Endothelin-1: a predictor of extracapsular extension in clinically localized prostate cancer?

OBJECTIVE: To assess the value of endothelin-1 (ET-1) expression in predicting extracapsular extension (ECE) in clinically localized prostate cancer (PCa). PATIENTS AND METHODS: ET-1 expression was determined by immunohistochemistry on archival needle biopsies (NBs) from 94 patients (49 pT2 and 45 pT3a) who underwent radical prostatectomy (RP) for clinical T1-T2 PCa. Each sample was analysed independently by two pathologists blinded to the clinical data. RESULTS: In univariate analysis, high ET-1 expression in NBs, pre-operative prostate-specific antigen (PSA) level >10 ng/ml, percentage of positive biopsy cores and NB Gleason score ≥7 were significantly associated with ECE as determined on subsequent RP. No significant association was found between clinical stage and ECE. In multivariate analysis, there was a significant association with high ET-1 expression in NBs (p = 0.006), pre-operative PSA level >10 ng/ml (p = 0.049), and NB Gleason score ≥7 (p = 0.002). These three pre-operative factors combined provided the best model for predicting ECE with 93.3% sensitivity, 49% specificity, 62.5% positive predictive value, 88.9% negative predictive value. The combination yielded a higher concordance index (0.760 vs 0.720) and offered a higher log partial likelihood than the same model without ET1 (112.8 vs 105.7, p = 0.01). CONCLUSIONS: ET-1 expression was strongly associated with ECE and, when combined with pre-operative PSA level and Gleason score, improved the predictive accuracy of pre-operative NBs. Its assessment in patients with localized PCa might be useful when making treatment decisions. Further studies with standardisation of immunohistochemical staining and multi-institutional validation are now needed to establish the appropriate use of ET-1 staining in PCa staging and to evaluate inter-observer reproducibility.

HPV prevalence, viral load and physical state of HPV-16 in cervical smears of patients with different grades of CIN.

Human papillomavirus (HPV) infection is the most important event in malignant transformation of human cervical epithelium. We analysed in cervical smears, HPV genotypes with a focus on single/multiple infections, then characteristics of HPV-16 infections (presence of other genotypes, viral load and physical state) according to the grade of histological lesions. The purpose of this study was to know if these parameters could allow to differentiate histological diagnoses. DNA was extracted from 363 cervical samples corresponding to 24 cases without lesion, 96 CIN1, 92 CIN2, 144 CIN3 and 7 cancers. Our results show that HPV-16 was predominant and its prevalence increased with the severity of lesions (CIN1: 27.1%; CIN3: 65.3%). In addition, we showed that the frequency of single infections, as compared with multiple infections, increased with the severity of the lesion (CIN1: 25.0%; CIN3: 54.8%). Among HPV-16 positive samples (n = 170), we found that viral load, determined on cervical samples by real-time PCR, did not vary significantly according to the different CIN grades. Concerning HPV-16 integration, the mixed and integrated HPV-16 forms, already present in women with normal histology, increased to the benefit of pure episomal forms with the severity of lesions (normal cervix: 28.6%; CIN3: 73.8%). Thus, our data raise the question of the viral load as a valuable clinical parameter to discriminate between lesion grades. Moreover, we emphasize integration as an early event in cervical carcinogenesis, increasing with the severity of lesions. Finally, this study underlines the importance of single versus multiple infections linked to the severity of CIN.

Contribution of DNA ploidy image cytometry to the management of ASC cervical lesions.

BACKGROUND: The Bethesda system classifies smears that suggest an underlying cervical intraepithelial neoplasia (CIN) as ASC (atypical squamous cell) smears. ASC smears are subdivided into ASCUS (of undetermined significance) and ASCH (cannot exclude a high-grade lesion). Today the management of ASCUS is a triage with HR-HPV testing and colposcopy is recommended for ASCH. The aim was to conduct a study on ASC smears to determine DNA ploidy measurement for the detection of CIN2+. METHODS: The link between a suspect DNA ploidy assessed by image cytometry and/or a positive HR-HPV testing was analyzed on 69 ASCUS and 82 ASCH smears, and the presence of CIN2+ within 12 months after ASC diagnosis. The ploidy was suspect in case of aneuploidy, multiploidy, or in the presence of cells with a DNA content >5c or >9c. RESULTS: Every woman who had a CIN2+ had a suspect DNA profile in the ASCUS smears and every woman except 1 was HR-HPV-positive. The link between a positive HR-HPV test or a suspect DNA profile or both and a CIN2+ was high (P = .019, .023, and .008, respectively). The presence of >9c cells was particularly linked to CIN2+ (P = .0031). In all, 90.9% and 87.9% of the ASCH smears with CIN2+ were, respectively, HR-HPV positive or had a suspect ploidy (P = .0000 and P = .0043), and the presence of >9c cells was also linked to CIN2+ (P = .003). CONCLUSIONS: HR-HPV testing and determination of the ploidy profile with special attention to 9c-exceeding cells could be accurate for a better management of ASC smears.