Germline deletions in the EPCAM gene as a cause of Lynch syndrome – literature review

Purpose Lynch syndrome is an inherited tumor predisposition syndrome caused by germline mutations of DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2. Recently, germline deletions affecting the epithelial cell adhesion molecule (EPCAM) gene located upstream of MSH2 were identified as a novel mutational mechanism causing Lynch syndrome by epigenetic inactivation of the respective MSH2 allele. Immunohistochemical analysis of MMR protein expression is a hallmark of Lynch syndrome diagnostics, but it cannot distinguish between EPCAM deletion carriers and MSH2 mutation carriers. We hypothesized that EPCAM protein expression might be altered in tumors from patients with a germline EPCAM deletion. Patients and Methods Immunohistochemistry was used to assess EPCAM expression in Lynch syndrome–associated MSH2-negative tumors (n = 26). Multiplex ligation-dependent probe amplification (MLPA) analysis was performed to detect germline deletions of the EPCAM and MSH2 gene loci. Results In four MSH2-negative tumors, a concomitant lack of EPCAM expression was detected. MLPA analysis revealed heterozygous EPCAM deletions in all patients with EPCAM-negative tumors. In contrast, EPCAM expression was positive in all cancers from patients with germline alterations affecting MSH2 but not EPCAM. Two EPCAM deletions were detected in patients with an EPCAM-positive tumor. Conclusion These results indicate that loss of EPCAM protein expression is frequent in tumors from patients with EPCAM germline deletions. EPCAM immunohistochemistry therefore represents a promising novel tool for the identification of Lynch syndrome patients with EPCAM germline deletions.

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Su1089 Epcam Gene Mutations and Phenotype in Two Italian Lynch Syndrome Families

Gastroenterology ◽

10.1016/s0016-5085(13)61456-0 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-396

Author(s):

Mara Fornasarig ◽

Giulia Cini ◽

Vincenzo Canzonieri ◽

Renato Cannizzaro ◽

Chiara Pastrello ◽

...

Keyword(s):

Lynch Syndrome ◽

Gene Mutations ◽

Epcam Gene

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The influence of STK11 mutation on acquired resistance to immunotherapy in advanced non-small cell lung cancer with Lynch syndrome: a case report and literature review

Annals of Palliative Medicine ◽

10.21037/apm-20-1639 ◽

2021 ◽

Vol 10 (4) ◽

pp. 4-4

Author(s):

Yaling Long ◽

Yuan Tang ◽

Chengzhi Cai ◽

Min Yu ◽

Min Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Case Report ◽

Literature Review ◽

Lynch Syndrome ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Acquired Resistance ◽

Small Cell ◽

Small Cell Lung

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Effect of Computerized Auditory Training on Speech Perception of Adults With Hearing Impairment

Perspectives on Aural Rehabilitation and Its Instrumentation ◽

10.1044/arri20.3.91 ◽

2013 ◽

Vol 20 (3) ◽

pp. 91-106 ◽

Cited By ~ 6

Author(s):

Rachel Pizarek ◽

Valeriy Shafiro ◽

Patricia McCarthy

Keyword(s):

Hearing Loss ◽

Speech Perception ◽

Literature Review ◽

Low Cost ◽

Experimental Designs ◽

Auditory Training ◽

Hearing Impairments ◽

Communicative Disorders ◽

And Training

Computerized auditory training (CAT) is a convenient, low-cost approach to improving communication of individuals with hearing loss or other communicative disorders. A number of CAT programs are being marketed to patients and audiologists. The present literature review is an examination of evidence for the effectiveness of CAT in improving speech perception in adults with hearing impairments. Six current CAT programs, used in 9 published studies, were reviewed. In all 9 studies, some benefit of CAT for speech perception was demonstrated. Although these results are encouraging, the overall quality of available evidence remains low, and many programs currently on the market have not yet been evaluated. Thus, caution is needed when selecting CAT programs for specific patients. It is hoped that future researchers will (a) examine a greater number of CAT programs using more rigorous experimental designs, (b) determine which program features and training regimens are most effective, and (c) indicate which patients may benefit from CAT the most.

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