Lynch Syndrome – the Pathologist’s Diagnosis

Česká verzia

Authors: M. Dušek ^1,2; L. Hadravský ¹; K. Černá ² ; J. Stehlík ²; M. Švajdler ^1,2; B. Kokošková ^1,2; M. Dubová ¹; M. Michal ¹; O. Daum ^1,2
Authors place of work: Šiklův ústav patologie, LF UK a FN Plzeň ¹; Bioptická laboratoř, s. r. o., Plzeň ²
Published in the journal: Klin Onkol 2016; 29(3): 180-186
Category: Přehledy
doi: https://doi.org/10.14735/amko2016180

Summary

Lynch syndrome (formerly known as hereditary non-polyposis colorectal cancer) is the most common hereditary colorectal cancer syndrome. The syndrome is caused by a germline mutation of one of the mismatch repair (MMR) genes responsible for DNA replication error repair. Impaired function of the proteins encoded by these genes leads to microsatellite instability (MSI), which is associated with increased incidence of neoplasms: mainly colorectal cancer. According to recent estimates, up to 5% of all colorectal cancers are associated with Lynch syndrome. Due to this relatively high frequency, familial occurence, absence of premorbid phenotype, and development of malignant tumors at a reproductive age, a correct diagnosis is important not only from an ethical but also from an economical point of view. Unfortunately, clinical means of diagnosis, namely, the revised Bethesda guidelines designed to detect patients suitable for genetic testing for Lynch syndrome, lack sufficient sensitivity. The methods associated with modern pathology are more sensitive than the clinical criteria used to detect patients suspected of having Lynch syndrome. Pathological diagnostics are based on direct or indirect detection of MSI. Indirect methods include analysis of morphological signs associated with MSI in histological samples from colorectal carcinoma patients and immunohistochemical investigation of MMR protein expression. To rule out sporadic cases caused by epigenetic inactivation of an MMR gene, molecular genetic investigation of the BRAF gene and methylation analysis of the MLH1 promoter are performed during diagnostic workup. A suspicion of Lynch syndrome based on the results of the methods mentioned above should be proven by detection of a germline mutation in an MMR gene in peripheral blood leukocytes.

Key words:
colorectal cancer – Lynch syndrome – HNPCC – MSI – microsatellite instability

This work was supported by IGA NT14227 with contribution of SVV 260171/2015.

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 recommendation for biomedical papers.

Submitted:
9. 6. 2015

Accepted:
20. 3. 2016

Zdroje

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