ABSTRACT
An important issue in current oncological research is prevention as well as early detection of cancer. This includes also the difficulty to predict the progression of early or pre-cancerous lesions to invasive cancer. In this context, the characterization and categorization of pre-neoplastic lesions of squamous cell carcinoma [cervical intraepithelial neoplasia (CIN)] are an important task with major clinical impact. Screening programs are worldwide established with the aim to detect and eradicate such lesions with the potential to develop untreated into cervical cancer. From the literature it is known that around 5% of CIN 2 and 12% of CIN 3 cases will progress to cancer. The use of molecular markers extracted from cervical mucus might help to identify these high-risk cases and to exclude unnecessary biopsies or surgical treatment. Here we can show that micro RNA (miRNA) analysis from cervical mucus of 49 patients allowed us to distinguish between healthy patients and patients with CIN 3. The miRNA panel used in combination allowed for highly significant testing (P < 0.0001) of CIN 3 status. In parallel, the human papillomavirus status of the patients, the most important factor for the development of cervical cancer, significantly correlated with the miRNA markers hsa-miR-26b-5p, hsa-miR-191-5p and hsa-miR-143-3p, a subpanel of the original six miRNAs. We provide here a proof-of-concept for cervical mucus-based testing for pre-neoplastic stages of cervical squamous cell carcinoma.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/diagnosis , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adult , Carcinoma, Squamous Cell/genetics , Case-Control Studies , Early Detection of Cancer , Female , Gene Expression Profiling , Humans , Prognosis , Uterine Cervical Neoplasms/genetics , Uterine Cervical Dysplasia/geneticsABSTRACT
BACKGROUND AND PURPOSE: Positive surgical margins (PSM) after radical prostatectomy have been shown to be associated with impaired outcome. In pT3pN0 patients with PSM either immediate radiotherapy or clinical and biological monitoring followed by salvage radiotherapy is recommended by the latest guidelines of the European Association of Urology. MATERIALS AND METHODS: A retrospective, multicenter study of eight urological centers was conducted on 536 prostatectomy patients with pT3aN0/NxR1 tumors and no neoadjuvant/adjuvant therapy. A pathological re-review of all prostate specimens was performed. Association of clinical and pathological features with biochemical recurrence (BCR) was analyzed using univariate and multivariate analysis. RESULTS: With 48months median follow-up, BCR occurred in 39.7%. Preoperative PSA value, performance of pelvic lymph node dissection and Gleason score were significantly associated with BCR. In multivariate analysis, Gleason score was the only independent prognostic factor (p<0.001) for BCR. Five-year BCR-free survival rates were 74%, 70%, 38%, and 51% with Gleason score 6, 3+4=7a, 4+3=7b, and 8-10, respectively. CONCLUSIONS: In pT3aN0/NxR1 patients with no adjuvant/neoadjuvant treatment, Gleason Score permits independent prediction of the risk for BCR. These findings could help to estimate and discuss the individual risk for BCR with our patients on an individual basis.
