A DNA hypermethylation profile reveals new potential biomarkers for prostate cancer diagnosis and prognosis.

BACKGROUND: DNA hypermethylation has emerged as a novel molecular biomarker for the evaluation of prostate cancer diagnosis and prognosis. Defining the specific gene hypermethylation profile for prostate cancer could involve groups of genes that specifically discriminate patients with indolent and aggressive tumors. METHODS: Genome-wide methylation analysis was performed on 83 tumor and 10 normal prostate samples using the GoldenGate Methylation Cancer Panel I (Illumina, Inc.). All clinical stages of disease were considered. RESULTS: We found 41 genes hypermethylated in more than 20% of the tumors analyzed (P < 0.01). Of these, we newly identified GSTM2 and PENK as being genes that are hypermethylated in prostate cancer and that were simultaneously methylated in 40.9% of the tumors analyzed. We also identified panels of genes that are more frequently methylated in tumor samples with clinico-pathological indicators of poor prognosis: a high Gleason score, elevated Ki-67, and advanced disease. Of these, we found simultaneous hypermethylation of CFTR and HTR1B to be common in patients with a high Gleason score and high Ki-67 levels; this might indicate the population at higher risk of therapeutic failure. The DNA hypermethylation profile was associated with cancer-specific mortality (log-rank test, P = 0.007) and biochemical recurrence-free survival (log-rank test, P = 0.0008). CONCLUSIONS: Our findings strongly indicate that epigenetic silencing of GSTM2 and PENK is a common event in prostate cancer that could be used as a molecular marker for prostate cancer diagnosis. In addition, simultaneous HTR1B and CFTR hypermethylation could help discriminate aggressive from indolent prostate tumors.

Umbilical KeyPort bilateral laparoscopic orchiectomy in patient with complete androgen insensitivity syndrome.

MAIN FINDINGS: A 22-year-old woman with complete androgen insensitivity syndrome (CAIS) presenting with primary amenorrhea and normal female external genitalia was referred for laparoscopic gonadectomy. She had been diagnosed several years earlier but was reluctant to undergo surgery. Case HYPOTHESIS: Diagnosis of this X-linked recessive inherited syndrome characterizes by disturbance of virilization in males with an AR mutation, XY karyotipe, female genitalia and severely undescended testis with risk of malignization. The optimal time to orchidectomy is not settled; neither the real risk of malignancy in these patients. Early surgery impacts development of a complete female phenotype, with enlargement of the breasts. Based on modern diagnostic imaging using DCE-MRI and surgical technology with single port laparoscopic access we hypothesize that the optimum time for gonadectomy is not at the time of diagnosis, but once feminization has completed. PROMISING FUTURE IMPLICATIONS: An umbilical laparoendoscopic single-site access for bilateral gonadectomy appears to be the first choice approach as leaves no visible incision and diminishes the psychological impact of surgery in a patient with CAIS absolutely reassured as female. KeyPort, a single port access with duo-rotate instruments developed by Richard Wolf facilitates this surgery and allows excellent cosmetic results.

Umbilical KeyPort bilateral laparoscopic orchiectomy in patient with complete androgen insensitivity syndrome

MAIN FINDINGS: A 22-year-old woman with complete androgen insensitivity syndrome (CAIS) presenting with primary amenorrhea and normal female external genitalia was referred for laparoscopic gonadectomy. She had been diagnosed several years earlier but was reluctant to undergo surgery. CASE HYPOTHESIS: Diagnosis of this X-linked recessive inherited syndrome characterizes by disturbance of virilization in males with an AR mutation, XY karyotipe, female genitalia and severely undescended testis with risk of malignization. The optimal time to orchidectomy is not settled; neither the real risk of malignancy in these patients. Early surgery impacts development of a complete female phenotype, with enlargement of the breasts. Based on modern diagnostic imaging using DCE-MRI and surgical technology with single port laparoscopic access we hypothesize that the optimum time for gonadectomy is not at the time of diagnosis, but once feminization has completed. PROMISING FUTURE IMPLICATIONS: An umbilical laparoendoscopic single-site access for bilateral gonadectomy appears to be the first choice approach as leaves no visible incision and diminishes the psychological impact of surgery in a patient with CAIS absolutely reassured as female. KeyPort, a single port access with duo-rotate instruments developed by Richard Wolf facilitates this surgery and allows excellent cosmetic results.

Clinicopathological study of regressed testicular tumors (apparent extragonadal germ cell neoplasms).

PURPOSE: Testicular germ cell tumors sometimes regress spontaneously and manifest exclusively by metastasis. We report our experience with extragonadal germ cell tumors of probable testicular origin to study the frequency of this entity, and clinical, ultrasound and histopathological correlations in a series of patients. MATERIALS AND METHODS: A retrospective 16-year review of 1.2 million inhabitants in Spain revealed 17 with regressed testicular tumors treated at a total of 4 institutions. We analyzed clinical information, ultrasound features and histopathological characteristics of testicular lesions and metastasis, and highlight the main findings. RESULTS: A primary testicular origin was confirmed in all cases. This entity is more common than initially suspected since it accounts for 4% of consecutive germ cell tumors. Clinical manifestations varied according to metastatic site with an abdominal palpable mass (47% of cases), loin pain (35%) and transient testicular pain (29%) the most common complaints. No evidence of testicular neoplasms was found on physical examination in any case. Metastasis histology was nonseminomatous in 53% of cases, pure seminoma in 29% and mixed in 18%. The most common ultrasound features were calcifications in 65% of cases, hyperechogenic linear images in 59% and hypoechogenic nodular areas in 41%. Histological findings consisted of fibrotic areas in 100% of cases, hemosiderin deposits in 65%, seminiferous tubule atrophy in 59% and psammoma bodies in 29%. In testicular parenchyma or spermatic chord intratubular neoplasms and viable tumor foci were also noted (47% and 41% of cases, respectively). CONCLUSIONS: Spontaneous regression of a germ cell testicular tumor should be considered in each patient with extragonadal germ cell neoplasms. Ultrasound diagnosis of and surgical treatment for these primary testicular tumors appear critical to prevent relapse because residual disease develops in a significant proportion of cases.