CD31-positive microvessel density within adenomas of Lynch Syndrome patients is similar compared to adenomas of non-Lynch patients

 

 Permissions and Reprints

Abstract

Background and study aims Microsatellite instability accelerates colorectal cancer development in patients with Lynch syndrome (LS). Previous research showed that virtual chromoendoscopy increases detection of adenomas during colonoscopy surveillance of patients with LS. Because previous research revealed that Lynch patients have an increased vascular network in the oral mucosa, we hypothesized that increased vascularization of LS-associated adenomas is the cause of better detection with virtual chromoendoscopy.

Patients and methods In this pilot study, patients with LS having a proven germline mutation were selected from two tertiary referral hospitals and non-LS patients from an outpatient colonoscopy center. Adenomas from patients with LS were exactly matched in size and histology with adenomas from non-LS patients. Initial adenoma diagnosis was confirmed by a specialist pathologist. All adenomas were stained with CD31 and adenomatous tissue was annotated by the specialist pathologist. Image analysis of CD31-positive microvessel density was conducted using FIJI software.

Results Colonoscopy of 63 patients with LS and 24 non-LS patients provided 40 adenomas that could be exactly matched in size and histology. In image-analysis, the CD31-positive microvessel density (2.49 % vs. 2.47 %, P = 0.96), the average size of CD31-positive structures (514 μm² vs. 523 μm², P = 0.26) nor the amount of vascular structures per mm² (183 vs. 176, P = 0.50) differed between adenomas of LS patients and non-Lynch patients.

Conclusion The outcomes of this pilot case-control study did not provide further insights into the mechanism of increased adenoma detection in LS patients using virtual chromoendoscopy techniques.

^* These authors contributed equally.

• References

• 1 Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 2003; 348: 919-932
  CrossrefPubMedGoogle Scholar
• 2 Jarvinen HJ, Aarnio M, Mustonen H. et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000; 118: 829-834
  CrossrefPubMedGoogle Scholar
• 3 Giardiello FM, Allen JI, Axilbund JE. et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer. Am J Gastroenterol 2014; 109: 1159-1179
  CrossrefPubMedGoogle Scholar
• 4 Vasen HF, Blanco I, Aktan-Collan K. et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 2013; 62: 812-823
  CrossrefPubMedGoogle Scholar
• 5 Stoffel EM, Mangu PB, Gruber SB. et al. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. J Clin Oncol 2015; 33: 209-217
  PubMedGoogle Scholar
• 6 Dove-Edwin I, Sasieni P, Adams J. et al. Prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: 16 year, prospective, follow-up study. BMJ 2005; 331: 1047
  CrossrefPubMedGoogle Scholar
• 7 Vasen HF, Abdirahman M, Brohet R. et al. One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome. Gastroenterology 2010; 138: 2300-2306
  CrossrefPubMedGoogle Scholar
• 8 Haanstra JF, Vasen HF, Sanduleanu S. et al. Quality colonoscopy and risk of interval cancer in Lynch syndrome. Int J Colorectal Dis 2013; 28: 1643-1649
  CrossrefPubMedGoogle Scholar
• 9 Edelstein DL, Axilbund J, Baxter M. et al. Rapid development of colorectal neoplasia in patients with Lynch syndrome. Clin Gastroenterol Hepatol 2011; 9: 340-343
  CrossrefPubMedGoogle Scholar
• 10 Rondagh EJ, Gulikers S, Gomez-Garcia EB. et al. Nonpolypoid colorectal neoplasms: a challenge in endoscopic surveillance of patients with Lynch syndrome. Endoscopy 2013; 45: 257-264
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Lecomte T, Cellier C, Meatchi T. et al. Chromoendoscopic colonoscopy for detecting preneoplastic lesions in hereditary nonpolyposis colorectal cancer syndrome. Clin Gastroenterol Hepatol 2005; 3: 897-902
  CrossrefPubMedGoogle Scholar
• 12 Hurlstone DP, Karajeh M, Cross SS. et al. The role of high-magnification-chromoscopic colonoscopy in hereditary nonpolyposis colorectal cancer screening: a prospective “back-to-back” endoscopic study. Am J Gastroenterol 2005; 100: 2167-2173
  CrossrefPubMedGoogle Scholar
• 13 Stoffel EM, Turgeon DK, Stockwell DH. et al. Missed adenomas during colonoscopic surveillance in individuals with Lynch Syndrome (hereditary nonpolyposis colorectal cancer). Cancer Prev Res (Phila) 2008; 1: 470-475
  CrossrefPubMedGoogle Scholar
• 14 Huneburg R, Lammert F, Rabe C. et al. Chromocolonoscopy detects more adenomas than white light colonoscopy or narrow band imaging colonoscopy in hereditary nonpolyposis colorectal cancer screening. Endoscopy 2009; 41: 316-322
  Article in Thieme ConnectPubMedGoogle Scholar
• 15 Rahmi G, Lecomte T, Malka D. et al. Impact of chromoscopy on adenoma detection in patients with Lynch syndrome: a prospective, multicenter, blinded, tandem colonoscopy study. Am J Gastroenterol 2015; 110: 288-298
  CrossrefPubMedGoogle Scholar
• 16 Bisschops R, Tejpar S, Willekens H. et al. Virtual chromoendoscopy (I-SCAN) detects more polyps in patients with Lynch syndrome: a randomized controlled crossover trial. Endoscopy 2017; 49: 342-350
  Article in Thieme ConnectPubMedGoogle Scholar
• 17 East JE, Suzuki N, Stavrinidis M. et al. Narrow band imaging for colonoscopic surveillance in hereditary non-polyposis colorectal cancer. Gut 2008; 57: 65-70
  PubMedGoogle Scholar
• 18 Kaminski MF, Hassan C, Bisschops R. et al. Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2014; 46: 435-449
  Article in Thieme ConnectPubMedGoogle Scholar
• 19 Nagorni A, Bjelakovic G, Petrovic B. Narrow band imaging versus conventional white light colonoscopy for the detection of colorectal polyps. Cochrane Database Syst Rev 2012; 1: Cd008361
  PubMedGoogle Scholar
• 20 Pasha SF, Leighton JA, Das A. et al. Comparison of the yield and miss rate of narrow band imaging and white light endoscopy in patients undergoing screening or surveillance colonoscopy: a meta-analysis. Am J Gastroenterol 2012; 107: 363-370
  CrossrefPubMedGoogle Scholar
• 21 Hong SN, Choe WH, Lee JH. et al. Prospective, randomized, back-to-back trial evaluating the usefulness of i-SCAN in screening colonoscopy. Gastrointest Endosc 2012; 75: 1011-1021.e2
  CrossrefPubMedGoogle Scholar
• 22 De Felice C, Latini G, Bianciardi G. et al. Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome. Gut 2003; 52: 1764-1767
  CrossrefPubMedGoogle Scholar
• 23 IJspeert JE, van Doorn SC, van der Brug YM. et al. The proximal serrated polyp detection rate is an easy-to-measure proxy for the detection rate of clinically relevant serrated polyps. Gastrointest Endosc 2015; 82: 870-877
  CrossrefPubMedGoogle Scholar
• 24 Umar A, Boland CR, Terdiman JP. et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004; 96: 261-268
  CrossrefPubMedGoogle Scholar
• 25 Bosman FTC, Hruban RH, Theise ND. WHO Classification of Tumours of the Digestive System, Fourth Edition. WHO Classification of Tumours 2010; Volume 3
  PubMedGoogle Scholar
• 26 Schindelin J, Arganda-Carreras I, Frise E. et al. Fiji: an open-source platform for biological-image analysis. Nat Methods 2012; 9: 676-682
  CrossrefPubMedGoogle Scholar
• 27 Staton CA, Chetwood AS, Cameron IC. et al. The angiogenic switch occurs at the adenoma stage of the adenoma carcinoma sequence in colorectal cancer. Gut 2007; 56: 1426-1432
  CrossrefPubMedGoogle Scholar
• 28 Hanrahan V, Currie MJ, Gunningham SP. et al. The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma-carcinoma sequence during colorectal cancer progression. J Pathol 2003; 200: 183-194
  CrossrefPubMedGoogle Scholar
• 29 Tjalma JJ, Garcia-Allende PB, Hartmans E. et al. Molecular fluorescence endoscopy targeting vascular endothelial growth factor A for improved colorectal polyp detection. J Nucl Med 2016; 57: 480-485
  CrossrefPubMedGoogle Scholar