BRAF-V600E AND P53 MUTATION AS A POTENTIAL PROGNOSTIC MARKERS OF REMISSION DURATION
(Abstract release date: 05/21/15)
EHA Library. Kriachok I. 06/12/15; 102834; PB1945
Disclosure(s): National Cancer InstituteOncohematology
Prof. Dr. Iryna Kriachok
Contributions
Contributions
Abstract
Abstract: PB1945
Type: Publication Only
Background
Langerhans Cell Histiocytosis (LCH) is an orphan disease of clonal dendritic cells which may affect any organ of the body.It is most often diagnosed in childhood, but can occur at any age. Clinically, LCH manifestations range from isolated bone lesions to multisystem disease, with outcomes ranging from spontaneous remission to progressionon therapy. Morphologically, LCH cells are for CD1a and/or CD207 (Langerin), S-100 positive. Recent identification of cancer-associated mutation BRAF V600E and p53 in LCH cases provided molecular evidence of the neoplastic nature of LCH.
Aims
To investigate the frequency of BRAF V600E and correlation with p53 mutations in histiocytosis, and it clinical significance as a potential biomarker of early relapse or refractory disease.
Methods
Formalin-fixed, paraffin embedded (FFPE) tissuegenotyped for BRAF-V600E mutations with allele-specific, real-time PCR assays and immunohistochemistry (IHC) with moAb p53 in order to study an expression of tumor protein p53.
Results
During last 5 years in our Institute we diagnosed 5 cases of LCH. All patients have multisystem LCH and were immunohistochemically positive for S-100, CD1a. Patients received the same therapy: 6 cycles of chemo according to LCH – 1 study protocol: etoposide – 150 mg/m2 i.v. (day 1-3), methylprednisolone – 30 mg/kg i.v. (day1-3). We assessed BRAF-V600E status in FFPE samples from all 5 patients (4 men and 1 woman, age between 23-55 years old, median age 39 y.o). BRAF-V600E mutation was found only in one patient. P53 was found at the same patient with positive BRAF-V600E. Compared with patients in which mutation of BRAF-V600Eand p53 have not been identified, this patient demonstrated early relapse (in 6 months after treatment). Two patients without mutation had late relapse (in 46 and 24 months – median 35 months), 1 patient had transformation in Hodgkin’s lymphoma (in 12 months) and 1 patient is still in remission (for 36 months).
Summary
BRAF V600E and p53 mutations were found in 1 out of 5 patients with LCH. This patient had short remission duration in comparison with patients without BRAF and p53 abnormalities. Probably BRAF and p53 could be considered as a potential prognostic markers of remission duration.
Keyword(s): Monoclonal antibody, Mutation, Prognostic factor, Remission
Session topic: Publication Only
Type: Publication Only
Background
Langerhans Cell Histiocytosis (LCH) is an orphan disease of clonal dendritic cells which may affect any organ of the body.It is most often diagnosed in childhood, but can occur at any age. Clinically, LCH manifestations range from isolated bone lesions to multisystem disease, with outcomes ranging from spontaneous remission to progressionon therapy. Morphologically, LCH cells are for CD1a and/or CD207 (Langerin), S-100 positive. Recent identification of cancer-associated mutation BRAF V600E and p53 in LCH cases provided molecular evidence of the neoplastic nature of LCH.
Aims
To investigate the frequency of BRAF V600E and correlation with p53 mutations in histiocytosis, and it clinical significance as a potential biomarker of early relapse or refractory disease.
Methods
Formalin-fixed, paraffin embedded (FFPE) tissuegenotyped for BRAF-V600E mutations with allele-specific, real-time PCR assays and immunohistochemistry (IHC) with moAb p53 in order to study an expression of tumor protein p53.
Results
During last 5 years in our Institute we diagnosed 5 cases of LCH. All patients have multisystem LCH and were immunohistochemically positive for S-100, CD1a. Patients received the same therapy: 6 cycles of chemo according to LCH – 1 study protocol: etoposide – 150 mg/m2 i.v. (day 1-3), methylprednisolone – 30 mg/kg i.v. (day1-3). We assessed BRAF-V600E status in FFPE samples from all 5 patients (4 men and 1 woman, age between 23-55 years old, median age 39 y.o). BRAF-V600E mutation was found only in one patient. P53 was found at the same patient with positive BRAF-V600E. Compared with patients in which mutation of BRAF-V600Eand p53 have not been identified, this patient demonstrated early relapse (in 6 months after treatment). Two patients without mutation had late relapse (in 46 and 24 months – median 35 months), 1 patient had transformation in Hodgkin’s lymphoma (in 12 months) and 1 patient is still in remission (for 36 months).
Summary
BRAF V600E and p53 mutations were found in 1 out of 5 patients with LCH. This patient had short remission duration in comparison with patients without BRAF and p53 abnormalities. Probably BRAF and p53 could be considered as a potential prognostic markers of remission duration.
Keyword(s): Monoclonal antibody, Mutation, Prognostic factor, Remission
Session topic: Publication Only
Abstract: PB1945
Type: Publication Only
Background
Langerhans Cell Histiocytosis (LCH) is an orphan disease of clonal dendritic cells which may affect any organ of the body.It is most often diagnosed in childhood, but can occur at any age. Clinically, LCH manifestations range from isolated bone lesions to multisystem disease, with outcomes ranging from spontaneous remission to progressionon therapy. Morphologically, LCH cells are for CD1a and/or CD207 (Langerin), S-100 positive. Recent identification of cancer-associated mutation BRAF V600E and p53 in LCH cases provided molecular evidence of the neoplastic nature of LCH.
Aims
To investigate the frequency of BRAF V600E and correlation with p53 mutations in histiocytosis, and it clinical significance as a potential biomarker of early relapse or refractory disease.
Methods
Formalin-fixed, paraffin embedded (FFPE) tissuegenotyped for BRAF-V600E mutations with allele-specific, real-time PCR assays and immunohistochemistry (IHC) with moAb p53 in order to study an expression of tumor protein p53.
Results
During last 5 years in our Institute we diagnosed 5 cases of LCH. All patients have multisystem LCH and were immunohistochemically positive for S-100, CD1a. Patients received the same therapy: 6 cycles of chemo according to LCH – 1 study protocol: etoposide – 150 mg/m2 i.v. (day 1-3), methylprednisolone – 30 mg/kg i.v. (day1-3). We assessed BRAF-V600E status in FFPE samples from all 5 patients (4 men and 1 woman, age between 23-55 years old, median age 39 y.o). BRAF-V600E mutation was found only in one patient. P53 was found at the same patient with positive BRAF-V600E. Compared with patients in which mutation of BRAF-V600Eand p53 have not been identified, this patient demonstrated early relapse (in 6 months after treatment). Two patients without mutation had late relapse (in 46 and 24 months – median 35 months), 1 patient had transformation in Hodgkin’s lymphoma (in 12 months) and 1 patient is still in remission (for 36 months).
Summary
BRAF V600E and p53 mutations were found in 1 out of 5 patients with LCH. This patient had short remission duration in comparison with patients without BRAF and p53 abnormalities. Probably BRAF and p53 could be considered as a potential prognostic markers of remission duration.
Keyword(s): Monoclonal antibody, Mutation, Prognostic factor, Remission
Session topic: Publication Only
Type: Publication Only
Background
Langerhans Cell Histiocytosis (LCH) is an orphan disease of clonal dendritic cells which may affect any organ of the body.It is most often diagnosed in childhood, but can occur at any age. Clinically, LCH manifestations range from isolated bone lesions to multisystem disease, with outcomes ranging from spontaneous remission to progressionon therapy. Morphologically, LCH cells are for CD1a and/or CD207 (Langerin), S-100 positive. Recent identification of cancer-associated mutation BRAF V600E and p53 in LCH cases provided molecular evidence of the neoplastic nature of LCH.
Aims
To investigate the frequency of BRAF V600E and correlation with p53 mutations in histiocytosis, and it clinical significance as a potential biomarker of early relapse or refractory disease.
Methods
Formalin-fixed, paraffin embedded (FFPE) tissuegenotyped for BRAF-V600E mutations with allele-specific, real-time PCR assays and immunohistochemistry (IHC) with moAb p53 in order to study an expression of tumor protein p53.
Results
During last 5 years in our Institute we diagnosed 5 cases of LCH. All patients have multisystem LCH and were immunohistochemically positive for S-100, CD1a. Patients received the same therapy: 6 cycles of chemo according to LCH – 1 study protocol: etoposide – 150 mg/m2 i.v. (day 1-3), methylprednisolone – 30 mg/kg i.v. (day1-3). We assessed BRAF-V600E status in FFPE samples from all 5 patients (4 men and 1 woman, age between 23-55 years old, median age 39 y.o). BRAF-V600E mutation was found only in one patient. P53 was found at the same patient with positive BRAF-V600E. Compared with patients in which mutation of BRAF-V600Eand p53 have not been identified, this patient demonstrated early relapse (in 6 months after treatment). Two patients without mutation had late relapse (in 46 and 24 months – median 35 months), 1 patient had transformation in Hodgkin’s lymphoma (in 12 months) and 1 patient is still in remission (for 36 months).
Summary
BRAF V600E and p53 mutations were found in 1 out of 5 patients with LCH. This patient had short remission duration in comparison with patients without BRAF and p53 abnormalities. Probably BRAF and p53 could be considered as a potential prognostic markers of remission duration.
Keyword(s): Monoclonal antibody, Mutation, Prognostic factor, Remission
Session topic: Publication Only
{{ help_message }}
{{filter}}