KR9700231 KAERI/RR-1648/96
Mantle cell lymphoma^l 3!^ gl bcl-1
Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement
? 13
Z 9 -.. 0 1 KAERI/RR-1648/96
Mantle cell lymphoma^ 3!# ^ bcl-1
Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement
=? 12 m J±JL>M5- "mantle cell lymphoma^ ^i^ ^ bcl~l
1996^
04 ^ ^: o] £ ^ JGL
I. -: Mantle cell lymphoma bcl-1
II. Mantle cell lymphoma (MCL)fe NCI Working Formulation0)14 RappaportWtJ.5-5.fe i-5.^ Kiel Classification«.5.fe centrocytic lymphoma<^l
<&=?-
°l- REAL classification^
S.7V in. ^ ^x^ig^oflA^ 19911£ 1995^ 371^2] ^^ S. REAL classification^ ^fl^-^-w ^S.*]-55l4. Low-grade B-ceU lymphoma^ll Sfl^^fe T-ceU(UCHL-l), B-ceU(CD19, CD20), MT-KCD43), CD5» i, MCL 4*«fl tfl*><^ cyclin DNA# ^-stq PCR5. bcl-1 gene rearrangement -^.S.'«i MCL IV. REAL classification^^. -g-ff-SS-irnJI, diffuse large B-cell lymphoma? r 51.7%^. •*! J}^ ^3L T-cell lymphoma ^°flA1 peripheral T-cell lymphoma, unspecified angiocentric lymphoma (75%P\ o. 4^-jo.5. fe^ «!£-& M-E^cf. <*\^ extranodal lymphoma7V v] &&;n. follicular lymphomaSl «l2E7]- nfl-f \£_o.u} (4.5%), low-grade lymphoma^l «l£.7l- ^o]-, 80% °1#°1 intermediate-graded ^•^•cf. -fslM-Bl- ^H^^r cfl^^- intermediate graded ^«>£L5. o] groups cfl^: ^^2j Afl^.^-7> u^ ,8.^-sH ^^^ REAL classification«l -fr-g-^ ^-T-7> S4. Mantle ceU lymphomafe 14*43.*! ^j«|^ 3.8%!- ^>^l«>5aj ^ ^ T^-& low-grade B-cell lymphomaSl- «151*H slDlSlfe mitoses 3,*\ MCL<4^fe ^S 17/lOHPF^H small biopsy* 10/10HPF o|^o]5atf. CD5-&, MCL^lAife 7/8, .fe MCL^ SLL^l l-. PCR «8"^ Ji4 cyclinDl sensitivity^} fej5.iH, ¥ *^ 5L^ MCL^^^l specific*|-5a4. (PCR ^; 3/10, ^^S^^^'S^ «3=>8; 7/9) Low-grade B-cell lympnoma 1 ) «H-r (p=0.12), MCL^l- m^l low-grade B-cell lymphomas (SLL+MALT+LPL) «4fe -fr^* ^>ol7> SI*.*] (p=0.01), (p<0.05).
V. 1. £- «?!?•* f-*B lymphoma ^ 43.3- ^-^-^^ REAL classification^: NCI Working Formualtion4 W*H ^"H *Y%-W °1*
2. bcl-1 PCR Jit|- ^V^«>al reproducible^ cyclinDl
3. ^l^l^H-fe f-^-^O-S. &o]*\ Q*Q autoclave!- CD54 cyclinDlsl ^AIJ^ 5^
4. ۥ ^4fe ^^ SUMMARY
I. Project Title Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement
II. Objectives and Importance of the Project Recently mantle cell lymphoma (MCL) has been classified as a distinct clinicopathologic entity of B-cell lymphoma, associated with the overexpression of PRADl/cyclinDl, Ilql3 translocation and its molecular counterpart bcl-1 gene rearrangement MCL is not readily classifiable by NCI working formulation, and belongs to centrocytic lymphoma by Kiel classification. Although the diagnosis of MCL is important to manage the MCL patients, conventional methods for lymphoma classificationa and routine immunohistochemistry cannot make an accurate diagnosis. Moreover, there has been no Korean report on MCL. We examined non-Hodgkin's lymphomas according to REAL classification and obtained the incidence of MCL. We tried to study clinicopathologic features and reliable diagnostic methods for MCL in Korea. It may be a first trial in Koreans. Our results may support the management of MCL patients and will be an meaningful trial to study lymphoma.
III. Scope and Contents of the Project We reclassified a large series of 371 non-Hogkin's lymphoma patients at Korea Cancer Center Hospital from 1991 to 1995, according to REAL classification. We classified the low-grade B-cell lymphoma cases by immunophenotypic study using UCHL-1, CD20, CD43, and CDS, and tried to compare cyclinDl immunohisto- chemistry and PCR for bcl-1 gene rearrangement. By these methods we want to determine the easy and the most reliable diagnostic methods for MCL and apply this for routine diagnosis. We showed statistical significance of clinical outcome.
in IV. Results of the Project By REAL classification, diffuse large B-cell lymphoma was the most common type (51.8%) and was followed by peripheral T-cell lymphoma-unspecified(10%) and angiocentric lymphoma(7.5%). In contrast with foreign reports, extranodal lymphoma was more common thannodal type in Korea. Incidence of low-grade lymphoma was low and majority (more than 80%) of Korean lymphoma belons to intermediate grade. Therefore REAL classification may be useful in Korea. MCL comprised 3.8% (14 cases) among non-Hodgkin's lymphoma. The most reliable histologic finding was mitosis in making a differential diagnosis from other low-grade B-cell lymphomas.. Mitoses of MCL were 17/10HPF in average and all the cases showed more than 10/10HPF. CD5 were positive in 7/8 of MCL and 2/5 of SLL, and CD43 were positive in 3 cases of MCL and SLL, respectively. Immunophenotypic study alone cannot lead to a differential diagnosis between MCL and SLL, and the overexpression of cyclinDl was the most important for diagnosis of MCL. Both immunohistochemistry for cyclinDl and PCR for bcl-1 were specific for MCL, and immunohistochemistry was more sensitive than PCR. Statistical analysis showed a different survival rate between MCL and the other low-grade B-cell lymphomas (SLL+MALT+LPL) and a difference between MCL and SLL. Immunohistochemical detection of cyclinDl has a practical useful- ness in making routine diagnosis of MCL. The initial accurate diagnosis of MCL will help clinicians make a proper management
V. Proposal for Application 1. In addition to NCI Working Formulation, we will apply the REAL classification to make a routine diagnosis with immunophenotypic study. 2. We plan the application for immunohistochemical study for cyclinDl to diagnostic practice, in the background of our results. 3. We can use the autoclave pretreatment method for immunohistochemical study for CD5, cyclinDl, and other difficult antibodies. 4. Our results of this project will serve important basic materials in studying lymphoma and MCL.
IV CONTENTS
Chapter 1 Introduction : i
Chapter 2 International and Domestic Situation of the Project 2
Chapter 3 Contents and Results of the Project 4
Chapter 4 Accomplishment of Objectives and External Contribution of the Project 12
Chapter 5 Proposal for application of the Project 13
Chapter 6 References 14 2%
3% ^lnF-vfl-8- 31
12
13
14
VI Mantle cell lymphomafe- 3^- ^$*\9l £*r-fr#*H ip^ si B-M]S. %*^<>.3. &^s\3. Sa^1"6'. °K= 7l$s] 3*^31 ^^-^?1 NCI Working Formulation^ *4 Rappaport ^f^A^ %%*}?& #£€ <£ £^ Kiel Classification.5-.5Lfe- centrocytic lymphoma^ll ^f?:^61. Mantle cell lymphoma fe- ^Efl^M-^JiL intermediate differentiation^ lymphocytes^, T1-^-^^, vaguely nodular ^hcr diffuse pattern-i: #l^:al, mantle zone pattern, naked germinal center &±g. s\6\ Xt^1'7', ^^a^l^ CD5, IgM, IgD ^ofl <#^ , CD10, CD23 £-^
«> mantle cell lymphoma^ ^1^ * x}£.<>\] ^^- Jt^-§- 7l-^«^ 17) Hql3 translocationo]M- bcl-1 gene rearrangementi- 7l^£ sacf. o]o]i ^-^ ^s]i4^oflA^ mantle cell lymphoma^ ^»|wl£# ^°-\t\jl o]^ ##% ^ ^^ 7];§.-g. 4^^ «^o] ^^.«> , °1# fl*H ^^l-^^-S0)!^ small cleaved cell types} ^£?A5. mantle cell lymphomaS ^s)fe °fll-^- ^"Jl °1# ^ PCR ^si ^^^- °l-8-*H ^?l^aL^l- ^4. a^: cyclin bcl-1 gene<^l tfltt PCR^ ^^1-
mantle ceU lymphoma^l
- 1- 1. REAL classification molecular biology^ ^AS. %E.^2) >$£.•$: entity7} 4^4? ^31*1^, 1982 N?H &<^-& the Working Formulation for clinical usage21' disease entity* M-E^ ^ $cHr €-*13^ SH*HI *1^ g 2) hematopathologists-l-^l 1993^ m*«H S.<*\ A ^H^^I QA biologyl- o.^. ^5.* ^-^-^-i- ^1^-^SIJI, oil- REAL classification (Revised European- American Classification of Lymphoid Neoplasm) ^1^ «}$ i}22"231. «:>1 ^r lymphomas] biology* w>^-^.5. 7fl7fl3l ol-fr^^-i:
^ A disease entity 1
mantle ceU lymphoma^
2. Mantle cell lymphoma 1970^tfl ^^, cl^-3] Berard^18)^r «131^1^1 ^H^ 7f£c-fl well differentiated (small lymphocytic) Hlfe poorly differentiated (small cleaved cell) lymphoma $\ 6]± ^^ofl£ ^ ^x] ^-fe «15:^1?1 ^^^ ^l^-^ tfl«>c=| intermediate differentiation^ lymphocytic lymphomael-fe -S-
-2- pattern-i- 3-<& Wr follicular lymphoma^l £.*] consensus meeting^!]*] mantle cell lymphoma (MCU^l-fe °l-§-.5-Jr. i}1'. ZL 0}$. ^ 3-4^^1 £3 ©1 MCL^l iflejS*U}- 1H3^ t(ll;14)(ql3;q32) translocation ^ bcl-1 gene rearrangement^ -g^o] ol-g-3>7iJ£ ^4. ^^-6)1 bcl-1 gene rearrangementl- single- step PCR^ A]£5}oi 5-^0.14, «*fl7l-*m hemi-nested PCR^^l 7V^ antibody7> sa-s- 3 fife- °fl -^^l-^'i-^^l^ ^1^^ ^^^^- ^|^S.*M mantle cell lymphoma^l -3- REAL classification-i- ^, REAL classification^] ni-S- ^-i* ^AJ-^^JI, NCI Working Formulation^}- «1 51*>S4. REAL classification^ T-cell, B-cell ^ ^^a^l^A>7> £-4H) 7l^- 3J6.S. ^JEL*>S.S. ^^S^l^Af7> <>l.f*1*l*l ^r^ia c|^-c| cfl«H T-ceU (UCHL-1), B-cell (126) ^^^ tJ-'flifl Ki-l(CD30), CD43, CD5, Leu Ml . REAL classification^ mantle cell lymphoma^l ^^^, ^^3^^t^^ ^ ^SH ^-^4 cyclin 2±*}-s\3L <$^*) s-^3)- "fl^'S^:^^- 3:AVs>^cf. Cyclin Dl cyclin Dl ^^1 (Neomarker, USA)* <>l-§-^: ^^S!-^^^ bcl-1 MTC primer:5'-CCTCTCTCCAA ATTCCTG-3', JH primer: 5'-GGA CTCACCTGAGGAGACGGTGACC-3'-i- ^l-§-«>^ PCR#^5-S. a}^:^ ^^-1- «1S«>^1^. ^^IS}-*}-^^ ^$.3LvH^Z\<$ aj-S-«l-^jo.H, 0.01M citrate buffer^ ^^o\ microwave JE^ autoclave^. 21*1*1 *M ^^1*>5514. &% mantle cell lymphomaSf ^•1g^!^-i- A*Vfe cf-S- low grade B-cell lymphoma (small lymphocytic lymphoma, immunocytoma, MALT median survival rate!- product-limit surviwal estimate, log-rank tests. -4- 1.. *><§ Table 1. REAL classification«1] n|-& -S-3E ^ MCL^ US. (KCCH, 1991-1995) B-CELL NEOPLASMS (71.4%) I. Precursor B-cell neoplasm: B-ALL/LBL II. Peripheral B-cell neoplasms 1. B-cell CLL/SLL 7 (1.9%) 2. Lymphoplasmacytoid lymphoma 10 (2.7%) (Immunocytoma) 3. Mantle cell lymphoma 14 (3.8%) 4. Follicular center cell lymphoma 16 (4.3%) 5. Marginal zone B-cell lymphoma 15 (40%) (including MALT lymphoma) 6. Splenic marginal zone lymphoma 0 7. Hairy cell leukemia 0 8. Plasamacytoma/Plasma cell myeolma (28) 9. Diffuse large B-cell lymphoma 192 (51.7%) 10. Burkitt's lymphoma 6 (1.6%) 11. High-grade B-cell lymphoma, Burkitt-like 5 (1.3%) T-CELL and NK-CELL NEOPLASMS (25.3%) I. Precursor T-cell neoplasm: T-ALL/LBL 16 (4.3%) II. Peripheral T-cell and NK-cell neoplasms 1. T-cell chronic lymphocytic leukemia 0 2. Large granular lymphocytic leukemia 1 (0.3%) 3. Mycosis fungoides/Sezary syndrome 1 (0.3%) 4. Peripheral T-cell lymphoma, unspecified 38 (10%) : medium-sized cell 13 (3.5%) mixed, medium and large cell 14 (3.8%) large cell 9 (2.4%) (Subcutaneous panniculitic T-cell lymphoma) 2 (0.5%) 5. Angioimmunoblastic T-cell ltmphoma 3 (0.8%) 6. Angiocentric lymphoma 28 (7.5%) 7. Intestinal T-cell lymphoma 1 (0.3%) 8. Adult T-cell lymphoma/leukemia 1 (0.3%) 9. Anaplastic large cell lymphoma (ALCL) 3 (0.8%) CD30+, T and null-cell types 10. Anaplastic large cell lymphoma, Hodgkin-like 2 (0.5%) UNCLASSIFIED (3.2%) -5- Table 2. NCI Working Formulation^ n|-S- £-3. Histological type KCCH(%) USA(1992) Low-grade A. ML, small lymphocytic 4.6 14 B. ML, follicular, predominantly small cleaved celL 0.8 5 C. ML, folliculr, mixed, small cleaved and large cell 0.5 12 Intermediate-grade D. ML, follicular, predominantly large cell 3.2 15 E. ML, diffuse, small cleaved cell 12.7 6 F. ML, diffuse, mixed small and large cell 192 6 G. ML, diffuse, large cell 45.6 22 High-grade H. ML, large cell, immunoblastic 6.5 15 I. ML, lymphoblastic 4.3 2 J. ML, small noncleaved cell 2.2 3 Table 3. &Z. (1991-1995, KCCH) Lymph node 42.3 % Nasal cavity 3.8 % Chest wall 1.1 % Tonsil 12.1 % Soft tissue 3.0 % Mediastinum 0.8 % Stomach 11.9 % Brain 3.0 % Salivary 0.8 % Nasopharynx Bone 2.2 % Thyroid 0.5 % Oropharynx 4.9 % Oral cavity 2.4 % (Esophagus.breast, Palate Orbit 1.6 % endometrium, pancreas) Colon & ileum 4.1 % Retroperitoneum, abdomen & omentum 1.6 % 7\. REAL classification^ S]t}^. diffuse large B-cell Iymphoma7r 5l.7%3.*\ 7} J 6 A # I&JL T-cell lymphoma ?r ll l peripheral T-cell lymphoma, unspecified (10%)s}- angiocentric lymphoma (7.5%)7> ZL ^-§-5.^- ^^ SlS.1- M-E^-ifl^, andgiocentric lymphoma^ S1S.7V ^^ %-$: upper respiratory tracts extra- nodal lymphoma7V ^-cfl^^-5. ^^r ^ -fr^V^, Epstein-Barr virus 14. extranodal Iymphoma7> :z|j!}-o|Ef. Extranodal tonsil0]^, GI tracts}- upper respiratory tractor extranodal lymphoma -6- 2* * . n]^- Jf A^ofl ul«fl follicular lymphoma^ Sl£7> Dfl-f \£O_D| (4.5%), low grade lymphoma^l QS-A \£°r, 80% ^l^h^l intermediate-graded ^^4. M-^s] 3^£- tfl^-^-o] intermediate-graded <*r«>H.5. °) group0)] tflfl- 3 ^l-S-Sl-71- c]^- J8.?-S]^ m-El-A-1 REAL classification^ k Mantle cell lymphomafe 14<4S.*\ ^^11^ 3.8% «l«fl T-ceU lymphoma^ Hl-frol ^tj.. (KCCH; 25.3%, USA; 12.5%) «>. ^^ofl yl«B low-grade B-cell lymphomasi 2.. Mantle cell lymphoma (MCL) ^1 ^^ 5? Low grade B-cell lymphoma^ A. f1 T^-^- low-grade B-cell lymphoma2}- u mitoses 5.-H MCL^l^fe ^3" 17/10HPF<>H small biopsy* ^] 10/10HPF ol^-ol^c}. ojofl i£«H ^-^^ low-grade B-ceU lymphomafe ^ 10/10HPF ^l?V^l5i4. ^^a^l^^V* ^^ 4€- low-grade B-cell lymphoma 4^ ^J-^c>l <>|i^ ^S. ^r^-*}-^, small lymphocytic lymphoma (SLL) 4-3 ^-^ol o1^4, £. c|^.o|A)3 2:2lit^3 ^ol-g- Table 4°fl &*]*} . Mantle cell lymphomaSl 3i3]i^fil ^-^^ Figure H Table 4. Comparison of pathologic findings of MCL vs. SLL Histological features MCL(%) SLL(%) Growth pattern diffuse 6 (43) 6 (86) nodular+diffuse 8 (57) 1 (14) Germinal center 4 (30) 2 (15) Mantle zone pattern 2 (15) 0 Nuclear size small 3 (21) 5 (83) intermediate 11 (79) 1 (17) Mitoses > 10/10 HPF 14 (100) 0 mean 17/10HPF 4/10HPF -7- cvclin Dial ?j#(Table 5 & Table 6) low-grade B-cell lymphoma- £.•¥• UCHL-1 (pan T-cell markerH £-^<>H, L26 (pan B-cell marker)^ Ji^fe <^11-^- Efl^-5.5. *>84. CD5TT T-cell marker* "g-3^ SU-^-M-, mantle cell lymphomS}- small lymphocytic lymphoam^ 7/8, , cycUn Dl^l ^#^1 MCL - PCR f}-^ Sic]- cyclin Dl B5^3:^S|-«]- Table 5. Immunophenotypes of various B-lymphocytic lymphomas and MCL Diagnosis Total No. CD5 CD43 L26 UCHL-1 Mantle cell lymphoma 14 7/8 3/10 14/14 0/14 B-cell CLL/SLL 7 2/5 3/5 7/7 0/7 Lymphoplasmacytoid lymphoma 10 0/6 0/6 10/10 0/10 MALT lymphoma 15 0/8 1/10 15/15 0/15 Table 6. Expression of Cyclin Dl Total PCR detectable Cyclin Dl Diagnosis No. JH/bcl-1 MTCU IHC59 Mantle cell lymphoma(MCL) 14 3/10 7/9 B-cell CLL/SLL 7 0/5 0/5 Lymphoplasmacytoid lymphoma 10 0/5 0/6 MALT lymphoma 15 0/5 0/7 11 : formalin-fixed paraffin-embedded tissue <>l-§-( bcl-1 MTC primerS'-CCTCTCTCCAA ATTCCTG-3', JH primer: 5'-GGACTCACCTGAGGAGACGGTGACC-3' 2) -Cydin Dl (Neomarker, USA) in paraffin tissue with microwave pretreatment in 0.01M citrate buffer, Of immunohistochemical staining -8- Figure 1. Mantle cell lymphoma. A: Low power view of vague nodular patern, B: Monotonous population of lymphocytes of intermediate differentiation Figure 2. Immunohistochemical study for cyclinDl protein. Note positive nuclear staining (arrows). -9- 12 3 4 5 6 /26 bp bOO bp Figure 3. Polymerase chain reaction for bcl-1 gene rearrangement Lane 1 and lane 4 showed positive band at 726 bp. MCL vs. SLL 100-* SLL 3" 80- I 60- CO 40. MCL p<0.05 (log rank) 20 0 12 24 36 48 60 72 84 96 108120132144 Time (month) Figure 4. Survival curve of MCL vs. SLL - 10- 1) MCL^ o^^^-ife 52-70^1 <>H, ^g-^l^^r 60-MI, tf^lfe 2: 2) Log-rank test for survival rate - Low-grade B-cell lympnoma AA&\ group^lfe ^^-§-^ QtiA. (p=0.12) - MCL^l- M-^^l low-grade B-cell lymphomas (SLL+MALT+LPL) ^o]7> 5a^ 3-5.3. 14^^0.14 (p=0.01), 4 groups (p<0.05, Figure 4)). o]^ MCL©1, "fl^ofl Xi°l, 4^ low-grade B-ceU lymphoma^l- x}ol§ median survival time^r 43711-iS. -11- REAL classification (1994)* -5-5. <>H »&£€ «> $14. REAL classifi- cation^ sm tH-^ 3^**1 «H§^- sj-e^ ^ 5Ufe 7iayt|-as.^s| si^7> 3 -fi-g-^^- ig7K>7l ^^ ^elAl^^ 71^. •£# 71 REAL classification^ ^5. JE^ disease entity^ 71 1, Mantle cell lymphomafe ^2i«}-^, ^^-^^.S. 4-€- ^if^^fe 4-S- «>>4^ disease entitiy5.^; o]^ QH-$r ^.«Vfe 4€- low-grade B-cell lymphoma^l 371^ 7>^iHl I4tgc>l mantle cell lymphomaSlaL mantle cell lymphoma°H ^ mantle ce 7}3L A%.7\ ^ ^°1^, # ^T1-^ mantle cell lymphoma* ^SRr - 12- lymphoma 3 . 3^**1 ^\2-6)l REAL classification-i- the Working Formualtion for clinical usages Conference ¥ ^^Wl-M^l communication-!- **IH #*}-<>] 2. ^ifi- ^^-o( REAL classification^: °i ^7]-^ ^JSL^T ^^a^l^^rl- Alfl*|-ji, mantle cell lymphoma^ cycUn Disl ^^^^]E tMH ^1 CD5, CD43 gj cyclin ^^-^^.S. &ol^| ^^ autoclave cyclin «• "fl ^^ zl- £oH| saol-Hsi ^^-*>JL specific^ 3. Mantle cell lymphoma^Mi^ PCRHJ-^-t- ^-^ bcl-l^i cycUn D1S} ^^-§- «lm^-o_5.^ ^^fr ic^sl- ^l?hS- Jfi-*Rr PCR reproducible^ cyclin Dl ^^ai^S}-*!-^^*! ^>fl mantle cell lymphomal- - 13- 1. Banks PM, Chan J, deary ML, et al: Mantle cell lymphoma: A proposal for unification of morphologic, immunologic, and molecular data. Am J Surg Pathol 16:637, 1992 2. Zucca E, Stein H, Coffier B: European Lymphoma Task Force (ELTF): Report of the workshop on mantle cell lymphoma (MCL). Ann Oncol 5:507, 1994 3. Segal GH, Masih AS, Fox AC, et al: CD5-expressing B-cell non-Hodgkin's lymphoma with bcl-1 gene rearrangement have a relatively homogeneous immunophenotype and are associated with an overall poor prognosis. Blood 85:1570, 1995 4. Pittaluga S, Wlodaaarska I, Stul MS, et al: Mantle cell lymphoma: A clinico- pathologic study of 55 cases. Histopathology 2617, 1995 5. Yang WI, Zukerberg LR, Motokura T, et al: Cyclin Dl (bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia. Am J Pathol 103:756, 1995 6. Weisenburger DD, Armitage JO: Mantle cell lymphoma-An entity comes of age. Blood 87:4483, 1996 7. Perry A, Bast MA,Armitage JO, et al: Diffuse intermediate lymphocytic lymphoma: A clinicopathologic study and comparison with small lymphocytic lymphoma and diffuse small cleaved cell lymphoma. Cancer 66:1995-2000, 1990 8. Doraman DM, Pinkus GS: Distinction between small lymphocytic and mantle cell lymphoma by immunoreactivity for CD23. Mod pathol 7:326-31, 1994 9. Zukerberg LR, Medeiros LJ, Ferry JA, et al: Diffuse low-grade B-cell lymphomas. Four clinically distinct subtypes defined by a combination of morphologic and immunophenotypic features. Am J Clin Pathol 100:373-85, 1993 -14- 10. Kilo MN, Dorfman, DM: The utility of flow cytometric immunophenotypic analysis in the distinction of small lymphocytic lymphoma/chronic lymphocytic leukemia from mantle cell lymphoma . Am J Clin Pathol 105:451-7, 1996 11. Komatsu H, Yoshida K, Seto M, et al: Overexpression of PRAD1 in a mantle zone lymphoma patients with a t(ll;22) (q!3;qll) translocation. Br J Haematol 85:427-9, 1993 12. Komatsu H, Yoshida K, Seto M, et al: A variant chromosome translocation at Ilql3 idntifying PRADl/cyclin Dl as the BCL-1 gene. Blood 84:1226-31, 1994 13. Motokura T, Arnold A: Cyclin D and oncogenesis. Curr Opin Genet Dev 3:5-10, 1993 14. Raffeld M, Sander CA, Yano T, Jaffe ES: Mantle cell lymphoma: an update. Leukemia Lymphoma 8:161-6, 1992 15. Seto S, Yamamoto K, Iida S, et al: Gene rearrangement and overexpression of PRAD1 in lymphoid malignancy with t(ll;14) ql3;q32) translocation. Oncogene 7:1401-6, 1992 16. Withers DA, Harvey RC, Faust JB, Melnyk T, Carey K, Meeker TO Characterization of a andidate bcl-1 gene. Mol Cell Biol 11:4846-53, 1991 17. Teodorvic BI, Pittaluga S, Kluin-Nelemans JC, et al: Efficacy of Four different regimens in 64 mantle cell lymphoma cases: Clinicopathologic comparison with 498 other non-Hodgkin's lymphoma subtypes. J Clin Oncol 13:2819-26, 1995 18. Berard CW, Dorfman RF: Histopathology of malignant lymphomas. Clin Haematol 3:39, 1974 19. Lennert K, Stein H, Kaiserling E: Cytological and functional criteria for the classification of malignant lymphomata. Br J Cancer 31:29, 1975 20. Tolksdorf G, Stein H, Lennert K: Morphological and immunological definition of a malignant lymphoma derived from germinal center cells with cleaved nuclei (centrocytes). Br J Cancer 41:168, 1980 - 15- 21. Non-Hodgkin's lymphoma pathologic classification project: National Cancer Institute sposored study of classifications of non-Hodgkin's lymphomas: Summary and description of a Working Formulation for clinical usage. Cancer 49:2112, 1982 22. Harris NL, Jaffe ES, Stein H, et al: A revised European-American classification of lymphoid neoplasms: A proposal from the international lymphoma study group. Blood 84:1361-92, 1994 23. Chan JKC, Banks PM, Cleary ML: A revised European-American classification of lymphoid neoplasms proposed by the international lymphoma study group: A summary version. Am J Clin Pathol 103:543-60, 1995 24. Weisenburger DD, Kim H, Rappaport H: Mantle-zone lymphoma. A follicular variant of intermediate lymphocytic lymphoma. Cancer 49:1429, 1982 25. Palutke M, Eisenberg L, Mirchandani T, Tabaczka P, Husain M: Malignant of small cleaved lymphocytes of the follicular mantle zone. Blood 59:317, 1992 26. Kuroda H, Komatsu H, Nakamura S: The positive nuclear staining observed with monoclonal antibody against PRADl/Cyclin Dl correlates with mRNA expression in mantle cell lymphoma. Jpn J Cancer Res 86:890-8, 1995 27. Yatabe Y, Nakamura S, Seto M, et al. Clinicopathologic study of PRADl/Cyclin Dl overexpressing lymphoma with special reference to mantle cell lymphoma: A distinct molecular pathologic entity. Am J Surg Pathol 20:1110-1122, 1996. -16- BIBLIOGRAPHIC INFORMATION SHEET Performing Org. Sponsoring Org. Standard Report INIS Subject Report No. Report No. No. Code KAERI/RR-1648/96 Title/Subtitle Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement Project Manager and Dept. Seung-Sook Lee (Dept. of Anatomic Pathology) Researcher and Dept. Kyung-Ja Cho (Dept. of Anatomic Pathology) Sun-Joo Lee (Laboratory of Experimental Pathology) Pub. Place Seoul Pub. Org. KCCH. KAERI Pub. Date Dec. 31, 1996 Page 23 Fig. and Tab. Yes(O). No( ) Size 26 cm Note Classified Open( 0 ). Outside( ), Class Report Type Research Report Sponsoring Org. Contract No. No Abstract (About 300 Words) We reclassified a large series of non-Hogkin's lymphoma diagnosed at Korea Cancer Center Hospital from 1991 to 1995, according to REAL classification, and compared the efficacy of immunohistochemical study for cyclin Dl protein and PCR for bcl-1 gene re- arrangement to diagnose mantle cell lymphoma (MCL). By REAL classification, 1%), diffuse large B-cell lymphoma was the most common type (51.8%) and was followed by peripheral T-cell lymphoma-unspecified(10*) and angiocentric lymphoma(7.5*). The most reliable histologic finding was mitosis to make a differential diagno- sis. Mitoses of MCL were 17/10HPF in average and all the cases showed more than 10/10HPF. Immunophenotypic study alone cannot lead to a differential diagnosis between MCL and SLL, and the overexpression of cyclin Dl was the most important for diagnosis of MCL. Both immunohistochemistry for cyclin Dl and PCR for bcl-1 were specific for MCL and immunohistochemistry was more sensitive than PCR. Statistical analysis showed a different survival rate between MCL and the other low-grade B-cell lymphomas (SLL+MALT+LPL) and a difference between MCL and SLL. Immunohistochemical detection of cyclin Dl has a practical usefulness in making routine diagnosis of MCL. The initial accurate diagnosis of MCL will help clinicians make a proper management. Subject Keywords (About 10 Words) Mantle cell Lymphoma, bcl-1, cyclin Dl immunohistochemistry, PCR INIS KAERI/RR- 1648/96 Mantle cell lymphoma£| bcl-1 *J 1996.12.31 23 JE IE 3. 71 26 cm '96 0 ), 1991\d -f-^ 1995\1 ^.5. REAL classification!- <§• low-grade B-cell lymphoma-f-ofl^ mantle cell lymphoma-i- S.*}$5lt:}. REAL classification^ diffuse large B-cell lymphoma (51.8*)7> 7}^- ?ilL peripheral T-cell lymphoma, unspecified (10*), angiocentric lymphoma (7.5*)2] <& low-grade B-cell 17/10HPF<>H ^ oflofl^ MCL4 SLL5^ ^»gol mantle cell lymphoma, bcl-1, cyclin Dl, ( PCR