Prognostic factors for recurrence in early stage adult granulosa cell tumor of the ovary.

OBJECTIVE: Adult granulosa cell tumors (AGCTs) account for less than 5 % of all ovarian malignancies, whereas the majority (95 %) occurs after the age of 30 (adult-type) and present at an early stage. Aim of this study is to identify clinical and pathological risk factors for recurrence in early stage AGCTs. METHODS: Retrospective review of patients with AGCT of the ovary, treated surgically at our institution from 1996 to 2011. Clinical, pathological and follow-up data were collected. Systematic analysis was performed to determine variables for predicting recurrence. RESULTS: In total, 43 patients were identified. The mean age at diagnosis was 54.3 years and 65.1 % of them were postmenopausal. All patients underwent surgical staging and intraoperative rupture of the tumor occurred in four of them (9.3 %). The majority of the cases were staged as IA (72.1 %) while 10 (23.3 %) were staged as IC and only two patients as IIB. Mitotic index was 4 or more in 34.9 % of the patients and nuclear atypia was moderate to high in 60.5 %. During follow-up period (mean 9.2 years), recurrence occurred in three patients (7 %) with no deaths recorded so far. The cumulative recurrence free rate for the first 2 years was 97.6 % (SE = 2.4 %), for 5 years 94.9 % (SE = 3.5 %) and for 10 years 91.0 % (SE = 5.1 %).Tumor size, stage and mitotic index proved to be independent predictors for recurrence at the multivariate analysis. CONCLUSIONS: Recurrence in early stage AGCT seems to be associated with stage, tumor size and mitotic index. All the above should be taken into consideration when tailored postoperative management is planned.

Ultrasonographic markers and preoperative CA-125 to distinguish between borderline ovarian tumors and stage I ovarian cancer.

OBJECTIVE: Preoperative evaluation of ovarian masses has become increasingly important for optimal planning of treatment. The aim of this study was to assess the role of preoperative serum cancer antigen 125 (CA-125) levels in correlation with ultrasonographic features in order to distinguish between borderline ovarian tumors (BOTs) and stage I epithelial ovarian carcinoma (EOC). DESIGN: Retrospective study. SETTING: Tertiary University Hospital. POPULATION: We reviewed all women with BOTs and stage I EOC from January 2000 to December 2010. Data from 165 women (66 BOTs and 99 stage I EOC) were analyzed. METHODS: Multivariable logistic regression with stepwise selection of variables was used to determine which clinical variables, ultrasound features and CA-125 level were independently associated with invasiveness. MAIN OUTCOME MEASURES: Utility of ultrasonographic markers and CA-125 in the preoperative differential diagnosis between BOTs and stage I EOC. RESULTS: Women with CA-125 > 100 IU mL(-1) had almost three times greater likelihood of belonging in the EOC group [odds ratio (OR) 3.02; confidence interval (CI) 95%: 1.13-8.12]. Furthermore, the presence of large solid component (≥20% of the tumor comprised of solid components) was associated with 4.25 times greater odds of it to representing ovarian cancer rather than a BOT (OR 4.25; 95% CI: 2.05-8.82). In contrast, the presence of papillary projections was associated with a 73% lower likelihood of EOC (OR 0.27; 95% CI: 0.13-0.58). CONCLUSIONS: Preoperative CA-125 > 100 IU mL(-1) combined with the presence of a large solid component and the absence of papillary projections seems to improve the discriminative ability in favor of stage I EOC.

Insight into long-term histological, proliferative and apoptotic modifications in ileal orthotopic neobladder and conduit mucosa.

AIMS AND BACKGROUND: To assess the long-term histological, apoptotic and proliferating alterations of the intestinal mucosa of ileal conduits and orthotopic neobladders. METHODS: Fifty patients (46 males, 4 females), aged 52-78 years, who underwent urinary diversion with either ileal orthotopic neobladder (group ON, 20 patients) or conduit (group IC, 30 patients) from 2001 to 2005, were included in this prospective study. Ileal samples were collected during surgery (controls) and by random mucosal biopsies 6, 12, 24, 36 and 48 months later. Histological (villi height, crypt depth, eosinophil cell count), proliferation (Ki67 immunochemistry), and apoptotic (Bcl-2 immunochemistry, TUNEL) parameters were assessed. RESULTS: During the 4-year follow-up, we recorded progressive villi area, height and crypt depth reduction, mucosa flattening, and inflammatory and eosinophilic infiltration. Villi height: crypt depth ratio showed a statistically significant difference (P < 0.05) between the two groups from the 6th month. Dysplasia, metaplasia, and neoplasia were not observed. Bcl-2 values showed a progressive increase until 24 months in group ON and 12 months in group IC, followed by a decline thereafter. Ki-67 values showed a progressive increase after 6 months in group ON and an increase until 24 months followed by a decline thereafter in group IC. TUNEL showed two peaks, at 24 and 48 months. CONCLUSIONS: Histological adaptation was revealed in both groups, with statistically significant differences in favor of orthotopic substitution. Proliferative and apoptotic pathways are implicated as demonstrated by relevant modifications of Bcl-2, Ki-67 and TUNEL, in accord with the histological adaptation.

Evaluation of the prognostic value of cellular inhibitor of apoptosis protein in epithelial ovarian cancer using automated quantitative protein analysis.

PURPOSE: The cellular inhibitor of apoptosis protein (cIAP) is regarded as an important prognostic biomarker in cancer. Here, we sought to determine the prognostic value of cIAP protein levels in epithelial ovarian cancer using a novel method of compartmentalized in situ protein analysis. METHODS: A tissue array composed of 150 advanced-stage ovarian cancers, treated with surgical debulking followed by platinum/paclitaxel-based combination chemotherapy, was constructed. For evaluation of protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis. RESULTS: The mean follow-up time for the entire cohort was 34.4 months. Patients with tumors bearing high cIAP membranous expression had a 3-year survival rate of 31% compared with 73% for patients with low cIAP expressing tumors (P = 0.0020). In multivariable analysis, adjusting for well-characterized prognostic variables, low membranous cIAP expression level was the only significant prognostic factor for overall survival. CONCLUSIONS: Our results indicate that cIAP protein levels have prognostic value in ovarian cancer patients. Modulation of cIAP levels may improve clinical outcome in ovarian cancer.

Subcellular localization and protein levels of cyclin-dependent kinase inhibitor p27 independently predict for survival in epithelial ovarian cancer.

PURPOSE: p27 protein is regarded as a valuable prognostic biomarker in cancer with a potential use as a molecular target. However, different methods of immunohistochemical assessment have yielded conflicting results. Here, we sought to determine the prognostic value of p27 in ovarian cancer using a novel method of compartmentalized in situ protein analysis. EXPERIMENTAL DESIGN: A tissue array composed of 150 advanced stage ovarian cancers uniformly treated, with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of p27 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis [automated quantitative analysis (AQUA)]. RESULTS: The mean follow-up time of the patients was 34.3 months. Patients with low Fédération Internationale des Gynaecologistes et Obstetristes stage were more likely to have low nuclear p27 expression (P = 0.008). Low nuclear p27 expression was associated with improved 3-year overall survival (66% versus 20%, P = 0.0047) and disease-free survival (27% versus 12%, P = 0.022). In multivariable analysis, adjusting for well-characterized prognostic variables, low nuclear p27 expression level was the most significant prognostic factor for both disease-free and overall survival. CONCLUSIONS: Our results indicate that quantitative assessment of nuclear p27 expression level by automated in situ quantitative analysis is a strong predictor for outcome in ovarian cancer.

Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer.

BACKGROUND: Several lines of laboratory evidence support the epidermal growth factor receptor (EGFR) as an adverse prognostic indicator in ovarian cancers. However, different methods of immunohistochemical assessment have yielded conflicting results. Here, we sought to determine the prognostic value of EGFR in ovarian cancer using a novel method of compartmentalized in situ protein analysis. METHODS: A tissue array composed of 150 advanced-stage ovarian cancers uniformly treated, with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of EGFR protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). RESULTS: Mean follow-up time for the entire cohort was 34.4 months. Eighty-one of 150 cases had sufficient tissue for AQUA analysis. High tumor EGFR expression was associated with poor outcome for overall survival (P=0.0001) and disease-free survival (P=0.0005) at 3 years. In multivariable analysis, adjusting for well-characterized prognostic variables, EGFR expression status was the most significant prognostic factor for disease-free and overall survival. CONCLUSION: The conflicting results in the literature regarding the prognostic value of EGFR may be due to the technical difficulties inherent in assessing EGFR with immunocytochemistry. In the present study, we show that measurement of EGFR protein levels in ovarian cancer using AQUA is feasible and can give important prognostic information.

Modified S-pouch neobladder vs ileal conduit and a matched control population: a quality-of-life survey.

OBJECTIVES: To measure the quality-of-life (QoL) outcome and urinary and sexual function and bother after radical cystectomy and different types of urinary tract reconstruction (Bricker vs modified S-pouch neobladder), also assessing differences between them and a normal population. PATIENTS, SUBJECTS AND METHODS: Two groups of patients with bladder cancer were assessed; group 1 comprised 58 (mean age 65 years, mean follow-up 28 months) with an ileal conduit diversion, and group 2, 50 (mean age 61 years, mean follow-up 26 months) with a modified S-pouch neobladder. All were disease-free. Group 3 comprised 54 healthy subjects (a control population) of similar age, gender and comorbidities other than bladder cancer. A QoL questionnaire was used to study changes in QoL, and a specific questionnaire for urinary and sexual function and bother was also constructed. RESULTS: There were no differences in the QoL scores among the three groups; group 3 (control) tended to have a better QoL for all domains except emotional functioning. Urinary function was seriously affected in group 1, with more daytime leakage than in groups 2 and 3 (37.8% vs 10%, P = 0.005, and 9.3%, P = 0.01), night loss of urine (39.5% vs 28%, P = 0.07, and 3.7%, P = 0.002) and urine odour (58.6% vs 4%, and 5.5%, both P = 0.001). Patients in group 2 differed from healthy individuals only in night loss of urine. Consequently urinary bother was more pronounced in group 1, as fewer were satisfied (68.9% vs 86% and 83.2%, both P = 0.03). Sexual function was seriously and similarly affected in groups 1 and 2; the erection rate was 28.9% for group 1, 35.5% for group 2 (P = 0.1) and 83.3% in group 3 (P = 0.003), while firm erections were present at 17.7%, 22.2% (P = 0.2) and 83.3% (P = 0.002). Women reported equivalent dysfunction in all three groups (15.4%, 20% and 16.6%, P = 0.3). Sexual desire was also equal in all groups (48.2%, 50% and 48.1). Patients in group 1 expressed more bother, while those in group 2 seemed more satisfied by their sexual life (84.4%, 68% and 68.5%, P = 0.04). CONCLUSIONS: Radical cystectomy does not affect QoL whichever urinary reconstruction is used, and this implies a determination by the patients to live and adjust to their new conditions. On the contrary, urinary and sexual function are affected and related to the method used to reconstruct the urinary system.