结直肠腺癌组织中MLH1、PMS2、MSH2及MSH6的表达和病理意义

目的 探索结直肠腺癌组织中MLH1、PMS2、MSH2及MSH6的表达和病理意义。方法 回顾性收集本院于2020年2月至2023年2月收治的行腹腔镜下结直肠癌根治术的患者100例的临床资料进行分析。采用免疫组化的方法检测其组织中的错配修饰蛋白MLH1、PMS2、MSH2及MSH6表达情况,统计纳入人群的错配修饰蛋白的缺失情况。分析其稳定性和强度,同时探究其临床病理意义。结果所纳入的100例患者中包括有48例直肠缐癌患者,52例结肠癌患者。MLH1表达缺失12例（12%）、MSH2表达缺失7例（7%）、 PMS2表达缺失13例（13%）、MSH6表达缺失9例（9%）。年龄对于稳定性具备一定的关联性,P<0.05,而性别、肿瘤最大径、肿瘤分期、淋巴结是否转移和分化程度和其稳定性没有显著关联性,P>0.05。直肠腺癌组织中的MLH1、PMS2、MSH2及MSH6表达均显著高于癌周边组织,差异具备统计学意义,P<0.05。结论 MLH1、PMS2、MSH2及MSH6的表达和肿瘤的稳定性和表达强度具备一定的关联,对结直肠缐癌的评估具有一定的指导意义。     

Lynch 综合征相关结直肠癌患者临床特征

目的 探讨Lynch综合征相关结直肠癌的临床特征。方法 收集广州市番禺区中医院212例结直肠癌病例的临床资料与病理资料,通过免疫组化检测肿瘤组织的PMS2、MSH6、MLH1和MSH2,并结合临床资料进行统计分析。结果 212例结直肠癌患者中,共19例出现了MMR蛋白表达缺失,占8.96%。其中MLHl（-）/PMS2（-）7例,MSH2（-）/MSH6（-）5例,MSH6（-）3例,PMS2（-）4例。MMR蛋白表达缺失与患者年龄、肿瘤部位有关,与性别、肿瘤分化程度、TNM分期无关。结论 Lynch综合征相关结直肠癌好发于年轻患者与右半结肠。     

错配修复在遗传性非息肉性结直肠癌中的研究进展

遗传性非息肉性结直肠癌是最具遗传特性的一种大肠癌,随着分子遗传学检测方法的发展,目前已经能够应用多种方法检测出突变的错配修复基因,并应用于遗传性非息肉性结直肠癌患者的筛选.在此分别就MSH2、MLH1、MSH6、PMS1、PMS2、MLH3和EX01等错配修复基因与遗传性非息肉性结直肠癌相关性研究进展进行综述.     

葡萄糖调节蛋白78kD和热休克蛋白20在左半及右半结肠癌差异表达的初步研究

目的分析左半结肠癌与右半结肠癌肿瘤组织中差异蛋白表达情况。方法收集人左半结肠癌和右半结肠癌组织标本各7例．提取组织蛋白并进行二维凝胶电泳、质谱分析及生物信息学分离．鉴定二者中差异表达蛋白质。应用免疫组织化学sP法检测葡萄糖调节蛋白78kD（GRP78）和热休克蛋白20（HSP20）在50例左半和50例右半结肠癌组织中的表达情况。结果筛选并成功鉴定出左半和右半结肠癌中16种差异表达蛋白质：与右半结肠癌比较,左半结肠癌10种蛋白表达上调,6种蛋白表达下调,其中GRP78在左半结肠癌中表达上调,HSP20在左半结肠癌中表达下调。免疫组织化学检测示．GRP78在左半和右半结肠癌组织的阳性表达率分别为78％（39／50）和56％（28／50）,差异有统计学意义（P〈0．05）;HSP20在左半和右半结肠癌的阳性表达率分别为34％（17／50）和72％（36／50）,差异亦有统计学意义（P〈0．05）。GRP78表达与肿瘤分化程度、浸润层次、TNM分期、有无淋巴结转移以及有无肝转移有关（P〈0．05）,而HSP20的表达与肿瘤大体形态、TNM分期以及有无淋巴结转移有关（P〈0．05）。结论左半结肠癌和右半结肠癌的蛋白质组存在蒡异．这些可能是左半与右半结肠癌生物学行为存在差异的原因。     

错配修复、微卫星不稳定性与散发性结肠直肠癌

近年来研究发现ＤＮＡ修复基因突变引起ＤＮＡ错配修复系统的功能降低或丧失 ,从而引起遗传物质不稳定 ,主要表现为微卫星不稳定性 ,进而导致肿瘤的发生。我们采用ＰＣＲ技术对 48例散发性结肠直肠癌检测了错配修复基因ｈｍｓｈ3、ｈｍｓｈ6和 4个位点的微卫星不稳定性 ,现将结果报告如下。1.材料与方法 :(1)临床资料 :我院1997～ 1998年经手术切除的新鲜结、直肠癌标本 48例 ,其中男女各 2 4例 ;年龄2 6～ 72岁 ,平均 5 3岁 ;结肠癌 2 9例 (右半结肠癌 15例 ,左半结肠癌 14例 ) ,直肠癌 19例 ;高分化癌 19例 ,中分化癌 2 2例 ,低分化癌 7例…     

错配修复蛋白在直肠癌中的表达及其对新辅助放化疗敏感性的预测价值

背景与目的：术前新辅助放化疗（nCRT）是治疗中低位局部进展期直肠癌的金标准,完全病理缓解（pCR）患者远期预后较好,尽管有新的分子生物学发展和诊疗技术进步,但对nCRT前可预测良好病理反应的潜在生物标志物甚少。本研究探讨错配修复（MMR）蛋白在局部进展期中低位直肠癌患者中表达情况,及其与nCRT敏感性的关系。 方法：选取2014年1月—2019年12月在铜陵市人民医院胃肠外科住院治疗的162例中低位局部进展期直肠癌,所有患者均在nCRT后接受手术治疗。用免疫组化检测初诊肠镜活检组织标本中MMR蛋白（MLH1、MSH2、MSH6、PMS2）的表达,分析MMR蛋白表达状态与患者临床资料及nCRT疗效[按RECIST 1.1标准与肿瘤退缩分级（TRG）评分]的关系,以及患者TRG评分与临床病理因素及MMR蛋白表达状态的关系,并通过多因素Logistic回归模型分析pCR的影响因素。 结果：162例直肠癌患者中22例（13.4%）存在MMR蛋白缺失（dMMR）,其中MLH1蛋白缺失17例（10.5%）、MSH2蛋白缺失10例（6.2%）、MSH6蛋白缺失8例（4.9%）、PMS2蛋白缺失11例（6.8%）。组织学类型、术前临床分期、TRG评分与MMR蛋白表达状态有关（均P<0.05）;dMMR患者RECIST 1.1评估nCRT的有效率高于MMR蛋白表达完整（pMMR）患者（59.1% vs. 36.4%,P=0.043）。患者性别、年龄、肿瘤位置、分化程度、组织学类型、CEA水平、同步化疗方案以及MLH1、MSH2、MSH6、PMS2蛋白的表达与TRG评分无明显关系（均P>0.05）;临床T分期、临床N分期、术前临床分期、MMR蛋白的表达状态（dMMR或pMMR）与TRG评分有关（均P<0.05）。Logistic多因素回归分析发现dMMR是患者pCR的独立影响因素（OR=0.327,95% CI=0.109~0.984,P=0.047）。 结论：在局部进展期中低位直肠癌患者中,肠镜初诊活检组织中dMMR蛋白表型预示较好的nCRT疗效;MMR蛋白的表达状态可作为直肠癌患者nCRT疗效的预测指标。     

大肠腺瘤及其癌变组织hMLH1和hMSH2表达及其临床意义

目的探讨错配修复基因hMLH1和hMSH2在大肠腺瘤癌变中的意义。方法采用免疫组化方法对63例大肠腺瘤、20腺瘤癌变、20例大肠癌的hMLH1和hMSH2表达进行了检测。结果显示错配修复基因hMLH1、hMSH2在大肠腺瘤、腺瘤癌变和大肠癌表达率逐渐降低，且随腺瘤不典型增生加重表达率也逐渐降低，hMLH1、hMSH2表达缺失率与肿瘤发生部位相关，右半结肠明显高于左半结肠。结论DNA错配修复基因功能缺失与大肠癌的发生有关，可能系大肠癌发生过程中的早期事件，且左、右半结肠大肠癌的发生机制可能有所不同。     

大肠腺瘤及其癌变组织hMLH1和hMSH2表达及其临床意义

目的　探讨错配修复基因hMLH1和hMSH2在大肠腺瘤癌变中的意义。方法　采用免疫组化方法对 6 3例大肠腺瘤、2 0腺瘤癌变、2 0例大肠癌的hMLH1和hMSH2表达进行了检测。结果　显示错配修复基因hMLH1、hMSH2在大肠腺瘤、腺瘤癌变和大肠癌表达率逐渐降低 ,且随腺瘤不典型增生加重表达率也逐渐降低 ,hMLH1、hMSH2表达缺失率与肿瘤发生部位相关 ,右半结肠明显高于左半结肠。结论　DNA错配修复基因功能缺失与大肠癌的发生有关 ,可能系大肠癌发生过程中的早期事件 ,且左、右半结肠大肠癌的发生机制可能有所不同。     

MLH1蛋白与近端散发性结肠癌瘤内菌群特征关系的生物信息学分析

背景与目的：mutL同源物1 (MLH1)基因的突变会导致DNA错配修复（MMR）系统失活,从而增加结直肠癌的发生风险。此外,越来越多的研究表明,肠道菌群的组成和功能异常与结直肠癌的发生和发展密切相关。然而,MLH1蛋白表达与肠道菌群是否有关联目前尚不十分明确。因此,本研究通过分析中国东北地区不同MLH1蛋白表型近端散发性结肠癌（SCC）患者的肿瘤组织中微生物组的差异,探讨两者之间的潜在关系。方法：收集黑龙江省哈尔滨市第一医院和黑龙江省医院2020—2021年407例近端SCC肿瘤组织样本与临床资料,用免疫组化法筛选出其中MLH1蛋白缺失病例（缺失组）与MLH1蛋白完整病例（对照组）。采用16S rRNA基因测序技术,对提取的肠道肿瘤组织内微生物DNA,进行生物信息学分析,并分析临床病理特征以及特定类群的物种与菌群多样性的关系。结果：共筛选出缺失组病例20例,对照组18例,初步临床数据分析显示,肿瘤越大,MLH1蛋白缺失的风险越高（P<0.05）。不同MLH1状态下肿瘤组织内菌群的α多样性除Shannon指数外（P=0.042）,其他指数差异均无统计学意义（均P>0.05）...     

右半结肠癌淋巴结转移的相关病理因素分析

目的探讨影响右半结肠癌淋巴结转移的相关病理因素。方法回顾性分析广西医科大学第一附属医院结直肠外科2008年9月至2011年10月行根治性切除的168例右半结肠癌患者病理资料,采用单因素分析和Logistic多因素回归分析方法,研究右半结肠癌淋巴结转移与临床病理因素之间的关系。结果单因素分析显示右半结肠癌淋巴结转移与年龄、性别、肿瘤部位、大体类型、肿瘤直径等因素无关(P>0.05);肿瘤病理类型、分化程度、浸润深度与淋巴结转移有关(P<0.05);Logistic多因素回归分析显示,肿瘤分化程度、浸润深度是影响右半结肠癌淋巴结转移的独立因素(P<0.05)。结论右半结肠癌淋巴结转移与肿瘤病理类型、分化程度、肠壁浸润深度有关,其中肠壁浸润深度是影响淋巴结转移的最重要因素。     

Strategy in clinical practice for classification of unselected colorectal tumours based on mismatch repair deficiency

Objective Deficiency of DNA mismatch repair (MMR) causes microsatellite instability (MSI) in a subset of colorectal cancers. Patients with these tumours have a better prognosis and may have an altered response to chemotherapy. Some of the tumours are caused by hereditary mutations (hereditary nonpolyposis colon cancer or Lynch syndrome), but most are epigenetic changes of sporadic origin. The aim of this study was to define a robust and inexpensive strategy for such classification in clinical practice. Method Tumours and blood samples from 262 successive patients with colorectal adenocarcinomas were collected. Expression of the MMR proteins MLH1, MSH2, and MSH6 by immunohistochemistry (IHC) was compared with MSI DNA analysis. Methylation analysis of MLH1 and mutation analysis for BRAF V600E were compared in samples with MSI and/or lack of MLH1 expression to determine if the tumour was likely to be sporadic. Results Thirty‐nine (14.9%) of the tumours showed MMR deficiency by IHC or by microsatellite analysis. Sporadic inactivation by methylation of MLH1 promoter was found in 35 patients whereby the BRAF activating V600E mutation, indicating sporadic origin, was found in 32 tumours. On the basis of molecular characteristics we found 223 patients with intact MMR, 35 patients with sporadic MMR deficiency, and four patients who were likely to have hereditary MMR deficiency. Conclusion To obtain the maximal benefit for patients and clinicians, MMR testing should be supplemented with MLH1 methylation or BRAF mutation analysis to distinguish sporadic patients from likely hereditary ones. MMR deficient patients with sporadic disease can be reassured of the better prognosis and the likely hereditary cases should receive genetic counselling.     

Patients with Lynch Syndrome Mismatch Repair Gene Mutations Are at Higher Risk for Not Only Upper Tract Urothelial Cancer but Also Bladder Cancer

Background

Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse.

Objective

To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations.

Design, setting, and participants

Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2).

Outcome measurements and statistical analysis

Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors.

Results and limitations

Eleven of 177 patients with MSH2 mutations (6.21%, p < 0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p > 0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p < 0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias.

Conclusions

LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.     

Neoadjuvant therapy induces loss of MSH6 expression in colorectal carcinoma

Immunohistochemical stains are routinely used to detect abnormal DNA mismatch repair (MMR) protein expression in colorectal carcinomas, particularly when Lynch syndrome is suspected. Complete loss of MMR protein expression is often associated with underlying microsatellite instability (MSI), and the combined results of mutL homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), mutS homolog 2 (MSH2), or mutS homolog 6 (MSH6) immunostains may point to the defective MMR protein in tumors with MSI. We have noted that some neoadjuvantly treated colorectal carcinomas display loss of MMR protein immunoexpression, despite a lack of underlying MSI and preserved staining in pretreatment tumor samples. The purpose of this study was to determine the frequency of this finding. We identified 51 neoadjuvantly treated resected colorectal cancers. Posttreatment tumor samples were immunohistochemically stained with MLH1, PMS2, MSH2, and MSH6 antibodies. Loss of staining for any marker was followed by analysis for MSI and assessment of MMR protein expression in pretreatment tumor samples. All of the 51 posttreatment tumor samples showed preserved MLH1, PMS2, and MSH2, but 10 posttreatment tumor samples (20%) showed decreased MSH6 staining. Of these, 9 posttreatment tumor samples displayed loss of staining in less than 100% of tumor cells, but preserved MSH6 expression in pretreatment tumor samples. One case showed a complete absence of MSH6 staining in both pretreatment and posttreatment tumor samples. All 10 cases were microsatellite stable. We conclude that extensive loss of MSH6 immunoexpression is common among neoadjuvantly treated colorectal carcinomas, but generally does not reflect underlying MSI. Therefore, diminished MSH6 staining in treated tumors should prompt immunohistochemical evaluation of pretreatment biopsy samples before genetic testing for Lynch syndrome.     

Elevated levels of the mismatch repair protein PMS2 are associated with prostate cancer

BACKGROUND: Defects in mismatch repair (MMR) proteins have been identified in various types of cancer. However, an association with prostate cancer has been controversial. Defective MMR results in genome instability with detrimental consequences that significantly contribute to tumorigenesis. This study determined alterations in key MMR protein levels in prostate cancer with the goal to identify prognostic markers. METHODS: Prostatectomy samples were immunohistochemically stained and the relative presence or absence of key proteins MSH2, MLH1, and PMS2 determined. Cancer tissue of distinct grades was compared with the normal surrounding tissue. Microsatellite instability (MSI) in altered tissues was determined according to NCI guidelines. RESULTS: In contrast to reports that associate a lack of individual MMR proteins with tumorigenesis, a significant increase in PMS2 levels was identified in PIN lesions and prostate cancer tissue. This elevation in PMS2 was independent of changes in levels in its heterodimeric partner, MLH1. Prostate tumors with elevated levels of PMS2 were genetically unstable, which was corrected by MLH1 co-elevation. CONCLUSIONS: This is the first documentation of detrimental consequences associated with the increase in a MMR protein in human cancer. This study recognizes PMS2 elevation as a prognostic marker in pre-neoplastic and prostate cancer lesions. This result has significant implications for future diagnostic and treatment measures.     

MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass

BackgroundMicrosatellite instability (MSI), a hypermutator phenotype described in many cancers, has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in bladder cancer, but data on the possible extent of intratumoral heterogeneity are lacking.MethodsTo study MSI heterogeneity in bladder cancer, a tissue microarray (TMA) comprising 598 muscle-invasive urothelial carcinomas of the bladder was utilized to screen for MSI by immunhistochemistry with antibodies for MLH1, PMS2, MSH2, and MSH6.ResultsIn 9 cases suspicious for MSI, MMR status was further evaluated by large section examination and polymerase chain reaction (PCR)-based analysis of microsatellites (“Bethesda panel”) resulting in the identification of 5 validated MSI cases from 448 interpretable cancers (prevalence 1.1%). MMR deficiency always involved PMS2 loss, in 3 cases with additional loss or reduction of MLH1 expression. Four cancers were MSI-high and 1 was MSI-low in the PCR analysis. Parallel sequencing revealed an inactivating MLH1 mutation in 1 tumor but no further known pathogenic MMR gene mutations were found. Immunostaining of all available 72 cancer-containing tissue blocks of the 5 confirmed bladder cancer with MSI including prior and subsequent biopsies showed complete homogeneity of the MMR protein defects and the status of the 4 MMR proteins did not markedly change in sequential resections. In all 4 cases with noninvasive precursor lesions, MSI was also detectable.ConclusionThese data suggest that MSI occurs early in invasive bladder cancer and immunohistochemical MMR analysis on limited biopsy material is sufficient to estimate MMR status of the entire cancer mass.     

Mismatch repair deficiency occurs very rarely in seminomas

BackgroundDense tumor-associated lymphocyte infiltration is linked to mismatch repair (MMR) deficiency in colorectal and endometrial cancer. MMR deficiency is of high clinical importance as MMR deficient cancers tend to react favorably to treatment with immune checkpoint inhibitors. Strong lymphocytic infiltration is a morphological hallmark of seminomas. We thus asked whether seminomas may exhibit MMR deficiency at relevant frequency.MethodsTo screen for tumors with MMR deficiency, protein expression of MLH1, PMS2, MSH2, and MSH6 was analyzed by immunohistochemistry (IHC) on a tissue microarray (TMA) containing 574 seminomas.ResultsIn total, 536 cases were evaluable resulting in 481 seminomas with unequivocally intact MMR protein expression. In 55 cancers, one or several IHC stains were equivocal and lacked detectable MMR protein in both tumor and stromal cells. Large section IHC analysis of all 55 equivocal cases demonstrated substantial staining issues due to improper fixation in 54 cases and identified one tumor with clear-cut MLH1 and PMS2 protein loss. This seminoma showed homogeneous loss of MLH1 and PMS2 in the entire tumor mass whereas minor adjacent foci of associated germ cell neoplasia in situ (GCNIS) were MMR intact. Polymerase chain reaction (PCR) analysis using the 5 microsatellite loci of the “Bethesda Panel” revealed instability in 1 of 4 interpretable loci (“MSI-low”) and additional instability of the complex tetra-penta repeat locus MYCL1 in this tumor.ConclusionsIn summary, one single seminoma with MMR deficiency, characterized by protein loss of MLH1 and PMS2, was identified among 536 interpretable seminomas (0.19%). MMR deficiency is not a relevant determinant of lymphocyte influx in seminoma.     

Interpretation of immunohistochemistry for mismatch repair proteins is only reliable in a specialized setting

We examined the validity of immunohistochemistry for mismatch repair (MMR) proteins in colorectal cancer specimens to identify patients at risk for Lynch syndrome (hereditary nonpolyposis colorectal cancer) and patients with sporadic microsatellite instable colorectal cancer. This was assessed by observer agreement for and accuracy of interpretation of immunohistochemistry. Seven pathologists from 5 different pathology laboratories evaluated 100 molecularly defined colorectal cancers stained for MLH1, PMS2, MSH2, and MSH6. Two of the pathologists were experienced in interpretation of immunohistochemistry for MMR proteins. After evaluation of a subset of 20 cases, a discussion meeting was organized, after which pathologists evaluated all 100 cases. Staining patterns were interpreted as aberrant, normal, or indefinite. In 82% of tumors, 5 or more pathologists reached the same interpretation, which was considered the consensus diagnosis. Consensus was reached slightly less frequently in microsatellite instable than in stable tumors, and interobserver variation was moderate to substantial (kappa: 0.49-0.79). More microsatellite instable tumors showed an indefinite staining pattern compared with microsatellite stable tumors. Three out of 7 pathologists, including the 2 experienced pathologists, did not miss a microsatellite instable tumor. Each pathologist found at least 1 tumor with an aberrant staining pattern, whereas consensus was a normal staining pattern and the tumor was microsatellite stable. We conclude that, if restricted to experienced pathologists, immunohistochemistry is a valid tool to identify patients at risk for Lynch syndrome and patients with sporadic microsatellite instable colorectal cancer. An indefinite or aberrant staining result has to be followed by molecular microsatellite instability analysis to confirm the presence of a defective DNA MMR system.     

Mismatch Repair Proteins in Oropharyngeal Squamous Cell Carcinoma: A Retrospective Observational Study

Cases of oropharyngeal squamous cell carcinoma are on the rise and the disease now ranks as the most common human papillomavirus-related cancer. Although risk factors have been extensively discussed in the literature, the role of the DNA mismatch repair system remains unanswered. To evaluate the impact of the DNA mismatch repair (MMR) protein immunostaining on the tumor progression and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). This retrospective observational study comprised 50 cases of OPSCC. Immunohistochemistry for MSH2, MSH6, PMS2, MLH1, Ki67, p16 and caspase-3 was performed. The expression of these proteins was assessed in surgical resection margins, primary tumor (PT), and lymph node metastasis (LNM) of p16+ and p16- OPSCC. Clinical-pathological involvement in immunostaining was evaluated with Kruskal–Wallis/Dunn or Mann–Whitney test, Wilcoxon test and Spearman’s correlation. Overall survival (OS) was analyzed with Log-Rank Mantel-Cox and Cox regression. MSH6 and caspase-3 showed high expression in PT (p16+ and p16 −) and in LNM (p16+ and p16−), and high levels of MSH2 were found in LNM (p16+ and p16 −). An imbalance in MutSα also was observed. PMS2 and caspase-3 expression was associated with poor survival in p16- OPSCC and, in multivariate analysis, MSH2, MSH6 and MLH1 had the poorest prognostic impact in p16+ OPSCC. MMR protein immunostaining is involved in OPSCC progression, dissemination and prognosis. The overexpression of MMR proteins as a response to increased DNA mismatch caused by cell proliferation and MSH2, MSH6 and MLH1 proteins might constitute a prognostic marker in p16+ OPSCC.     

Microsatellite instability and mismatch repair protein defects in ovarian epithelial neoplasms in patients 50 years of age and younger

Ovarian malignancies occurring in the setting of hereditary nonpolyposis colorectal carcinoma syndrome typically present in young women, often as the first or "sentinel" cancer, but the frequency of microsatellite instability (MSI) and mismatch repair (MMR) defects in ovarian surface epithelial malignancies in women 相似文献