Title (srp)

Značaj epitelno-mezenhimalne tranzicije u kolorektalnoj karcinogenezi


Ranković, Branislava, 1980-


Zidar, Nina, 1960-
Boštjančič, Emanuela, 1979-
Rosić, Mirko, 1958-
Cvetković, Aleksandar, 1977-
Krstić, Miljan, 1973-

Description (srp)

ABSTRACT:The development of colorectal carcinoma (CRC) is divided in several stages, from normalmucosa to adenoma and invasive carcinoma. In routine diagnostic work, the correct diagnosisof colorectal adenoma, adenoma with epithelial misplacement and CRC is of utmostimportance, enabling to choose the optimal treatment. Endoscopic removal is the treatmentof choice for adenomas and adenomas with epithelial misplacement, since these lesions donot metastasize and additional surgical treatment is not necessary. In contrast, CRC includingearly stages (malignant adenomas) are capable to metastasize. It is important to make thecorrect diagnosis and to evaluate the risk for metastases and additionally treat these patientswith surgical removal of the colon if needed. Despite meticulous microscopic investigationof histological slides, it is not always possible to distinguish between various lesions.Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism in thedevelopment of CRC, but the information on EMT particularly in early stages of CRCdevelopment is missing. Previous studies have demonstrated some micro RNAs (e.g., miR141, miR-200a/b/c and miR-429) to be good markers of EMT.Our study included formalin-fixed paraffin-embedded biopsy samples of 62 patients (10adenomas and 30 cases of CRC with corresponding normal mucosa, 10 malignant adenomas,and 12 adenomas with pseudoinvasion). Expression of miR-141, miR-200a/b/c and miR-429and their target genes (CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2) wasanalysed using quantitative real-time PCR. Expression of E-cadherin was analysed usingimmunohistochemistry.All miRNAs were down-regulated and their target genes showed the opposite expression inCRC compared to adenoma. Down-regulation of the miR-200 family at the invasive front incomparison to the central part of tumour was observed as well as a correlation of expressionof the miR200b, CDKN1B, ONECUT2 and ZEB2 to nodal metastases. Expression of the miR200 family and SOX2 also correlated with E-cadherin staining. In addition, down-regulationof the miR-200 family and PTPN13 and upregulation of CDKN1B in early carcinomacompared to adenomas and adenomas with epithelial misplacement was observed.These results suggest that the miR-200 family and their target genes contribute to progressionof adenoma to CRC, invasive properties and development of metastases. Our results stronglysupport the postulated hypotheses of partial EMT and intra-tumour heterogeneity during CRCcancerogenesis.

Description (srp)


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