- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05151159
Prognostic Value of Protein IMP3 Expression in Cervical Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Molecular biomarkers could selectively identify patients with a more unfavorable clinical course. One of these biomarkers is IMP3 - insulin-like growth factor II mRNA binding protein.
The IGF group is a complex regulatory network at the cellular and substantial levels and plays a key physiological role in the development of the organism and the maintenance of normal cellular function during fetal and postnatal life. Overexpression of growth factors and their receptors is a common event during carcinogenesis. The IGF signaling system is under strict control of the normal physiological state and a deviation in this delicate balance can be a trigger for many molecular events leading to the development of malignancy. One member of the IGF system is the insulin-like growth factor II mRNA binding protein (IMP) which has been found to be an activator of IGF-II translation mRNA thus gaining a dominant role in controlling IGF-II-dependent cell proliferation.
The IMP protein family contains 3 proteins (IMP1, IMP2, IMP3). IMP3 is normally expressed in fetal tissues during embryogenesis. In adulthood, it appears as an oncoprotein that is expressed only in tumor tissues without the presence in the surrounding (adjacent) benign tissue. Previous in vitro studies have shown that IMP3 stimulates tumor cell proliferation by activating IGF II translation and adhesion and invasion via adhesion molecules and matrix metalloproteinases 1.
The results of recent research on cervical cancer and its precancerous lesions have linked the expression of IMP3 protein to cervical dysplasia and the possibility of severe cervical dysplasia (CIN III) progressing to squamous cell carcinoma. A higher expression of IMP3 protein was found in the cytoplasms of severe cervical dysplasia (CIN III) cells and invasive tumor cells compared to CIN I and CIN II change cells. The sensitivity of IMP3 expression in tumor cells was 96%. In preparations that were IMP3 negative, no further monitoring and treatment revealed squamous cell carcinoma. Further analyzes indicated the possibility of determining IMP3 expression on first cervical biopsy specimens in patients with HSIL lesions as a biomarker to detect a subset of patients in whom lesion invasiveness can be expected.
Based on previous studies, a monoclonal antibody specific for IMP3 has been developed and is successfully used in routine immunohistochemical methods that study the expression of IMP3 proteins in various malignancies. It has recently been found that the expression of IMP3 protein is associated with a more aggressive clinical course and a less favorable outcome in both gynecological and malignant diseases of other organ systems.
Research issues
Despite previous knowledge of prevention, detection and treatment, cervical cancer still causes great pain and mortality. The clinical course has so far been overlooked with regard to the clinical and pathological stage of the disease, and based on histological parameters and anatomical extent of the disease, a decision was made on further treatment and prognosis of the disease.
Previous research has only provided an introduction to the association of IMP3 protein expression with cervical cancer. An association was found between the increased expression of IMP3 protein in gynecological and other cancers in the body with a poorer disease outcome.
This study would look at the expression of IMP3 protein in cervical squamous cell carcinoma with the aim of detecting and linking the increased expression of IMP3 protein in patients who are expected to have an unfavorable clinical course and a poorer prognosis. Only patients in FIGO 1A1 and 1B1 disease stages will be observed, which has not been done in previous studies. In this way, patients who would be treated surgically would be singled out, and in whom a worse clinical outcome could be predicted and additional treatment could be planned individually.
Purpose of research
The study will determine the importance of immunohistochemical expression of IMP3 protein in cervical squamous cell carcinoma as a prognostic factor associated with higher tumor histological grade, higher FIGO stage, poorer course and disease outcome.
Reasearch hypothesis
Immunohistochemical expression of IMP3 protein in cervical squamous cell carcinoma was associated with poorer clinical course and disease outcome, shorter disease-free interval duration, and poorer 5-year survival outcomes.
Immunohistochemical determination of IMP3 protein expression in cervical cancer - as a new prognostic factor
The following will be excluded from the research:
- patients who have undergone pre-operative chemo and / or radiotherapy
- patients with associated gynecological or other malignancies
- patients with other histological types of tumors (adenocarcinoma, adenosquamous, neuroendocrine, etc.) The research will be performed on pathohistological preparations of surgical material of patients operated for cervical cancer in SKB Mostar in the above period.
The expression of IMP3 protein will be determined by immunohistochemical method and statistical analysis will be used to assess the association of expression with clinical and pathological disease progression and survival parameters.
Insight into medical documentation (patient medical histories and medical documentation of oncology patients from the Department of Oncology and Gynecology Clinic SKB Mostar) will provide clinical data on the age of patients, clinical stage of the disease determined by FIGO classification criteria, recurrence / length of period without signs of disease and clinical outcome.
Research methods:
Tumor samples for analysis will be obtained by 4μ sections of archived paraffin blocks.
Mouse monoclonal antihuman antibodies an IMP3 (DAKO) at a dilution of 1: 100 will be used for immunohistochemical analysis.
The immunohistochemical process will begin by dewaxing the tissue first in xylene and then rehydrating in alcohols of ever lower concentrations. Incubation in 0.1% H2O2 (30 minutes at room temperature) inactivated endogenous peroxidase. In order to detect antigenic sites, the sections will be boiled in citrate buffer, pH 9, in a microwave oven at 95 ° C for 10 minutes, then washed in phosphate buffered saline (PBS). After cooling to room temperature, the sections were incubated with primary antibodies for 60 minutes. After one hour of incubation with the primary antibody and washing in PBS, secondary detection with diaminobenzidine (DAB) will be used. An antibody-independent EnVision Detection Systems Peroxidase (DAB, Rabbit / Mouse K 5007) will be used for this purpose. After a 30-minute incubation and washing in PBS, the sections will be stained with diaminobenzidine (DAB) for 10 minutes at room temperature and washed in distilled water, and stained with hemalaun. The incisions will then be fitted into the fitting medium and covered with coverslips. Cells that reacted with the appropriate primary antibodies should have stained cytoplasms.
The results of immunohistochemical staining will be interpreted semiquantitatively. Samples with cytoplasmic staining in more than 10% of tumor cells will be considered as positive expression, and will be classified into 5 categories: 0 (1% -10% of stained cells), 1 (11% -25%), 2 (26% 50) %), 3 (51% -75%) and 4 (76% -100%). The intensity of IMP3 expression will be classified as negative, weak, moderate, or severe.
Sections intended for negative control by immunohistochemical staining of each antigen will be subjected, along with other sections, to the same procedure, except that they will not incubate with the primary antibody, but will be in PBS during that time. Control slides by the manufacturer will be used as a positive control.
The specimens will be examined with an Olympus BX40 light microscope (Olympus, Tokyo, Japan).
Total patient survival (OS) was defined as the time period between the date of surgery and the date of the last clinical control or death from cervical cancer.
Disease-free interval (DFS) is defined as the time interval between the date of surgery and the date of disease recurrence.
Statistical data processing:
The obtained research results will be stored in the MS Excel 2007 database, for all statistical analyzes the SPSS 17 statistical program will be used. Descriptive statistics methods will be used in data analysis. Nonparametric variables will be displayed as frequency and percentage. Depending on the data distribution, the parametric variables will be displayed as the arithmetic mean and standard deviation or as the median and interquartile range. The data distribution will be tested by the Kolmogorov-Smirnov test. A chi-square test and Fisher's exact test will be used to test for differences between groups for categorical variables where necessary. Student t-test and one-way analysis of variance (ANOVA) or Mann-Whitney U test and Kruskal-Wallis test as non-parametric alternatives in case the data distribution deviates from normal will be used to test the difference between parametric variables. Appropriate correlation and regression tests will be used to test the correlation between the examined variables. In the analysis of survival and disease recurrence, the Kaplan-Meier method and the Cox-Mantel log-rank test or the Mantel-Haenszel test will be used depending on the data obtained. The probability level of p <0.005 will be taken as statistically significant.
Study Type
Enrollment (Actual)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- operated women diagnosed with squamous cell carcinoma of the cervix at the figo stage 1a1, 1a2, 1b1 and 1b2
Exclusion Criteria:
- patients who underwent preoperative chemo and / or radiotherapy
- patients with associated gynecological or other malignant diseases
- patients with other histological types of tumors (adenocarcinoma, adenosquamous, neuroendocrine, etc.)
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
FIGO group 1A1
20 subjects with tumor invasion depth up to 1 mm
|
|
FIGO group 1A2
20 subjects with an invasion depth of 1 - 3 mm
|
|
FIGO group 1B1
20 subjects with invasion depth up to 2 cm
|
|
FIGO group 1B2
20 subjects with tumor invasion depth> 2 cm 20 subjects with tumor invasion depth> 2 cm
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
High expression of IMP3 protein in cervical squamous cell carcinoma is associated with a poorer disease outcome.
Time Frame: 10 Years ( 2003-2013)
|
Investigators are about to examine the association between IMP3 protein expression and disease spread according to the FIGO classification (clinical-pathological grading of the disease)
|
10 Years ( 2003-2013)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Krešić Tanja, Mr.sc, University Mostar
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IMP3, cervical cancer
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cervical Carcinoma
-
National Cancer Institute (NCI)TerminatedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Carcinoma | Cervical Carcinoma, Non-SquamousTypeUnited States
-
Zhujiang HospitalUnknownStudy of Nimotuzumab Combined With Concurrent Chemoradiotherapy for Locally Advanced Cervical CancerNeoplasms | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Cervical Adenosquamous Cell Carcinoma | Cervical Squamous Cell Carcinoma in SituChina
-
National Cancer Institute (NCI)Gynecologic Oncology Group; NCIC Clinical Trials GroupTerminatedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Cervical Adenosquamous Cell CarcinomaUnited States, Canada
-
University of WashingtonNational Cancer Institute (NCI); National Institutes of Health (NIH)TerminatedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Recurrent Cervical Carcinoma | Cervical Undifferentiated Carcinoma | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage... and other conditionsUnited States, Hong Kong, Canada
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma | Cervical Small Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
-
National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma | Recurrent Cervical Carcinoma | Stage IVA Cervical Cancer | Stage IVB Cervical Cancer | Stage IIIA Cervical Cancer | Stage IIIB Cervical CancerCanada
-
National Cancer Institute (NCI)NRG OncologyCompletedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma | Recurrent Cervical Carcinoma | Cervical Small Cell Carcinoma | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma | Cervical Small Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
-
National Cancer Institute (NCI)CompletedOxaliplatin and Paclitaxel in Treating Patients With Locally Recurrent or Metastatic Cervical CancerCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma | Recurrent Cervical Carcinoma | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)TerminatedLymph Node Mapping and Sentinel Lymph Node Identification in Patients With Stage IB1 Cervical CancerCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma | Stage I Cervical CancerUnited States
Clinical Trials on immunohistochemical analysis with murine monoclonal antihuman antibodies IMP3
-
Northwestern UniversityNational Cancer Institute (NCI); Celgene; The Leukemia and Lymphoma SocietyWithdrawnPrimary Myelofibrosis | Polycythemia Vera, Post-Polycythemic Myelofibrosis PhaseUnited States
-
University of WashingtonNational Cancer Institute (NCI)WithdrawnMicrosatellite Instability | Hormone-Resistant Prostate Cancer | Castration Levels of TestosteroneUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedHuman Papillomavirus Infection | Stage IVA Oral Cavity Squamous Cell Carcinoma | Stage IVA Oropharyngeal Squamous Cell Carcinoma | Stage IVB Oropharyngeal Squamous Cell Carcinoma | Stage IVC Oropharyngeal Squamous Cell Carcinoma | Stage I Oropharyngeal Squamous Cell Carcinoma | Stage II Oropharyngeal... and other conditionsUnited States
-
John ReneauActive, not recruitingRecurrent T-Cell Non-Hodgkin Lymphoma | Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma | Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma | Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma | Primary Cutaneous Anaplastic Large Cell Lymphoma | Refractory Primary Cutaneous T-Cell Non-Hodgkin... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Stage IV Renal Cell Cancer | Type 1 Papillary Renal Cell Carcinoma | Type 2 Papillary Renal Cell CarcinomaUnited States, Taiwan, Australia
-
Roswell Park Cancer InstituteGlaxoSmithKlineActive, not recruitingClear Cell Renal Cell Carcinoma | Stage IV Renal Cell CancerUnited States
-
SWOG Cancer Research NetworkNational Cancer Institute (NCI)CompletedRecurrent Squamous Cell Lung Carcinoma | Stage IV Squamous Cell Lung Carcinoma AJCC v7United States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingSezary Syndrome | Recurrent Mycosis Fungoides | Refractory Mycosis Fungoides | Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma | Folliculotropic Mycosis Fungoides | Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified | Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma | Refractory Cutaneous...United States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedMLH1 Gene Mutation | Stage IV Colorectal Cancer | Stage IVA Colorectal Cancer | Stage IVB Colorectal Cancer | Metastatic Carcinoma in the Liver | MSH6 Gene Mutation | PMS2 Gene MutationUnited States
-
SWOG Cancer Research NetworkNational Cancer Institute (NCI)CompletedRecurrent Squamous Cell Lung Carcinoma | Stage IV Squamous Cell Lung Carcinoma AJCC v7United States