CoChat
Sign Up
Cited by 43

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

RHAMM, p21 Combined Phenotype Identifies Microsatellite Instability-High Colorectal Cancers with a Highly Adverse Prognosis

Zlobec, Inti, Baker, Kristi, Terracciano, Luigi M., Lugli, Alessandro·2008·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-07-5103
Open this paper in CoChat — free account

Abstract

Purpose: The aim of this study was to identify prognostic subgroups of microsatellite instability-high (MSI-H) colorectal cancers by combined analysis of 10 well-established immunohistochemical tumor markers and 7 clinicopathologic features. Experimental Design: Using a tissue microarray, immunohistochemistry was done on 223 cases of MSI-H cancers for the following protein markers: raf-1 kinase inhibitor protein, receptor for hyaluronic acid–mediated motility, apoptosis protease activating factor-1, mammalian sterile20-like kinase 1, p21, p27, p53, ephrin B2 receptor, Ki-67, and epidermal growth factor receptor. Seven clinicopathologic features and all tumor markers were evaluated in univariate and multivariable analyses. Results: RHAMM overexpression [P < 0.001; hazard ratio [HR; 95% confidence interval (95% CI)], 3.86 (2.19-6.81)], loss of p21 [P = 0.002; 0.33 (0.16-0.67)], and higher N stage [P < 0.001; 3.31 (1.9-5.8)] were independent adverse prognostic factors. RHAMM/p21 combinations were evaluated by N stage. Significant differences in survival were observed with various RHAMM/p21 combinations (P < 0.001). Both node-negative and node-positive patients with RHAMM− tumors survived more than 120 months. Node-positive RHAMM+ patients had a strikingly worse prognosis [16.0 (10.0-63.0) months] and could further be divided into p21− patients [14.0 (9.0-27.0) months] and p21+ patients surviving 47.0 months. RHAMM+/p21− node-negative patients had a significantly shorter survival time than RHAMM+/p21+ tumors (P = 0.021). Conclusion: These results suggest that the combined phenotype of RHAMM and p21 expression is an invaluable independent prognostic immunohistochemical profile in MSI-H colorectal cancer. Based on the prognostic subgroups identified in our cohort, node-negative patients overexpressing RHAMM but with loss of p21 may derive a potential benefit from postoperative treatment, whereas adjuvant chemotherapy should be reconsidered for MSI-H node-positive RHAMM− tumors.

Overview

Integrity signals

Registry

Crossref · 10.1158/1078-0432.ccr-07-5103

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Show all 3 references

Research works printed but not linked: 58

  1. Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988;319:525–32. · DOI
  2. Jass JR, Young J, Leggett BA. Evolution of colorectal cancer: change of pace and change of direction. J Gastroenterol Hepatol 2002;17:17–26. · DOI
  3. Jass JR. Sporadic versus hereditary forms of colorectal cancer with the DNA microsatellite instability phenotype: to “lump” or “split”? Fam Cancer 2004;3:83. · DOI
  4. Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 2006;38:787–93. · DOI
  5. Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996;87:159–70. · DOI · Paper page
  6. Markowitz S, Wang J, Myeroff L, et al. Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science 1995;268:1336–8. · DOI
  7. Malesci A, Laghi L, Bianchi P, et al. Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res 2007;13:3831–9. · DOI
  8. Benatti P, Gafa R, Barana D, et al. Microsatellite instability and colorectal cancer prognosis. Clin Cancer Res 2005;11:8332–40. · DOI · Paper page
  9. Gryfe R, Kim H, Hsieh ET, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 2000;342:69–77. · DOI
  10. Sankila R, Aaltonen LA, Jarvinen HJ, Mecklin JP. Better survival rates in patients with MLH1-associated hereditary colorectal cancer. Gastroenterology 1996;110:682–7. · DOI
  11. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 2005;23:609–18. · DOI
  12. Andreyev HJ, Norman AR, Cunningham D, Oates JR, Clarke PA. Kirsten ras mutations in patients with colorectal cancer: the multicenter “RASCAL” study. J Natl Cancer Inst 1998;90:675–84. · DOI · Paper page
  13. Klump B, Nehls O, Okech T, et al. Molecular lesions in colorectal cancer: impact on prognosis? Original data and review of the literature. Int J Colorectal Dis 2004;19:23–42. · DOI
  14. Baker K, Zlobec I, Tornillo L, Terracciano L, Jass JR, Lugli A. Differential significance of tumour infiltrating lymphocytes in sporadic mismatch repair deficient versus proficient colorectal cancers: a potential role for dysregulation of the transforming growth factor-β pathway. Eur J Cancer 2007;43:624–31. · DOI
  15. Linnebacher M, Gebert J, Rudy W, et al. Frameshift peptide-derived T-cell epitopes: a source of novel tumor-specific antigens. Int J Cancer 2001;93:6–11. · DOI
  16. Barnetson RA, Tenesa A, Farrington SM, et al. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N Engl J Med 2006;354:2751–63. · DOI
  17. Carethers JM, Chauhan DP, Fink D, et al. Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 1999;117:123–31. · DOI
  18. Meyers M, Wagner MW, Hwang HS, Kinsella TJ, Boothman DA. Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. Cancer Res 2001;61:5193–201.
  19. Warusavitarne J, Schnitzler M. The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer. Int J Colorectal Dis 2007;22:739–48. · DOI
  20. Duffy MJ, van Dalen A, Haglund C, et al. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur J Cancer 2007;43:1348–60. · DOI
  21. Lugli A, Zlobec I, Gunthert U, et al. Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer. Mod Pathol 2006;19:1302–9. · DOI
  22. Hampel H, Stephens JA, Pukkala E, et al. Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology 2005;129:415–21. · DOI
  23. Minoo P, Zlobec I, Baker K, et al. Loss of raf-1 kinase inhibitor protein expression is associated with tumor progression and metastasis in colorectal cancer. Am J Clin Pathol 2007;127:820–7. · DOI
  24. Minoo P, Zlobec I, Baker K, et al. Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer. Mod Pathol 2007;20:331–8. · DOI
  25. Tornillo L, Lugli A, Zlobec I, et al. Prognostic value of cell cycle and apoptosis regulatory proteins in mismatch repair-proficient colorectal cancer: a tissue microarray-based approach. Am J Clin Pathol 2007;127:114–23. · DOI
  26. Zlobec I, Minoo P, Baker K, et al. Loss of APAF-1 expression is associated with tumour progression and adverse prognosis in colorectal cancer. Eur J Cancer 2007;43:1101–7. · DOI
  27. Zlobec I, Vuong T, Hayashi S, et al. A simple and reproducible scoring system for EGFR in colorectal cancer: application to prognosis and prediction of response to preoperative brachytherapy. Br J Cancer 2007;96:793–800. · DOI
  28. Lugli A, Spichtin H, Maurer R, et al. EphB2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancers. Clin Cancer Res 2005;11:6450–8. · DOI
  29. Zlobec I, Steele R, Terracciano L, Jass JR, Lugli A. Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol 2007;60:1112–6. · DOI
  30. Zlobec I, Baker K, Minoo P, Jass JR, Terracciano L, Lugli A. Node-negative colorectal cancer at high-risk of distant metastasis identified by combined analysis of lymph node status, vascular invasion and RKIP expression. Clin Cancer Res. In press 2008;14:143–8. · DOI
  31. Katz M. Multivariable analysis: a practical guide for clinicians. 2nd ed. Cambridge: Cambridge University Press; 2006. · DOI
  32. Benson AB III, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 2004;22:3408–19. · DOI
  33. Sobrero A. Should adjuvant chemotherapy become standard treatment for patients with stage II colon cancer? For the proposal. Lancet Oncol 2006;7:515–6. · DOI
  34. Bendardaf R, Lamlum H, Ristamaki R, Korkeila E, Syrjanen K, Pyrhonen S. Mismatch repair status is a predictive factor of tumour response to 5-fluorouracil and irinotecan chemotherapy in patients with advanced colorectal cancer. Tumour Biol 2007;28:212–20. · DOI
  35. Carethers JM, Smith EJ, Behling CA, et al. Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 2004;126:394–401. · DOI
  36. Jover R, Zapater P, Castells A, et al. Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer. Gut 2006;55:848–55. · DOI
  37. Turner RR, Li C, Compton CC. Newer pathologic assessment techniques for colorectal carcinoma. Clin Cancer Res 2007;13:6871–6s. · DOI
  38. Hamilton SR, Fard SF, Paiwand FF, et al. The hyaluronan receptors CD44 and Rhamm (CD168) form complexes with ERK1,2 that sustain high basal motility in breast cancer cells. J Biol Chem 2007;282:16667–80. · DOI
  39. Samuel SK, Hurta RA, Spearman MA, Wright JA, Turley EA, Greenberg AH. TGF-β1 stimulation of cell locomotion utilizes the hyaluronan receptor RHAMM and hyaluronan. J Cell Biol 1993;123:749–58. · DOI
  40. Delpech B, Girard N, Bertrand P, Courel MN, Chauzy C, Delpech A. Hyaluronan: fundamental principles and applications in cancer. J Intern Med 1997;242:41–8. · DOI
  41. Misra S, Toole BP, Ghatak S. Hyaluronan constitutively regulates activation of multiple receptor tyrosine kinases in epithelial and carcinoma cells. J Biol Chem 2006;281:34936–41. · DOI
  42. Zhang S, Chang MC, Zylka D, Turley S, Harrison R, Turley EA. The hyaluronan receptor RHAMM regulates extracellular-regulated kinase. J Biol Chem 1998;273:11342–8. · DOI
  43. Wang C, Thor AD, Moore DH II, et al. The overexpression of RHAMM, a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase and is a significant parameter in breast cancer progression. Clin Cancer Res 1998;4:567–76.
  44. Assmann V, Gillett CE, Poulsom R, Ryder K, Hart IR, Hanby AM. The pattern of expression of the microtubule-binding protein RHAMM/IHABP in mammary carcinoma suggests a role in the invasive behaviour of tumour cells. J Pathol 2001;195:191–6. · DOI
  45. Assmann V, Marshall JF, Fieber C, Hofmann M, Hart IR. The human hyaluronan receptor RHAMM is expressed as an intracellular protein in breast cancer cells. J Cell Sci 1998;111:1685–94. · DOI
  46. Duval A, Rolland S, Compoint A, et al. Evolution of instability at coding and non-coding repeat sequences in human MSI-H colorectal cancers. Hum Mol Genet 2001;10:513–8. · DOI
  47. Hardwick C, Hoare K, Owens R, et al. Molecular cloning of a novel hyaluronan receptor that mediates tumor cell motility. J Cell Biol 1992;117:1343–50. · DOI
  48. Blundell R. The biology of p21(Waf1/Cip1). Am J Biochem Biotechnol 2006;2:33–40. · DOI
  49. Roninson IB. Oncogenic functions of tumour suppressor p21(Waf1/Cip1/Sdi1): association with cell senescence and tumour-promoting activities of stromal fibroblasts. Cancer Lett 2002;179:1–14. · DOI · Paper page
  50. Jenkins MA, Hayashi S, O'Shea AM, et al. Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology 2007;133:48–56. · DOI
  51. Gafa R, Maestri I, Matteuzzi M, et al. Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability. Cancer 2000;89:2025–37. · DOI
  52. Soreide K. Molecular testing for microsatellite instability and DNA mismatch repair defects in hereditary and sporadic colorectal cancers—ready for prime time? Tumour Biol 2007;28:290–300. · DOI
  53. Lindor NM, Burgart LJ, Leontovich O, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 2002;20:1043–8. · DOI
  54. Marcus VA, Madlensky L, Gryfe R, et al. Immunohistochemistry for hMLH1 and hMSH2: a practical test for DNA mismatch repair-deficient tumors. Am J Surg Pathol 1999;23:1248–55. · DOI
  55. Cawkwell L, Gray S, Murgatroyd H, et al. Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair. Gut 1999;45:409–15. · DOI
  56. Dieumegard B, Grandjouan S, Sabourin JC, et al. Extensive molecular screening for hereditary non-polyposis colorectal cancer. Br J Cancer 2000;82:871–80. · DOI
  57. Terdiman JP, Gum JR, Jr., Conrad PG, et al. Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing. Gastroenterology 2001;120:21–30. · DOI
  58. Jass JR. Re: Ward et al. Routine testing for mismatch repair deficiency in sporadic colorectal cancer is justified. J Pathol 2005;207:377–84. J Pathol 2006;208:590–1. · DOI

Cited by

Sorted by citations

See all 43

Metadata

Authors
Zlobec, I., Baker, K., Terracciano, L. M., & Lugli, A.
Affiliations
  • 1Institute of Pathology, University Hospital of Basel, Basel, Switzerland; and
  • 2Department of Pathology, McGill University, Montreal, Quebec, Canada
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2008-06-15
Volume
14
Issue
12
Pages
3798-3806
ISSN
  • 1078-0432
  • 1557-3265
DOI
10.1158/1078-0432.ccr-07-5103
Cited by
43
References
3
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review