Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients

Immunoradiometric and immunohistochemical analysis of Cathepsin D in ovarian cancer: lack of association with clinical outcome.

The aim of this study was to analyse the clinical significance of Cathepsin D (Cath D) content as determined by an immunoradiometric assay in a series of primary untreated ovarian cancers from 162 patients. In addition, immunohistochemical analysis of Cath D was also performed on a subset of 86 tumours. Cath D levels were distributed in an asymmetrical way and were skewed towards the lower values (median value 20.8 pmol mg(-1) protein, range 2.0-99.0 pmol mg(-1) protein). No correlation was found between Cath D levels and clinicopathological parameters. However, the percentage of Cath D positivity was significantly higher in oestrogen receptor-positive (57%) compared with oestrogen receptor-negative (36%) cases (P= 0.01). The percentage of Cath D-positive staining was not significantly different for both epithelial (27%) and stromal components (40%). Immunoradiometrically detected Cath D levels were not different according to Cath D stromal immunostaining (P= 0.18), while higher Cath D levels were measured in Cath D-positive than in Cath D-negative tumour epithelial cells (P = 0.027). Survival analysis was conducted on 161 primary untreated ovarian cancer patients. The 5-year overall survival rate was 57% and 55% in Cath D-positive and Cath D-negative patients respectively (P = 0.69). As far as time to progression was concerned, there was no significant difference in the survival rate of patients with either high or low Cath D content (P = 0.56). Similar results have been obtained in the subset of patients in which Cath D was analysed by immunohistochemistry. In conclusion, Cath D measurement in tumour extracts appears to have a limited usefulness in improving the prognostic characterization of ovarian cancer patients

Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy.

The expression of epidermal growth factor receptor (EGFR), oestrogen receptor (ER) and progesterone receptor (PR) was assayed by a radioreceptor method in 117 primary ovarian cancers. EGFR was not significantly related to any of the clinicopathological parameters examined. In patients with stage II-IV disease who underwent second-look surgery after primary chemotherapy, a significant correlation between high EGFR levels and poor response to chemotherapy was demonstrated (P = 0.031). Moreover, post-operative residual tumour showed an independent role in predicting chemotherapy response (P = 0.0007) and EGFR status showed a borderline significance (P = 0.052) in the multivariate analysis. No correlation between steroid hormone receptors and clinicopathological parameters was observed. Whereas a significant relationship was shown between EGFR positivity and a shorter overall survival (OS) (P = 0.0022) and progression-free survival (PFS) (P = 0.0033), patient survival was not related to steroid hormone receptor status. Among the parameters tested only stage, ascites and EGFR status retained an independent prognostic value in the multivariate analysis

Nm23 expression in endometrial and cervical cancer: inverse correlation with lymph node involvement and myometrial invasion.

The expression of nm23 has been shown to correlate in some solid tumours with their metastatic potential and to be associated with a favourable prognosis in human breast cancer and melanoma. In breast and ovarian cancer nm23 expression is also correlated with lymph node involvement. We analysed the expression of nm23-H1 and -H2 in normal endometrium and in endometrial and cervical cancer by both Northern and Western blotting. Cellular localisation of Nm23-H1 was visualised by immunohistochemistry mostly in the cytoplasm. Both isoforms of Nm23 were present in all the samples analysed, and a clear direct correlation between Nm23-H1 and -H2 levels was evident. Median nm23-H2 levels were higher than than -H1 levels in both tissues. Cervical cancer patients with lymph node involvement were shown to have significantly lower protein levels of Nm23 (P < 0.007 for H1 and P < 0.009 for H2), and a similar trend was also evident in endometrial cancer. Furthermore, the degree of myometrial invasion in endometrial cancer patients was also inversely correlated with Nm23-H1 levels of expression (P < 0.003). Nm23 level may therefore be taken into consideration as a new marker in the prognostic characterisation and in the treatment planning of uterine tumour patients

Cathepsin D and epidermal growth factor in human breast cyst fluid.

Cathespin D (Cath D) is a proteolytic enzyme secreted by human breast cancer cells with a growth promoting activity in vitro. In the present study, we measured Cath D and Epidermal Growth Factor/alpha Transforming Growth Factor (EGF/alpha-TGF) concentrations in the breast cyst fluid (BCF) of 43 patients with gross cystic disease of the breast. Both Cath D (median 2.45 pmoles mg-1 protein; range 0-4.84 vs 0.98 pmoles mg-1 protein; range 0-3.11) and EGF/alpha-TGF (28.71 ng mg-1 protein; range 7.05-50.63 vs 10.83 ng mg-1 protein; range 0.06-30.55) levels were higher in BCF of apocrine than flattened cysts (P less than 0.0005 and P less than 0.01, respectively). Premenopausal patients showed higher concentrations of Cath D (P less than 0.05) and EGF/alpha-TGF (P less than 0.05) than postmenopausal patients. A positive correlation was obtained between intracystic concentrations of Cath D and EGF/alpha-TGF (P less than 0.00001). The higher levels of Cath-D and EGF/alpha-TGF found in apocrine cysts could provide an explanation for the increased risk of subsequent breast cancer in women with this type of cyst

Prognostic significance of epidermal growth factor receptor in laryngeal squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) content was determined by a radioligand receptor assay in 140 primary laryngeal squamous cell carcinomas (median value of 8.4 fmol mg-1 protein, range 0-169.9 fmol mg-1 protein). Cox univariate regression analysis using EGFR as a continuous variable showed that EGFR levels are directly associated with the risk of death (chi 2 = 14.56, P-value = 0.0001) and relapse (chi 2 = 7.77, P-value = 0.0053). A significant relationship between EGFR status and survival was observed at the different arbitrary cut-off values chosen (8, 16 and 20 fmol mg-1 protein). The cut-off value of 20 fmol mg-1 protein was the best prognostic discriminator. In fact, the 5 year survival was 81% for patients with EGFR- tumours compared with 25% for patients with EGFR+ tumours (P < 0.0001). The 5 year relapse-free survival was 77% for patients with EGFR- tumours compared with 24% for patients with EGFR+ tumours (P < 0.010). When clinicopathological parameters and EGFR status were examined in the multivariate analysis, T classification and EGFR status retained an independent prognostic value. In this study we demonstrated that high EGFR levels single out patients with poor prognosis in laryngeal cancer

Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: correlation with histopathological features and epidermal growth factor receptors.

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer