肺鳞状细胞癌特异性甲基化候选诊断标志物的识别

甲基化异常是肿瘤早期的频发事件,DNA甲基化随着时间的推移相对稳定,并且可以在血液中非侵入性地检测到,因此DNA甲基化具有成为癌症早期诊断生物标志物的巨大潜力.为了找到肺鳞状细胞癌(LUSC)潜在的诊断标志物,本文提出了一种LUSC特异性候选诊断标志物的识别方法,使用癌症基因组图谱数据库(TCGA)的LUSC的甲基化数据集,通过比较LUSC与正常肺组织和其他癌症类型,得到了6个LUSC特异性甲基化位点,使用支持向量机建立诊断模型,采用六折交叉划分数据集,验证特异性标志物的有效性. 6个标志物的组合在预测LUSC方面达到约93%～99%的灵敏度,在排除正常组织时达到100%的特异性,在排除其他癌症时达到约99%的特异性.我们的研究为LUSC的早期诊断提供了潜在的生物标志物.     

Neuron-specific enolase in the diagnosis and therapy monitoring of lung cancer: a comparison with CEA, TPA, ferritin and calcitonin

The significance of neuron-specific enolase (NSE) in the diagnosis and treatment monitoring of lung cancer was investigated in comparison with such established tumour markers as carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin and calcitonin. We determined the serum concentrations of these tumour markers in 25 patients with small cell lung cancer (SCLC), 30 patients with non small cell lung cancer (NSCLC), and 38 patients with benign pulmonary diseases (BPD). In 14 patients with lung cancer, it was possible to follow up the behaviour of the tumour markers under treatment for up to 16 months. Calcitonin proved to have a surprisingly low sensitivity for SCLC. The utility of TPA and of ferritin was restricted, although the sensitivity was comparably high, by the high rate of false positive results. For NSCLC, CEA proved to be the best tumour marker. At present, NSE appears to be the tumour marker with the greatest specificity and sensitivity for SCLC. Its determination in the diagnosis, treatment and follow-up of SCLC makes good sense.     

Tumor markers (CEA, TPA and CA 19-9) in urine of bladder cancer patients

This study was carried out to evaluate the usefulness of determining urinary levels of carcinoembryogenic antigen (CEA), tissue-polypeptide antigen (TPA), and gastro-intestinal cancer antigen (Ca19-9) in addition to the usual diagnostic procedures for bladder cancer. Sixty-seven patients with transitional bladder cancer, 40 healthy controls and 20 patients with inflammatory diseases of the urinary tract were considered. All urine samples were obtained from patients with intact renal function and no urinary tract infection. TPA and Ca19-9 urinary levels in patients with G3 bladder tumors were significantly higher than in those with lower graded neoplasms. The sensitivity, specificity, and predictive value of a positive (PV+) or negative (PV-) test and the diagnostic accuracy were also evaluated. Ca19-9 was the best urinary marker for bladder cancer (sensitivity 71.6%, specificity 91.6%, PV+ 90.5%, PV- 74.3%, diagnostic accuracy 81%).     

A suite of DNA methylation markers that can detect most common human cancers

Cancer-specific DNA methylation from the tumor derived fraction of cell free DNA found in blood samples could be used for minimally invasive detection and monitoring of cancer. The knowledge of marker regions with cancer-specific DNA methylation is necessary to the success of such a process. We analyzed the largest cancer DNA methylation dataset available—TCGA Illumina HumanMethylation450 data with over 8,500 tumors—in order to find cancer-specific DNA methylation markers for most common human cancers. First, we identified differentially methylated regions for individual cancer types and those were further filtered against data from normal tissues to obtain marker regions with cancer-specific methylation, resulting in a total of 1,250 hypermethylated and 584 hypomethylated marker CpGs. From hypermethylated markers, optimal sets of six markers for each TCGA cancer type were chosen that could identify most tumors with high specificity and sensitivity [area under the curve (AUC): 0.969-1.000] and a universal 12 marker set that can detect tumors of all 33 TCGA cancer types (AUC >0.84). In addition to hundreds of new DNA methylation markers, our approach also identified markers that are in current clinical use, SEPT9 and GSTP1, indicating the validity of our approach and a significant potential utility for the newly discovered markers. The hypermethylated markers are linked to polycomb associated loci and a significant fraction of the discovered markers is within noncoding RNA genes; one of the best markers is MIR129-2. Future clinical testing of herein discovered markers will confirm new markers that will improve minimally invasive diagnosis and monitoring for multiple cancers.     

Biomarkers and molecular imaging in gastroenteropancreatic neuroendocrine tumors

Neuroendocrine gastrointestinal and pancreatic tumors (GEP-NETs) are a heterogenous group of cancers with various clinical expressions. All tumors produce and secret various amines and peptides, which can be used as tissue and circulating markers. Chromogranin A (CgA) is a general tumor marker stored in secretory granules within the tumor cell and released upon stimulation. CgA is the best general tumor marker at the moment, expressed in 80-90% in all patients with GEP-NETs. CgA and NSE are used as tissue markers for the delineation of the neuroendocrine features of the tumors, but recently also the proliferation marker Ki-67 has been included in the standard procedure for evaluation of the proliferation. GEP-NETs are classified into well differentiated neuroendocrine tumors (Ki-67<2%), well-differentiated neuroendocrine carcinoma (Ki-67 2-20%), poorly differentiated neuroendocrine carcinoma (Ki-67>20%). The molecular imaging of NETs is based on the ability of these tumor cells to express somatostatin receptors as well as the APUD features. Octreoscan has been applied for imaging and staging of the disease for more than 2 decades and will nowadays be replaced by 68Ga-DOTA-Octreotate, with higher specificity and sensitivity. 18Fluoro-DOPA and 11C-5HTP are specific tracers for NETs with high specificity and selectivity. A new potential biomarker is auto-antibodies to paraneoplastic antigen MA2, which might indicate early recurrence of carcinoids after surgery with a curative intent. Circulating tumor cells (CTC) have been applied in GEP-NETs quite recently. There is still an unmet need for new markers.     

Diagnosis of rheumatoid arthritis: multivariate analysis of biomarkers.

OBJECTIVE: To test if a combination of biomarkers can increase the classification power of autoantibodies to cyclic citrullinated peptides (anti-CCP) in the diagnosis of rheumatoid arthritis (RA) depending on the diagnostic situation. METHODS: Biomarkers were subject to three inclusion/exclusion criteria (discrimination between RA patients and healthy blood donors, ability to identify anti-CCP-negative RA patients, specificity in a panel with major non-rheumatological diseases) before univariate ranking and multivariate analysis was carried out using a modelling panel (n = 906). To enable the evaluation of the classification power in different diagnostic settings the disease controls (n = 542) were weighted according to the admission rates in rheumatology clinics modelling a clinic panel or according to the relative prevalences of musculoskeletal disorders in the general population seen by general practitioners modelling a GP panel. RESULT: Out of 131 biomarkers considered originally, we evaluated 32 biomarkers in this study, of which only seven passed the three inclusion/exclusion criteria and were combined by multivariate analysis using four different mathematical models. In the modelled clinic panel, anti-CCP was the lead marker with a sensitivity of 75.8% and a specificity of 94.0%. Due to the lack in specificity of the markers other than anti-CCP in this diagnostic setting, any gain in sensitivity by any marker combination is off-set by a corresponding loss in specificity. In the modelled GP panel, the best marker combination of anti-CCP and interleukin (IL)-6 resulted in a sensitivity gain of 7.6% (85.9% vs. 78.3%) at a minor loss in specificity of 1.6% (90.3% vs. 91.9%) compared with anti-CCP as the best single marker. CONCLUSION: Depending on the composition of the sample panel, anti-CCP alone or anti-CCP in combination with IL-6 has the highest classification power for the diagnosis of established RA.     

The diagnostic value of RNA oncomarkers in evaluation of malignant breast tumors

The levels of the RNA oncomarkers, telomerase (hTERT), cytokeratin-19 (CK-19), and mammaglobin (MAM) have been investigated in capillary blood of female patients with mammary ductal carcinoma. The study revealed overexpression of all three factors in patients with this pathology. This overexpression was not found in healthy donors and female patients with mammary fibroadenoma. Levels of the RNA oncomarkers return to the normal level within 10 days after successful tumor resection. These results have been used for the development of diagnostic kits, which may be applicable for differential diagnostics, screening and postoperation monitoring of patients with malignant breast tumors.     

Mammaglobin in peripheral blood and the tumor of breast cancer patients

Currently, no molecular biological markers do exist for early diagnosis of breast cancer. One of the possible candidates for the marker of early breast cancer is mammaglobin (MGB1) or SCGB2A2 (secretoglobin, family 2A, member 2), characterized by the maximal expression level in early breast cancer. Using the RT-PCR method MGB1 mRNA expression was examined in 57 tumor tissue samples and 57 samples of morphologically non-malignant tissue (MNT) of breast cancer (BC) patients. Specificity and sensitivity of the MGB1 mRNA assay in peripheral blood of BC patients was evaluated by nested PCR. 169 blood samples (from 95 BC patients, 22 from patients with benign breast tumors, 28 from patients with tumors of other localizations, and 24 samples from healthy donors) have been analyzed. MGB1 expression was significantly higher in BC tissue samples compared to MNT (p = 0.0019). The maximal expression level was in the samples T1 (p = 0.013), stage I BC (p = 0.037), GI (p = 0.0019). MGB1 expression positively correlated with expression of estrogen (p = 0.034) and progesterone (p = 0.0004) receptors. Sensitivity and specificity of the MGB1 mRNA assay in peripheral blood were 60.6 and 92.3%, respectively. Expression of MGB1 was higher in BC than MNT and it decreased during BC progression. The sensitivity and specificity of the MGB1 mRNA assay may be used as an additional diagnostic method.     

The diagnostic performance of current tumour markers in surveillance for recurrent testicular cancer: A diagnostic test accuracy systematic review

In this diagnostic test accuracy systematic review we summarise the evidence on the diagnostic accuracy of blood α-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) in surveillance for testicular cancer recurrence in adults. We searched four electronic databases for studies that reported the diagnostic accuracy of HCG, AFP, and/or LDH in sufficient detail for sensitivity and specificity to be calculated by extracting a 2 × 2 table comparing biomarker positivity with testicular cancer recurrence. Screening, data extraction and QUADAS-2 quality assessment were completed by two independent reviewers. From 2406 studies, nine met our inclusion criteria. Eight reported data at the per-patient level. Sample sizes were small (range 5 to 449 patients) and clinical heterogeneity precluded meta-analysis. In most studies the specificity for recurrence with AFP and HCG was high (90–100%) but sensitivity was often relatively low, suggesting that many recurrences would not be detected by tumour markers alone. The diagnostic performance of LDH appears poorer. Studies were methodologically weak, with probable selection, incorporation and partial verification bias, and many studies were excluded for not reporting on recurrence-free patients. Limitations including small sample sizes, high heterogeneity, and inconsistent and incomplete reporting mean these results must be interpreted with caution. Despite inclusion of biomarkers in international surveillance guidance, there remains a lack of high quality evidence about their accuracy, optimal thresholds, and the most effective surveillance strategy in relation to contemporary investigative modalities. Higher quality research using data from modern-day follow-up cohorts is necessary to identify opportunities to reduce unnecessary testing.     

Cerebrospinal fluid markers in differential diagnosis of Alzheimer's disease and vascular dementia

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common causes of dementia in old people. They remain difficult to differentiate in practice because of lack of sensitivity and specificity of current clinical diagnostic criteria. Recent molecular and cellular advancements indicate that the use of cerebrospinal fluid markers may improve early detection and differential diagnosis of AD. Our objective in this study was to determine diagnostic accuracy of three cerebrospinal (CSF) markers: total tau protein (t-tau), tau protein phosphorylated on threonine 181 (p-tau181) and tau protein phosphorylated on serine 199 (p-tau199). Using commercially available ELISA kits concentrations of t-tau, p-tau181 and p-tau199 were analyzed in 12 patients with probable AD, 9 patients with VaD and 12 NC subjects. The median levels of all three markers were significantly higher in AD group versus VaD and NC groups. However, when the sensitivity levels were set to 85% or higher, only t-tau and p-tau199 satisfied consensus recommendations (specificity more than 75%) when differentiating AD from VaD. In conclusion, our preliminary data on a small group of selected subjects suggest that the CSF t-tau and p-tau199 levels are useful markers for differentiating AD from VaD.     

Early diagnosis of lung cancer by detection of tumor liberated protein

Tumor liberated protein (TLP) is a protein that can be used to reveal the early development of a tumor. Besides being formed in the tumor, TLP is released in the blood when a patient starts producing cancer cells, which in turn enables the physician to intervene at a stage when the cancer is operable. To date, the available studies of tumor markers in lung cancer patients are CEA, NSE, TPA, Chromogranine, CA125, CA19-9, and Cyfra 21-1. The sensitivity and specificity for serum markers ranges between 50 and 90%, depending on the study and the clinical samples analyzed. Most of these markers show an increased rate of positivity as the stage advances. There are very limited data on TLP to draw any firm conclusion regarding the diagnostic value of this marker. TLP has been detected in 53.1% of non-small cell lung cancer (NSCLC) patients (N = 534) with 75% being positive in the early stage (stage I) and dropping to 45% in the late stage (stage IV). However, 7.6% blood donor sera and 17.4% chronic lung disease sera have also tested positive. In a confirmation study, the specificity was 89.94% and the sensibility was 63.63% from stage III to IV NSCLC patients. In an initial study of TLP as a marker for early detection in stage I, NSCLC patients showed a sensitivity of 66.7% and a specificity of 80% for TLP compared to a sensitivity of 33.3% for CA19-9, 11.1% for Cyfra 21-1 and CA125, and 0% for CEA; the specificity for all four of the latter markers was 100%. Using immunohistochemical analysis with peroxidase anti-peroxidase (PAP), we observed that NSCLC cells were positive; we used the specific rabbit antiserum to TLP, which turned out negative in the presence of 1 mg/ml of the synthetized peptide. The pre-serum was also negative. The same reactivity was found early in the modified epithelial cells of interstitial lung fibrosis and might be a predictive marker of cell transformation. The site of the peroxidase positivity was cytoplasmic, of diffuse and/or granular type.     

Preoperative prediction of postoperative edema and effusion in pediatric cardiac surgery by altered antigen expression patterns on granulocytes and monocytes

Postoperative edema and effusion (POEE) following cardiopulmonary bypass (CPB) surgery in children retards recovery and may aggravate postpericardiotomy (PPS), capillary leak syndrome (CLS), or multiorgan failure (MOF). Compared with complication-free children, POEE affected children have different preoperative serum levels of circulating cytokines and adhesion molecules. These levels may be used preoperatively to assess POEE, but their determination is time consuming, costly, and a substantial blood volume is required. Altered serum levels of cytokines and adhesion molecules also may be reflected in altered antigen expression on circulating blood leukocytes. The predictive potential of flow cytometric (FCM) leukocyte immunophenotyping was explored as a sensitive and fast method that required small blood samples. Blood samples taken 24 h preoperatively from 49 patients (3-18 years old) were stained with monoclonal antibodies for adhesion molecules (ICAM-1, LFA-1, Mac-1) or constitutive/activation markers (CD4, CD14, CD16, CD25, CD54, CD69, HLA-DR) and measured on a microbead calibrated FCM. Neutrophils, monocytes, and eosinophils from POEE patients express higher preoperative levels of LFA-1, monocytes, HLA-DR, and other activation markers (all P < 0.03). Over 89% of the patients were classified correctly by using two discriminant analysis methods (sensitivity, >76%; specificity, >86%; positive prediction, >80%; negative prediction, >83%). Granulocytes and monocytes of postoperative POEE patients exhibit significant preoperative immune activation, suggesting an increased risk for patients with atopic/allergic predisposition. Surgical trauma and CPB cause additional immune activation, leading to POEE by a summative response. Most patients at risk for POEE can be identified preoperatively by using data pattern analysis on FCM-derived parameters.     

Diagnosis of rheumatoid arthritis: multivariate analysis of biomarkers

Objective. To test if a combination of biomarkers can increase the classification power of autoantibodies to cyclic citrullinated peptides (anti-CCP) in the diagnosis of rheumatoid arthritis (RA) depending on the diagnostic situation. Methods. Biomarkers were subject to three inclusion/exclusion criteria (discrimination between RA patients and healthy blood donors, ability to identify anti-CCP-negative RA patients, specificity in a panel with major non-rheumatological diseases) before univariate ranking and multivariate analysis was carried out using a modelling panel (n=906). To enable the evaluation of the classification power in different diagnostic settings the disease controls (n=542) were weighted according to the admission rates in rheumatology clinics modelling a clinic panel or according to the relative prevalences of musculoskeletal disorders in the general population seen by general practitioners modelling a GP panel. Results. Out of 131 biomarkers considered originally, we evaluated 32 biomarkers in this study, of which only seven passed the three inclusion/exclusion criteria and were combined by multivariate analysis using four different mathematical models. In the modelled clinic panel, anti-CCP was the lead marker with a sensitivity of 75.8% and a specificity of 94.0%. Due to the lack in specificity of the markers other than anti-CCP in this diagnostic setting, any gain in sensitivity by any marker combination is off-set by a corresponding loss in specificity. In the modelled GP panel, the best marker combination of anti-CCP and interleukin (IL)-6 resulted in a sensitivity gain of 7.6% (85.9% vs. 78.3%) at a minor loss in specificity of 1.6% (90.3% vs. 91.9%) compared with anti-CCP as the best single marker. Conclusions. Depending on the composition of the sample panel, anti-CCP alone or anti-CCP in combination with IL-6 has the highest classification power for the diagnosis of established RA.     

Preliminary study on serum levels of mucinous like cancer antigen (MCA) in patients with breast disease: comparison with CEA

MCA (mucinous-like cancer antigen) can be measured in the biological fluids of patients by means of a solid phase enzyme immunoassay. This study describes the results of MCA determination in sera of 230 patients with benign (99) and malignant (131) breast diseases. MCA levels were significantly higher in breast cancer patients than in non cancer patients and in healthy subjects (p less than 0.001). MCA concentrations tended to increase as the stage of the disease advanced. The 95th percentile of MCA value distribution in normal subjects showed a diagnostic sensitivity in breast cancer patients of 16.3% at stage I, 26.2% at stages II-III and 52% at stage IV. In a group of 118 cancer patients, MCA and CEA were tested simultaneously. The diagnostic sensitivity and specificity of MCA and CEA assays was very similar; nevertheless the association of the two tests showed 11 cases with high levels of MCA and low levels of CEA and 9 patients with high levels of CEA and low levels of MCA. Seventy-four out of 118 patients were negative for both markers and in 22 out of 118 patients markers were positive. The new marker MCA appeared to correlate with breast cancer and gave different information complementary to CEA.     

Gamma-glutamyltranspeptidase isoenzyme forms and lipoproteins in normal and pathological sera

The molecular nature of serum (from normal subjects and from patients affected by various hepatobiliary diseases) gamma-glutamyltranspeptidase (GGT) isoenzymes has been studied by selective lipoprotein precipitation. Some fractions co-precipitate with LDL + VLDL (pre-beta-, beta-, beta/gamma-, gamma-, and dep-GGT fractions) or with HDL (partial precipitation of alpha 1-GGT in cirrhosis). Alpha 1-GGT + alpha 2-GGT in normal subjects, and Alb-GGT did not precipitate with either of the precipitation treatments. Total GGT and its isoenzymes were stable at 4 degrees C and at -20 degrees C for at least 20 days, with the exception of Alb-GGT which at -20 degrees C decreased by 20%. The percentage of GGT associated with LDL + VLDL appeared to be a possible marker to discriminate liver tumors from cirrhosis. A cut-off value of 20 U/L of this marker yielded a diagnostic sensitivity of 87% and a diagnostic specificity of 85%.     

A model free approach to combining biomarkers

For most diseases, single biomarkers do not have adequate sensitivity or specificity for practical purposes. We present an approach to combine several biomarkers into a composite marker score without assuming a model for the distribution of the predictors. Using sufficient dimension reduction techniques, we replace the original markers with a lower-dimensional version, obtained through linear transformations of markers that contain sufficient information for regression of the predictors on the outcome. We combine the linear transformations using their asymptotic properties into a scalar diagnostic score via the likelihood ratio statistic. The performance of this score is assessed by the area under the receiver-operator characteristics curve (ROC), a popular summary measure of the discriminatory ability of a single continuous diagnostic marker for binary disease outcomes. An asymptotic chi-squared test for assessing individual biomarker contribution to the diagnostic score is also derived.     

Use of tumor markers in the management of head and neck cancer

Serologic tumor markers have been evaluated in the diagnosis, management and follow-up of patients with head and neck cancer. However, to the authors' knowledge no tumor marker has yet been shown to be useful for monitoring the response to chemotherapy in this type of disease, in particular for undifferentiated tumors. The pretreatment levels of CEA, TPA, SCC and ferritin were evaluated in 98 patients with advanced head and neck cancer. Of this group 64 patients were studied sequentially every month during planned chemotherapy and three weeks after treatment using standard commercial kits. The results showed the following sensitivity values: TPA 50%, CEA 36%, SCC 34% and ferritin 19%. The incidence and magnitude of the marker elevations were correlated with the extent of disease. In patients with squamous cell cancer SCC and CEA were elevated (by 68% and 54%, respectively) in tumors with good differentiation (G1), but only by 13% (both markers) in tumors classified as poorly differentiated (G3). CEA, SCC and ferritin serum levels were not correlated with response to chemotherapy, while TPA values correlated with the clinical response to treatment in 100% of patients with undifferentiated cancer and in 75% of those with squamous cell cancer. Our data indicate that in patients with head and neck cancer TPA appears to be a sensitive marker, followed in decreasing order of sensitivity by CEA, SCC and ferritin. However, SCC and CEA seem to be the most suitable markers for squamous cell cancer and in particular for more differentiated tumors (G1). Finally, TPA has proved to be a useful marker for monitoring the response to chemotherapy in patients with head and neck cancer, in particular for undifferentiated tumors.     

Simultaneous determination of urinary CEA, ferritin and TPA in Egyptian bladder cancer patients.

Urinary carcinoembryonic antigen (CEA), ferritin (Fer) and tissue polypeptide antigen (TPA) were determined in 328 cases (106 with bladder cancer, 152 with non-malignant urinary tract disease and 70 healthy controls). CEA was determined by the kit supplied by Roche Diagnostica (CEA EIA Doumab 60), ferritin by the Tandem-E Fer kit supplied by Hybritech and TPA by the Prolifigen TPA-IRMA kit supplied by Sangtec Medical. The results of this work revealed that combined determination of urine CEA and Fer, CEA and TPA or Fer and TPA showed higher sensitivity than determination of the individual markers. There was no significant difference between combined and individual marker determination with respect to false positivity in non-malignant urinary tract diseases. At 97% specificity, the sensitivities of urine CEA, Fer and TPA were 82.1%, 71.7% and 90.6%, respectively, while combined urine CEA & Fer, CEA & TPA and Fer & TPA showed sensitivities of 92.5%, 99.1% and 98.1%, respectively. When the specificity was related to the entire non-cancer group (patients with benign urinary tract diseases and normal controls), some reduction in the sensitivities of the combined markers was noted compared to the normal group only. In conclusion, combined determination of urine markers is superior to determination of individual markers in the diagnosis of bladder cancer.     

Determination of carbohydrate-deficient transferrin separated by lectin affinity chromatography for detecting chronic alcohol abuse.

Carbohydrate-deficient transferrin (CDT) has been established as a valuable biological marker for detecting chronic alcohol abuse. To improve the diagnostic efficiency, we studied new CDT determination procedures involving the use of lectin affinity chromatography with Allomyrina dichotoma agglutinin (allo A) and Trichosanthes japonica agglutinin I (TJA-I) to isolate the CDT isoforms CDT-allo A and CDT-TJA, respectively. These procedures, based on detection of the CDT-allo A and CDT-TJA isoforms in sera, showed high sensitivity (100% and 98%, respectively) and high specificity (93% and 85%, respectively). These results demonstrate that the new procedures involving the use of lectin affinity chromatography are more useful for isolating markers in the CDT test than the conventional charge-based separation method.     

Improved Detection of Microsatellite Instability in Early Colorectal Lesions

Microsatellite instability (MSI) occurs in over 90% of Lynch syndrome cancers and is considered a hallmark of the disease. MSI is an early event in colon tumor development, but screening polyps for MSI remains controversial because of reduced sensitivity compared to more advanced neoplasms. To increase sensitivity, we investigated the use of a novel type of marker consisting of long mononucleotide repeat (LMR) tracts. Adenomas from 160 patients, ranging in age from 29–55 years old, were screened for MSI using the new markers and compared with current marker panels and immunohistochemistry standards. Overall, 15 tumors were scored as MSI-High using the LMRs compared to 9 for the NCI panel and 8 for the MSI Analysis System (Promega). This difference represents at least a 1.7-fold increase in detection of MSI-High lesions over currently available markers. Moreover, the number of MSI-positive markers per sample and the size of allelic changes were significantly greater with the LMRs (p = 0.001), which increased confidence in MSI classification. The overall sensitivity and specificity of the LMR panel for detection of mismatch repair deficient lesions were 100% and 96%, respectively. In comparison, the sensitivity and specificity of the MSI Analysis System were 67% and 100%; and for the NCI panel, 75% and 97%. The difference in sensitivity between the LMR panel and the other panels was statistically significant (p<0.001). The increased sensitivity for detection of MSI-High phenotype in early colorectal lesions with the new LMR markers indicates that MSI screening for the early detection of Lynch syndrome might be feasible.