多原发大肠癌微卫星不稳定研究

[目的]研究散发性多原发大肠癌微卫星不稳定发生频率,探讨其与异时多原发大肠癌的发生及散发性多原发大肠癌患者预后的关系.[方法]对上海肿瘤医院1985年～2000年病理资料完整的70例散发性多原发大肠癌患者的124个存档蜡块,以及随访3年以上的35例散发性单原发大肠癌患者的肿瘤组织进行微卫星不稳定测定.PCR法检测BAT25、BAT26两个位点来判断肿瘤组织微卫星不稳定情况,两个位点均阳性作为判断微卫星不稳定标准.微卫星不稳定结果与临床病理参数之间的比较采用x2检验,生存分析采用Kaplan-Meier生存曲线、Log-Rank检验分析.P值＜0.05作为差异有统计学意义的界限.[结果]散发性多原发大肠癌中,25.8%的肿瘤表现高度微卫星不稳定(MSI-H),单原发大肠癌为5.7%(25.8%vs.5.7%,P=0.01).其中同时多原发大肠癌MSI阳性率为15.6%,异时多原发大肠癌为36.7%(15.6%vs.36.7%,p=0.007);40岁以下,阳性率为53.8%,40岁以上为22.5%(53.8%vs.22.5%,P=0.015);右结肠阳性率为41.2%,左结肠阳性率为15.1%(41.2%vs.15.1%,P=0.001);Dukes'A、B、C、D期阳性率分别为25.0%、33.3%、22.2%、11.1%(P＞0.05);高、中、低分化腺癌及黏液腺癌分别为20.0%、25.9%、21.1%、31.6%(P＞0.05).70例患者平均随访61个月,MSI-H患者和MSS患者5年生存率分别为80.95%和57.14%(P＜0.05).[结论]MSI可以作为一个重要的独立的危险因素预测异时大肠癌的发生,亦可作为一个重要指标判断散发性多原发大肠癌患者的预后.     

应用流式细胞术探讨大肠癌细胞DNA倍体类型与预后的关系

目的探讨大肠癌细胞DNA倍体类型与预后的关系.方法应用流式细胞术对125例大肠癌术后标本的石蜡包埋组织块进行DNA含量分析.结果异倍体肿瘤占63.2%(79/125),二倍体肿瘤占36.8%(46/125).二倍体肿瘤的DNA含量明显低于异倍体肿瘤;二倍体肿瘤的G0/G1期细胞数明显高于异倍体肿瘤,而S、G2M期细胞数则明显低于异倍体肿瘤.大肠癌DNA倍体类型与病人一般临床病理特征如:年龄、性别、病理分级,Dukes分期等均无明显关系,但与病人的预后有明显的关系:二倍体肿瘤病人的五年生存率为76.8%;非二倍体肿瘤病人的五年生存率为23.9%,二者经统计学处理的极显著差异(P＜0.01).在同一临床分期及病理分级中,也显示同样的结果.结论大肠癌DNA倍体性的分析可以作为判定病人预后的一项客观指标,是对Dukes分期及病理组织学分级的一个极有价值的补充指标.     

中国北方人HNPCC微卫星不稳定性的研究

目的:通过对遗传性非息肉病性大肠癌(hereditary nonposis colorectal cancer,HNPCC)与普通遗传性大肠癌微卫星不稳定性(microsatellite instability,MSI)的检测,为临床筛检HNPCC家系提供依据。方法:选取符合中国人HNPCC诊断标准家系(A组)和普通遗传性大肠癌诊断标准家系(B组)的先证者各20例,另选散发性大肠癌(C组)20例为对照组,用PCR-SSCP的方法对上述肿瘤标本进行MSI检测。结果:A、B、C3组高度微卫星不稳定性(MSI-H)的发生率分别为55.0%(17/20)、40.0%(8/20)和10.0%(2/20),3组之间比较差异有统计学意义,P<0.05。MSI-H在A、B、C3组平均发病年龄分别为43.6、52.2和61.8岁,逐渐升高;右半结肠癌发生率分别为55.0%(11/20)、25.0%(5/20)和0,逐渐下降,差异有统计学意义,P<0.05。所选5个位点中BAT26和BAT25的表达率最高,均为94.1%(16/17)。在MSI-H中,A组低分化腺癌占70.6%(12/17),明显高于B、C两组的4/8和1/2,P<0.05。结论:MSI与HNPCC的临床病理特征高度相关,该方法经济、易行,可作为HNPCC的筛检手段。     

散发性结直肠癌中微卫星不稳定研究及其临床病理意义

目的检测散发性结直肠癌(SCRC)中的微卫星不稳定状态,并探讨其与临床病理特征的关系。方法应用荧光标记多重PCR法扩增微卫星位点BAT-25和BAT-26,将PCR扩增产物在荧光毛细管中进行电泳,以GenScan3.1软件扫描分析两个微卫星位点状况。结果112例SCRC患者中,BAT-25和BAT-26两个位点均阳性者14例,MSI-H发生率为12.5(14/112);BAT-25单位点阳性者4例,BAT-26单位点阳性者6例;两个位点均阴性者88例,MSS发生率为78.6。SCRC中MSI-H和MSS两组的比较显示:MSI-H者发病部位以近端结肠癌多见(P=0.034),组织学类型以黏液腺癌、印戒细胞癌相对多见(P=0.023),分化程度以低分化癌多见(P=0.039),而MSI-H与MSS两者在性别、年龄、肿瘤浸润深度、淋巴结转移、远处转移等方面差异无统计学意义。结论SCRC中微卫星不稳定是一个常见的分子事件,微卫星不稳定的SCRC好发于右半结肠,具有低分化的倾向。     

DNA倍体分类与癌组织生物学特性的关系

目的　探讨恶性肿瘤DNA倍体分类的某些生物学特性的依据。方法　采用流式细胞术对 1 0 0例恶性肿瘤的癌组织和癌旁组织进行了DNA含量分析 ,并对癌组织不同倍体类型与某些生物学特性的关系进行了探讨。结果　把癌组织DNA倍体类型分为 :二倍体 (D)、近二倍体 (ND)、四倍体 (T)、非整倍体 (AN)和多异倍体 (M)。后四种倍体类型统称为DNA异倍体 (H)。癌组织DNA类型不同 ,其增殖活性明显不同。从D→ND→T→AN→M ,其SPF和PI逐渐升高 ;在DNA异倍体肿瘤患者中 ,其癌旁组织DNA异倍体检出率也逐渐升高 ;另外DNA异倍体患者癌旁组织异倍体检出率显著高于二倍体者 (P <0 0 5)。结论　癌组织DNA倍体类型从D→ND→T→AN→M ,其SPF、PI和癌旁组织DNA异倍体的检出率均逐渐升高。这表明从D→ND→T→AN→M ,肿瘤细胞恶性度愈来愈高。这为癌组织DNA倍体分类提供了生物学依据。     

DNA 倍体类型与鼻咽癌放射敏感性及预后关系的研究

 目的 探讨DNA倍体类型与鼻咽癌放射敏感性及预后的关系。方法 应用流式细胞术(FCM)分析45例放疗前鼻咽癌细胞的DNA倍体，放疗结束六个月评定疗效。对患者进行定期随访，分析DNA倍体性与鼻咽癌放射敏感性及预后有无相关性。结果 DNA倍体性与鼻咽癌临床分期、近期疗效、放射敏感性及预后均有明显的相关性，但与性别、病理类型无关。早期肿瘤(Ⅰ+Ⅱ期)的DNA异倍体率为11．11％(2／18)远低于晚期(Ⅲ+Ⅳ期)者的40．74％(11／27)(P<0．05)，异倍体肿瘤较二倍体肿瘤对放疗更敏感(P<0．01)，且异倍体肿瘤的近期疗效明显好于二倍体肿瘤(P<0．05)，但异倍体肿瘤的预后较二倍体肿瘤差(P<0．01)。结论 DNA倍体类型可作为评估鼻咽癌放射敏感性和预后的一个独立指标。FCM的肿瘤细胞DNA倍体分析可能成为鼻咽癌选择放疗分割方案的客观指标。     

微卫星状态与术后大肠癌患者的临床及病理特征相关性研究

  目的  分析微卫星状态与术后大肠癌患者的临床及病理特征的相关性。  方法  选取南京大学医学院附属鼓楼医院2014年6月至2017年6月病理诊断确诊的572例大肠癌患者的临床及病理资料,并对其手术切除标本进行微卫星状态与KRAS、NRAS突变状态的检测,同时采用免疫组织化学法检测组织中Ki-67、EGFR、MGMT及Lgr5的表达情况。按照微卫星不稳定性（microsatellite instability,MSI）状态,分为高度微卫星不稳定（high-frequency MSI,MSI-H）大肠癌组与微卫星稳定状态（microsatellite stability,MSS）和低度微卫星不稳定（low-frequency MSI,MSI-L）大肠癌组,比较组间的临床、病理等资料的差异。  结果  572例大肠癌患者中40例（7.0%）为MSI-H,532例（93.0%）为MSS/MSI-L。与MSS/MSI-L组大肠癌病例相比MSI-H组具有以下特征:1）病灶常位于右半结肠;2）不同年龄段的发病比例相当;3）肿瘤分期较早,即Ⅰ/Ⅱ期分期比例较大（P=0.003）;4）淋巴结转移比例较低（P= 0.023）;5）形成癌结节比例较低（P=0.005）;6）KRAS第2外显子突变率较低（P=0.004）,NRAS未突变。两组在MGMT、EGFR、Lgr5、Ki-67免疫组织化学阳性率检测未见显著性差异。  结论  微卫星状态与大肠癌患者的年龄相关,与MSS/MSI-L的大肠癌患者相比,MSI-H的患者具有其特殊的临床病理特征,且NRAS及KRAS第2外显子的突变率低,MGMT甲基化率高,可为大肠癌的个体化诊断和治疗提供依据。      

钙网蛋白在不同病理分型大肠癌患者中的表达分析

目的:研究钙网蛋白(CRT)在不同病理分型大肠癌患者中的表达及探讨其与大肠癌的关系。方法:大肠癌患者150例,按照病理分型分为4组:高分化腺癌组、中分化腺癌组、低分化腺癌组、黏液腺癌组,同时设立健康对照组。ELISA法检测血清CRT含量。结果:大肠癌患者血清CRT含量远较健康对照组高,差异有统计学意义(P=0.00)。其中不同病理分型的大肠癌患者CRT含量也不完全相同。高、中分化腺癌组之间比较差异无统计学意义(P=0.057),但与低分化腺癌组及黏液腺癌组比较差异有统计学意义(P=0.00),而低分化腺癌组及黏液腺癌组之间比较差异无统计学意义(P=0.10)。结论:大肠癌细胞存在CRT的过度表达,且CRT表达水平能够评估大肠癌患者的预后。     

大肠癌组织中p27蛋白表达与微卫星不稳定性的关系

目的探讨大肠癌组织中p27蛋白表达与微卫星不稳定(MSI)的关系。方法采用免疫组化、PCRSSCP法对53例散发性大肠癌分别进行p27蛋白表达水平和D18S34,TGFβRⅡ,APC(1),TCF2,p53(1)及Rb6个碱基序列位点的检测。结果53例大肠癌中25例存在微卫星不稳定,总阳性率为47.2%,其中23例存在2个以上位点的MSI,呈复制误差阳性(RER阳性),占43.4%。RER 者p27高表达率(82.6%)显著高于RER阴性者(43.3%),2组比较有非常显著性差异(P<0.01)。结论大肠癌MSI的发生可能对p27蛋白的表达有一定的上调作用。p27等一些细胞周期负调控因子在RER阳性大肠癌中的表达水平相对上调,可能是其细胞增殖活性较低、生物学行为较好的原因。     

Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability

BACKGROUND: Widespread microsatellite instability (MSI) occurs in nearly 15% of sporadic colorectal cancers. Large bowel carcinomas with high-frequency MSI (MSI-H) (instability at > or = 30% of microsatellite loci) are believed to display distinctive pathologic features and to behave less aggressively than microsatellite-stable (MSS) tumors and carcinomas with low-frequency MSI (MSI-L) (instability at < 30% of microsatellite loci). The aim of the current study was to accurately define the clinicopathologic and biologic features of MSI-H sporadic colorectal carcinomas. METHODS: MSI status was evaluated in 216 large bowel adenocarcinomas using polymerase chain reaction (PCR) and 6 microsatellite markers. Tumors that showed instability with at least two microsatellite markers were classified as MSI-H, whereas the other tumors were classified as MSI-L (instability at one locus) or MSS (no instability). Expression of p53, hMLH1, and hMSH2 gene products was determined by immunohistochemistry, and DNA ploidy pattern was determined by flow cytometry. The prognostic significance of MSI status was assessed by univariate and multivariate survival analyses. RESULTS: The significantly different pathologic features of MSI-H carcinomas were proximal location; large size; mucinous and medullary histotype; poor differentiation; expanding pattern of growth; more frequent Crohn-like conspicuous lymphoid reaction; and low incidence of extramural vein invasion. Most MSI-H tumors were DNA diploid (33 of 40 tumors; 82.5%) and p53 negative (34 of 44 tumors; 77.3%). Conversely, DNA aneuploidy and p53 overexpression were observed in 82.3% (130 of 158 tumors; P < 0.0001) and 54.1% (93 of 172 tumors; P = 0.0002) of MSI-L/MSS tumors, respectively. Loss of hMLH1 or hMSH2 expression was detected in a high fraction of MSI-H carcinomas (86. 0%). Patients with MSI-H tumors showed a better clinical outcome than patients with MSI-L/MSS tumors (P = 0.0017). Furthermore, in multivariate analysis that included conventional clinicopathologic parameters, MSI status, and p53 expression as covariates, MSI status was a significant independent prognostic indicator of disease specific survival. CONCLUSIONS: Assessment of MSI status is an essential step in the genetic characterization of large bowel carcinomas and identifies a subset of tumors with distinct clinical, pathologic, and biologic features.     

Relationship between genetic alterations and prognosis in sporadic colorectal cancer

Because chromosomal chromosomal instability (CIN) and microsatellite instability (MSI) are important genetic alterations in colorectal cancers, we classified the sporadic colorectal cancers (CRC) on the status of the CIN and MSI and explored their molecular profiles. A total of 213 colorectal tumors were collected for analysis of DNA ploidy, MSI, loss of heterozygosity (LOH), mutation of p53 (exons 5 to 9), Ki-ras (exons 1 and 2) and BRAF (V599E). Relationships between clinicopathological variables and molecular analyses were analyzed with the chi(2) test (Yates' correction). Kaplan-Meier survival curves were compared using log-rank test. Variables with p < 0.1 were entered into the Cox regression hazard model for multivariate analysis. High microsatellite instability (MSI-H) existed in 19 tumors (8.9%), which were more likely to be right-sided (31.6%) with poor differentiation (26.3%). Seventy-one (33.3%) tumors were diploid and 142 (66.7%) were aneuploid. Mutations in p53, Ki-ras and BRAF were found in 45.1%, 41.8% and 4.2% of tumors, respectively. Based on MSI, and CIN, 3 classes were defined: (i) High microsatellite instability MSI-H tumors: young age, high carcinoembryonic antigen (CEA) level, right colon, poorly differentiated, mucin production, high BRAF mutation, lower allelic loss and relatively good prognosis; (ii) Microsatellite stability (MSS) diploid tumors: right colon, poorly differentiated, less infiltrative tumor, mucin production, lower allelic loss and low p53, BRAF mutation; (iii) MSS aneuploid tumors: more infiltrative invasion, greater allelic loss and high p53 mutation. According to multivariate analysis, tumor stage and p53 mutation were significantly associated with disease progression. The MSS diploid and MSS aneuploid CRCs could be subtyped with p53 mutation and had different prognostic outcome and molecular profiles. The 4-year disease-free survival (DFS) of patients with MSS-diploid, wild-type p53 tumors was 67% and significantly higher than those of patients with MSS-diploid, mutant p53 CRC (30%, p = 0.003). The same trend was found in patients with MSS-aneuploid CRC(wild p53 vs. mutant p53, 64% vs. 41%, p = 0.009). We concluded that CIN, MSI and p53 mutation status might be used as a multiple parameter profile for the prognosis of sporadic colorectal cancer.     

Microsatellite instability and hMLH1/hMSH2 expression in Barrett esophagus-associated adenocarcinoma

BACKGROUND: Microsatellite instability (MSI) has been documented in malignancies associated with hereditary nonpolyposis colon carcinoma and in sporadic malignancies of the colon, stomach, and endometrium. In these malignancies, MSI is associated with defects in the DNA mismatch repair enzymes hMSH2 and hMLH1. Defects in these enzymes result in a phenotype characterized by instability of multiple microsatellite repeat sequences throughout the genome. This study sought to determine the prevalence of MSI in 80 primary Barrett esophagus-associated adenocarcinomas (BEAd) and to examine the relation of MSI with the clinical and pathologic features of the tumors. METHODS: Eighty BEAd were evaluated for the presence of MSI by using the microsatellite markers BAT25, BAT26, D10S219, D10S541, and D10S551. These tumors also were evaluated for immunohistochemical expression of hMSH2 and hMLH1. RESULTS: High levels of MSI were not found in any of the tumors examined. Furthermore, immunohistochemical expression of hMSH2 and hMLH1 was retained in all cases evaluated. Evidence of low level MSI was found in 16% of tumors. In none of these tumors, however, was MSI present in more than two of five loci. The presence of MSI did not correlate with patient age, tumor stage, degree of differentiation, or with patient survival. CONCLUSIONS: High level MSI and loss of hMLH1/hMSH2 expression is uncommon in BEAd. A subset of BEAd demonstrate low level MSI. The presence of low level MSI was not associated with the clinicopathologic features of the tumors examined.     

hMLH1 and hMSH2 expression in human hepatocellular carcinoma

The role of microsatellite instability (MSI) in the pathogenesis of hepatocellular carcinoma (HCC) is incompletely defined. Although high-frequency MSI (MSI-H) is infrequently seen in HCC, some studies have suggested a role for MSI in HCC development. While MSI has been clearly defined for a subset of tumors, in particular colorectal, gastric and endometrial cancers, generally accepted criteria have not been developed for other tumors. Colorectal cancers (CRC) are classified as MSI-H if >30-40% of >5 microsatellite loci analyzed show instability. The MSI-H phenotype is associated with defective DNA mismatch repair (MMR) and is observed in the majority of tumors from patients with hereditary non-polyposis colon cancer (HNPCC) and also in 15% of sporadic CRCs. Inactivating mutations of the hMLH1 or hMSH2 genes lead to defects in MMR in HNPCC. In sporadic CRCs, MMR is usually due to hypermethylation of the hMLH-1 promoter. The role of defective MMR in hepatocellular carcinogenesis is controversial. Immunohistochemistry for hMLH1 and hMSH2 reliably indicates hMLH1 or hMSH2 loss in MSI-H CRC tumors. To investigate the role of defective MMR in HCC carcinogenesis, we performed immunohistochemistry for hMLH1 and hMSH2 on 36 HCCs. BAT26, a microsatellite marker that reliably predicts MSI-H was also examined. All 36 of the tumors stained positively for both hMLH1 and hMSH2, strongly suggesting an absence of either inactivating mutations of hMLH1 and hMSH2 or promoter hypermethylation of hMLH1. None of the tumors showed MSI at the BAT26 locus. These findings suggest that defective MMR does not contribute significantly to hepatocellular carcinogenesis.     

Frequent Bax frameshift mutations in gastric cancer with high but not low microsatellite instability

Widespread microsatellite instability (MSI) due to the defective DNA mismatch repair underlies the pathogenesis of the majority of hereditary non-polyposis colorectal cancer and a subset of various sporadic malignant tumors. Using 5 microsatellite markers and the criteria of MSI proposed by the National Cancer Institute (NCI) workshop, we analyzed 205 gastric adenocarcinomas for MSI. Based on the number of markers showing instability per tumor, the tumors were divided into three groups; those with two or more of the five markers displaying instability (high MSI, MSI-H), those with one of five markers displaying instability (low MSI, MSI-L), and those with no instability (microsatellite stable, MSS). Among 205 tumors, 30 (15%) were MSI-H, 15 (7%) were MSI-L, and 160 (78%) were MSS. All of the 30 MSI-H tumors demonstrated instability at BAT26, a sensitive marker for the widespread MSI, while none of the 15 MSI-L tumors did. MSI-H tumors were significantly associated with distal location and well or moderate differentiation, but MSI-L tumors were indistinguishable from MSS tumors. Bax frameshift mutations were detected in 60% of the 30 MSI-H tumors, while not in any of the 15 MSI-L tumors. These results suggest that microsatellite analysis using the criteria proposed by the NCI workshop may be appropriate for gastric cancers because it unveils real differences in genotype and phenotype.     

Value of the identification of microsatellite instability in colorectal cancer

Objective  Recent studies defend a possible prognostic and therapeutic value of the identification of microsatellite instability (MSI) in colorectal cancer. This work tries to assess the impact that the identification of MSI tumours can have in clinical practice. Material and methods  We recovered tumour samples from 92 of the 143 patients operated on for colorectal cancer in our institution between 1995 and 2000. Five MSI markers (BAT 25, BAT 26, D2S123, D5S346 and D17S250) were studied on them. The rate and clinicopathologic characteristics of MSI tumours were investigated along with their impact on the global and disease-free survival as compared with microsatellite stable (MSS) tumours. Results  All 5 microsatellite markers’ status were established in 73 patients (79.3% of the samples). Among them, 7 tumours showed instability in just one marker (low microsatellite instability [MSI-L]) whereas 5 tumours had mutations in 2 or more markers (high microsatellite instability [MSI-H]), for a total 15.4% rate of MSI tumours. All MSI-H tumours were located in the right colon. We could not find any impact from MSI detection on global or disease-free survival. Conclusions  MSI determination did not identify groups of patients with a different prognosis. Moreover, with such low incidence its determination can only be justified in those cases that fulfill Bethesda’s criteria to identify families with Lynch’s syndrome.     

Chk1 frameshift mutation in sporadic and hereditary non-polyposis colorectal cancers with microsatellite instability.

AIM: Protein kinase Chk1 (hChk1) is essential in human cells for cell cycle arrest in response to DNA damage, and has been shown to play an important role in the G2/M checkpoint. The BRAF mutations have been suggested to be linked with defective mismatch repair in colorectal cancers. The aim of this study was to investigate whether a frameshift mutation within the Chk1 gene contribute to the development or progression of eastern sporadic and hereditary non-polyposis colorectal cancer (HNPCC) with microsatellite instability (MSI). METHODS: We analyzed MSI using the 6 microsatellite markers and a frameshift mutation in the BRAF gene and in poly(A)9 within the Chk1 gene in 51 sporadic colorectal cancer and 14 HNPCC specimens. RESULTS: Eleven of the 51 sporadic colorectal cancers and all of the 14 HNPCCs were MSI-positive. Chk1 frameshift mutations were observed in 2 and 3 sporadic colon cancers and HNPCC, respectively, whereas no BRAF mutations were detected in these samples. Interestingly, all cases with the Chk1 frameshift mutation had high-frequency MSI. CONCLUSION: These results suggest that the Chk1 gene is a target of genomic instability in MSI-positive colorectal cancers and that the Chk1 framshift mutations might be involved in colorectal tumourigenesis through a defect in response to DNA damage in a subset of sporadic colorectal cancers and HNPCCs.     

Is early‐onset microsatellite and chromosomally stable colorectal cancer a hallmark of a genetic susceptibility syndrome?

Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome.