Browsing by Author "Leach, FS"

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    Clinicopathologic implications of hMSH2 gene expression and microsatellite instability in prostate cancer
    (2002) Velasco, A; Albert, PS; Rosenberg, H; Martinez, C; Leach, FS
    Human mismatch repair (MMR) genes encode highly conserved interacting proteins that correct replication errors predisposing to hereditary gastrointestinal and genitourinary malignancies. We previously investigated expression of the prototype MMR gene hMSH2 in normal, benign prostatic hyperplasia and malignant prostate tissues (Velasco et al., Cancer 94:690-699, 2002). An association was detected between reduced. hMSH2 staining and favorable outcome as determined by undetectable serum prostate specific antigen (PSA) after radical prostatectomy. We now investigate the association between clinicopathological variables and hMSH2 expression or microsatellite instability (MSI). A statistically significant association was found between tumors exhibiting MSI (MSI+ tumors) and lower preoperative serum PSA values, smaller tumor volumes and lower frequency of surgical specimens with extracapsular extension of tumor. No statistically of significant association (P value less than or equal to 0.05) was found between hMSH2 staining and these clinicopathologic variables. Based on our analysis, we conclude that MMR deficiency has important clinicopathologic implications in prostate cancer. Furthermore, specific MMR genes may have different effects on prostate cancer biology.
  • No Thumbnail Available
    Item
    Differential expression of the mismatch repair gene hMSH2 in malignant prostate tissue is associated with cancer recurrence
    (2002) Velasco, A; Hewitt, SM; Albert, PS; Saboorian, MH; Rosenberg, H; Martinez, C; Sagalowsky, AI; McConnell, JD; Linehan, WM; Leach, FS
    BACKGROUND. Mismatch repair (MMR) genes are responsible for coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating mutations in MMR genes have been described in sporadic cancers and a hereditary cancer predisposition syndrome. Mismatch repair deficiency causes instability at microsatellites and increased mutation rates. Although microsatellite instability (MSI) has been described in high-grade and lymph node positive prostate carcinoma specimens, an analysis comparing hMSH2 expression, MSI, and outcome in clinically organ confined prostate carcinoma has not been reported.
  • Thumbnail Image
    Item
    Microsatellite instability and loss of heterozygosity have distinct prognostic value for testicular germ cell tumor recurrence
    (TAYLOR & FRANCIS INC, 2004) Velasco, A; Riquelme, E; Schultz, M; Wistuba, II; Villarroel, L; Koh, MS; Leach, FS
    Germ cell tumor (GCT) is the most common genitourinary malignancy of men between the ages of 18 and 35 years. Therapy is ultimately successful in over 90% of patients, however significant morbidity and mortality can be associated with adjuvant treatment and relapse. Molecular markers that predict treatment response and/or poor outcome would have immediate clinical benefit since adjuvant treatment could be selectively reserved for patients at higher risk for relapse and those patients most likely to respond to treatment. In order to identify potential prognostic molecular markers, we evaluated 118 GCT for microsatellite instability (MSI), loss of heterozygosity (LOH) and MSH2 immunostaining to identify tumors associated with relapse and/or poor outcome following initial surgical, medical and/or radiation therapy.
  • No Thumbnail Available
    Item
    Mismatch repair gene expression and genetic instability in testicular germ cell tumor
    (2004) Velasco, A; Riquelme, E; Schultz, M; Wistuba, II; Villarroel, L; Pizarro, J; Berlin, A; Ittmann, M; Koh, MS; Leach, FS
    Human mismatch repair (MMR) genes encode highly conserved interacting proteins that correct replication errors predisposing to hereditary gastrointestinal and genitourinary malignancies. A subset of sporadic genitourinary tumors also exhibits MMR deficiency and can be identified by measuring the frequency of microsatellite instability (MSI) in cancer cell DNA. We investigated expression of the two most commonly mutated MMR genes, MSH2 and MLH1, in sporadic testicular germ cell tumor (GCT) in order to: (1) determine the expression pattern of MSH2 and MLH1 proteins in normal seminiferous tubules and histologically distinct GCT subtypes, (2) correlate MMR gene expression with genetic instability in GCT and (3) develop a panel of molecular markers that can identify genetically distinct subsets of GCT for prognostic assessment.