ABSTRACT
BACKGROUND: The aim of this study was to evaluate association of expression of survivin and p53 with the effects of neoadjuvant chemotherapy (NAC) in patients with advanced ovarian cancer (AOC). METHODS: We retrospectively evaluated 60 consecutive patients with AOC (International Federation of Gynecology and Obstetrics stage IIIC-IV) treated with NAC. The expression of p53 and survivin was assessed immunohistochemically. The median of expression total score survivin equals 2 was adopted to dichotomize the group. The positive and negative expression of p53 was used to dichotomize the group. RESULTS: The expression of survivin in tumor tissue taken before and after NAC was a significant difference in the percentage of stained nuclei (P = 0.0002), the intensity of staining (P = 0.0003), and total score (P = 0.0001). There was a significant difference in p53 expression in tumor tissue before and after NAC in the percentage of stained nuclei (P = 0.0424). Survivin expression, in contrast to p53 expression, was a prognostic factor in patients with AOC treated with NAC (P = 0.0484). The expression of survivin and p53 was not a predictive factor. Independent adverse predictor factors were as follows: lack of optimal interval debulking surgery and the lack of an objective response (the respective hazard ratio was 3.93 [95% confidence interval, 2.07-7.46; P < 0.0001] and 2.36 [95% confidence interval,1.25-4.47; P = 0.0080]). The suboptimal range of interval debulking surgery, resistance to platinum, and the lack of paclitaxel in the NAC were adverse prognostic factors (the respective hazard ratio was 2.61 [95% confidence interval, 1.17-5.83], 2.72 [95% confidence interval, 1.07-6.89], and 2.56 [95% confidence interval, 1.06-6.18]; P < 0.05]). CONCLUSIONS: High expression of survivin could be a prognostic factor in patients treated with NAC for AOC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Inhibitor of Apoptosis Proteins/metabolism , Ovarian Neoplasms/metabolism , Peritoneal Neoplasms/metabolism , Adenocarcinoma, Clear Cell/drug therapy , Adenocarcinoma, Clear Cell/metabolism , Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/metabolism , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/mortality , Cystadenocarcinoma, Serous/pathology , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Staging , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Prognosis , Retrospective Studies , Survival Rate , Survivin , Tumor Suppressor Protein p53/metabolismABSTRACT
BACKGROUND: ß-catenin is the key protein in the WNT signalling pathway and it forms adherent junctions together with E-cadherin. In ovarian carcinoma, abnormal expression of ß-catenin, E-cadherin and WNT-1 was observed, but their prognostic and predictive role is unclear. The aim of this study was to clarify the prognostic and predictive role of E-cadherin, ß-catenin and WNT-1 in advanced epithelial ovarian carcinoma (AEOC). METHODS: The expression of E-cadherin, ß-catenin and WNT-1 was determined by immunohistochemistry in AEOC. The correlation between expression of these proteins and progression-free survival (PFS) and overall survival (OS) was evaluated. Statistical analyses included Kaplan-Meier estimation, log-rank test, Spearman correlation and Cox proportional-hazards model. RESULTS: In ovarian cancer, intense expression of E-cadherin, ß-catenin and WNT-1 was found. In multivariate analysis, strong membrane ß-catenin expression was an independent unfavourable predictor for PFS (HR 2.19, 95% CI 1.09-4.39; p = 0.028), while in univariate analysis, strong membrane ß-catenin expression was a prognostic factor for OS in patients with AOC (p = 0.039). In multivariate analysis, only resistance to first-line chemotherapy was an adverse independent prognostic factor for OS (HR 16.84; 95% CI 5.07-55.98; p < 0.0001). Additionally, strong membranous ß-catenin expression was associated with resistance to platinum-based chemotherapy (p = 0.027). CONCLUSIONS: These findings support that WNT/ß-catenin pathway and E-cadherin are important factors in advanced epithelial ovarian cancer.
Subject(s)
Cadherins/analysis , Neoplasms, Glandular and Epithelial/chemistry , Ovarian Neoplasms/chemistry , Wnt Signaling Pathway , Wnt1 Protein/analysis , beta Catenin/analysis , Aged , Antigens, CD , Biopsy , Carcinoma, Ovarian Epithelial , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Middle Aged , Multivariate Analysis , Neoplasms, Glandular and Epithelial/mortality , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Proportional Hazards Models , Risk Factors , Time FactorsABSTRACT
BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) is found in many types of neoplasms. The aim of the study was to evaluate EGFR expression in colorectal cancer (CRC) specimens and to determine whether EGFR expression correlates with clinicopathological data and overall survival. PATIENTS AND METHODS: Tissue specimens from 181 consecutive CRC patients treated at the Military Institute of Medicine in 2006-2010 were collected and examined for EGFR expression, by immunohistochemistry staining. The staining intensity and percentage of cells with membranous EGFR expression were scored and then grouped according to the parameters of the Allred Scoring system. Cutoff values were subjected to further statistical analysis. Univariate tests and a multivariate Cox proportional hazards model were used in data analysis. RESULTS: EGFR was overexpressed in 96 of 181 CRC specimens (53%). EGFR expression was not correlated with other clinicopathological variables. On univariate analysis, overexpression of EGFR, determined by PS (percentage score) (>3) and total score (sum of PS and intensity score) (>4), was associated with poor overall survival. On multivariate analysis, EGFR overexpression (PS > 3) was an independent adverse prognostic factor (hazard ratio [HR] 1.62; 95% confidence interval [CI]: 1.03-2.53). Elevated carcinoembryonic antigen (CEA) serum concentration before treatment, performance status (Word Health Organization [WHO]-2), and tumor localized in colon and liver metastases were also independent unfavorable prognostic factors. CONCLUSION: EGFR overexpression (PS > 3) in a CRC patient population was an independent adverse prognostic factor. Implementation of the Allred Scoring system criteria into clinical practice might facilitate treatment decisions in CRC patients.
ABSTRACT
Wnt/ß-catenin pathway plays an important role in initiation and progression of colorectal oncogenesis. The aim of this study was to determine expression and localization of E-cadherin, ß-catenin and Wnt-1 proteins in colorectal tumors. Expression of ß-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on advanced colorectal cancers. Abnormal expression of E-cadherin, ß-catenin, Wnt-1 was observed. Additionally, we revealed correlations between levels of studied proteins and histoclinical data. In multivariate analysis nuclear ß-catenin, higher carcinoembryonic antigen serum level before treatment, female sex and tumor localized in colon or rectum were independent unfavorable prognostic factors. These findings support the hypothesis that Wnt/ß-catenin pathway plays an important role in advanced colorectal carcinoma.
