The Cleveland Clinic adult clinical scoring system is a weighted method that permits estimation of individual patient probability of PTEN mutation. This was derived through analysis of the only prospective, and largest-known multicenter study executed in the genetics community setting.1 This study involved 3,024 probands recruited over 10 years from North America, Europe and Asia, to two major cancer genetics centers, the Cleveland Clinic and Ohio State University. It has been demonstrated to be superior in performance1 relative to the current NCCN clinical criteria (2010)2 and thus, the Cleveland Clinic score represents standard of care for risk evaluation in genetic counseling.
The web calculator implementing specific weights and calculations is located at http://www.lerner.ccf.org/gmi/ccscore/ and is able to calculate a risk probability of PTEN mutation for adult patients without a family history of PTEN mutation. Individuals who have family members with PTEN mutations should be evaluated by specialist medical/genetics professionals for their own risk.
For eligible patients, the Genomic Medicine Institute at the Cleveland Clinic recommends PTEN testing for adults with a threshold probability of 3% and up. At this threshold, there is a projected sensitivity of 90% for detection of patients with PTEN mutations.1 The individual score may be useful for counseling patients in terms of risk and thus for informed decision-making. Individual centers may derive thresholds based on center-specific standards for sensitivity and specificity; these values at varying threshold probabilities have been provided in the reference.
1Tan MH, Mester M, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C (2011). A Clinical Scoring System for Selection of Patients for PTEN Mutation Testing is Proposed on the Basis of a Prospective Study of 3,042 Probands. Am J Hum Genet. (in press)
2The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer (Version 1.2010). © 2010 National Comprehensive Cancer Network, I. Available at: NCCN.org. Accessed [Nov 24, 2010]. To view the most recent and complete version of the NCCN Guidelines™, go on-line to NCCN.org.