Tumor Microsatellite Instability and Clinical Outcome in Young Patients with Colorectal Cancer
Robert Gryfe, M.D., Hyeja Kim, M.Sc., Eugene T.K. Hsieh, M.D., Melyssa D. Aronson, M.Sc., Eric J. Holowaty, M.D., Shelley B. Bull, Ph.D., Mark Redston, M.D., and Steven Gallinger, M.D.
Background Colorectal cancer can arise through two distinctmutational pathways: microsatellite instability or chromosomalinstability. We tested the hypothesis that colorectal cancersarising from the microsatellite-instability pathway have distinctiveclinical attributes that affect clinical outcome.
Methods We tested specimens of colorectal cancer from a population-basedseries of 607 patients (50 years of age or younger at diagnosis)for microsatellite instability. We compared the clinical featuresand survival of patients who had colorectal cancer characterizedby high-frequency microsatellite instability with these characteristicsin patients who had colorectal cancers with microsatellite stability.
Results We found high-frequency microsatellite instability in17 percent of the colorectal cancers in 607 patients, and ina multivariate analysis, microsatellite instability was associatedwith a significant survival advantage independently of all standardprognostic factors, including tumor stage (hazard ratio, 0.42;95 percent confidence interval, 0.27 to 0.67; P< 0.001).Furthermore, regardless of the depth of tumor invasion, colorectalcancers with high-frequency microsatellite instability had adecreased likelihood of metastasizing to regional lymph nodes(odds ratio, 0.33; 95 percent confidence interval, 0.21 to 0.53;P< 0.001) or distant organs (odds ratio, 0.49; 95 percentconfidence interval, 0.27 to 0.89; P=0.02).
Conclusions High-frequency microsatellite instability in colorectalcancer is independently predictive of a relatively favorableoutcome and, in addition, reduces the likelihood of metastases.
Source Information
From the Centre for Cancer Genetics (R.G., H.K., E.T.K.H., M.R., S.G.) and the Division of Clinical Epidemiology (S.B.B.), Samuel Lunenfeld Research Institute; the Departments of Surgery (R.G., M.D.A., S.G.), Laboratory Medicine and Pathobiology (E.T.K.H., M.R.), and Public Health Sciences (E.J.H., S.B.B.), University of Toronto; and Cancer Care Ontario (E.J.H.) — all in Toronto.
Address reprint requests to Dr. Gallinger at Mount Sinai Hospital, 600 University Ave., Suite 1225, Toronto, ON M5G 1X5, Canada, or at sgallinger{at}mtsinai.on.ca.
Zaanan, A., Cuilliere-Dartigues, P., Guilloux, A., Parc, Y., Louvet, C., de Gramont, A., Tiret, E., Dumont, S., Gayet, B., Validire, P., Flejou, J.-F., Duval, A., Praz, F.
(2009). Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin. Ann Oncol
0: mdp383v1-mdp383
[Abstract][Full Text]
Woerner, S. M., Yuan, Y. P., Benner, A., Korff, S., von Knebel Doeberitz, M., Bork, P.
(2009). SelTarbase, a database of human mononucleotide-microsatellite mutations and their potential impact to tumorigenesis and immunology. Nucleic Acids Res
0: gkp839v1-gkp839
[Abstract][Full Text]
Llobet, D, Pallares, J, Yeramian, A, Santacana, M, Eritja, N, Velasco, A, Dolcet, X, Matias-Guiu, X
(2009). Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. J. Clin. Pathol.
62: 777-785
[Abstract][Full Text]
Kauff, N. D.
(2009). ATR Mutations in Endometrial Cancer: A Window Into the Role of Mismatch Repair Defects. JCO
27: 3077-3078
[Full Text]
Vilar, E., Mukherjee, B., Kuick, R., Raskin, L., Misek, D. E., Taylor, J. M.G., Giordano, T. J., Hanash, S. M., Fearon, E. R., Rennert, G., Gruber, S. B.
(2009). Gene Expression Patterns in Mismatch Repair-Deficient Colorectal Cancers Highlight the Potential Therapeutic Role of Inhibitors of the Phosphatidylinositol 3-Kinase-AKT-Mammalian Target of Rapamycin Pathway. Clin. Cancer Res.
15: 2829-2839
[Abstract][Full Text]
Bertagnolli, M. M., Niedzwiecki, D., Compton, C. C., Hahn, H. P., Hall, M., Damas, B., Jewell, S. D., Mayer, R. J., Goldberg, R. M., Saltz, L. B., Warren, R. S., Redston, M.
(2009). Microsatellite Instability Predicts Improved Response to Adjuvant Therapy With Irinotecan, Fluorouracil, and Leucovorin in Stage III Colon Cancer: Cancer and Leukemia Group B Protocol 89803. JCO
27: 1814-1821
[Abstract][Full Text]
Bertagnolli, M. M., Warren, R. S., Niedzwiecki, D., Mueller, E., Compton, C. C., Redston, M., Hall, M., Hahn, H. P., Jewell, S. D., Mayer, R. J., Goldberg, R. M., Saltz, L. B., Loda, M.
(2009). p27Kip1 in Stage III Colon Cancer: Implications for Outcome following Adjuvant Chemotherapy in Cancer and Leukemia Group B Protocol 89803. Clin. Cancer Res.
15: 2116-2122
[Abstract][Full Text]
Asaka, S.-i., Arai, Y., Nishimura, Y., Yamaguchi, K., Ishikubo, T., Yatsuoka, T., Tanaka, Y., Akagi, K.
(2009). Microsatellite instability-low colorectal cancer acquires a KRAS mutation during the progression from Dukes' A to Dukes' B. Carcinogenesis
30: 494-499
[Abstract][Full Text]
Lenz, H.-J.
(2009). Established Biomarkers for Colon Cancer. Am Soc Clin Oncol Ed Book
2009: 215-219
[Abstract][Full Text]
Poynter, J. N., Siegmund, K. D., Weisenberger, D. J., Long, T. I., Thibodeau, S. N., Lindor, N., Young, J., Jenkins, M. A., Hopper, J. L., Baron, J. A., Buchanan, D., Casey, G., Levine, A. J., Marchand, L. L., Gallinger, S., Bapat, B., Potter, J. D., Newcomb, P. A., Haile, R. W., Laird, P. W., for the Colon Cancer Family Registry Investigators,
(2008). Molecular Characterization of MSI-H Colorectal Cancer by MLHI Promoter Methylation, Immunohistochemistry, and Mismatch Repair Germline Mutation Screening. Cancer Epidemiol. Biomarkers Prev.
17: 3208-3215
[Abstract][Full Text]
Pal, T., Permuth-Wey, J., Kumar, A., Sellers, T. A.
(2008). Systematic Review and Meta-analysis of Ovarian Cancers: Estimation of Microsatellite-High Frequency and Characterization of Mismatch Repair Deficient Tumor Histology. Clin. Cancer Res.
14: 6847-6854
[Abstract][Full Text]
Zlobec, I., Baker, K., Terracciano, L. M., Lugli, A.
(2008). RHAMM, p21 Combined Phenotype Identifies Microsatellite Instability-High Colorectal Cancers with a Highly Adverse Prognosis. Clin. Cancer Res.
14: 3798-3806
[Abstract][Full Text]
Chan, J. A., Meyerhardt, J. A., Niedzwiecki, D., Hollis, D., Saltz, L. B., Mayer, R. J., Thomas, J., Schaefer, P., Whittom, R., Hantel, A., Goldberg, R. M., Warren, R. S., Bertagnolli, M., Fuchs, C. S.
(2008). Association of Family History With Cancer Recurrence and Survival Among Patients With Stage III Colon Cancer. JAMA
299: 2515-2523
[Abstract][Full Text]
Lo, R. S., Witte, O. N.
(2008). Transforming Growth Factor-{beta} Activation Promotes Genetic Context-Dependent Invasion of Immortalized Melanocytes. Cancer Res.
68: 4248-4257
[Abstract][Full Text]
Le Gouvello, S, Bastuji-Garin, S, Aloulou, N, Mansour, H, Chaumette, M-T, Berrehar, F, Seikour, A, Charachon, A, Karoui, M, Leroy, K, Farcet, J-P, Sobhani, I
(2008). High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas. Gut
57: 772-779
[Abstract][Full Text]
Ortega, P., Moran, A., de Juan, C., Frias, C., Hernandez, S., Lopez-Asenjo, J.-A., Sanchez-Pernaute, A., Torres, A., Iniesta, P., Benito, M.
(2008). Differential Wnt Pathway Gene Expression and E-Cadherin Truncation in Sporadic Colorectal Cancers with and without Microsatellite Instability. Clin. Cancer Res.
14: 995-1001
[Abstract][Full Text]
Bakkum-Gamez, J. N., Gonzalez-Bosquet, J., Laack, N. N., Mariani, A., Dowdy, S. C.
(2008). Current Issues in the Management of Endometrial Cancer. Mayo Clin Proc.
83: 97-112
[Abstract][Full Text]
Nijhuis, E R, Nijman, H W, Oien, K A, Bell, A, ten Hoor, K A, Reesink-Peters, N, Boezen, H M, Hollema, H, van der Zee, A G J
(2007). Loss of MSH2 protein expression is a risk factor in early stage cervical cancer. J. Clin. Pathol.
60: 824-830
[Abstract][Full Text]
Malesci, A., Laghi, L., Bianchi, P., Delconte, G., Randolph, A., Torri, V., Carnaghi, C., Doci, R., Rosati, R., Montorsi, M., Roncalli, M., Gennari, L., Santoro, A.
(2007). Reduced Likelihood of Metastases in Patients with Microsatellite-Unstable Colorectal Cancer. Clin. Cancer Res.
13: 3831-3839
[Abstract][Full Text]
Kazama, Y., Watanabe, T., Kanazawa, T., Tanaka, J., Tanaka, T., Nagawa, H.
(2007). Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum: relationship to clinicopathological features. J. Clin. Pathol.
60: 701-704
[Abstract][Full Text]
Zighelboim, I., Goodfellow, P. J., Gao, F., Gibb, R. K., Powell, M. A., Rader, J. S., Mutch, D. G.
(2007). Microsatellite Instability and Epigenetic Inactivation of MLH1 and Outcome of Patients With Endometrial Carcinomas of the Endometrioid Type. JCO
25: 2042-2048
[Abstract][Full Text]
Wolpin, B. M., Meyerhardt, J. A., Mamon, H. J., Mayer, R. J.
(2007). Adjuvant Treatment of Colorectal Cancer. CA Cancer J Clin
57: 168-185
[Abstract][Full Text]
Boardman, L. A., Johnson, R. A., Petersen, G. M., Oberg, A. L., Kabat, B. F., Slusser, J. P., Wang, L., Morlan, B. W., French, A. J., Smyrk, T. C., Lindor, N. M., Thibodeau, S. N.
(2007). Higher Frequency of Diploidy in Young-Onset Microsatellite-Stable Colorectal Cancer. Clin. Cancer Res.
13: 2323-2328
[Abstract][Full Text]
Kim, G. P., Colangelo, L. H., Wieand, H. S., Paik, S., Kirsch, I. R., Wolmark, N., Allegra, C. J.
(2007). Prognostic and Predictive Roles of High-Degree Microsatellite Instability in Colon Cancer: A National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. JCO
25: 767-772
[Abstract][Full Text]
Boland, C. R.
(2007). Clinical Uses of Microsatellite Instability Testing in Colorectal Cancer: An Ongoing Challenge. JCO
25: 754-756
[Full Text]
Xicola, R. M., Llor, X., Pons, E., Castells, A., Alenda, C., Pinol, V., Andreu, M., Castellvi-Bel, S., Paya, A., Jover, R., Bessa, X., Giros, A., Duque, J. M., Nicolas-Perez, D., Garcia, A. M., Rigau, J., Gassull, M. A.
(2007). Performance of Different Microsatellite Marker Panels for Detection of Mismatch Repair-Deficient Colorectal Tumors. JNCI J Natl Cancer Inst
99: 244-252
[Abstract][Full Text]
Akao, J., Matsuyama, H., Yamamoto, Y., Sasaki, K., Naito, K.
(2006). Chromosome 20q13.2 Gain May Predict Intravesical Recurrence after Nephroureterectomy in Upper Urinary Tract Urothelial Tumors. Clin. Cancer Res.
12: 7004-7008
[Abstract][Full Text]
Locker, G. Y., Hamilton, S., Harris, J., Jessup, J. M., Kemeny, N., Macdonald, J. S., Somerfield, M. R., Hayes, D. F., Bast, R. C. Jr
(2006). ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer. JCO
24: 5313-5327
[Abstract][Full Text]
Hecht, J. L., Mutter, G. L.
(2006). Molecular and Pathologic Aspects of Endometrial Carcinogenesis. JCO
24: 4783-4791
[Abstract][Full Text]
You, J.-F., Hsieh, L.-L., Changchien, C. R., Chen, J.-S., Chen, J.-R., Chiang, J.-M., Yeh, C. Y., Hsieh, P.-S., Fan, C.-W., Liu, C.-T., Tang, R.
(2006). Inverse effects of mucin on survival of matched hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer patients.. Clin. Cancer Res.
12: 4244-4250
[Abstract][Full Text]
Barnetson, R. A., Tenesa, A., Farrington, S. M., Nicholl, I. D., Cetnarskyj, R., Porteous, M. E., Campbell, H., Dunlop, M. G.
(2006). Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer.. NEJM
354: 2751-2763
[Abstract][Full Text]
Carethers, J M
(2006). Prospective evaluation of fluorouracil chemotherapy based on the genetic makeup of colorectal cancer.. Gut
55: 759-761
[Full Text]
Jover, R, Zapater, P, Castells, A, Llor, X, Andreu, M, Cubiella, J, Pinol, V, Xicola, R M, Bujanda, L, Rene, J M, Clofent, J, Bessa, X, Morillas, J D, Nicolas-Perez, D, Paya, A, Alenda, C, for the Gastrointestinal Oncology Group of the Spa,
(2006). Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer. Gut
55: 848-855
[Abstract][Full Text]
Lanza, G., Gafa, R., Santini, A., Maestri, I., Guerzoni, L., Cavazzini, L.
(2006). Immunohistochemical Test for MLH1 and MSH2 Expression Predicts Clinical Outcome in Stage II and III Colorectal Cancer Patients. JCO
24: 2359-2367
[Abstract][Full Text]
Sinicrope, F. A., Rego, R. L., Halling, K. C., Foster, N. R., Sargent, D. J., La Plant, B., French, A. J., Allegra, C. J., Laurie, J. A., Goldberg, R. M., Witzig, T. E., Thibodeau, S. N.
(2006). Thymidylate synthase expression in colon carcinomas with microsatellite instability.. Clin. Cancer Res.
12: 2738-2744
[Abstract][Full Text]
Yamamoto, Y., Matsuyama, H., Kawauchi, S., Furuya, T., Liu, X. P., Ikemoto, K., Oga, A., Naito, K., Sasaki, K.
(2006). Biological characteristics in bladder cancer depend on the type of genetic instability.. Clin. Cancer Res.
12: 2752-2758
[Abstract][Full Text]
Black, D., Soslow, R. A., Levine, D. A., Tornos, C., Chen, S. C., Hummer, A. J., Bogomolniy, F., Olvera, N., Barakat, R. R., Boyd, J.
(2006). Clinicopathologic Significance of Defective DNA Mismatch Repair in Endometrial Carcinoma. JCO
24: 1745-1753
[Abstract][Full Text]
Deckers, M., van Dinther, M., Buijs, J., Que, I., Lowik, C., van der Pluijm, G., ten Dijke, P.
(2006). The Tumor Suppressor Smad4 Is Required for Transforming Growth Factor {beta}-Induced Epithelial to Mesenchymal Transition and Bone Metastasis of Breast Cancer Cells. Cancer Res.
66: 2202-2209
[Abstract][Full Text]
Chao, E. C., Lipkin, S. M.
(2006). Molecular models for the tissue specificity of DNA mismatch repair-deficient carcinogenesis. Nucleic Acids Res
34: 840-852
[Abstract][Full Text]
Benatti, P., Gafa, R., Barana, D., Marino, M., Scarselli, A., Pedroni, M., Maestri, I., Guerzoni, L., Roncucci, L., Menigatti, M., Roncari, B., Maffei, S., Rossi, G., Ponti, G., Santini, A., Losi, L., Di Gregorio, C., Oliani, C., Ponz de Leon, M., Lanza, G.
(2005). Microsatellite Instability and Colorectal Cancer Prognosis. Clin. Cancer Res.
11: 8332-8340
[Abstract][Full Text]
Giacomini, C. P., Leung, S. Y., Chen, X., Yuen, S. T., Kim, Y. H., Bair, E., Pollack, J. R.
(2005). A Gene Expression Signature of Genetic Instability in Colon Cancer. Cancer Res.
65: 9200-9205
[Abstract][Full Text]
Erill, N., Colomer, A., Calvo, M., Vidal, A., Roman, R., Verdu, M., Cordon-Cardo, C., Puig, X.
(2005). A Novel Multiplexing, Polymerase Chain Reaction-Based Assay for the Analysis of Chromosome 18q Status in Colorectal Cancer. J. Mol. Diagn.
7: 478-485
[Abstract][Full Text]
Findeisen, P., Kloor, M., Merx, S., Sutter, C., Woerner, S. M., Dostmann, N., Benner, A., Dondog, B., Pawlita, M., Dippold, W., Wagner, R., Gebert, J., von Knebel Doeberitz, M.
(2005). T25 Repeat in the 3' Untranslated Region of the CASP2 Gene: A Sensitive and Specific Marker for Microsatellite Instability in Colorectal Cancer. Cancer Res.
65: 8072-8078
[Abstract][Full Text]
Westra, J. L., Schaapveld, M., Hollema, H., de Boer, J. P., Kraak, M. M.J., de Jong, D., ter Elst, A., Mulder, N. H., Buys, C. H.C.M., Hofstra, R. M.W., Plukker, J. T.M.
(2005). Determination of TP53 Mutation Is More Relevant Than Microsatellite Instability Status for the Prediction of Disease-Free Survival in Adjuvant-Treated Stage III Colon Cancer Patients. JCO
23: 5635-5643
[Abstract][Full Text]
Eaton, A. M., Sandler, R., Carethers, J. M., Millikan, R. C., Galanko, J., Keku, T. O.
(2005). 5,10-Methylenetetrahydrofolate Reductase 677 and 1298 Polymorphisms, Folate Intake, and Microsatellite Instability in Colon Cancer. Cancer Epidemiol. Biomarkers Prev.
14: 2023-2029
[Abstract][Full Text]
Durno, C, Aronson, M, Bapat, B, Cohen, Z, Gallinger, S
(2005). Family history and molecular features of children, adolescents, and young adults with colorectal carcinoma. Gut
54: 1146-1150
[Abstract][Full Text]
Allen, W. L., Johnston, P. G.
(2005). Role of Genomic Markers in Colorectal Cancer Treatment. JCO
23: 4545-4552
[Abstract][Full Text]
Ricciardiello, L., Ceccarelli, C., Angiolini, G., Pariali, M., Chieco, P., Paterini, P., Biasco, G., Martinelli, G. N., Roda, E., Bazzoli, F.
(2005). High Thymidylate Synthase Expression in Colorectal Cancer with Microsatellite Instability: Implications for Chemotherapeutic Strategies. Clin. Cancer Res.
11: 4234-4240
[Abstract][Full Text]
Moran, A., Iniesta, P., de Juan, C., Garcia-Aranda, C., Diaz-Lopez, A., Benito, M.
(2005). Impairment of Stromelysin-1 Transcriptional Activity by Promoter Mutations in High Microsatellite Instability Colorectal Tumors. Cancer Res.
65: 3811-3814
[Abstract][Full Text]
Kohonen-Corish, M. R.J., Daniel, J. J., Chan, C., Lin, B. P.C., Kwun, S. Y., Dent, O. F., Dhillon, V. S., Trent, R. J.A., Chapuis, P. H., Bokey, E. L.
(2005). Low Microsatellite Instability Is Associated With Poor Prognosis in Stage C Colon Cancer. JCO
23: 2318-2324
[Abstract][Full Text]
Oda, S., Maehara, Y., Ikeda, Y., Oki, E., Egashira, A., Okamura, Y., Takahashi, I., Kakeji, Y., Sumiyoshi, Y., Miyashita, K., Yamada, Y., Zhao, Y., Hattori, H., Taguchi, K.-i., Ikeuchi, T., Tsuzuki, T., Sekiguchi, M., Karran, P., Yoshida, M. A.
(2005). Two modes of microsatellite instability in human cancer: differential connection of defective DNA mismatch repair to dinucleotide repeat instability. Nucleic Acids Res
33: 1628-1636
[Abstract][Full Text]
Hatch, S. B., Lightfoot, H. M. Jr., Garwacki, C. P., Moore, D. T., Calvo, B. F., Woosley, J. T., Sciarrotta, J., Funkhouser, W. K., Farber, R. A.
(2005). Microsatellite Instability Testing in Colorectal Carcinoma: Choice of Markers Affects Sensitivity of Detection of Mismatch Repair-Deficient Tumors. Clin. Cancer Res.
11: 2180-2187
[Abstract][Full Text]
Fukushima, T., Katayama, Y., Watanabe, T., Yoshino, A., Ogino, A., Ohta, T., Komine, C.
(2005). Promoter Hypermethylation of Mismatch Repair Gene hMLH1 Predicts the Clinical Response of Malignant Astrocytomas to Nitrosourea. Clin. Cancer Res.
11: 1539-1544
[Abstract][Full Text]
Popat, S., Hubner, R., Houlston, R.S.
(2005). Systematic Review of Microsatellite Instability and Colorectal Cancer Prognosis. JCO
23: 609-618
[Abstract][Full Text]
Banerjea, A., Clark, S., Dorudi, S.
(2005). The changing face of familial colorectal cancer. BMJ
330: 2-3
[Full Text]
Zaniboni, A., Labianca, R.
(2004). Adjuvant therapy for stage II colon cancer: an elephant in the living room?. Ann Oncol
15: 1310-1318
[Abstract][Full Text]
Roupret, M, Catto, J, Coulet, F, Azzouzi, A-R, Amira, N, Karmouni, T, Fromont, G, Sibony, M, Vallancien, G, Gattegno, B, Meuth, M, Hamdy, F C, Cussenot, O
(2004). Microsatellite instability as indicator of MSH2 gene mutation in patients with upper urinary tract transitional cell carcinoma. J. Med. Genet.
41: e91-e91
[Full Text]
Pfister, D. G., Benson, A. B. III, Somerfield, M. R.
(2004). Surveillance Strategies after Curative Treatment of Colorectal Cancer. NEJM
350: 2375-2382
[Full Text]
Gill, S., Loprinzi, C. L., Sargent, D. J., Thome, S. D., Alberts, S. R., Haller, D. G., Benedetti, J., Francini, G., Shepherd, L. E., Francois Seitz, J., Labianca, R., Chen, W., Cha, S. S., Heldebrant, M. P., Goldberg, R. M.
(2004). Pooled Analysis of Fluorouracil-Based Adjuvant Therapy for Stage II and III Colon Cancer: Who Benefits and by How Much?. JCO
22: 1797-1806
[Abstract][Full Text]
Wang, Y., Jatkoe, T., Zhang, Y., Mutch, M. G., Talantov, D., Jiang, J., McLeod, H. L., Atkins, D.
(2004). Gene Expression Profiles and Molecular Markers To Predict Recurrence of Dukes' B Colon Cancer. JCO
22: 1564-1571
[Abstract][Full Text]
Parc, Y, Gueroult, S, Mourra, N, Serfaty, L, Flejou, J-F, Tiret, E, Parc, R
(2004). Prognostic significance of microsatellite instability determined by immunohistochemical staining of MSH2 and MLH1 in sporadic T3N0M0 colon cancer. Gut
53: 371-375
[Abstract][Full Text]
Wild, P. J., Reichle, A., Andreesen, R., Rockelein, G., Dietmaier, W., Ruschoff, J., Blaszyk, H., Hofstadter, F., Hartmann, A.
(2004). Microsatellite Instability Predicts Poor Short-Term Survival in Patients with Advanced Breast Cancer after High-Dose Chemotherapy and Autologous Stem-Cell Transplantation. Clin. Cancer Res.
10: 556-564
[Abstract][Full Text]
Ponz de Leon, M, Benatti, P, Borghi, F, Pedroni, M, Scarselli, A, Di Gregorio, C, Losi, L, Viel, A, Genuardi, M, Abbati, G, Rossi, G, Menigatti, M, Lamberti, I, Ponti, G, Roncucci, L
(2004). Aetiology of colorectal cancer and relevance of monogenic inheritance. Gut
53: 115-122
[Abstract][Full Text]
Allegra, C. J., Kim, G., Kirsch, I. R., Iacopetta, B., Elsaleh, H., Zeps, N., Jimenez, J. J., Blanes, A., Diaz-Cano, S. J., Gryfe, R., Ribic, C. M., Sargent, D. J.
(2003). Microsatellite Instability in Colon Cancer. NEJM
349: 1774-1776
[Full Text]
Ward, R. L., Cheong, K., Ku, S.-L., Meagher, A., O'Connor, T., Hawkins, N. J.
(2003). Adverse Prognostic Effect of Methylation in Colorectal Cancer Is Reversed by Microsatellite Instability. JCO
21: 3729-3736
[Abstract][Full Text]
Fallik, D., Borrini, F., Boige, V., Viguier, J., Jacob, S., Miquel, C., Sabourin, J.-C., Ducreux, M., Praz, F.
(2003). Microsatellite Instability Is a Predictive Factor of the Tumor Response to Irinotecan in Patients with Advanced Colorectal Cancer. Cancer Res.
63: 5738-5744
[Abstract][Full Text]
Catto, J. W. F., Linkens, D. A., Abbod, M. F., Chen, M., Burton, J. L., Feeley, K. M., Hamdy, F. C.
(2003). Artificial Intelligence in Predicting Bladder Cancer Outcome: A Comparison of Neuro-Fuzzy Modeling and Artificial Neural Networks. Clin. Cancer Res.
9: 4172-4177
[Abstract][Full Text]
Nash, G.M., Gimbel, M., Shia, J., Culliford, A.T., Nathanson, D.R., Ndubuisi, M., Yamaguchi, Y., Zeng, Z.S., Barany, F., Paty, P.B.
(2003). Automated, Multiplex Assay for High-Frequency Microsatellite Instability in Colorectal Cancer. JCO
21: 3105-3112
[Abstract][Full Text]
Mori, Y., Selaru, F. M., Sato, F., Yin, J., Simms, L. A., Xu, Y., Olaru, A., Deacu, E., Wang, S., Taylor, J. M., Young, J., Leggett, B., Jass, J. R., Abraham, J. M., Shibata, D., Meltzer, S. J.
(2003). The Impact of Microsatellite Instability on the Molecular Phenotype of Colorectal Tumors. Cancer Res.
63: 4577-4582
[Abstract][Full Text]
Ribic, C. M., Sargent, D. J., Moore, M. J., Thibodeau, S. N., French, A. J., Goldberg, R. M., Hamilton, S. R., Laurent-Puig, P., Gryfe, R., Shepherd, L. E., Tu, D., Redston, M., Gallinger, S.
(2003). Tumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer. NEJM
349: 247-257
[Abstract][Full Text]
Graziano, F., Cascinu, S.
(2003). Prognostic molecular markers for planning adjuvant chemotherapy trials in Dukes' B colorectal cancer patients: how much evidence is enough?. Ann Oncol
14: 1026-1038
[Abstract][Full Text]
Chung, D. C., Rustgi, A. K.
(2003). The Hereditary Nonpolyposis Colorectal Cancer Syndrome: Genetics and Clinical Implications. ANN INTERN MED
138: 560-570
[Abstract][Full Text]
Shannon, C., Kirk, J., Barnetson, R., Evans, J., Schnitzler, M., Quinn, M., Hacker, N., Crandon, A., Harnett, P.
(2003). Incidence of Microsatellite Instability in Synchronous Tumors of the Ovary and Endometrium. Clin. Cancer Res.
9: 1387-1392
[Abstract][Full Text]
Peltomaki, P.
(2003). Role of DNA Mismatch Repair Defects in the Pathogenesis of Human Cancer. JCO
21: 1174-1179
[Abstract][Full Text]
Lynch, H. T., de la Chapelle, A.
(2003). Hereditary Colorectal Cancer. NEJM
348: 919-932
[Full Text]
Diep, C. B., Thorstensen, L., Meling, G. I., Skovlund, E., Rognum, T. O., Lothe, R. A.
(2003). Genetic Tumor Markers With Prognostic Impact in Dukes' Stages B and C Colorectal Cancer Patients. JCO
21: 820-829
[Abstract][Full Text]
Ashktorab, H., Smoot, D. T., Carethers, J. M., Rahmanian, M., Kittles, R., Vosganian, G., Doura, M., Nidhiry, E., Naab, T., Momen, B., Shakhani, S., Giardiello, F. M.
(2003). High Incidence of Microsatellite Instability in Colorectal Cancer from African Americans. Clin. Cancer Res.
9: 1112-1117
[Abstract][Full Text]
Allegra, C., Sargent, D.
(2003). Molecular Diagnostics: Assays, Tissues, Progress, and Pitfalls. JCO
21: 395-396
[Full Text]
Bilchik, A. J., Nora, D. T., Saha, S., Turner, R., Wiese, D., Kuo, C., Ye, X., Morton, D. L., Hoon, D. S. B.
(2002). The Use of Molecular Profiling of Early Colorectal Cancer to Predict Micrometastases. Arch Surg
137: 1377-1383
[Abstract][Full Text]
Rashid, A., Ueki, T., Gao, Y.-T., Houlihan, P. S., Wallace, C., Wang, B.-S., Shen, M.-C., Deng, J., Hsing, A. W.
(2002). K-ras Mutation, p53 Overexpression, and Microsatellite Instability in Biliary Tract Cancers: A Population-based Study in China. Clin. Cancer Res.
8: 3156-3163
[Abstract][Full Text]
Farrand, K., Jovanovic, L., Delahunt, B., McIver, B., Hay, I. D., Eberhardt, N. L., Grebe, S. K. G.
(2002). Loss of Heterozygosity Studies Revisited: Prior Quantification of the Amplifiable DNA Content of Archival Samples Improves Efficiency and Reliability. J. Mol. Diagn.
4: 150-158
[Abstract][Full Text]
Nakata, B., Qing Wang, Y., Yashiro, M., Nishioka, N., Tanaka, H., Ohira, M., Ishikawa, T., Nishino, H., Hirakawa, K.
(2002). Prognostic Value of Microsatellite Instability in Resectable Pancreatic Cancer. Clin. Cancer Res.
8: 2536-2540
[Abstract][Full Text]
Moran, A., Iniesta, P., de Juan, C., Gonzalez-Quevedo, R., Sanchez-Pernaute, A., Diaz-Rubio, E., Cajal, S. R. y, Torres, A., Balibrea, J. L., Benito, M.
(2002). Stromelysin-1 Promoter Mutations Impair Gelatinase B Activation in High Microsatellite Instability Sporadic Colorectal Tumors. Cancer Res.
62: 3855-3860
[Abstract][Full Text]
Stoehlmacher, J., Park, D. J., Zhang, W., Groshen, S., Tsao-Wei, D. D., Yu, M. C., Lenz, H.-J.
(2002). Association Between Glutathione S-Transferase P1, T1, and M1 Genetic Polymorphism and Survival of Patients With Metastatic Colorectal Cancer. JNCI J Natl Cancer Inst
94: 936-942
[Abstract][Full Text]
Dolcetti, R., Guidoboni, M., Viel, A., Boiocchi, M., Samowitz, W. S., Slattery, M. L.
(2002). Correspondence re: Samowitz et al., Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol. Biomark. Prev., 10: 917-923, 2001. Cancer Epidemiol. Biomarkers Prev.
11: 499-500
[Full Text]
Richman, S., Adlard, J.
(2002). Left and right sided large bowel cancer. BMJ
324: 931-932
[Full Text]
Colangelo, L. A., Gapstur, S. M., Gann, P. H., Dyer, A. R., Liu, K.
(2002). Colorectal Cancer Mortality and Factors Related to the Insulin Resistance Syndrome. Cancer Epidemiol. Biomarkers Prev.
11: 385-391
[Abstract][Full Text]
Park, J., Betel, D., Gryfe, R., Michalickova, K., Di Nicola, N., Gallinger, S., Hogue, C. W. V., Redston, M.
(2002). Mutation Profiling of Mismatch Repair-deficient Colorectal Cancers Using an in Silico Genome Scan to Identify Coding Microsatellites. Cancer Res.
62: 1284-1288
[Abstract][Full Text]
Halford, S., Sasieni, P., Rowan, A., Wasan, H., Bodmer, W., Talbot, I., Hawkins, N., Ward, R., Tomlinson, I.
(2002). Low-Level Microsatellite Instability Occurs in Most Colorectal Cancers and Is a Nonrandomly Distributed Quantitative Trait. Cancer Res.
62: 53-57
[Abstract][Full Text]
van Rijnsoever, M., Elsaleh, H., Iacopetta, B., Guidoboni, M., Viel, A., Del Tin, L., Boiocchi, M., Dolcetti, R., Gafa, R., Lanza, G., Doglioni, C., Macri, E., Russo, A., Santini, A.
(2002). Microsatellite Instability in Colorectal Cancer: Prognostic, Predictive or Both?. Am. J. Pathol.
160: 384-386
[Full Text]
Young, J., Simms, L. A., Biden, K. G., Wynter, C., Whitehall, V., Karamatic, R., George, J., Goldblatt, J., Walpole, I., Robin, S.-A., Borten, M. M., Stitz, R., Searle, J., McKeone, D., Fraser, L., Purdie, D. R., Podger, K., Price, R., Buttenshaw, R., Walsh, M. D., Barker, M., Leggett, B. A., Jass, J. R.
(2001). Features of Colorectal Cancers with High-Level Microsatellite Instability Occurring in Familial and Sporadic Settings : Parallel Pathways of Tumorigenesis. Am. J. Pathol.
159: 2107-2116
[Abstract][Full Text]
Kambara, T., Matsubara, N., Nakagawa, H., Notohara, K., Nagasaka, T., Yoshino, T., Isozaki, H., Sharp, G. B., Shimizu, K., Jass, J., Tanaka, N.
(2001). High Frequency of Low-Level Microsatellite Instability in Early Colorectal Cancer. Cancer Res.
61: 7743-7746
[Abstract][Full Text]
Onda, M., Nakamura, I., Suzuki, S., Takenoshita, S., Brogren, C.-H., Stampanoni, S., Li, D., Rampino, N.
(2001). Microsatellite Instability in Thyroid Cancer: Hot Spots, Clinicopathological Implications, and Prognostic Significance. Clin. Cancer Res.
7: 3444-3449
[Abstract][Full Text]
Ramsey, S. D., Clarke, L., Etzioni, R., Higashi, M., Berry, K., Urban, N.
(2001). Cost-Effectiveness of Microsatellite Instability Screening as a Method for Detecting Hereditary Nonpolyposis Colorectal Cancer. ANN INTERN MED
135: 577-588
[Abstract][Full Text]
Wu, A. H., Shibata, D., Yu, M. C., Lai, M.-Y., Ross, R. K.
(2001). Dietary heterocyclic amines and microsatellite instability in colon adenocarcinomas. Carcinogenesis
22: 1681-1684
[Abstract][Full Text]
Samowitz, W. S., Curtin, K., Ma, K.-N., Schaffer, D., Coleman, L. W., Leppert, M., Slattery, M. L.
(2001). Microsatellite Instability in Sporadic Colon Cancer Is Associated with an Improved Prognosis at the Population Level. Cancer Epidemiol. Biomarkers Prev.
10: 917-923
[Abstract][Full Text]
Houlston, R S
(2001). What we could do now: molecular pathology of colorectal cancer. Mol. Pathol.
54: 206-214
[Abstract][Full Text]
Lal, G., Ash, C., Hay, K., Redston, M., Kwong, E., Hancock, B., Mak, T., Kargman, S., Evans, J. F., Gallinger, S.
(2001). Suppression of Intestinal Polyps in Msh2-deficient and Non-Msh2-deficient Multiple Intestinal Neoplasia Mice by a Specific Cyclooxygenase-2 Inhibitor and by a Dual Cyclooxygenase-1/2 Inhibitor. Cancer Res.
61: 6131-6136
[Abstract][Full Text]
Guidoboni, M., Gafa, R., Viel, A., Doglioni, C., Russo, A., Santini, A., Del Tin, L., Macri, E., Lanza, G., Boiocchi, M., Dolcetti, R.
(2001). Microsatellite Instability and High Content of Activated Cytotoxic Lymphocytes Identify Colon Cancer Patients with a Favorable Prognosis. Am. J. Pathol.
159: 297-304
[Abstract][Full Text]
