Impact of clinical and molecular factors on the estimation of colorectal adenomatous polyps recurrence in long-term clinical follow-up patients

Česká verzia

Authors: Š. Suchánek ¹; M. Minárik ²; L. Benešová ²; B. Belšánová ²; P. Mináriková ¹; P. Hrabal ⁴; P. Frič ¹; L. Dušek ³; M. Zavoral ¹
Authors place of work: Interní klinika 1. LF UK a ÚVN – VFN, Praha ¹; Genomac International, s. r. o, Centrum aplikované genomiky solidních nádorů, Praha ²; Institut biostatistiky a analýz, Masarykova univerzita, Brno ³; Oddělení patologie, ÚVN – VFN, Praha ⁴
Published in the journal: Gastroent Hepatol 2013; 67(5): 348-353
Category: Gastrointestinal Oncology: Original Article

Summary

Colorectal neoplasms development stages (adenomas) are determined by histopathological staging assessing the risk level of cancer development. Colorectal adenomas recurrence increases the requirements for patients’ follow-up. The malignant transformation process of the normal tissue is accompanied by characteristic changes of the level of genetic and epigenetic disorders. The main study objective was a long-term (6–11 years) monitoring of patients after endoscopic polypectomy, mainly in relation to the presence of recurrent adenomas. Another goal was to study the genetic profile of the most common somatic DNA copy number variations and their possible relation to adenoma histopathology characteristics.

Material and methods:
Patients included in the study went through a colonoscopy examination with their adenomas removed in the period of 2002–2006. A standard specimen histopathology examination was carried out and correlated with the examination of a selected panel of somatic mutations (genes APC, TP53, KRAS and BRAF), which are typical for sporadic colorectal cancers. A sub-group of patients was followed up by colonoscopy in recommended intervals with a focus on the relation between the removed adenoma mutation and the presence of recurrent adenomas in the interval a) ≤ 3 years or b) > 3 years.

Results:
48 patients (39 men, 9 women – mean age 62) were examined in total. Follow-up colonoscopies were performed in 30 patients. Recurrent adenoma in the interval ≤ 3 years was diagnosed in 11 of them (37%). In 19 patients (63%) no adenoma was detected or the interval of the adenoma recurrence was longer than 3 years. In both groups primary adenoma mutations were found: in 10 patients from the group with adenoma recurrence in ≤ 3 years and in 8 patients from the second group (90% and 42% resp.; p = 0.0249). Mutations were observed in 60% of patients (29/48): with an advanced adenoma (size ≥ 10mm, villous structure, high-grade dysplasia) and with an early adenoma (21 patients, 72%; 8 patients, 28% respectively).

Conclusion:
Follow-up in recommended intervals is an important tool to prevent the colorectal cancer development, mainly in the not negligible group of patients who develop repeated recurrent adenomas. The pilot results imply that the chromosomal instability phenotype (CIN) may represent an independent factor of an increased risk of such recurrence.

Key words:
colorectal neoplasms – adenoma – cancerogenesis – DNA copy number variations

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
6. 9. 2013

Accepted:
1. 10. 2013

Zdroje

1. Dušek L, Mužík J, Pavlík T et al. Epidemiologie zhoubných nádorů trávicího traktu v České republice – současný stav a predikce. Gastroent Hepatol 2012; 66(5): 331–339.

2. Zavoral M, Suchanek S, Zavada F et al. Colorectal cancer screening in Europe. World J Gastroenterol 2009; 15(47): 5907–5915.

3. Atkin W, Valori R, Kuipers EJ et al. Evaluation and interpretation of screening outcomes. In: Segnan N, Patnick J, von Karsa L (eds). European guidelines for quality assurance in colorectal cancer screening and diagnosis, 1st ed. Luxembourg: Publications Office of the European Union 2010; 273–298.

4. Quirke P, Risio M, Lambert R et al. Quality assurance in pathology in colorectal cancer screening and diagnosis. In: Segnan N, Patnick J, von Karsa L (eds). European guidelines for quality assurance in colorectal cancer screening and diagnosis, 1st ed. Luxembourg: Publications Office of the European Union 2010; 205–232.

5. Minarik M, Minarikova L, Hrabikova M et al. Application of cycling gradient capillary electrophoresis to detection of APC, K-ras, and DCC point mutations in patients with sporadic colorectal tumors. Electrophoresis 2004; 25(7–8): 1016–1021.

6. Imperiale TF, Wagner DR, Lin CY et al. Risk of advanced proximal neoplasms in asymptomatic adults according to the distal colorectal findings. N Engl J Med 2000; 343(3): 169–174.

7. Zavoral M, Suchánek Š, Májek O et al. Národní program screeningu kolorektálního karcinomu v České republice – minulost, přítomnost a budoucnost. Gastroent Hepatol 2012; 66(5): 345–349.

8. Suchanek S, Majek O, Vojtechova G et al. Colorectal cancer prevention in the Czech Republic: time trends in performance indicators and current situation after 10 years of screening. Eur J Cancer Prev 2013. [In press].

9. Robertson DJ, Greenberg ER, Beach M et al. Colorectal cancer in patients under close colonoscopic surveillance. Gastroenterology 2005; 129(1): 34–41.

10. Martinez ME, Baron JA, Liebermann DA et al. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology 2009; 136(3): 832–841.

11. Caldarella A, Crocetti E, Messerini L et al. Trends in colorectal incidence by anatomic subsite from 1985 to 2005: a population-based study. Int J Colorectal Dis 2013; 28(5): 637–641.

12. Issa JP. Colon cancer: it's CIN or CIMP. Clin Cancer Res 2008; 14(19): 5939–5940.

13. Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 2007; 50(1): 113–130.

14. Nishihara R, Wu K, Lochhead P et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013; 369(12): 1095–1105.

15. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990, 61(5): 759–767.

16. Habermann JK, Brucker CA, Freitag--Wolf S et al. Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma. Mod Pathol 2011; 24(4): 542–555.