Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02788669 |
| Other study ID # |
PO15124 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
May 20, 2016 |
| Last updated |
June 1, 2016 |
| Start date |
November 2015 |
| Est. completion date |
May 2017 |
Study information
| Verified date |
May 2016 |
| Source |
CHU de Reims |
| Contact |
Camille Boulagnon |
| Phone |
326784218 |
| Email |
cboulagnon[@]chu-reims.fr |
| Is FDA regulated |
No |
| Health authority |
France: Commission nationale de l'informatique et des libertés |
| Study type |
Observational
|
Clinical Trial Summary
Colorectal cancer (CRC) is a major public health problem in France and worldwide. CRC is the
third most common cancer in incidence and mortality in France. The vast majority of these
cancers are adenocarcinomas that arise sporadically and develop from precursor lesions:
adenoma. All CCR with the same disease stage do not have the same prognosis. Various
parameters have been identified as factors influencing the prognosis and allows adjustment
of the treatment. The poor histoprognostic factors are vessels and nerves invasion by the
tumor or the mucinous adenocarcinoma subtype. At the molecular level, the presence of
microsatellite instability (MSI) improves the prognosis, while the presence of a BRAF
mutation is an independent poor prognostic factor.
LRP-1 is a multifunctional endocytic receptor that belongs to the family of LDL receptors.
It is involved in the clearance of matrix proteases. A loss of expression or a decrease of
the LRP-1 activity is correlated with an increase of aggressiveness of cancer cells. This
effect was demonstrated in vitro in vesicular thyroid carcinomas after LRP-1 blocking. The
decrease in the immunohistochemical expression and LRP-1 genomic in hepatocellular
carcinomas and lung adenocarcinomas was correlated with a decrease in the overall survival.
In CRC, only one immunohistochemical expression study of LRP-1 in colonic adenocarcinoma has
been published to date. This study shows that tumor cells express LRP-1, but in nearly half
the cases, weaker than in normal colonic cells. The clinical and prognostic impact of LRP-1
expression in colon cancer and its association with a particular molecular or morphological
profile has not been studied to date.
In this work, the investigators will study the immunohistochemical and genic expression of
LRP-1 in a series of colorectal cancers.
Description:
Colorectal cancer (CRC) is a major public health problem in France and worldwide. CRC is the
third most common cancer in incidence and mortality in France. The vast majority of these
cancers are adenocarcinomas that arise sporadically and develop from precursor lesions:
adenoma. All CRC with the same disease stage do not have the same prognosis. Various
parameters have been identified as factors influencing the prognosis and allows adjustment
of the treatment. The poor histoprognostic factors are the presence of tumor vessels and
nerves invasion or the mucinous adenocarcinoma subtype. At the molecular level, the presence
of microsatellite instability (MSI) improves the prognosis, while the presence of a BRAF
mutation is an independent poor prognostic factor.
Low density lipoprotein related Protein Receptor 1 (LRP-1) is a multifunctional endocytic
receptor that belongs to the family of LDL receptors. He is involved in the clearance of
enzymes responsible for the degradation of the extracellular matrix: the matrix proteases.
This role of matrix proteolysis modulator associated with a function of cell migration
regulator give to this protein an anticancer role. The antitumor property of LRP-1 has been
demonstrated in thyroid cancers in vitro. In these studies, loss of LRP-1 expression or a
decrease in the LRP-1 activity was correlated with an increase of cancer cells migration and
invasion. However, the opposite effect was observed in prostate cancer cell lines.
The clinical impact of the level of LRP-1 expression on overall survival of cancer patients
has been assessed in two studies: one on patients suffering from hepatocellular carcinoma
and one on patients suffering from primitive lung adenocarcinomas. In both studies, the
decrease of immunohistochemical and gene expression of LRP-1 correlated with overall
survival decrease. In CRC, only one immunohistochemical expression study of LRP-1 has been
published to date. This study shows that adenocarcinomatous cells express LRP-1, but in
nearly half the cases, weaker than in normal colonic cells. The clinical and prognostic
impact of LRP-1 expression in colon cancer and its association with a particular molecular
or morphological profile has not been studied to date.
In this work, the investigators will study the immunohistochemical and genic expression of
LRP-1 in a well-characterized series of CRC.
The main objective of this study is to study by genic and immunohistochemical approaches the
role of LRP-1 in the aggressiveness of colon adenocarcinomas.
The secondary objective of this study is to search for associations between LRP-1 expression
level and morphological or molecular profiles of colonic adenocarcinomas
This study will be the first to explore the expression of LRP-1 in well characterized colon
cancers of different morphological and molecular profiles. This study will help to increase
knowledge of the prognostic role of LRP-1 in colon cancer and its possible association with
clinical, morphological or molecular parameters.
There will be a retrospective cohort study, single center.
The investigators will first design the list of all eligible patients by using a request in
the software DIAMIC of th pathology department with component code "colon", damage code
"adenocarcinoma " and period "between 2006 and 2012". Patients suffering from Lynch syndrome
or other familial cancer syndrome will be excluded of the study. Informed consent will be
send to all the selected patients.
Once the patients list will be completed:
- The patients' medical records will be reviewed for: sociodemographic and clinical data
colonic tumor location, presence of synchronous metastases, treatment type and
duration, patient follow up to the date of 01/06/2014 point (metastases occurrence,
disease recurrence, patient death, ...).
- A central review of all pathological slides will be performed for these criteria:
adenocarcinoma subtype according to WHO 2010 classification, differentiation,
association with polyps and their types, pTNM stage, invasion front and budding, stroma
type, presence and amount of tumor necrosis).
- Immunohistochemical analysis on formalin fixed and paraffin embedded tissue will be
performed:
- qualitative and semi-quantitative evaluation of LRP1 immunoexpression with
anti-5A6 and 8G1 antibodies
- RER phenotype research (MLH1, MSH2, MSH6 and PMS2 immunohistochemistry) and BRAF
V600E immunohistochemistry
- Molecular analyzes:
- analysis of LRP-1 gene expression on frozen tissue
- for selected cases: search for microsatellite instability, search for BRAF V600E,
KRAS (exon 2, 3 and 4) and NRAS (exons 2, 3 and 4) mutation on formalin fixed and
paraffin embedded tissue
Statistical analysis:
- Data description: mean and standard deviation for quantitative variables; number and
percentage for categorical variables.
- Comparison of tumors having a high expression of LRP-1 and tumors not or little
expressing LRP-1 by univariate analysis (Student's test and the Wilcoxon test, Chi2 or
Fisher's exact) and multivariate (logistic regression).
- Search factors associated with patient outcomes, including the expression of LRP1, by
univariate analysis (log-rank test) and multivariate (Cox model).
Colorectal cancer (CRC) is a major public health problem in France and worldwide. CRC is the
third most common cancer in incidence and mortality in France. The vast majority of these
cancers are adenocarcinomas that arise sporadically and develop from precursor lesions:
adenoma. All CRC with the same disease stage do not have the same prognosis. Various
parameters have been identified as factors influencing the prognosis and allows adjustment
of the treatment. The poor histoprognostic factors are the presence of tumor vessels and
nerves invasion or the mucinous adenocarcinoma subtype. At the molecular level, the presence
of microsatellite instability (MSI) improves the prognosis, while the presence of a BRAF
mutation is an independent poor prognostic factor.
Low density lipoprotein related Protein Receptor 1 (LRP-1) is a multifunctional endocytic
receptor that belongs to the family of LDL receptors. He is involved in the clearance of
enzymes responsible for the degradation of the extracellular matrix: the matrix proteases.
This role of matrix proteolysis modulator associated with a function of cell migration
regulator give to this protein an anticancer role. The antitumor property of LRP-1 has been
demonstrated in thyroid cancers in vitro. In these studies, loss of LRP-1 expression or a
decrease in the LRP-1 activity was correlated with an increase of cancer cells migration and
invasion. However, the opposite effect was observed in prostate cancer cell lines.
The clinical impact of the level of LRP-1 expression on overall survival of cancer patients
has been assessed in two studies: one on patients suffering from hepatocellular carcinoma
and one on patients suffering from primitive lung adenocarcinomas. In both studies, the
decrease of immunohistochemical and gene expression of LRP-1 correlated with overall
survival decrease. In CRC, only one immunohistochemical expression study of LRP-1 has been
published to date. This study shows that adenocarcinomatous cells express LRP-1, but in
nearly half the cases, weaker than in normal colonic cells. The clinical and prognostic
impact of LRP-1 expression in colon cancer and its association with a particular molecular
or morphological profile has not been studied to date.
In this work, the investigators will study the immunohistochemical and genic expression of
LRP-1 in a well-characterized series of CRC.
The main objective of this study is to study by genic and immunohistochemical approaches the
role of LRP-1 in the aggressiveness of colon adenocarcinomas.
The secondary objective of this study is to search for associations between LRP-1 expression
level and morphological or molecular profiles of colonic adenocarcinomas
This study will be the first to explore the expression of LRP-1 in well characterized colon
cancers of different morphological and molecular profiles. This study will help to increase
knowledge of the prognostic role of LRP-1 in colon cancer and its possible association with
clinical, morphological or molecular parameters.
There will be a retrospective cohort study, single center.
The investigators will first design the list of all eligible patients by using a request in
the software DIAMIC of th pathology department with component code "colon", damage code
"adenocarcinoma " and period "between 2006 and 2012". Patients suffering from Lynch syndrome
or other familial cancer syndrome will be excluded of the study. Informed consent will be
send to all the selected patients.
Once the patients list will be completed:
- The patients' medical records will be reviewed for: sociodemographic and clinical data
colonic tumor location, presence of synchronous metastases, treatment type and
duration, patient follow up to the date of 01/06/2014 point (metastases occurrence,
disease recurrence, patient death, ...).
- A central review of all pathological slides will be performed for these criteria:
adenocarcinoma subtype according to WHO 2010 classification, differentiation,
association with polyps and their types, pTNM stage, invasion front and budding, stroma
type, presence and amount of tumor necrosis).
- Immunohistochemical analysis on formalin fixed and paraffin embedded tissue will be
performed:
- qualitative and semi-quantitative evaluation of LRP1 immunoexpression with
anti-5A6 and 8G1 antibodies
- RER phenotype research (MLH1, MSH2, MSH6 and PMS2 immunohistochemistry) and BRAF
V600E immunohistochemistry
- Molecular analyzes:
- analysis of LRP-1 gene expression on frozen tissue
- for selected cases: search for microsatellite instability, search for BRAF V600E,
KRAS (exon 2, 3 and 4) and NRAS (exons 2, 3 and 4) mutation on formalin fixed and
paraffin embedded tissue
Statistical analysis:
- Data description: mean and standard deviation for quantitative variables; number and
percentage for categorical variables.
- Comparison of tumors having a high expression of LRP-1 and tumors not or little
expressing LRP-1 by univariate analysis (Student's test and the Wilcoxon test, Chi2 or
Fisher's exact) and multivariate (logistic regression).
- Search factors associated with patient outcomes, including the expression of LRP1, by
univariate analysis (log-rank test) and multivariate (Cox model).
