African-American heredity prostate cancer study: a model for genetic research.

A genome-wide scan of high-risk prostate cancer families in North America has demonstrated linkage of a particular marker to Chromosome 1q (HPC1). An even greater proportion of African-American families have shown linkage to HPC1. Therefore, investigators at the National Human Genome Research Institute (NHGRI) in collaboration with Howard University and a predominantly African-American group of urologists established the African-American Hereditary Prostate Cancer (AAHPC) Study Network to confirm the suggested linkage of HPC in African Americans with a gene on Chromosome 1. Blood samples from recruited families were sent to Howard University for extraction of DNA. The DNA was sent to NHGRI at NIH where the genotyping and genetic sequence analysis was conducted. Genotype data are merged with pedigree information so that statistical analysis can be performed to establish potential linkage. From March 1, 1998, to June 1, 1999, a total of 40 African-American families have been recruited who met the study criteria. Preliminary results suggest that racial/ethnicity grouping may affect the incidence and extent of linkage of prostate cancer to specific loci. The importance of these findings lays in the future treatment of genetic-based diseases.

African-American heredity prostate cancer study: a model for genetic research.

A genome-wide scan of high-risk prostate cancer families in North America has demonstrated linkage of a particular marker to Chromosome Iq (HPC11. An even greater proportion of African-American families have shown linkage to HPC 1. Therefore, investigators at the National Human Genome Research Institute [NHGRI] in collaboration with Howard University and a predominantly African-American group of urologists established the African-American Hereditary Prostate Cancer (AAHPC) Study Network to confirm the suggested linkage of HPC in African Americans with a gene on Chromosome 1. Blood samples from recruited families were sent to Howard University for extraction of DNA. The DNA was sent to NHGRI at NIH where the genotyping and genetic sequence analysis was conducted. Genotype data are merged with pedigree information so that statistical analysis can be performed to establish potential linkage. From March 1, 1998, to June 1, 1999, a total of 40 African-American families have been recruited who met the study criteria. Preliminary results suggest that racial/ethnicity grouping may affect the incidence and extent of linkage of prostate cancer to specific loci. The importance of these findings lays in the future treatment of genetic-based diseases.

Disease-free and overall survival after cryosurgical monotherapy for clinical stages B and C carcinoma of the prostate: a 20-year followup.

PURPOSE: We attempt to provide insight into the historical efficacy of cryosurgical monotherapy for prostate carcinoma through a single institution, retrospective, long-term followup. MATERIALS AND METHODS: From 1973 to 1977, 66 men underwent cryosurgical monotherapy for prostate carcinoma. Patient charts were reviewed to determine age, clinical stage, tumor grade, and progression-free, overall and cause specific survival status. RESULTS: Of 51 patients 47 to 81 years old (mean age 67.2) with clinically localized carcinoma 11 had clinical stage B and 40 had stage C disease. Tumor grade was well differentiated in 11 cases, moderately differentiated in 26, poorly differentiated in 11 and undetermined in 3. Recurrence was documented in 40 of the 51 men (78.4%) as local in 34 and unspecified in 6. Following recurrence all patients were treated with adjuvant therapy. All but 2 patients were followed until death with a mean followup of 93.7 months. Of the 51 men 24 (47.1%) died of disease and 17 (33.3%) died of an unspecified cause. Kaplan-Meier analysis demonstrated median overall progression-free survival of 34 months and median overall survival of 75 months. Median progression-free survival by grade was 34 months for well differentiated, 36 for moderately differentiated and 14 for poorly differentiated disease (p = 0.0288), and 57 for stage B and 30 for stage C disease (p = 0.0377). Median overall survival by grade was 114 months for well differentiated, 80 for moderately differentiated and 82 for poorly differentiated disease (p = 0.4437), and 60 months for stage B and 78.5 for stage C disease (p = 0.4915). CONCLUSIONS: As performed in this series cryosurgery was poorly effective for local control of prostatic carcinoma. Stage and grade correlated with the duration of tumor response but not with overall survival.

Cellular adhesion molecules in urologic malignancies.

Cell adhesion molecules (CAMs) are important in cell-cell interaction and interactions between cells and components of the extracellular matrix. CAMs have been associated with invasion and metastasis in a wide variety of human malignancies, including tumors of the genitourinary tract. Cadherins are transmembrane glycoproteins that bind cells by homophilic, homotypic interactions. Loss of expression of E-cadherin has been associated with dedifferentiation, invasion, and metastasis in prostate cancer and transitional cell neoplasia of the urinary bladder. CD44, a family of transmembrane glycoproteins principally involved in cell-extracellular matrix interactions, also has been associated with invasion and metastasis in urologic malignancies. Through alternative splicing, a variety of CD44 isoforms can be expressed that can undergo extensive posttranslational modification. CD44 variants have been associated with metastasis in a variety of human malignancies, particularly in the gastrointestinal system. Although loss of expression of CD44 standard form has been associated with aggressive prostate gland and bladder cancers, no specific isoform has been associated with metastasis of these neoplasms. Integrins are transmembrane glycoproteins with wide cellular distribution that bind a variety of extracellular matrix components. Integrins have been studied extensively in prostate cancer in which altered integrin expression has been associated with malignant prostatic epithelium. Additional adhesion molecules that have been studied to a variable degree in urologic malignancies include selectins and the immunoglobulin super-family. CAMs are fundamental to diverse biologic processes and appear capable of regulating intracellular signaling events that appear to have significant importance in human malignancy, including cancers of the urogenital tract.