Details

Autor(en) / Beteiligte

• Müller, Annegret
• Giuffre, Giuseppe
• Edmonston, Tina Bocker
• Mathiak, Micaela
• Roggendorf, Beate
• Heinmöller, Ernst
• Brodegger, Thomas
• Tuccari, Giovanni
• Mangold, Elisabeth
• Buettner, Reinhard
• Rüschoff, Josef

Titel

Challenges and Pitfalls in HNPCC Screening by Microsatellite Analysis and Immunohistochemistry

Ist Teil von

• The Journal of molecular diagnostics : JMD, 2004-11, Vol.6 (4), p.308-315

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2004

Link zum Volltext

Quelle

ScienceDirect

Beschreibungen/Notizen

• Hereditary non-polyposis colorectal cancer (HNPCC) accounts for approximately 2 to 4% of the total colorectal cancer burden. For economic reasons a diagnostic “stepladder” is recommended. After evaluation of the family history, diagnostic microsatellite instability (MSI) analysis has found its place as a valuable screening tool for HNPCC. Immunohistochemical analysis can help to pinpoint the affected gene. The detection of a mutation in one of the responsible mismatch repair gene confirmed the diagnosis HNPCC. Here we demonstrate our experience of some important pitfalls that will be discussed in this study. In MSI testing, one potential source for false-negative results is intralesional heterogeneity. We demonstrate examples of a flat adenoma and a carcinoma, which required laser microdissection to correctly determine the microsatellite status. In these lesions manual microdissection, the most frequently applied method, was not sufficient. However, the number of cells obtained by using laser microdisssection can fall below a necessary minimum, which can also cause false-negative results of MSI analysis, as shown here in a mucinous carcinoma. In addition, evaluation of immunohistochemically stained tissue slides requires experience to avoid false-positive or false-negative interpretation. A case with two synchronous colorectal cancers revealed loss of MSH2 expression in one carcinoma, whereas the second carcinoma stained positively leading to a false-negative interpretation. In some cases, false-positive results can be obtained, if a perinuclear-staining pattern is interpreted as positive. In summary, there are several potential pitfalls in the molecular screening for HNPCC. Therefore the importance of correct interpretation of clinical data, immunohistochemistry, and microsatellite analysis in combination, performed by a pathologist with experience in molecular genetics is essential. In addition, laser microdissection of tumor areas that have been chosen by a pathologist is highly recommended in cases that cannot be resolved with manual microdissection.