다발성 골수종에서 p53 및 bcl-2 종양단백 발현

최종원,서진태 대한임상병리학회 1996 대한임상병리학회지 Vol.16 No.6

다발성 골수종 환자에서 kaposi`s sarcoma-associated herpesvirus(KSHV) 감염의 임상적 의의

김찬규(Chan Kyu Kim),홍대식(Dae Sik Hong),박성규(Sung Kyu Park),이규택(Gyu Taeg Lee),원종호(Jong Ho Won),백승호(Seung Ho Baick),이동화(Dong Wha Lee),박희숙(Hee Sook Park) 대한내과학회 2000 대한내과학회지 Vol.58 No.2

N/A Background : Kaposi's sarcoma-associated herpesvirus (KSHV) been shown to be associated with human diseases including Kaposi's sarcoma, pleural effusion lymphoma, multicentric Castleman's disease. The IL-6 may both stimulate myeloma growth and prevent apoptosis of malignant plasma cells. Interestingly, viral IL-6(vIL-6), homolog to human interleukin-6(IL-6) in KSHV genome retains biologic activity. Thus, oncogenic role of the KSHV has been proposed as a pathogenesis of the multiple myeloma. We used ISH to determine the frequency of patients with multiple myeloma and plasmacytosis associated with KSHV-infected BM cells in fresh core biopsies and to determine the correlation between KSHV infection and clinical characteristics. Methods : Bone marrow(BM) biopsy samples from 16 cases of multiple myeloma, 2 cases of monoclonal gammopathy of undetermined significance(MGUS) were obtained from the pathology division of Soon Chun Hyang University Hospital, Seoul, Korea. Biopsy sample of Kaposi's sarcoma for positive control and BM biopsy samples of myelodysplastic syndrome(MDS) and malignant lymphoma for negative control were obtained. Bitinylated probe to KSHV were prepared with the following sequences: 5' to 3' TGCAGCAGCTGTTGGTGTACCACATATCT. and in situ hybridization (ISH) was performed. Results : Among the 18 patients. Two patients were MGUS and among 16 patients with multiple myeloma, 1 in stage IB disease, 1 stage IIB disease, 8 stage IIIA disease, 4 stage IIIB diseases and 2 in variant of multiple myeloma, extramedullary plasmacytoma. Strong positive signal was detected in nuclei and cytoplasm of the malignant cells of biopsy sample from 1 cases of Kaposi's sarcoma by ISH(positive control). Signal was not detected in BM biopsy samples of 7 cases from MDS and malignant lymphoma(negative control). Among 16 patients with multiple myeloma, 15 demonstrated viral positive cells and 2 cases with MGUS also showed viral positive cells by ISH. Signal was detected in nuclei and cytoplasm of stromal cells. Signal was strongly detected in MGUS than multiple myeloma. Positivity of the KSHV was not related with stage of the patients with multiple myeloma. One patients with multiple myeloma was studied at diagnosis and after chemotherapy. After chemotherapy KSHV was not detected. Conclusion : In MGUS and multiple myeloma, KSHV infects the stromal cells of BM rather than malignant plasma cells. On the basis of these data, we have supposed KSHV to play a role in transformation from MGUS to multiple myeloma. Particularly, due to the fact that signal of ISH was strongly detected in MGUS and was not detected in one case with multiple myeloma, it was presumed that KSHV was not major role in already advanced multiple myeloma but statistic significance was not demonstrated because of small numbers of cases. Further studies to reveal the correlation of KSHV and pathogenesis of multiple myeloma are needed.(Korean J Med 58:213-220, 2000)

Labelled Streptavidin Biotin 방법을 이용한 IgD형 다발성 골수종의 진단

나준,서을주,지현숙 대한임상병리학회 1996 대한임상병리학회지 Vol.16 No.6

Ki-67 Immunostaining and its Correlation with Microvessel Density in Patients with Mutiple Myeloma

Himani, Bhankar,Meera, Sikka,Abhimanyu, Sharma,Usha, Rusia Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5

Purpose: To compare Ki-67 index and microvessel density MVD) in multiple myeloma and non-myeloma patients and their correlation with each other and other prognostic markers. Materials and Methods: Forty patients were enrolled in this study between 2011-2013, 30 with multiple myelomas and 10 with non-malignant disease as controls. Proliferative activity was analyzed by Ki-67 and microvessel density (MVC) was assessed by CD34 and compared between two groups. In myeloma patients, correlation between Ki-67, MVD and other prognostic factors was assessed by Pearson correlation coefficient. Results: According to Durie Salmon staging criteria, 13 patients were of stage 1, 5 of stage II and 12 of stage III. Ki-67 expression showed a positive correlation with MVD (r=0.729, p<0.001) and was significantly higher (p<0.0001) in myeloma patients (range 35-80%, mean 60.1 %) as compared to controls (range 8-25%, mean 18.1%). $MVD/mm^2$ was also significantly (p<0.0001) higher in myeloma patients (range $62-237/mm^2$, mean $178.0/mm^2$) than controls (range $5.2-50/mm^2$, mean $18.3/mm^2$). Ki-67 and MVD, both increased progressively with increasing stage of myeloma. Ki-67 showed significant positive correlation with blood urea and lactate dehydrogenase and a significant negative correlation with serum albumin. MVD showed a significant positive correlation with blood urea, lactate dehydrogenase, serum creatinine, ${\beta}2$ microglobulin and skeletal lesions. Conclusions: Ki-67 and MVD are indicators of aggressiveness and poor prognosis having significant correlation with each other and other prognostic markers of multiple myeloma. Routine assessment of these markers may help to identify high risk patients, who may benefit from with more aggressive therapy.

다발성 골수종에서 혈관내피성장인자와 Interleukin-6의 발현

박사영,임석아,남은미,김도연,최영아,이경은,성주명,이순남,구혜수,김성숙 大韓血液學會 2001 大韓血液學會誌 Vol.36 No.1

Soluble syndecan-1 at diagnosis and during follow up of multiple myeloma: a single institution study

Ji Myung Kim,이정애,조인성,임춘화 대한혈액학회 2010 Blood Research Vol.45 No.2

Background Syndecan-1 is a heparan sulfate proteoglycan expressed on plasma cells, especially myeloma cells, and can exist in serum as soluble syndecan-1 after shedding from the cell surface. Soluble syndecan-1 has been suggested to promote myeloma cell growth and to be an independent prognostic factor for multiple myeloma. We aimed to evaluate the effect of soluble syndecan-1 levels at the time of diagnosis and during therapy on therapeutic response and prognosis for patients with multiple myeloma. Methods We analyzed soluble syndecan-1 levels in 28 patients with multiple myeloma and 50 normal controls, and compared its levels with Durie-Salmon stage and other markers of myeloma. In addition, we evaluated the therapeutic response and determined the 3-year survival rates of these patients. Results We observed that the median soluble syndecan-1 level in myeloma patients was higher than that in the normal controls (P<0.0001), and the soluble syndecan-1 levels in 21 (75%) patients were higher than the cut-off level (162 ng/mL). Soluble syndecan-1 levels correlated with disease stage, percentage of plasma cells in the bone marrow, b2 microglobulin level, serum M-component concentration, and creatinine level. The baseline levels of soluble syndecan-1 at the time of diagnosis in the patients who responded to chemotherapy were lower than those in the non-responders (P=0.04); however, the baseline level was not a significant predictor of therapeutic response. The 3-year overall survival rate of the patients with high soluble syndecan-1 levels at the time of diagnosis and 6 months after chemotherapy was lower than the corresponding survival rates of the patients with low levels of soluble syndecan-1; however, the overall survival rate was not statistically significant. Conclusion The use of soluble syndecan-1 has limitations in the diagnosis of multiple myeloma. Soluble syndecan-1 levels correlate with known prognostic factors; however, we could not assess the prognostic value of high levels of soluble syndecan-1 at the time of diagnosis and after chemotherapy.

가성고인산혈증을 동반한 다발성 골수종

한지연(Ji Youn Han),이제훈(Je Hoon Lee),최병길(Byung Gil Choi),문연숙(Youn Sook Moon),진승원(Seong Won Jin),한원희(Won Hee Han),김용구(Yong Gu Kim),홍영선(Young Sun Hong),김훈교(Hoon Kyo Kim),김병기(Byoung Kee Kim),이경식(Kyung Shik 대한내과학회 1996 대한내과학회지 Vol.51 No.2

N/A Objectives: Pseudohyperphosphatemia without clinical manifestations of hyperphosphatemia can be developed in multiple myeloma without renal failure due to the interference with the colorimetric assay by high serum globulin concentrations or due to the specific biochemical feature of paraprotein. We re- viewed the clinical spectrums of multiple myeloma patients with pseudohyperphosphatemia and assessed the mechanism of pseudohyperphosphatemia. Methods: Six patients with pseudohyperphosphatemia out of 67 patients with multiple myeloma diagnosed at a single institution between 1984 and 1994 were analysed. Serum inorganic phosphate concentrations were rechecked after deproteinization processing with 5% trichloracetic acid or 5% ammonium sulfate by Hitachi-747 automatic analyzer in 2 patients. Results: Pseudohyperphosphatemia with hyperglobulinemia involved six patients ; three were male and the median age was 47.5 years old. Six patients diagnosed as multiple myeloma stage IIIA; three were at the initial presentation and the othre three were during the period of disease progression. Three patients died; two were due to disease progession and 1 was due to acute respiratory failure with pneumonia. The concentrations of serum phosphate showed linear correlation with the concentrations of the serum globulin, and returned to normal value after effective treatments of multiple myeloma including chemotherapy and plasmapheresis. The concentrations of phosphate in deproteinized sera were normal in 2 patients. Conclusion: Pseudohyperphosphatemia was developed in 6 out of 67 patients with multiple myeloma(9.0%) during the peak of hyperglobulinemia and accompanied by hyperviscosity syndrome, The concentrations of serum inorganic phosphate showed liner correlation with the concentrations of serum globulin and normalized after effective treatment of multiple myeloma. These data suggest that pseudohyperphosphatemia needs the effective treatment for the underlying multiple myeloma rather than the hyperphosphatemia itself.

다발성 골수종에서 ras 및 p53 유전자 점돌연변이에 관한 연구

김정희(Jeong Hee Kim),김영일(Young Il Kim),김시영(Si Young Kim),윤희중(Hwi Joong Yoon),조경삼(Kyung Sam Cho) 대한내과학회 1998 대한내과학회지 Vol.54 No.3

N/A Background: Multiple myeloma is a malignant proliferation of plasma cells producing monoclonal immunoglobulins. The pathogenesis of this disease is still unknown. Karyotypic complexity and stepwise disease progression in multiple myeloma suggest that the development of multiple myeloma is a multistep process in genetic events, such as oncogene activation or tumor suppressor gene inactivation. Alterations of ras oncogene or p53 tumor suppressor gene are involved in various type of human cancers. The aim of this study was to determine the frequency of ras and p53 gene mutations in multiple myeloma, and to analyze its association with clinical parameter and clinical outcome. Methods: Mutations of N-, K-ras exon 1 & 2 and p53 exon 5-8 were observed in 33 patients with multiple myeloma. Genomic DNA was isolated from mononuclear cells separated from bone marrow samples, Extracted DNAs were screened for mutations by single-strand conformation polymorphism analysis of PCR products (PCR-SSCP). DNA fragments displaying an altered electrophoretic mobility were further studied by direct sequencing to confirm and characterize the nature of the mutations. Results: No mutation was found at N-, K-ras exon 1, K-ras exon 2 or p53 exon 5-8, Only one patient has N-ras exon 2 mutation(1/33 patients, 3%). By direct sequencing of PCR products, I confirmed and detected a CAA-->AAA transversion(glutamine-->lysine). The patient was a 61-year-old male in progressive state. M protein was IgG/kappa type. Bone marrow aspirate revealed a 67% plasma cell infiltration. Conclusion: Although the number of patients is small, these data revealed low frequency of N-ras, K-ras and p53 gene mutation in multiple myeloma. Bas and p53 gene mutations may have limited role in pathogenesis of mulitple myeloma and may associate with tumor progression rather than initiation.

복수를 동반한 다발성 골수종 1예

송동섭(Dong Seob Song),한지연(Ji Youn Han),권희정(Hi Jeong Kwen),민기옥(Ki Ouk Min),이성수(Seong Su Lee),김현숙(Hyeon Sook Kim),서은주(Eun Joo Seo),이경식(Kyung Shik Lee),김문희(Moon Hee Kim),이은희(Eun Hee Lee) 대한내과학회 2000 대한내과학회지 Vol.58 No.6

N/A Ascites is a rare complication of multiple myeloma. When it develops, it is usually associated with extensive liver infiltration with plasma cells, infectious peritonitis or myelomatous peritoneal infiltration. Ascites caused by peritoneal infiltration is even less frequent than others. The majority of previously reported cases were characterized by an IgA paraprotein and lack of skeletal lesions. This rare extramedullary complication of myeloma has been unresponsive to therapy and rapidly fatal. Therefore, it is important to recognize myeloma as a cause of ascites and the presence of ascites heralds a poor prognosis of myeloma. We recently experienced a case of myeloma with ascites and reviewed the relevant literature of human myeloma presenting with the triad of ascites, relative or absolute sparing of the skeleton, and an IgA paraprotein. A 76-year-old man was presented with ascites early in the course of myeloma. He had no evidence of intra-abdominal plasmacytoma and skeletal lesions. Myelomatous ascites was demonstrated by the monoclonal immunoglobulin of IgA type in ascitic fluid. He was treated by plasmapheresis due to hyperviscosity syndrome and VAD combination chemotherapy. He was discharged with the improved clinical condition.(Korean J Med 58:686-691, 2000)

다발성 골수종 환자의 골수 소견과 예후와의 관련성

황상현,박찬정,1지현숙,이제환,김우건,2김상희 대한임상병리학회 1999 대한임상병리학회지 Vol.19 No.1