Results of morphological screening for Lynch syndrome during the period 2013-2016

Czech version

Authors: Martin Dušek ^1,2; Ladislav Hadravský ³; Jan Stehlík ²; Kateřina Černá ²; Radmila Čurčíková ^2,4; Marián Švajdler ^1,2; Bohuslava Šašková ^1,2; Magdaléna Dubová ^1,2; Michal Michal ¹; Tomáš Jirásek ^3,4; Ondřej Daum ^1,2
Authors‘ workplace: Šiklův ústav patologie LF UK v Plzni a FN Plzeň ¹; Bioptická laboratoř, s. r. o., Plzeň ²; Ústav patologie 3. LF UK a FN Královské Vinohrady Praha ³; Oddělení patologie Krajské nemocnice Liberec, a. s. ⁴
Published in: Čes.-slov. Patol., 54, 2018, No. 2, p. 86-92
Category: Original Article

Overview

The introduction of a screening system for Lynch syndrome in pathology laboratories in Plzen yielded 24 diagnoses of Lynch syndrome during the period of 2013-2016, 20 of them presenting with colorectal cancer. In 8 of those 24 cases germline mutations of MMR genes, previously not recognized as pathogenic with certainty, were detected. Although the frequency of Lynch syndrome in patients with colorectal cancer was only 0.34 % in total, following introduction of the universal immunohistochemical investigation of MMR (mismatch repair) proteins expression in all colorectal cancers examined in Sikl´s Institute of Pathology the frequency per year in this department reached 2.4 %. The results favor universal immunohistochemical screening for Lynch syndrome in colorectal and endometrial cancer cases over a selective approach based on a combination of clinical and morphological criteria. Increased effectiveness of the universal approach is not brought about only by higher sensitivity of the immunohistochemical examination per se, but also by the possibility of automation of the process leading to increased adherence even of pathologists not directly engaged in Lynch syndrome management. However, the introduction of a nation-wide universal screening system requires support from the government and health insurance companies.

Keywords:

colorectal cancer – endometrial cancer – immunohistochemistry – Lynch syndrome – MMR – screening

Sources

1. Pai RK. A practical approach to the evaluation of gastrointestinal tract carcinomas for Lynch syndrome. Am J Surg Pathol 2016; 40(4): e17-34.

2. Nystrom-Lahti M, Wu Y, Moisio AL, et al. DNA mismatch repair gene mutations in 55 kindreds with verified or putative hereditary non-polyposis colorectal cancer. Hum Mol Genet 1996; 5(6): 763-769.

3. Gazzoli I, Loda M, Garber J, Syngal S, Kolodner RD. A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumor. Cancer Res 2002; 62(14): 3925-3928.

4. Hitchins MP, Wong JJ, Suthers G, et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. N Engl J Med 2007; 356(7): 697-705.

5. Ligtenberg MJ, Kuiper RP, Chan TL, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3’ exons of TACSTD1. Nat Genet 2009; 41(1): 112-117.

6. Kovacs ME, Papp J, Szentirmay Z, Otto S, Olah E. Deletions removing the last exon of TACSTD1 constitute a distinct class of mutations predisposing to Lynch syndrome. Hum Mutat 2009; 30(2): 197-203.

7. Kacerovská D, Kazakov DV, Černá K, et al. Muir-Torre syndrom - fenotypická varianta Lynchova syndromu. Cesk Patol 2010; 46(4): 86-94.

8. Hampel H, de la Chapelle A. The search for unaffected individuals with Lynch syndrome: do the ends justify the means? Cancer Prev Res (Phila) 2011; 4(1): 1-5.

9. Chen S, Wang W, Lee S, et al. Prediction of germline mutations and cancer risk in the Lynch syndrome. JAMA 2006; 296(12): 1479-1487.

10. Jenkins MA, Baglietto L, Dowty JG, et al. Cancer risks for mismatch repair gene mutation carriers: a population-based early onset case-family study. Clin Gastroenterol Hepatol 2006; 4(4): 489-498.

11. Quehenberger F, Vasen HF, van Houwelingen HC. Risk of colorectal and endometrial cancer for carriers of mutations of the hMLH1 and hMSH2 gene: correction for ascertainment. Journal of Medical Genetics 2005; 42(6): 491-496.

12. Zeimet AG, Mori H, Petru E, et al. AGO Austria recommendation on screening and diagnosis of Lynch syndrome (LS). Arch Gynecol Obstet 2017; 296(1): 123-127.

13. Sehgal R, Sheahan K, O’Connell PR, Hanly AM, Martin ST, Winter DC. Lynch syndrome: an updated review. Genes (Basel) 2014; 5(3): 497-507.

14. Barrow E, Hill J, Evans DG. Cancer risk in Lynch Syndrome. Fam Cancer 2013; 12(2): 229-240.

15. Lynch HT, de la Chapelle A. Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 1999; 36(11): 801-818.

16. Jass JR, Stewart SM. Evolution of hereditary non-polyposis colorectal cancer. Gut 1992; 33(6): 783-786.

17. 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(8): 1159-1179.

18. Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 1991; 34(5): 424-425.

19. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 1999; 116(6): 1453-1456.

20. 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(4): 261-268.

21. Hampel H, Frankel WL, Martin E, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 2005; 352(18): 1851-1860.

22. Liu T, Yan H, Kuismanen S, et al. The role of hPMS1 and hPMS2 in predisposing to colorectal cancer. Cancer Res 2001; 61(21): 7798-7802.

23. van der Klift H, Wijnen J, Wagner A, et al. Molecular characterization of the spectrum of genomic deletions in the mismatch repair genes MSH2, MLH1, MSH6, and PMS2 responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Genes Chromosomes Cancer 2005; 44(2): 123-138.

24. Dovrat S, Figer A, Fidder HH, et al. Mutational analysis of hMsh6 in Israeli HNPCC and HNPCC-like families. Fam Cancer 2005; 4(4): 291-294.

25. Hegde MR, Chong B, Blazo ME, et al. A homozygous mutation in MSH6 causes Turcot syndrome. Clin Cancer Res 2005; 11(13): 4689-4693.

26. Hendriks YM, Jagmohan-Changur S, van der Klift HM, et al. Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome). Gastroenterology 2006; 130(2): 312-322.

27. Daum O, Beneš Z, Hadravský L, et al. Lynchův syndrom v rukách patologa. Cesk Patol 2014; 50(1): 18-24.

28. Kokošková B, Daum O, Beneš Z, et al. Moderní diagnostika Lynchova syndromu. Gastroent a Hepatol 2014; 68(2): 157-165.

29. Dušek M, Hadravský L, Černá K, et al. Diagnóza Lynchova syndromu od patologa. Klin Onkol 2016; 29(3): 180-186.

30. Hartman DJ, Brand RE, Hu H, et al. Lynch syndrome-associated colorectal carcinoma: frequent involvement of the left colon and rectum and late-onset presentation supports a universal screening approach. Hum Pathol 2013; 44(11): 2518-2528.

31. Mvundura M, Grosse SD, Hampel H, Palomaki GE. The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Genet Med 2010; 12(2): 93-104.

32. Mills AM, Liou S, Ford JM, Berek JS, Pai RK, Longacre TA. Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer. Am J Surg Pathol 2014; 38(11): 1501-1509.

33. Mills AM, Longacre TA. Lynch syndrome screening in the gynecologic tract: current state of the art. Am J Surg Pathol 2016; 40(4): e35-44.

34. Hyde A, Fontaine D, Stuckless S, et al. A histology-based model for predicting microsatellite instability in colorectal cancers. Am J Surg Pathol 2010; 34(12): 1820-1829.

35. Chan AO, Broaddus RR, Houlihan PS, Issa JP, Hamilton SR, Rashid A. CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol 2002; 160(5): 1823-1830.

36. Stenson PD, Mort M, Ball EV, et al. The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Hum Genet 2017; 136(6): 665-677.

37. Woods MO, Williams P, Careen A, et al. A new variant database for mismatch repair genes associated with Lynch syndrome. Hum Mutat 2007; 28(7): 669-673.

38. Thompson BA, Spurdle AB, Plazzer JP, et al. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nat Genet 2014; 46(2): 107-115.

39. Birney E, Soranzo N. Human genomics: The end of the start for population sequencing. Nature 2015; 526(7571): 52-53.

40. Choi Y, Chan AP. PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics 2015; 31(16): 2745-2747.

41. Mas-Moya J, Dudley B, Brand RE, et al. Clinicopathological comparison of colorectal and endometrial carcinomas in patients with Lynch-like syndrome versus patients with Lynch syndrome. Hum Pathol 2015; 46(11): 1616-1625.

42. Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010; 138(6): 2073-2087 e2073.

43. Vierkoetter KR, Ayabe AR, VanDrunen M, Ahn HJ, Shimizu DM, Terada KY. Lynch Syndrome in patients with clear cell and endometrioid cancers of the ovary. Gynecol Oncol 2014; 135(1): 81-84.

Labels

Anatomical pathology Forensic medical examiner Toxicology

Frozen section: history, indications, contraindications and quality assurance

Frozen section examination of pancreas, gallbladder, extrahepatic biliary tree, liver, and gastrointestinal tract

Intraoperative diagnosis of the head and neck lesions, thyroid and parathyroid gland, bone and soft tissue, and genitourinary tract

Esophageal dysplasia and adenocarcinoma: a study with double immunostaining for intestinal and gastric markers

Article was published in

Czecho-Slovak Pathology

2018 Issue 2