Impact of clinical and molecular factors on the estimation of colorectal adenomatous polyps recurrence in long-term clinical follow-up patients
Štěpán Suchánek1, Marek Minárik2,1, Lucie Benešová2, Barbora Belšánová3, Petra Mináriková4, Petr Hrabal, Přemysl Frič5, Ladislav Dušek6,7, Miroslav Zavoral1
1 Interní klinika 1. LF UK a ÚVN – VFN Praha
2 Genomac výzkumný ústav, s. r. o., Centrum aplikované genomiky solidních nádorů, Praha
3 Genomac International, s. r. o, Centrum aplikované genomiky solidních nádorů, Praha
4 Interní klinika 1. LF UK a ÚVN – VFN, Praha
5 Interní klinika 1. LF UK a VFN a ÚVN –VFN Praha
6 Ústav zdravotnických informací a statistiky ČR, Praha
7 Institut biostatistiky a analýz LF MU, Brno
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.
Keywordsadenoma, colorectal cancer
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