Luis Perez-Casanova - Academia.edu (original) (raw)

Papers by Luis Perez-Casanova

Research paper thumbnail of Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement

Modern Pathology, Dec 1, 2019

A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previousl... more A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previously in isolated cases of the synovial chondromatosis. To analyze further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%), and chondrosarcoma secondary to synovial chondromatosis (75%), showing that FN1 and/or AVCR2A gene rearrangements do not distinguish between benign and malignant synovial chondromatosis. RNA sequencing revealed the presence of the FN1-ACVR2A fusion in several cases that were negative by FISH suggesting that the true prevalence of this fusion is potentially higher than 57%. In soft tissue chondromas, FN1 alterations were detected by FISH in 50% of cases but no ACVR2A alterations were identified. RNA sequencing identified a fusion involving FN1 and fibroblast growth factor receptor 2 (FGFR2) in the case of soft tissue chondroma and FISH confirmed recurrent involvement of both FGFR1 and FGFR2. These fusions were present in a subset of soft tissue chondromas characterized by grungy calcification, a feature reminiscent of phosphaturic mesenchymal tumor. However, unlike the latter, fibroblast growth factor 23 (FGF23) mRNA expression was not elevated in soft tissue chondromas harboring the FN1-FGFR1 fusion. The mutual exclusivity of ACVR2A rearrangements observed in synovial chondromatosis and FGFR1/2 in soft tissue chondromas suggests these represent separate entities. There have been no reports of malignant soft tissue chondromas, therefore differentiating these lesions will potentially alter clinical management by allowing soft tissue chondromas to be managed more conservatively.

Research paper thumbnail of Pathology of paediatric bone tumours

Surgery (oxford), 2017

Primary bone tumours account for less than 0.2% of all neoplasms but malignant bone tumours repre... more Primary bone tumours account for less than 0.2% of all neoplasms but malignant bone tumours represent the 3 rd most common cause of cancer deaths in children and adolescents. The rarity of bone tumours in itself is a diagnostic challenge but is compounded by the number of tumour subtypes on top of which the imaging and histological features of degenerative and reactive processes, and benign bone tumours can simulate bone sarcomas. Furthermore, even in children bone lesions may represent metastatic disease. Hence the assessment of a bone tumour in a child or adolescent should be performed in a specialist referral bone tumour centre which has access to a multidisciplinary team and molecular diagnostic tests: the latter provides greater diagnostic accuracy. It is now appreciated that germline alterations occur more commonly than previously recognised in children and young adults presenting with osteosarcoma and Ewing sarcoma. Awareness of this is important as genetic counselling and screening may be appropriate. In this article epidemiology, radiology, pathology, genetics, treatment and prognosis of most commonly encountered bone tumours among the paediatric population are reviewed.

Research paper thumbnail of A Two-Step Diagnostic Approach for <i>NTRK</i> Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas

Oncologist, Mar 30, 2023

Background: It is of interest to determine the incidence and molecular characteristics of NTRK ge... more Background: It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers. Methods: Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels. Results: For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangiocarcinoma, IHC performed on a biopsy showed a weak focal cytoplasmic and nuclear staining. No other NTRK fusion was detected on the 16 other samples with both panels. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.7%. For pancreatic cancers, 319 samples have been selected and 297 were suitable to perform IHC. Nineteen samples were IHC positive. No fusion was detected by NGS. Conclusion: NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to possible treatment with specific TRK inhibitors.

Research paper thumbnail of Abstract P4-08-08: Biomarkers to predict distant recurrence free survival after neoadjuvant endocrine therapy in breast cancer. A long follow up retrospective study

Background: Neoadjuvant endocrine therapy (NET) is gaining more acceptances for the management of... more Background: Neoadjuvant endocrine therapy (NET) is gaining more acceptances for the management of estrogen receptor (ER) positive breast cancer (BC). Rate of patients achieving pathological complete response is very low and Ki67 suppression and PEPI score are the only prognostic factors associated with relapse free survival. The aim of our study was to identify biomarkers of prediction of distant relapse risk that could help clinicians in the decision-making of systemic adjuvant treatment in patients previously treated with NET Material &amp; Methods: Retrospective study of 119 postmenopausal women with ER or progesterone receptor (PR) positive BC treated with NET in ICO-HUB from 1997 to 2009. Clinical-pathological data and treatments administered were reviewed. IHC expression of ER, PR, Ki67, Androgen receptor (AR), BCL-2, Cyclin D1 (CD1), p16, p53, CD 44 and synaptophysin were analyzed in post-NET surgical formalin-fixed paraffin-embedded tumor samples through a tissue microarray. Survival was calculated by Kaplan-Meier method. Univariate and multivariate analysis of variables associated with distant relapse free survival (DRFS) was evaluated by Cox proportional hazard model. Results: Mean age was 74 (63-88). cT: T2 5%, T3 6.5%, T4 43.5%. cN: N0 59%, N1 25%, N2-3 16%. Stage: I 21%, II 49.5%, III 29.5%. Histological subtype: ductal 84%, lobular 6%, others 10%. Histological grade: G1 20%, G2 55%, G3 25%. Vascular invasion 15%. NET: Aromatase Inhibitors 64%, SERM 36%. Median duration of NET 8.5 months. Clinical Response: Complete 4%, Partial 55%, Stable 37%, Progression 4%. Surgery: Lumpectomy 72%, Mastectomy 28%;Lymphadenectomy 70.5%, Sentinel lymph node biopsy 6%, No surgical approach of axilla 23.5%. Surgical specimen: ypT1 36%, ypT2 54%, ypT3 6%, ypT4 4%; ypN0 28%, ypN1 22%, ypN2 13.5%, ypN3 12% ypNx 23.5%. Surgical margins: Negative 89% Positive 11%. Median fibrosis rate 20% (0-95). PR and Ki67 showed a statistically significant decrease after NET(p&lt;0,05) but no ER (p=0,29). Adjuvant treatment: chemotherapy 7%, radiotherapy 76%, endocrine therapy 96%. Median follow-up: 104 months. Only 21 patients developed distance relapse. Median OS was 139 months [95% CI = 98-181]. Univariate analysis for DRFS showed statistically significant differences in cN (HR=3), histological grade 3 (HR=3.61), ypN (HR=3.62), p16 (HR=6.1) and p53 (HR=2.79). Multivariate analysis of post-NET biomarkers showed that negative nuclear p16 expression (HR=4.79)and positive p53 (HR=2.83)were independently associated with worse DRFS. In multivariate analysis of all clinico-pathological and molecular factors, histological grade 3 (HR=2.82) was the sole DRFS independent factor. Conclusions: Negative nuclear p16 expression and positive p53 post-NET were associated with worseDRFS. Whenall clinico-pathological and molecular factors were analysed, G3 was the sole DRFS independent factor. Patients with G3, negative p16 or positive p53 after NET could probably benefit from adjuvant chemotherapy or CDK 4-6 inhibitors treatment. In our series, we did not find usefulness in analysing ER, PR and Ki67 post-NET changes to predict DRFS. Citation Format: Gil-Gil M, Morilla I, Petit A, Soler T, Perez-Martin X, Guma A, Pla MJ, Ortega R, Garcia-Tejedor A, Falo C, Montal R, Perez-Casanova L, Loayza C, Pernas S. Biomarkers to predict distant recurrence free survival after neoadjuvant endocrine therapy in breast cancer. A long follow up retrospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-08-08.

Research paper thumbnail of A Two-Step Diagnostic Approach for NTRK Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas

The Oncologist

Background It is of interest to determine the incidence and molecular characteristics of NTRK gen... more Background It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers. Methods Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels. Results For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangioca...

Research paper thumbnail of O-4 NTRK gene fusions in bilio-pancreatic cancers

Research paper thumbnail of NTRK gene fusions in bilio-pancreatic cancers

Journal of Clinical Oncology, 2020

e16664 Background: Gene fusions involving one of the 3 neurotrophic tyrosine receptor kinases ( N... more e16664 Background: Gene fusions involving one of the 3 neurotrophic tyrosine receptor kinases ( NTRK) have been identified in approximately 1% of solid tumors and inhibitors of TRK have been shown to have anti-tumor activity regardless of tumor type. NTRK gene fusions have been previously reported in bilio-pancreatic tumors. It is of interest therefore to determine incidence and molecular characteristics of NTRK gene fusions in these patients. Methods: Formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies or cytological samples of biliary tract tumors (BTC) including intra-hepatic (IH), extra-hepatic (EH), perihilar cholangiocarcinoma (PH) and gallbladder tumors (G), and pancreatic adenocarcinoma (PA) were retrieved from the tumor bank of CUB Hôpital Erasme between JAN 2010 and OCT 2019. A two-step diagnostic method incorporating immunohistochemistry (IHC) screening followed by NGS analysis was used. Pan–TRK IHC (monoclonal antibody clone EPR17341 [AbCa...

Research paper thumbnail of Clinical and Pathological Behavior of Well-Differentiated Pancreatic Neuroendocrine Tumors

American Journal of Clinical Pathology, 2015

Well-differentiated (WD) pancreatic neuroendocrine tumors (pNET) are uncommon neoplasms and one o... more Well-differentiated (WD) pancreatic neuroendocrine tumors (pNET) are uncommon neoplasms and one of the challenges lies in predicting tumor behavior and managing these patients. The aim of this study is to evaluate patient outcomes associated with the surgical management of WD pNET and to assess the prognostic and biological behavior differences between the two grades of WD pNET. Patients with surgically treated pNET in our institution in the last 15 years were retrospectively analyzed. Histopathologic findings, immunohistochemical (IHC) results, and actual status of patients with grade 1 (G1) and 2 (G2) WD pNET were collected. Forty-eight patients were classified as WD pNET (16 G1 and 32 G2). In the G1 patients, group mean tumor size was 1.6 cm. Two had vascular and/or neural invasion (12,5%), none was staged T3/T4, all were N0, and only one had distant metastasis. None showed local or distant recurrence and are actually disease free. By IHC 13/16 (81%) were diffuse or focally positive for Insulin and/or Glucagon, 5 were functional (Insulinomas). In the G2 patients group mean tumor size was 4,1cm. Seventeen had vascular and/or perineural invasion (53%), 14 were staged T3/T4 (43%), 12 were N1 (37,5%), 10 were M1 at diagnosis and two showed distant metastasis after it. Two showed local recurrence, two had metastasis recurrence and two died because of the pNET. By IHC 14/32 (43%) were positive for insulin and/or glucagon, four were functional (insulinomas). Although G2 pNET are considered well-differentiated neoplasm and not labeled as carcinomas, they show aggressive behavior and a worst prognosis. G1 pNETs are usually less than 2 cm and do not show aggressive behavior. Preoperative samples are important and determine if a surgical approach is the best therapeutic option

Research paper thumbnail of Pathology of paediatric bone tumours

Surgery (Oxford), 2017

Primary bone tumours account for less than 0.2% of all neoplasms but malignant bone tumours repre... more Primary bone tumours account for less than 0.2% of all neoplasms but malignant bone tumours represent the 3 rd most common cause of cancer deaths in children and adolescents. The rarity of bone tumours in itself is a diagnostic challenge but is compounded by the number of tumour subtypes on top of which the imaging and histological features of degenerative and reactive processes, and benign bone tumours can simulate bone sarcomas. Furthermore, even in children bone lesions may represent metastatic disease. Hence the assessment of a bone tumour in a child or adolescent should be performed in a specialist referral bone tumour centre which has access to a multidisciplinary team and molecular diagnostic tests: the latter provides greater diagnostic accuracy. It is now appreciated that germline alterations occur more commonly than previously recognised in children and young adults presenting with osteosarcoma and Ewing sarcoma. Awareness of this is important as genetic counselling and screening may be appropriate. In this article epidemiology, radiology, pathology, genetics, treatment and prognosis of most commonly encountered bone tumours among the paediatric population are reviewed.

Research paper thumbnail of Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement

Modern Pathology, 2019

A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previousl... more A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previously in isolated cases of the synovial chondromatosis. To analyze further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%), and chondrosarcoma secondary to synovial chondromatosis (75%), showing that FN1 and/or AVCR2A gene rearrangements do not distinguish between benign and malignant synovial chondromatosis. RNA sequencing revealed the presence of the FN1-ACVR2A fusion in several cases that were negative by FISH suggesting that the true prevalence of this fusion is potentially higher than 57%. In soft tissue chondromas, FN1 alterations were detected by FISH in 50% of cases but no ACVR2A alterations were identified. RNA sequencing identified a fusion involving FN1 and fibroblast growth factor receptor 2 (FGFR2) in the case of soft tissue chondroma and FISH confirmed recurrent involvement of both FGFR1 and FGFR2. These fusions were present in a subset of soft tissue chondromas characterized by grungy calcification, a feature reminiscent of phosphaturic mesenchymal tumor. However, unlike the latter, fibroblast growth factor 23 (FGF23) mRNA expression was not elevated in soft tissue chondromas harboring the FN1-FGFR1 fusion. The mutual exclusivity of ACVR2A rearrangements observed in synovial chondromatosis and FGFR1/2 in soft tissue chondromas suggests these represent separate entities. There have been no reports of malignant soft tissue chondromas, therefore differentiating these lesions will potentially alter clinical management by allowing soft tissue chondromas to be managed more conservatively.

Research paper thumbnail of Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement

Modern Pathology, Dec 1, 2019

A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previousl... more A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previously in isolated cases of the synovial chondromatosis. To analyze further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%), and chondrosarcoma secondary to synovial chondromatosis (75%), showing that FN1 and/or AVCR2A gene rearrangements do not distinguish between benign and malignant synovial chondromatosis. RNA sequencing revealed the presence of the FN1-ACVR2A fusion in several cases that were negative by FISH suggesting that the true prevalence of this fusion is potentially higher than 57%. In soft tissue chondromas, FN1 alterations were detected by FISH in 50% of cases but no ACVR2A alterations were identified. RNA sequencing identified a fusion involving FN1 and fibroblast growth factor receptor 2 (FGFR2) in the case of soft tissue chondroma and FISH confirmed recurrent involvement of both FGFR1 and FGFR2. These fusions were present in a subset of soft tissue chondromas characterized by grungy calcification, a feature reminiscent of phosphaturic mesenchymal tumor. However, unlike the latter, fibroblast growth factor 23 (FGF23) mRNA expression was not elevated in soft tissue chondromas harboring the FN1-FGFR1 fusion. The mutual exclusivity of ACVR2A rearrangements observed in synovial chondromatosis and FGFR1/2 in soft tissue chondromas suggests these represent separate entities. There have been no reports of malignant soft tissue chondromas, therefore differentiating these lesions will potentially alter clinical management by allowing soft tissue chondromas to be managed more conservatively.

Research paper thumbnail of Pathology of paediatric bone tumours

Surgery (oxford), 2017

Primary bone tumours account for less than 0.2% of all neoplasms but malignant bone tumours repre... more Primary bone tumours account for less than 0.2% of all neoplasms but malignant bone tumours represent the 3 rd most common cause of cancer deaths in children and adolescents. The rarity of bone tumours in itself is a diagnostic challenge but is compounded by the number of tumour subtypes on top of which the imaging and histological features of degenerative and reactive processes, and benign bone tumours can simulate bone sarcomas. Furthermore, even in children bone lesions may represent metastatic disease. Hence the assessment of a bone tumour in a child or adolescent should be performed in a specialist referral bone tumour centre which has access to a multidisciplinary team and molecular diagnostic tests: the latter provides greater diagnostic accuracy. It is now appreciated that germline alterations occur more commonly than previously recognised in children and young adults presenting with osteosarcoma and Ewing sarcoma. Awareness of this is important as genetic counselling and screening may be appropriate. In this article epidemiology, radiology, pathology, genetics, treatment and prognosis of most commonly encountered bone tumours among the paediatric population are reviewed.

Research paper thumbnail of A Two-Step Diagnostic Approach for <i>NTRK</i> Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas

Oncologist, Mar 30, 2023

Background: It is of interest to determine the incidence and molecular characteristics of NTRK ge... more Background: It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers. Methods: Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels. Results: For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangiocarcinoma, IHC performed on a biopsy showed a weak focal cytoplasmic and nuclear staining. No other NTRK fusion was detected on the 16 other samples with both panels. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.7%. For pancreatic cancers, 319 samples have been selected and 297 were suitable to perform IHC. Nineteen samples were IHC positive. No fusion was detected by NGS. Conclusion: NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to possible treatment with specific TRK inhibitors.

Research paper thumbnail of Abstract P4-08-08: Biomarkers to predict distant recurrence free survival after neoadjuvant endocrine therapy in breast cancer. A long follow up retrospective study

Background: Neoadjuvant endocrine therapy (NET) is gaining more acceptances for the management of... more Background: Neoadjuvant endocrine therapy (NET) is gaining more acceptances for the management of estrogen receptor (ER) positive breast cancer (BC). Rate of patients achieving pathological complete response is very low and Ki67 suppression and PEPI score are the only prognostic factors associated with relapse free survival. The aim of our study was to identify biomarkers of prediction of distant relapse risk that could help clinicians in the decision-making of systemic adjuvant treatment in patients previously treated with NET Material &amp; Methods: Retrospective study of 119 postmenopausal women with ER or progesterone receptor (PR) positive BC treated with NET in ICO-HUB from 1997 to 2009. Clinical-pathological data and treatments administered were reviewed. IHC expression of ER, PR, Ki67, Androgen receptor (AR), BCL-2, Cyclin D1 (CD1), p16, p53, CD 44 and synaptophysin were analyzed in post-NET surgical formalin-fixed paraffin-embedded tumor samples through a tissue microarray. Survival was calculated by Kaplan-Meier method. Univariate and multivariate analysis of variables associated with distant relapse free survival (DRFS) was evaluated by Cox proportional hazard model. Results: Mean age was 74 (63-88). cT: T2 5%, T3 6.5%, T4 43.5%. cN: N0 59%, N1 25%, N2-3 16%. Stage: I 21%, II 49.5%, III 29.5%. Histological subtype: ductal 84%, lobular 6%, others 10%. Histological grade: G1 20%, G2 55%, G3 25%. Vascular invasion 15%. NET: Aromatase Inhibitors 64%, SERM 36%. Median duration of NET 8.5 months. Clinical Response: Complete 4%, Partial 55%, Stable 37%, Progression 4%. Surgery: Lumpectomy 72%, Mastectomy 28%;Lymphadenectomy 70.5%, Sentinel lymph node biopsy 6%, No surgical approach of axilla 23.5%. Surgical specimen: ypT1 36%, ypT2 54%, ypT3 6%, ypT4 4%; ypN0 28%, ypN1 22%, ypN2 13.5%, ypN3 12% ypNx 23.5%. Surgical margins: Negative 89% Positive 11%. Median fibrosis rate 20% (0-95). PR and Ki67 showed a statistically significant decrease after NET(p&lt;0,05) but no ER (p=0,29). Adjuvant treatment: chemotherapy 7%, radiotherapy 76%, endocrine therapy 96%. Median follow-up: 104 months. Only 21 patients developed distance relapse. Median OS was 139 months [95% CI = 98-181]. Univariate analysis for DRFS showed statistically significant differences in cN (HR=3), histological grade 3 (HR=3.61), ypN (HR=3.62), p16 (HR=6.1) and p53 (HR=2.79). Multivariate analysis of post-NET biomarkers showed that negative nuclear p16 expression (HR=4.79)and positive p53 (HR=2.83)were independently associated with worse DRFS. In multivariate analysis of all clinico-pathological and molecular factors, histological grade 3 (HR=2.82) was the sole DRFS independent factor. Conclusions: Negative nuclear p16 expression and positive p53 post-NET were associated with worseDRFS. Whenall clinico-pathological and molecular factors were analysed, G3 was the sole DRFS independent factor. Patients with G3, negative p16 or positive p53 after NET could probably benefit from adjuvant chemotherapy or CDK 4-6 inhibitors treatment. In our series, we did not find usefulness in analysing ER, PR and Ki67 post-NET changes to predict DRFS. Citation Format: Gil-Gil M, Morilla I, Petit A, Soler T, Perez-Martin X, Guma A, Pla MJ, Ortega R, Garcia-Tejedor A, Falo C, Montal R, Perez-Casanova L, Loayza C, Pernas S. Biomarkers to predict distant recurrence free survival after neoadjuvant endocrine therapy in breast cancer. A long follow up retrospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-08-08.

Research paper thumbnail of A Two-Step Diagnostic Approach for NTRK Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas

The Oncologist

Background It is of interest to determine the incidence and molecular characteristics of NTRK gen... more Background It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers. Methods Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels. Results For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangioca...

Research paper thumbnail of O-4 NTRK gene fusions in bilio-pancreatic cancers

Research paper thumbnail of NTRK gene fusions in bilio-pancreatic cancers

Journal of Clinical Oncology, 2020

e16664 Background: Gene fusions involving one of the 3 neurotrophic tyrosine receptor kinases ( N... more e16664 Background: Gene fusions involving one of the 3 neurotrophic tyrosine receptor kinases ( NTRK) have been identified in approximately 1% of solid tumors and inhibitors of TRK have been shown to have anti-tumor activity regardless of tumor type. NTRK gene fusions have been previously reported in bilio-pancreatic tumors. It is of interest therefore to determine incidence and molecular characteristics of NTRK gene fusions in these patients. Methods: Formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies or cytological samples of biliary tract tumors (BTC) including intra-hepatic (IH), extra-hepatic (EH), perihilar cholangiocarcinoma (PH) and gallbladder tumors (G), and pancreatic adenocarcinoma (PA) were retrieved from the tumor bank of CUB Hôpital Erasme between JAN 2010 and OCT 2019. A two-step diagnostic method incorporating immunohistochemistry (IHC) screening followed by NGS analysis was used. Pan–TRK IHC (monoclonal antibody clone EPR17341 [AbCa...

Research paper thumbnail of Clinical and Pathological Behavior of Well-Differentiated Pancreatic Neuroendocrine Tumors

American Journal of Clinical Pathology, 2015

Well-differentiated (WD) pancreatic neuroendocrine tumors (pNET) are uncommon neoplasms and one o... more Well-differentiated (WD) pancreatic neuroendocrine tumors (pNET) are uncommon neoplasms and one of the challenges lies in predicting tumor behavior and managing these patients. The aim of this study is to evaluate patient outcomes associated with the surgical management of WD pNET and to assess the prognostic and biological behavior differences between the two grades of WD pNET. Patients with surgically treated pNET in our institution in the last 15 years were retrospectively analyzed. Histopathologic findings, immunohistochemical (IHC) results, and actual status of patients with grade 1 (G1) and 2 (G2) WD pNET were collected. Forty-eight patients were classified as WD pNET (16 G1 and 32 G2). In the G1 patients, group mean tumor size was 1.6 cm. Two had vascular and/or neural invasion (12,5%), none was staged T3/T4, all were N0, and only one had distant metastasis. None showed local or distant recurrence and are actually disease free. By IHC 13/16 (81%) were diffuse or focally positive for Insulin and/or Glucagon, 5 were functional (Insulinomas). In the G2 patients group mean tumor size was 4,1cm. Seventeen had vascular and/or perineural invasion (53%), 14 were staged T3/T4 (43%), 12 were N1 (37,5%), 10 were M1 at diagnosis and two showed distant metastasis after it. Two showed local recurrence, two had metastasis recurrence and two died because of the pNET. By IHC 14/32 (43%) were positive for insulin and/or glucagon, four were functional (insulinomas). Although G2 pNET are considered well-differentiated neoplasm and not labeled as carcinomas, they show aggressive behavior and a worst prognosis. G1 pNETs are usually less than 2 cm and do not show aggressive behavior. Preoperative samples are important and determine if a surgical approach is the best therapeutic option

Research paper thumbnail of Pathology of paediatric bone tumours

Surgery (Oxford), 2017

Primary bone tumours account for less than 0.2% of all neoplasms but malignant bone tumours repre... more Primary bone tumours account for less than 0.2% of all neoplasms but malignant bone tumours represent the 3 rd most common cause of cancer deaths in children and adolescents. The rarity of bone tumours in itself is a diagnostic challenge but is compounded by the number of tumour subtypes on top of which the imaging and histological features of degenerative and reactive processes, and benign bone tumours can simulate bone sarcomas. Furthermore, even in children bone lesions may represent metastatic disease. Hence the assessment of a bone tumour in a child or adolescent should be performed in a specialist referral bone tumour centre which has access to a multidisciplinary team and molecular diagnostic tests: the latter provides greater diagnostic accuracy. It is now appreciated that germline alterations occur more commonly than previously recognised in children and young adults presenting with osteosarcoma and Ewing sarcoma. Awareness of this is important as genetic counselling and screening may be appropriate. In this article epidemiology, radiology, pathology, genetics, treatment and prognosis of most commonly encountered bone tumours among the paediatric population are reviewed.

Research paper thumbnail of Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement

Modern Pathology, 2019

A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previousl... more A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previously in isolated cases of the synovial chondromatosis. To analyze further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%), and chondrosarcoma secondary to synovial chondromatosis (75%), showing that FN1 and/or AVCR2A gene rearrangements do not distinguish between benign and malignant synovial chondromatosis. RNA sequencing revealed the presence of the FN1-ACVR2A fusion in several cases that were negative by FISH suggesting that the true prevalence of this fusion is potentially higher than 57%. In soft tissue chondromas, FN1 alterations were detected by FISH in 50% of cases but no ACVR2A alterations were identified. RNA sequencing identified a fusion involving FN1 and fibroblast growth factor receptor 2 (FGFR2) in the case of soft tissue chondroma and FISH confirmed recurrent involvement of both FGFR1 and FGFR2. These fusions were present in a subset of soft tissue chondromas characterized by grungy calcification, a feature reminiscent of phosphaturic mesenchymal tumor. However, unlike the latter, fibroblast growth factor 23 (FGF23) mRNA expression was not elevated in soft tissue chondromas harboring the FN1-FGFR1 fusion. The mutual exclusivity of ACVR2A rearrangements observed in synovial chondromatosis and FGFR1/2 in soft tissue chondromas suggests these represent separate entities. There have been no reports of malignant soft tissue chondromas, therefore differentiating these lesions will potentially alter clinical management by allowing soft tissue chondromas to be managed more conservatively.