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Cancer. 1999 Feb 15;85(4):779-85.

Validation and simplification of Bethesda guidelines for identifying apparently sporadic forms of colorectal carcinoma with microsatellite instability.

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Serviço de Gastrenterologia, Instituto Português de Oncologia Francisco Gentil, Lisbon, Portugal.



Colorectal tumors with microsatellite instability (MSI) that do not comply with previously defined clinical criteria may be found in recently diagnosed hereditary nonpolyposis colorectal carcinoma families. Until recently, the indications for MSI testing were not clearly established. The objective of the current study was to validate the recently published Bethesda guidelines for MSI testing in a series of patients with apparently sporadic forms of colorectal carcinoma (CRC).


Sixty-two patients with so-called sporadic CRC were included in the current study. MSI was analyzed at seven poly(CA) repeat sequences and at one poly(A) locus.


Nine of 62 patients (14.5%) had tumors exhibiting MSI at > or = 2 loci and 7 patients (11%) had MSI at > or = 3 loci. Patients with MSI positive tumors were younger (P < 0.05), and their tumors more frequently were right-sided (P < 0.02) and more often exhibited a mucinous component (P < 0.05). The Bethesda guidelines were positive in 18% (11 of 62) of patients. The sensitivity of these guidelines in identifying tumors with MSI at > or = 3 loci was 43% and the positive predictive value (PPV) was 27% (3 of 11 cases). Other variables were considered as alternative criteria to identify CRCs with MSI: age < 45 years and/or a right-sided tumor with a mucinous component. Using these 2 criteria alone, sensitivity increased to 85% and PPV to 46%.


In this study group, the use of three clinical criteria as sole indicators for MSI testing in patients with apparently sporadic forms of CRC were significantly more discriminating compared with the Bethesda guidelines, in addition to being substantially easier.

[Indexed for MEDLINE]

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