ADDENDUM (MSI MOLECULAR DIAGNOSTIC FINDINGS): MICROSATELLITE INSTABILITY: STABLE IMMUNOHISTOCHEMISTRY FOR PROTEINS MLH1, PMS2, MSH2, AND MSH6 REVEALS A LOSS OF BOTH MLH1 AND PMS2 EXPRESSION, CONSISTENT WITH MSI “UNSTABLE” PHENOTYPE OF TUMOR. THIS FINDING IS CONSISTENT WITH THE MSI-H FINDING BY PCR (SEE BELOW).MICROSATELLITE INSTABILITY: HIGHTHIS PATIENT HAS A TUMOR WITH TWO OR MORE UNSTABLE MICROSATELLITE MARKERS. INTERPRETATION: MICROSATELLITE INSTABILITY HIGH (MSI-H) INDICATES AT LEAST 30% OF MICROSATELLITE INSTABILITY IN A TUMOR. MSI-H IS PRESENT IN >90% OF PATIENTS WITH HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (HNPCC) AND IN 15-20% OF SPORADIC COLORECTAL TUMORS. GENETIC COUNSELING AND/OR GERM-LINE MUTATION ANALYSIS OF MISMATCH-REPAIR GENES (MSH2, MLH1, AND MSH6) ARE ADVISED TO THE PATIENT/FAMILY WITH MICROSATELLITE INSTABILITY-HIGH TUMORS AND A HIGH SUSPICION OF HNPCC. PERFORMED ON USS--, BLOCK PERCENTAGE OF TUMOR CELLS IN MICRODISSECTED TISSUE: % TEST DESCRIPTION: OUR PCR-BASED TEST DETECTS A TUMOR'S GENOMIC MICROSATELLITE INSTABILITY AT THE FOLLOWING MONONUCLEOTIDE MICROSATELLITE MARKERS: BAT25, BAT26, NR21, NR24, AND MONO-27. TWO PENTANUCLEOTIDE REPEAT MARKERS ARE ALSO INCLUDED (PENTA-C AND PENTA-D) TO ENSURE SAMPLES COMING FROM THE SAME INDIVIDUAL. BOTH TUMOR AND NORMAL TISSUES ARE AMPLIFIED BY FLUORESCENT PCR AND ANALYZED BY CAPILLARY ELECTROPHORESIS. PATTERNS FOR EACH MARKER BETWEEN NORMAL AND TUMOR ARE COMPARED AND SCORED AS STABLE OR UNSTABLE. THE CLASSIFICATION OF MICROSATELLITE INSTABILITY WAS BASED ON GUIDELINES SUGGESTED BY A NATIONAL CANCER INSTITUTE WORKSHOP. WITH THE 5-LOCUS OF MICROSATELLITE MARKERS, TUMOR SAMPLES WITH TWO OR MORE INSTABILITY LOCUS ARE CLASSIFIED AS MSI-HIGH (MSI-H), LESS THAN TWO LOCUS ARE CLASSIFIED AS MSI-LOW (MSI-L), AND NO ALTERATIONS ARE CLASSIFIED AS MICROSATELLITE-STABLE (MSS). THE PERFORMANCE CHARACTERISTICS OF THIS TEST WERE VALIDATED BY UNIVERSITY OF FLORIDA-PATHOLOGY LABORATORIES. THE U.S. FOOD AND DRUG ADMINISTRATION (FDA) HAS NOT APPROVED OR CLEARED THIS TEST. HOWEVER, FDA APPROVAL OR CLEARANCE IS CURRENTLY NOT REQUIRED FOR CLINICAL USE OF THIS TEST. THE RESULTS ARE NOT INTENDED TO BE USED AS THE SOLE MEANS FOR CLINICAL DIAGNOSIS OR PATIENT MANAGEMENT DECISIONS. UF PATHOLOGY LABORATORIES IS AUTHORIZED UNDER CLINICAL LABORATORY IMPROVEMENT AMENDMENTS (CLIA) AND BY ALL STATES TO PERFORM HIGH-COMPLEXITY TESTING. THE ABOVE TESTING WAS PERFORMED AT UNIVERSITY OF FLORIDA PATHOLOGY LABORATORIES, 4800 SW 35TH DR., GAINESVILLE, FL 32608. PHONE: 352-265-9900.