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HLA-A2, -B52, -DR4 are candidate antigens related to lymph node metastasis in gastric cancer
27
Abstracts
P126
P127
ANALYSIS OF HLA-DRBI AND DQBI ALLELE AND HAPLOTYPE FREQUENCIES IN 27 IRANIAN B-CELL CHRONIC LYMPHATIC LEUKAEMIA (B-CLL) PATIENTS Ghaderi E, AmirzargarA, Shokri F, Jobson S, Mytilineos J, SchererS, Ala F Immunology Departments of Shiraz (lR), Ahwaz (lR), Tehran (lR) Birmingham (GB)and Heidelberg (D). Shiraz University of MedicalSciences,Departmentoflnununology, Shiraz, Iran. HLA class" gene and haplotype frequencies were investigated in 27 B-CLL Iranian patients. HLA-typing for lILA-ORBI, and -OQBJ was performed by PCR amplification with Sequence Specific Primers (PCR-SSP). The allele and haplotype frequencies were calculated and compared with 96 healthy Iranian controls. Chi square, and Fischer s exact test were used for statistical evaluation. A positive association was observed for the putative haplotype fILA-DRB 1*1301/06-0QBI "060Z13 (I 1.1% vs. 3.6%, p=008). This was also reflected in an increased frequency for the allele ORBI"1301/06 (11.1% vs. 3.6% p=0.08). In contrast, the frequency of OQB I "060Z/03 was less increased (130% vs 6.7% p=O.Z). None of the observed associations were statistically significant, most probably due to the small number of cases examined. Although the patient cohort was small, this study allows a preliminary description of class" gene associations in Iranian B-CLL patients.
P128
IOGH FREQUENCY OF HLA DIlIII"(M ALLEUS IN PATIENTS wrrn HIVULATID LYMPHOMA AND ASSOCIATION WI11I SHORT SURVIVAL
CiminoG, Elia L, Rap8notti Me, GaWIe G, G1l5laldi It. MaadettiF. Hematology, Deportment ofHuman 8ioplthology,Uoiw:rsity"La S8pieula" of Rome - ITALY. To eoaIuate the possibl< exisIaDa:of cone1alious _ HLADRBt -"Yp<, mv mfee1ioo, ond 8 IympIlomas, we ha.e n:1roOpee m:q""""l' ill 25 polWDts with mv...,1Btol:\>ed ill theC
P130 BOTH ClASS I AND CLASS SUSCEP11BIUTY FACTORS
.~udV In ~h. A •• aDI.~IDn af Nan-Hadgkln'. LYmpham. WI~h HLA
Xixiong Kang , Weizhong Wang, But.ons Sun Central Lab.China-Japan-Friendship Rospit- N.B Univ. Huan leucocyte antigen (HLA)-A. B. C. DR • DO typins vas carried out in 32 NUL patients and 62 noraal subJects.Peripheral Iyaphoc,tes vere tested for 130 different antigens by standard aicrocytntoxicity aethods. The results showed that the antigen frequenc, of HLA--A ••• B, •• B51 • Cw.. DR,o • DOw. were increased significantly in NHL patient group. Aanng the.to frequency of A2. B,.. DR,o are especially re aa r kab l e high (Pc less than 0.02), The study showed that: NHL in patients of HAN natinnality In North China has an association with HLA-AnBI.DR,o. Those p ear-i nx antigen may best a high risk of suffering from NHL. It is predicated that susceptible gen of NHL may have a 'close linkage v i t h HLA Jo c i . DR,o plays an
i.portant role in i.mune resPonse of NHL.
P129 HLA ANTIGENS AND PROLIFERATIVE ACTIVITY OF PLASMOCYTIC TUMOR
Petrochenkov A.N., Golenkov A.K., Sibiryakova L.G. Clinical Research Institute of Moscow Region, Moscow, Russia In patients (N=145) with multiple myeloma (MM) HLAantigens distribution was investigated, The main attention was paid to fILA-antigens distribution not in total group of patients but in the group having been formed according to the existence of the certain formalized criterion. The deviations in HLA class II were not noticed. HLA class I antigens were determined using standard lymphocytetoxic test. B7 antigen increase was marked in the group of patients with slower disease development (RR=8,9), vertebra damages (RR=6,9), low proliferative activity of tumor cells and slow reaction (but with prolongated effect) to therapy. All these associations are significant after correction on actual number of comparisons, and also significant being compared 10 alternative groups of patients. The associations analysis allows to conclude that antigen B7 characterizes tumors with [ow kinetic characteristics that is more expressed at preclinical stage. So a question is: can we say about a new type of MM - HLAB7-dependent MM whose manifestations have been described above or, B7 antigen marks any of slowly developed forms of plasmacyte tumors (essential monoclonal gammapathy, smoldering MM, and also MM common forms, but characterized by longer smooth development).
P131 Il lILA ANTIGENS ARE THYROID CANCER
Jorge Marttnez-Laso", Demetra Rigopoulou, Nieves Diaz-Camp· Gilberte Vargas. Alarcon", Francisco Martinez-TeHo+, Juan f. Alcalde", Federico Hawkins, Antonio Amaiz-vmenaDepartments of Endocrinology, "Immunology and + Pathology, Hospital 12 de Octubre,
HLA-A2, -852, -DR4 ARE CANDIDATE ANTIGENS RELATED TO LYMPH NODE METASTASIS INGASTRIC CANCER
Kyoji Ogoshi, Kimiyoshi Tsuji, Masao Miyaji, Kenji Nakamura,Yasumasa Kondoh, TomooTajima, ToshioMitomi, DEPARTMENT OF SURGERY, TOKAI UNIVERSITY, ISEHARA, JAPAN
Umversidad Ccmplutense, Madrid. Spain.
It has recentlybeen established that HlA. antigensare susceptibility factorsfor different cancers, includingtbyroidtumours. However, the diversityand sometimesweak and contradictory associations foundhavecreated the frequentopinionthat the HLA and tumorigenesis links mightbe the result of statisticalerrors. However,in the lest year it bas been established that if is indeed a currently complex RDd unexplained but feat phenomenon,whichmay be crucial LO prevent several types of cancer. In the present work we have found in a relativelylarge series of thyroidcancer
patients (n=161) that both HLA ciass [ (B35) and ciass Il (DRIl) antigens are susceptibility factors only in the papillary tumour group of patients, B35 association12 value is foundat the limit of significance (Pc(l:l:ll)=O.05); the follicular group did not show any HlA association, suggesting that the etiopathogenesis of each type of cancer is different.. HLA-B35 and DRll are not workingtogether to induce tumorigenesis and each of them seems to confer susceptibility by using different pathways or by being markersof distinct neighbouring susceptibility genes. DR4 has also been found in 86% (n=6) of Hurthle cell carcinoma. No essccarton has been found bet.....een 1ll..A and diseaseactivity. HLA mechanisms of associationto cancer are discussed and a world-wide Hl.AJtumangenic study is proposed to obtain a clear picture of the puzzling and controversial susceptibility markers found in different tumours and in different ethnic groups.
We investigatedthe relationbetween the HLA antigens and a riskof lymphnode metastasis in 864 patients who underwent resection of gastric cancer with the removal of lymph nodes. The microcytotoxicity assay was used to examine 51 HLA antigens of the A, 8, C, DR, and DOloci.In patients with from12to t4 tumors whichinvaded fromthe proper muscles to serosa, the incidenceof A2 antigen with lymph node metastasis was significantly iower than patients withoutlymph node metastasis (119/197 (37.7%)vs 60/45 (57.1%),RR:O.5, P:O.00071, Pc:O.036). In poorlydifferentiated adenocarcinoma (por),a significantly higherincidence of HLADR4antigen in patients with lymph node metastasis than in patients without iymph node metastasis was found (68/74(47.9%)vs 14/52 (21.2%),RR:3.4, P:O.00044, PC:O.022).In signet ring cell carcinoma (sig), the incidence of HLA 852 antigen with lymph node metastasis was Significantly higher than patients withoutlymph node metastasis (16/29 (35.6%) vs 16/118 (11.9%), RR:4.1, P:O.0008, Pc=O.0408). Lower lymph node metastatic tumors ( sig, tubl and moderately differentiated adenocarcinoma (tub2)) of t2-H gastric cancer with A2 antigen showed a significantly lowerincidence (43/102 (29.7%)vs 46/26 (63.9%),RR=O.2, P=O.OOO029, Pc:O.OO14) and better 5-year survivalrate than patients withoutA2 antigen (A2(+) vs A2(-): 78.6% vs 49.8%, log-ranktest p
Abstracts
P126
P127
ANALYSIS OF HLA-DRBI AND DQBI ALLELE AND HAPLOTYPE FREQUENCIES IN 27 IRANIAN B-CELL CHRONIC LYMPHATIC LEUKAEMIA (B-CLL) PATIENTS Ghaderi E, AmirzargarA, Shokri F, Jobson S, Mytilineos J, SchererS, Ala F Immunology Departments of Shiraz (lR), Ahwaz (lR), Tehran (lR) Birmingham (GB)and Heidelberg (D). Shiraz University of MedicalSciences,Departmentoflnununology, Shiraz, Iran. HLA class" gene and haplotype frequencies were investigated in 27 B-CLL Iranian patients. HLA-typing for lILA-ORBI, and -OQBJ was performed by PCR amplification with Sequence Specific Primers (PCR-SSP). The allele and haplotype frequencies were calculated and compared with 96 healthy Iranian controls. Chi square, and Fischer s exact test were used for statistical evaluation. A positive association was observed for the putative haplotype fILA-DRB 1*1301/06-0QBI "060Z13 (I 1.1% vs. 3.6%, p=008). This was also reflected in an increased frequency for the allele ORBI"1301/06 (11.1% vs. 3.6% p=0.08). In contrast, the frequency of OQB I "060Z/03 was less increased (130% vs 6.7% p=O.Z). None of the observed associations were statistically significant, most probably due to the small number of cases examined. Although the patient cohort was small, this study allows a preliminary description of class" gene associations in Iranian B-CLL patients.
P128
IOGH FREQUENCY OF HLA DIlIII"(M ALLEUS IN PATIENTS wrrn HIVULATID LYMPHOMA AND ASSOCIATION WI11I SHORT SURVIVAL
CiminoG, Elia L, Rap8notti Me, GaWIe G, G1l5laldi It. MaadettiF. Hematology, Deportment ofHuman 8ioplthology,Uoiw:rsity"La S8pieula" of Rome - ITALY. To eoaIuate the possibl< exisIaDa:of cone1alious _ HLADRBt -"Yp<, mv mfee1ioo, ond 8 IympIlomas, we ha.e n:1roOpe
P130 BOTH ClASS I AND CLASS SUSCEP11BIUTY FACTORS
.~udV In ~h. A •• aDI.~IDn af Nan-Hadgkln'. LYmpham. WI~h HLA
Xixiong Kang , Weizhong Wang, But.ons Sun Central Lab.China-Japan-Friendship Rospit- N.B Univ. Huan leucocyte antigen (HLA)-A. B. C. DR • DO typins vas carried out in 32 NUL patients and 62 noraal subJects.Peripheral Iyaphoc,tes vere tested for 130 different antigens by standard aicrocytntoxicity aethods. The results showed that the antigen frequenc, of HLA--A ••• B, •• B51 • Cw.. DR,o • DOw. were increased significantly in NHL patient group. Aanng the.to frequency of A2. B,.. DR,o are especially re aa r kab l e high (Pc less than 0.02), The study showed that: NHL in patients of HAN natinnality In North China has an association with HLA-AnBI.DR,o. Those p ear-i nx antigen may best a high risk of suffering from NHL. It is predicated that susceptible gen of NHL may have a 'close linkage v i t h HLA Jo c i . DR,o plays an
i.portant role in i.mune resPonse of NHL.
P129 HLA ANTIGENS AND PROLIFERATIVE ACTIVITY OF PLASMOCYTIC TUMOR
Petrochenkov A.N., Golenkov A.K., Sibiryakova L.G. Clinical Research Institute of Moscow Region, Moscow, Russia In patients (N=145) with multiple myeloma (MM) HLAantigens distribution was investigated, The main attention was paid to fILA-antigens distribution not in total group of patients but in the group having been formed according to the existence of the certain formalized criterion. The deviations in HLA class II were not noticed. HLA class I antigens were determined using standard lymphocytetoxic test. B7 antigen increase was marked in the group of patients with slower disease development (RR=8,9), vertebra damages (RR=6,9), low proliferative activity of tumor cells and slow reaction (but with prolongated effect) to therapy. All these associations are significant after correction on actual number of comparisons, and also significant being compared 10 alternative groups of patients. The associations analysis allows to conclude that antigen B7 characterizes tumors with [ow kinetic characteristics that is more expressed at preclinical stage. So a question is: can we say about a new type of MM - HLAB7-dependent MM whose manifestations have been described above or, B7 antigen marks any of slowly developed forms of plasmacyte tumors (essential monoclonal gammapathy, smoldering MM, and also MM common forms, but characterized by longer smooth development).
P131 Il lILA ANTIGENS ARE THYROID CANCER
Jorge Marttnez-Laso", Demetra Rigopoulou, Nieves Diaz-Camp· Gilberte Vargas. Alarcon", Francisco Martinez-TeHo+, Juan f. Alcalde", Federico Hawkins, Antonio Amaiz-vmenaDepartments of Endocrinology, "Immunology and + Pathology, Hospital 12 de Octubre,
HLA-A2, -852, -DR4 ARE CANDIDATE ANTIGENS RELATED TO LYMPH NODE METASTASIS INGASTRIC CANCER
Kyoji Ogoshi, Kimiyoshi Tsuji, Masao Miyaji, Kenji Nakamura,Yasumasa Kondoh, TomooTajima, ToshioMitomi, DEPARTMENT OF SURGERY, TOKAI UNIVERSITY, ISEHARA, JAPAN
Umversidad Ccmplutense, Madrid. Spain.
It has recentlybeen established that HlA. antigensare susceptibility factorsfor different cancers, includingtbyroidtumours. However, the diversityand sometimesweak and contradictory associations foundhavecreated the frequentopinionthat the HLA and tumorigenesis links mightbe the result of statisticalerrors. However,in the lest year it bas been established that if is indeed a currently complex RDd unexplained but feat phenomenon,whichmay be crucial LO prevent several types of cancer. In the present work we have found in a relativelylarge series of thyroidcancer
patients (n=161) that both HLA ciass [ (B35) and ciass Il (DRIl) antigens are susceptibility factors only in the papillary tumour group of patients, B35 association12 value is foundat the limit of significance (Pc(l:l:ll)=O.05); the follicular group did not show any HlA association, suggesting that the etiopathogenesis of each type of cancer is different.. HLA-B35 and DRll are not workingtogether to induce tumorigenesis and each of them seems to confer susceptibility by using different pathways or by being markersof distinct neighbouring susceptibility genes. DR4 has also been found in 86% (n=6) of Hurthle cell carcinoma. No essccarton has been found bet.....een 1ll..A and diseaseactivity. HLA mechanisms of associationto cancer are discussed and a world-wide Hl.AJtumangenic study is proposed to obtain a clear picture of the puzzling and controversial susceptibility markers found in different tumours and in different ethnic groups.
We investigatedthe relationbetween the HLA antigens and a riskof lymphnode metastasis in 864 patients who underwent resection of gastric cancer with the removal of lymph nodes. The microcytotoxicity assay was used to examine 51 HLA antigens of the A, 8, C, DR, and DOloci.In patients with from12to t4 tumors whichinvaded fromthe proper muscles to serosa, the incidenceof A2 antigen with lymph node metastasis was significantly iower than patients withoutlymph node metastasis (119/197 (37.7%)vs 60/45 (57.1%),RR:O.5, P:O.00071, Pc:O.036). In poorlydifferentiated adenocarcinoma (por),a significantly higherincidence of HLADR4antigen in patients with lymph node metastasis than in patients without iymph node metastasis was found (68/74(47.9%)vs 14/52 (21.2%),RR:3.4, P:O.00044, PC:O.022).In signet ring cell carcinoma (sig), the incidence of HLA 852 antigen with lymph node metastasis was Significantly higher than patients withoutlymph node metastasis (16/29 (35.6%) vs 16/118 (11.9%), RR:4.1, P:O.0008, Pc=O.0408). Lower lymph node metastatic tumors ( sig, tubl and moderately differentiated adenocarcinoma (tub2)) of t2-H gastric cancer with A2 antigen showed a significantly lowerincidence (43/102 (29.7%)vs 46/26 (63.9%),RR=O.2, P=O.OOO029, Pc:O.OO14) and better 5-year survivalrate than patients withoutA2 antigen (A2(+) vs A2(-): 78.6% vs 49.8%, log-ranktest p