title: Challenging cases encountered in colorectal cancer screening for Lynch syndrome reveal novel findings: nucleolar MSH6 staining and impact of prior chemoradiation therapy.
abstract: Many pathology laboratories have developed specific screening protocols to detect patients with Lynch syndrome. With recent recommendations to test all patients with newly diagnosed colorectal cancer for Lynch syndrome, the volume of testing will increase, and the most economic and reliable screening test will prevail. Although the detection of microsatellite instability by polymerase chain reaction and the detection of loss of the mismatch repair proteins by immunohistochemistry can each be used as a screening tool, each methodology has its strengths and weaknesses. During the time of our study, we used both polymerase chain reaction and immunohistochemistry to screen for Lynch syndrome in colorectal cancer specimens. We encountered 21 cases that posed significant interpretive challenges. A previously unpublished pattern of nucleolar MSH6 staining and potential spurious results induced by chemoradiation therapy are described. We feel that it is important to report these cases so that potential pitfalls in screening for Lynch syndrome can be avoided.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2546, USA.
authors.forename: Oana M
authors.initials: OM
authors.lastname: Radu
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.forename: Linda M
authors.initials: LM
authors.lastname: Farkas
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Krasinskas
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002466:Cell Nucleolus / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes