- Email: [email protected]
bc1-2 translocation in malignant lymphomas in hong kong chinese
CYTOGENETICS CYTOGENETICS AND CANCER 0. Margaret Garsonfc, Department of Cytogenetics, St. Vincent's Hospital, Fitzroy, Victoria, 3065.
bcl-2 TFANSLOCATION IN MALIGNANT LYMPHOMAS IN HON; KON; CHINESE
the diaghaematolSpecific abnormalogical disorders is well established. ities identify specific varieties of acute and chronic leukaemias and non-llodgkin's lymphoma, t o the extent that a cytogenetic classification of these diseases may be more useful to the treating clinician than standard morphology. In fact a new classification of acute leukaemia based on combined morphology, immunophenotype and cytogenetic abnormalities has been produced, which is considered a clinically useful refinement of the FAB classification.
The significance of chromosome abnormalities i n nosis and management of patients with malignant
Such conclusions have been reached because of great improvement in cytogenetic culture and identification techniques over the past 15 years. Similar studies in solid tumours have been hampered because of the relatively low mitotic rate in these malignancies, with the exception of paediatric tumours where abnormalities specific for the tumour variety have already been identified. However improved culture techniques are now allowing the recognition of specific abnormalities in carcinomas. Primary cytogenetic changes, considered to occur very early i n the malignant process, have been separated from secondary abnormalities which indicate progression and thus aggression of tumours. Non-random abnormalities have even been /found in benign tumours such as lipomas and adenomas. 'Molecular cytogenetics is adding another parameter to lour investigation of all malignancies by the identificat'ion of oncogene and growth factor rearrangements and amplifications associated with the structural chromosomal changes.
DECMONSTRATION OF ~ y ONCOGENE c PROTEIN PRODUCT IN MALIGNANT LYMPHOMA LOCALIZATION OF THE PROTEIN IN THE NUCLEUS.
-
S . L . , €,Y.
lL!B*, L l Q , LHQ,DEPARTMENT
PATHOLOGY, UNIVERSIM OF HOffi KO%.
OF
QUEEN MARY HOSPITAL
oncogene has been implicated t o be The c-myo dereguiated in the process of neogenesis in malignant lymphoma. However, there i s controversy concerning the presence o f its protein product In lymphoma as detected by immunohistochemistry. M o r e uncertain i s its subcellular locallzatlon in both normal and neoplastic tissues. With improved f ixation technique, we have demonstrated the presence of the c-myc oncogene protein product as detected by imnunohistochmistry with its localization i n nuclei of lymphana cells. This study was done on a serles of 30 cases of lymphoma including different histological and Immunophenotyper, uslng a murine monoclonal antibody (clone '6E10) against a synthetic ol igopeptide of 18 amino-acid residues analogous t o c-nryc protein. A high percentage of part of the lymphoma cells shows expresslon of the proteln in most cases irrespective of histological type. Depending on whether the specimen 1s optimally preserved. we are able to localize the protein mainly in the nucleus. Both cycling and non-cycling tumor cells as defined by the monoclonal antlbody Ki67 might contain 9 and stronger staining was observed in nuclei with an open chromatin pattern. We conclude that c-myc protein expression I s high in most malignant lymphanas irrespective of histolocial type. This may imply pathogenetic importance of c-myc deregulation in lymphmagenesis. but Its expresslon i s not helpful for histological classification.
LLLlLm.
S
.
v
G . S R I V A S T A Y A ,
DEPARTMENT OF PATHOLOGY. UNIVERSITY OF MARY HOSPITAL
€-HQ*P
HON; K O f f i ,
QUEEN
It has been reported that follicular lymphomas in Amerlcan patients are closely associated with the nonrandom translocation t(18;14) with juxtapositioning of the oncogene bcl-2 and the immunoglobulin (Ig) heavy chain gene loci. We have investigated the cccurence of such juxtaposltfonlng In malignant lymphanas in Hong Kong Chinese. Genomlc DNA from 10 cases of follicular lymphanas and 14 cases of diffuse lymphanas with proven B cell clonal pro1 iferation by imnunohistochmistry were digested with two o r t h r e e restrictive endonucleases. Southern blots of the samples were hybridized with probes t o the JH gene fragment of the Ig heavy chain and t o the ,major breakpoint cluster region of bcl-2. All cases showed rearrangement of at least one J H allele. 4 out of 10 o f the follicular lymphanas showed bcl-2 rearrangement bandcs) and all o f these rearrangement bands co-migrate with rearrangemnt bands of J H . N o n e of t h e diffuse lymphomas showed rearrangemnt of bcl-2. We conclude that bcl-2 rearrangement and juxtaposition to JH of the Ig heavy chain do occur in follicular lymphomas in Hong Kong Chinese, but t h e major breakpoint cluster region i s less frequently involved. Such infrequent involvement prevents t h e use of breakpoints in this cluster region as a marker of transformation of follicular lymphomas t o diffuse lymphanas in Hong Kong Chinese.
bcl-2 TFANSLOCATION IN MALIGNANT LYMPHOMAS IN HON; KON; CHINESE
the diaghaematolSpecific abnormalogical disorders is well established. ities identify specific varieties of acute and chronic leukaemias and non-llodgkin's lymphoma, t o the extent that a cytogenetic classification of these diseases may be more useful to the treating clinician than standard morphology. In fact a new classification of acute leukaemia based on combined morphology, immunophenotype and cytogenetic abnormalities has been produced, which is considered a clinically useful refinement of the FAB classification.
The significance of chromosome abnormalities i n nosis and management of patients with malignant
Such conclusions have been reached because of great improvement in cytogenetic culture and identification techniques over the past 15 years. Similar studies in solid tumours have been hampered because of the relatively low mitotic rate in these malignancies, with the exception of paediatric tumours where abnormalities specific for the tumour variety have already been identified. However improved culture techniques are now allowing the recognition of specific abnormalities in carcinomas. Primary cytogenetic changes, considered to occur very early i n the malignant process, have been separated from secondary abnormalities which indicate progression and thus aggression of tumours. Non-random abnormalities have even been /found in benign tumours such as lipomas and adenomas. 'Molecular cytogenetics is adding another parameter to lour investigation of all malignancies by the identificat'ion of oncogene and growth factor rearrangements and amplifications associated with the structural chromosomal changes.
DECMONSTRATION OF ~ y ONCOGENE c PROTEIN PRODUCT IN MALIGNANT LYMPHOMA LOCALIZATION OF THE PROTEIN IN THE NUCLEUS.
-
S . L . , €,Y.
lL!B*, L l Q , LHQ,DEPARTMENT
PATHOLOGY, UNIVERSIM OF HOffi KO%.
OF
QUEEN MARY HOSPITAL
oncogene has been implicated t o be The c-myo dereguiated in the process of neogenesis in malignant lymphoma. However, there i s controversy concerning the presence o f its protein product In lymphoma as detected by immunohistochemistry. M o r e uncertain i s its subcellular locallzatlon in both normal and neoplastic tissues. With improved f ixation technique, we have demonstrated the presence of the c-myc oncogene protein product as detected by imnunohistochmistry with its localization i n nuclei of lymphana cells. This study was done on a serles of 30 cases of lymphoma including different histological and Immunophenotyper, uslng a murine monoclonal antibody (clone '6E10) against a synthetic ol igopeptide of 18 amino-acid residues analogous t o c-nryc protein. A high percentage of part of the lymphoma cells shows expresslon of the proteln in most cases irrespective of histological type. Depending on whether the specimen 1s optimally preserved. we are able to localize the protein mainly in the nucleus. Both cycling and non-cycling tumor cells as defined by the monoclonal antlbody Ki67 might contain 9 and stronger staining was observed in nuclei with an open chromatin pattern. We conclude that c-myc protein expression I s high in most malignant lymphanas irrespective of histolocial type. This may imply pathogenetic importance of c-myc deregulation in lymphmagenesis. but Its expresslon i s not helpful for histological classification.
LLLlLm.
S
.
v
G . S R I V A S T A Y A ,
DEPARTMENT OF PATHOLOGY. UNIVERSITY OF MARY HOSPITAL
€-HQ*P
HON; K O f f i ,
QUEEN
It has been reported that follicular lymphomas in Amerlcan patients are closely associated with the nonrandom translocation t(18;14) with juxtapositioning of the oncogene bcl-2 and the immunoglobulin (Ig) heavy chain gene loci. We have investigated the cccurence of such juxtaposltfonlng In malignant lymphanas in Hong Kong Chinese. Genomlc DNA from 10 cases of follicular lymphanas and 14 cases of diffuse lymphanas with proven B cell clonal pro1 iferation by imnunohistochmistry were digested with two o r t h r e e restrictive endonucleases. Southern blots of the samples were hybridized with probes t o the JH gene fragment of the Ig heavy chain and t o the ,major breakpoint cluster region of bcl-2. All cases showed rearrangement of at least one J H allele. 4 out of 10 o f the follicular lymphanas showed bcl-2 rearrangement bandcs) and all o f these rearrangement bands co-migrate with rearrangemnt bands of J H . N o n e of t h e diffuse lymphomas showed rearrangemnt of bcl-2. We conclude that bcl-2 rearrangement and juxtaposition to JH of the Ig heavy chain do occur in follicular lymphomas in Hong Kong Chinese, but t h e major breakpoint cluster region i s less frequently involved. Such infrequent involvement prevents t h e use of breakpoints in this cluster region as a marker of transformation of follicular lymphomas t o diffuse lymphanas in Hong Kong Chinese.