Challenging cases encountered in colorectal cancer screening for Lynch syndrome reveal novel findings: nucleolar MSH6 staining and impact of prior chemoradiation therapy

Radu, Oana M.; Nikiforova, Marina N.; Farkas, Linda M.; Krasinskas, Alyssa M.

doi:10.1016/j.humpath.2010.11.016

Cited by 54 publications

(31 citation statements)

References 34 publications

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“…MSH6 is similarly related to MSH2. One should also keep in mind that nucleolar staining or complete loss of MSH6 staining has been described in colorectal cancer cases with prior radiation or chemotherapy, 3,4 and a significant reduction of MSH6 staining has been described in a small percentage of colorectal carcinomas with somatic mutations of the coding region microsatellites of the MSH6 gene in MLH1/PMS2-deficient carcinomas. 5 B: MLH1 Promoter Hypermethylation Analysis and BRAF Mutational Analysis.-Defective MMR in sporadic colorectal cancer is most often due to inactivation of the MLH1 gene promoter by hypermethylation (epigenetic silencing).…”

Section: Explanatory Notesmentioning

confidence: 99%

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Colon and Rectum

Bartley

Hamilton

Alsabeh

et al. 2014

Archives of Pathology & Laboratory Medicine

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Section: Explanatory Notesmentioning

confidence: 99%

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Colon and Rectum

Bartley

Hamilton

Alsabeh

et al. 2014

Archives of Pathology & Laboratory Medicine

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“…5 Increasing use of IHC for identification of Lynch syndrome has also led to recognition of novel patterns of staining that may cause difficulty in interpretation. 14 We describe a unique "null" immunophenotype in a Lynch syndrome associated colon cancer, which, to the best of our knowledge, has not been previously described in the literature.…”

mentioning

confidence: 65%

“…The latter is interpreted as being the result of a secondary MSH6 mutation in a germline MLH1 mutation carrier. 14 The coexistence of both a germline mutation and MLH1 hypermethylation has been described in 2 previous cases. In a series of 123 tumors, Rahner et al 15 found MLH1 promoter hypermethylation in 2 patients with pathogenic germline mutations, 1 a carrier of a germline MLH1 mutation and the other a carrier of an MSH2 mutation.…”

Section: Discussionmentioning

confidence: 92%

“Null Pattern” of Immunoreactivity in a Lynch Syndrome-Associated Colon Cancer Due to Germline MSH2 Mutation and Somatic MLH1 Hypermethylation

Hagen

Lefferts

Hornick

et al. 2011

American Journal of Surgical Pathology

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Lynch syndrome accounts for approximately 3% of newly diagnosed colorectal cancers and is caused by germline defects in DNA mismatch repair genes. Screening of patients for Lynch syndrome can be done by immunohistochemical staining for a panel of mismatch repair proteins and/or DNA testing for microsatellite instability. We describe a unique "null" immunophenotype in a Lynch syndrome associated colon cancer in a 71-year-old woman who also had a personal history of ureteral cancer and a strong family history of various malignancies. Immunohistochemical stains for MLH1, MSH2, PMS2, and MSH6 were completely negative in the tumor cells, with positive staining in stromal and inflammatory cells. Mutation analysis using peripheral blood showed a germline G587R mutation in the MSH2 gene. Further testing revealed the tumor to be positive for MLH1 promoter hypermethylation. Normal colonic mucosa adjacent to the tumor was negative for MLH1 promoter methylation. The lack of immunostaining for any of the 4 DNA mismatch repair proteins in this extremely unusual case was, therefore, related to a germline MSH2 mutation and somatic MLH1 promoter hypermethylation.

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“…75 A few studies have also reported a nucleolar-only staining pattern, which should still be interpreted as loss of expression, or complete loss of MSH6 expression in tumors that have been treated with chemotherapy or radiation therapy. 77,78 In those situations, evaluation of pretreatment biopsy specimens should be helpful before proceeding to further genetic workup. Microsatellite instability analysis by polymerase chain reaction is another helpful option.…”

Section: Interpretation Of Mismatch Repair Protein Immunostainsmentioning

confidence: 99%

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

Wang¹,

Kim²,

Koo³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly used to maximize the benefits of clinical management of patients with neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Objectives.— To review the characteristics of immunomarkers that are commonly used in surgical pathology practice for neoplasms of the gastrointestinal tract, liver, biliary tract, and pancreas, and to summarize the clinical usefulness of immunomarkers that have been discovered in recent years in these fields. Data Sources.— Data sources include literature review, authors' research data, and personal practice experience. Conclusions.— Immunohistochemistry is an indispensable tool for the accurate diagnosis of neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Useful immunomarkers are available to help distinguish malignant neoplasms from benign conditions, determine organ origins, and subclassify neoplasms that are morphologically and biologically heterogeneous. Specific immunomarkers are also available to help guide patient treatment and assess disease aggressiveness, which are keys to the success of personalized medicine. Pathologists will continue to play a critical role in the discovery, validation, and application of new biomarkers, which will ultimately improve patient care.

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Challenging cases encountered in colorectal cancer screening for Lynch syndrome reveal novel findings: nucleolar MSH6 staining and impact of prior chemoradiation therapy

Cited by 54 publications

References 34 publications

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Colon and Rectum

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Colon and Rectum

“Null Pattern” of Immunoreactivity in a Lynch Syndrome-Associated Colon Cancer Due to Germline MSH2 Mutation and Somatic MLH1 Hypermethylation

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

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