Genomic analysis of prostate carcinoma specimens obtained via ultrasound-guided needle biopsy may be of use in preoperative decision-making.

BACKGROUND: The widespread use of prostate-specific antigen (PSA) testing to screen for prostate carcinoma has led to significant overdiagnosis, due to the frequent detection of indolent malignancies on PSA screening. The detection of abnormal PSA levels typically is followed by ultrasound-guided needle biopsy. Therefore, in an effort to identify genetic markers that augment the information provided by standard histopathologic classification, the authors tested the feasibility of using these minute biopsy samples for genomic profiling via chromosome banding analysis and comparative genomic hybridization (CGH). METHODS: Ultrasound-guided needle biopsy specimens obtained preoperatively from 35 patients with prostate carcinoma were analyzed via chromosome banding analysis (after short-term culturing) and CGH. The findings of these analyses then were analyzed for potential correlations with clinicopathologic parameters. RESULTS: Chromosome banding analysis and CGH were possible in 34 and 33 of the 35 study specimens, respectively. Combined analysis revealed aberrations in 69% of all samples investigated. Copy number losses occurred most commonly at 8p (58% of all abnormal specimens), 16q (42%), and 13q (37%), whereas the only gains detected in more than 1 specimen were those that occurred at 8q (37%). Genomic imbalances and losses at 16q were significantly associated with more poorly differentiated subtypes of prostate carcinoma (P = 0.048 and P = 0.019, respectively), whereas gains at 8q and losses at 16q were significantly correlated with clinically advanced disease (P = 0.048 for the finding of a gain at 8q together with a loss at 16q; P = 0.01 for the finding of either aberration alone). CONCLUSIONS: The authors conclude that genomic analysis of suspected prostate carcinoma specimens obtained via ultrasound-guided needle biopsy is feasible. Thus, it may be possible to use genetic markers to obtain diagnostic and/or prognostic information that is useful in the making of preoperative decisions regarding prostate carcinoma management.

Lack of parental origin specificity of altered alleles at 11p15 in testicular germ cell tumors.

Allelic imbalance (AI) at loci on chromosome 11 has been shown in several types of human solid tumors, including testicular germ cell tumors (TGCTs). In this study we have focused on the 11p15 region, which is known for its high density of imprinted genes. Highly polymorphic microsatellite markers were analyzed in a series of 71 TGCTs, and AI was observed in 28 of the tumors (39%) at one or more of the loci analyzed. The AI data were evaluated against the chromosome 11 copy number, determined by fluorescence in situ hybridization with a centromere-specific probe. To evaluate preferential parental allele alterations, the patients' normal and tumor genotypes were compared with the parental genotypes. Both losses and gains of both paternal and maternal alleles were found, and this lack of parental origin specificity of the altered allele suggests that the remaining allele is not inactivated by imprinting. A smallest region of overlapping changes was identified between the markers D11S2351 and D11S2347. In summary, our results support the theory that a nonimprinted 11p15 tumor suppressor gene is involved in the development of a subgroup of TGCTs.

Gonadal function and fertility in patients with bilateral testicular germ cell malignancy.

OBJECTIVE: To evaluate gonadal function and fertility in patients with bilateral testicular cancer (TC). METHODS: In 1999, 63 patients with bilateral invasive TC or carcinoma in situ (CIS) in the contralateral testis completed a mailed questionnaire evaluating their fatherhood (Cases). Their gonadal function had also been assessed after the first orchiectomy for TC before further treatment. The results were compared with those from 174 patients with unilateral TC (Controls). RESULTS: In Cases the post-orchiectomy serum levels of FSH and LH were above those of the Controls (p<0.001). Serum testosterone was similar, whereas sperm concentrations were lower in Cases (p<0.001). In Cases with metachronous invasive TC the level of serum FSH was associated with the interval between the two diagnoses. After the first orchiectomy, 10 of 25 Cases (40%) initiated a pregnancy, in 4 Cases by assisted fertilization. In the Control group 74% of the patients who attempted fatherhood succeeded (p=0.002). CONCLUSIONS: After unilateral orchiectomy for TC elevated serum FSH and/or oligospermia represent a high-risk factor of metachronous bilateral TC or synchronous CIS. At least one-third of these patients attempting fatherhood are successful after the first orchiectomy. Assisted fertilization is often necessary and the overall paternity rate is below that of patients with unilateral TC.

Genome profiles of familial/bilateral and sporadic testicular germ cell tumors.

In order to investigate the genetics of testicular germ cell tumors (TGCTs), we examined 33 TGCTs, including 15 familial/bilateral and 18 sporadic tumors, using comparative genomic hybridization. The frequencies of the histological subtypes were comparable between the two groups. Gains of the whole or parts of chromosome 12 were found in 30 tumors (91%). Furthermore, increased copy number of the whole or parts of chromosomes 7, 8, 17, and X, and decreased copy number of the whole or parts of chromosomes 4, 11, 13, and 18 were observed in > or = 50% of the tumors. Sixteen smallest regions of overlapping changes were delineated on 12 different chromosomes. The chromosomal copy numbers of familial/bilateral and sporadic TGCTs were comparable, suggesting similar genetic pathways to disease in both groups. However, significant differences were observed between the two main histological subgroups. Gains from 15q and 22q were associated with seminomas (P = 0.005 and P = 0.02, respectively), whereas gain of the proximal 17q (17q11.2-21) and high-level amplification from chromosome arm 12p, and losses from 10q were associated with nonseminomas (P < 0.001, P = 0.04, and P = 0.03, respectively).

[Bone and soft tissue sarcomas treated at the Norwegian Radium Hospital 1980-99]. / Bein- og bløtvevssarkomer behandlet ved Det Norske Radiumhospital 1980-99.

BACKGROUND: The Norwegian Radium Hospital's sarcoma group is a multidisciplinary group with a leading role in the diagnosis and treatment of bone and soft tissue sarcomas in Norway. MATERIAL AND METHODS: From 1980 through 1999, 1,355 patients with soft tissue sarcoma and 458 patients with bone sarcoma were treated. In a retrospective analysis of trends over time, patients were allocated to consecutive five-year periods. RESULTS: Patient characteristics were relatively stable, but there was an increasing proportion of soft tissue sarcomas being referred without prior surgery. Treatment principles have remained unchanged, with surgery with or without radiotherapy dominating in soft tissue sarcoma and surgery with or without chemotherapy in bone sarcoma. The amputation rate for bone sarcoma has fallen from 78% to 17%, and survival has increased significantly for both soft tissue and bone sarcoma patients. INTERPRETATION: The results indicate significant improvements in the quality of treatment of soft tissue and bone sarcoma. More resources for treatment and organizational development of a multidisciplinary group may contribute to improved quality of care.