Kimura's disease is a rare chronic inflammatory disease of the lymphoid organs and this prese... more Kimura's disease is a rare chronic inflammatory disease of the lymphoid organs and this presents as painless nodules in the head and neck area. It occurs endemically in the Far East Asia and sporadically in the West. Its exact etiology is unknown and it has no potential to transform into malignant disease. However, it is often confused with malignant disease such as malignant lymphoma. We report a case of NK/T cell lymphoma patient who had Kimura's disease in the right thigh 3 years ago. She then suffered from sudden dyspnea. Radiological studies revealed multiple small nodules scattered in both lung fields. NK/T cell lymphoma was diagnosed by open lung biopsy. In addition, Epstein-Barr virus (EBV) was detected in the previous site of Kimura's disease and lung nodule by molecular pathologic examination. To the best of our knowledge, this is the first case of NK/T cell lymphoma complicating Kimura's disease with coexisting chronic EBV infection.
Circulating tumor cells (CTCs) have been identified in peripheral blood of cancer patients, and r... more Circulating tumor cells (CTCs) have been identified in peripheral blood of cancer patients, and reproducible detection of CTCs has demonstrated the potential as useful diagnostic and prognostic tools in several cancers. Present study aimed to determine the clinical relevance of CTCs in surgically resected non-small cell lung cancer (NSCLC) patients. CTC status in presurgery and postsurgery peripheral blood samples from 79 surgically resected NSCLC patients was investigated using thyroid transcription factor-1 (TTF-1) and cytokeratin19 (CK19) mRNA markers by nested real-time RT (reverse transcription)-PCR assay. Detection of TTF-1((+))CTCs was found to be specific to NSCLC patients. TTF-1((+))CTCs were detected in 36.1% (22/61) of patients before surgery and in 37.5% (18/48) after surgery. For CK19 mRNA-expressing CTCs (CK19((+))CTCs), the detection rate was 42.6% (26/61) before surgery, and 25.0% (12/48) after surgery. Cases with postsurgery TTF-1((+)) and/or CK19((+))TCs was more a...
Purpose: We investigated prognostic implications of microRNAs in extranodal NK/T cell lymphoma (N... more Purpose: We investigated prognostic implications of microRNAs in extranodal NK/T cell lymphoma (NKTL). Experimental Design: We measured miRNA expression in NKTL tissues and cell lines, using real-time PCR, and analyzed its role in NKTL, using cell lines. Results: Multivariate analysis showed low miR-146a expression (P < 0.001; HR = 13.110), primary non–upper aerodigestive tract lesion (non-UAT; P = 0.008; HR = 5.376) and high International Prognostic Index (IPI; ≥3; P = 0.013; HR = 3.584) to be independent poor prognostic factors. miR-146a expression could subdivide UAT-NKTL into 2 prognostic groups, resulting in the following prognostic groups: (i) UATLow-146a, (ii) UATHigh-146a, and (iii) non-UAT. Compared with UATHigh-146a, UATLow-146a showed distinctively poor prognosis (P < 0.001; HR = 15.620), similar to the non-UAT group. In vitro, miR-146a overexpression in NKTL cell lines, SNK6 and YT, inhibited nuclear factor κB (NFκB) activity, suppressed cell proliferation, induced...
We evaluated the association between tumor‐infiltrating FOXP3+ T cells and clinical outcomes in p... more We evaluated the association between tumor‐infiltrating FOXP3+ T cells and clinical outcomes in patients with ocular adnexal lymphoma of mucosa‐associated lymphoid tissue type (OAML). Pretreatment formalin‐fixed paraffin‐embedded tissues from 42 patients with OAML were stained with 236A/E7 anti‐FOXP3 murine monoclonal antibody as well as CD3, CD4 and CD8 antibodies. The amount of FOXP3+ T cells was numerically quantified using an image analysis program. Front‐line treatments were as follows: combination chemotherapy (n = 25); radiotherapy (n = 9); doxycycline (n = 6); and wait and see (n = 2). Complete response (CR) was observed in 20 (50%) of 40 evaluable patients. Median progression‐free survival (PFS) was 50 months. A high number of FOXP3+ T cells (n = 21, ≥180/0.58 mm2) showed a higher CR rate (33%vs 71%, P = 0.013) and tendency towards prolonged PFS (48 vs 67 months, P = 0.110). In the combination chemotherapy group, a high number of FOXP3+ T cells was significantly associated ...
The prognostic implications of miR-21, miR-17-92 and miR-155 were evaluated in diffuse large B-ce... more The prognostic implications of miR-21, miR-17-92 and miR-155 were evaluated in diffuse large B-cell lymphoma (DLBCL) patients, and novel mechanism by which miR-21 contributes to the oncogenesis of DLBCL by regulating FOXO1 and PI3K/AKT/mTOR pathway was investigated. The expressions of miR-21, miR-17-92 and miR-155 measured by quantitative reverse-transcription-PCR were significantly up-regulated in DLBCL tissues (n=200) compared to control tonsils (P=0.012, P=0.001 and P<0.0001). Overexpression of miR-21 and miR-17-92 was significantly associated with shorter progression-free survival (P=0.003 and P=0.014) and overall survival (P=0.004 and P=0.012). High miR-21 was an independent prognostic factor in DLBCL patients treated with rituximab-combined chemotherapy. MiR-21 level was inversely correlated with the levels of FOXO1 and PTEN in DLBCL cell lines. Reporter-gene assay showed that miR-21 directly targeted and suppressed the FOXO1 expression, and subsequently inhibited Bim trans...
Class III b-tubulin (TUBB3) expression in carcinoma is associated with resistance to tubulin-bind... more Class III b-tubulin (TUBB3) expression in carcinoma is associated with resistance to tubulin-binding chemotherapeutic agents. Recently, follicular dendritic cells (FDCs) were reported to express TUBB3 under physiologic conditions. We investigated TUBB3 expression in a wide range of lymphoproliferative disorders using immunohistochemistry. Dual immunostaining for Bcl-6 and TUBB3 revealed that some germinal center B cells also express TUBB3 in addition to FDCs. In Hodgkin lymphomas (HLs), 47.1% (40/85) expressed TUBB3 in the tumor cells with an all-or-none pattern. TUBB3 expression in HL was more common in mixed cellularity type than nodular sclerosis type (P = 0.032). Among non-HLs, 79.3% (23/29) of anaplastic large cell lymphoma (ALCL), 8% (2/25) of extranodal natural killer/T-cell lymphoma, and 75% (21/28) of Burkitt lymphoma showed TUBB3 expression with an allor-none pattern. Of diffuse large B-cell lymphoma, 15.2% (32/ 210) expressed TUBB3 in a heterogeneous pattern. In ALCL, TUBB3 expression was more common in systemic ALCL than in primary cutaneous ALCL (P = 0.046). Diffuse large B-cell lymphomas with a germinal center B-like subgroup exhibited TUBB3 expression more frequently than non À GCB-like subgroup (P = 0.01). Otherwise, none of the 18 angioimmunoblastic T-cell lymphomas; 18 peripheral T-cell lymphomas, not otherwise specified; 12 follicular lymphomas; 62 marginal zone lymphomas; 7 mantle cell lymphomas; 8 small lymphocytic lymphomas; or 2 FDC sarcomas expressed TUBB3. In angioimmunoblastic T-cell lymphoma and Castleman disease, TUBB3 was positive in immunoblasts corresponding to Epstein-Barr virus-infected or Kaposi sarcoma herpes virusinfected cells. A variety of neoplastic and non-neoplastic lymphoproliferative disorders exhibited characteristic TUBB3 expression patterns; these results suggest potential for diagnostic utility, some insight into the pathobiology of TUBB3 expression, and potential therapeutic implications.
Kimura's disease is a rare chronic inflammatory disease of the lymphoid organs and this prese... more Kimura's disease is a rare chronic inflammatory disease of the lymphoid organs and this presents as painless nodules in the head and neck area. It occurs endemically in the Far East Asia and sporadically in the West. Its exact etiology is unknown and it has no potential to transform into malignant disease. However, it is often confused with malignant disease such as malignant lymphoma. We report a case of NK/T cell lymphoma patient who had Kimura's disease in the right thigh 3 years ago. She then suffered from sudden dyspnea. Radiological studies revealed multiple small nodules scattered in both lung fields. NK/T cell lymphoma was diagnosed by open lung biopsy. In addition, Epstein-Barr virus (EBV) was detected in the previous site of Kimura's disease and lung nodule by molecular pathologic examination. To the best of our knowledge, this is the first case of NK/T cell lymphoma complicating Kimura's disease with coexisting chronic EBV infection.
Circulating tumor cells (CTCs) have been identified in peripheral blood of cancer patients, and r... more Circulating tumor cells (CTCs) have been identified in peripheral blood of cancer patients, and reproducible detection of CTCs has demonstrated the potential as useful diagnostic and prognostic tools in several cancers. Present study aimed to determine the clinical relevance of CTCs in surgically resected non-small cell lung cancer (NSCLC) patients. CTC status in presurgery and postsurgery peripheral blood samples from 79 surgically resected NSCLC patients was investigated using thyroid transcription factor-1 (TTF-1) and cytokeratin19 (CK19) mRNA markers by nested real-time RT (reverse transcription)-PCR assay. Detection of TTF-1((+))CTCs was found to be specific to NSCLC patients. TTF-1((+))CTCs were detected in 36.1% (22/61) of patients before surgery and in 37.5% (18/48) after surgery. For CK19 mRNA-expressing CTCs (CK19((+))CTCs), the detection rate was 42.6% (26/61) before surgery, and 25.0% (12/48) after surgery. Cases with postsurgery TTF-1((+)) and/or CK19((+))TCs was more a...
Purpose: We investigated prognostic implications of microRNAs in extranodal NK/T cell lymphoma (N... more Purpose: We investigated prognostic implications of microRNAs in extranodal NK/T cell lymphoma (NKTL). Experimental Design: We measured miRNA expression in NKTL tissues and cell lines, using real-time PCR, and analyzed its role in NKTL, using cell lines. Results: Multivariate analysis showed low miR-146a expression (P < 0.001; HR = 13.110), primary non–upper aerodigestive tract lesion (non-UAT; P = 0.008; HR = 5.376) and high International Prognostic Index (IPI; ≥3; P = 0.013; HR = 3.584) to be independent poor prognostic factors. miR-146a expression could subdivide UAT-NKTL into 2 prognostic groups, resulting in the following prognostic groups: (i) UATLow-146a, (ii) UATHigh-146a, and (iii) non-UAT. Compared with UATHigh-146a, UATLow-146a showed distinctively poor prognosis (P < 0.001; HR = 15.620), similar to the non-UAT group. In vitro, miR-146a overexpression in NKTL cell lines, SNK6 and YT, inhibited nuclear factor κB (NFκB) activity, suppressed cell proliferation, induced...
We evaluated the association between tumor‐infiltrating FOXP3+ T cells and clinical outcomes in p... more We evaluated the association between tumor‐infiltrating FOXP3+ T cells and clinical outcomes in patients with ocular adnexal lymphoma of mucosa‐associated lymphoid tissue type (OAML). Pretreatment formalin‐fixed paraffin‐embedded tissues from 42 patients with OAML were stained with 236A/E7 anti‐FOXP3 murine monoclonal antibody as well as CD3, CD4 and CD8 antibodies. The amount of FOXP3+ T cells was numerically quantified using an image analysis program. Front‐line treatments were as follows: combination chemotherapy (n = 25); radiotherapy (n = 9); doxycycline (n = 6); and wait and see (n = 2). Complete response (CR) was observed in 20 (50%) of 40 evaluable patients. Median progression‐free survival (PFS) was 50 months. A high number of FOXP3+ T cells (n = 21, ≥180/0.58 mm2) showed a higher CR rate (33%vs 71%, P = 0.013) and tendency towards prolonged PFS (48 vs 67 months, P = 0.110). In the combination chemotherapy group, a high number of FOXP3+ T cells was significantly associated ...
The prognostic implications of miR-21, miR-17-92 and miR-155 were evaluated in diffuse large B-ce... more The prognostic implications of miR-21, miR-17-92 and miR-155 were evaluated in diffuse large B-cell lymphoma (DLBCL) patients, and novel mechanism by which miR-21 contributes to the oncogenesis of DLBCL by regulating FOXO1 and PI3K/AKT/mTOR pathway was investigated. The expressions of miR-21, miR-17-92 and miR-155 measured by quantitative reverse-transcription-PCR were significantly up-regulated in DLBCL tissues (n=200) compared to control tonsils (P=0.012, P=0.001 and P<0.0001). Overexpression of miR-21 and miR-17-92 was significantly associated with shorter progression-free survival (P=0.003 and P=0.014) and overall survival (P=0.004 and P=0.012). High miR-21 was an independent prognostic factor in DLBCL patients treated with rituximab-combined chemotherapy. MiR-21 level was inversely correlated with the levels of FOXO1 and PTEN in DLBCL cell lines. Reporter-gene assay showed that miR-21 directly targeted and suppressed the FOXO1 expression, and subsequently inhibited Bim trans...
Class III b-tubulin (TUBB3) expression in carcinoma is associated with resistance to tubulin-bind... more Class III b-tubulin (TUBB3) expression in carcinoma is associated with resistance to tubulin-binding chemotherapeutic agents. Recently, follicular dendritic cells (FDCs) were reported to express TUBB3 under physiologic conditions. We investigated TUBB3 expression in a wide range of lymphoproliferative disorders using immunohistochemistry. Dual immunostaining for Bcl-6 and TUBB3 revealed that some germinal center B cells also express TUBB3 in addition to FDCs. In Hodgkin lymphomas (HLs), 47.1% (40/85) expressed TUBB3 in the tumor cells with an all-or-none pattern. TUBB3 expression in HL was more common in mixed cellularity type than nodular sclerosis type (P = 0.032). Among non-HLs, 79.3% (23/29) of anaplastic large cell lymphoma (ALCL), 8% (2/25) of extranodal natural killer/T-cell lymphoma, and 75% (21/28) of Burkitt lymphoma showed TUBB3 expression with an allor-none pattern. Of diffuse large B-cell lymphoma, 15.2% (32/ 210) expressed TUBB3 in a heterogeneous pattern. In ALCL, TUBB3 expression was more common in systemic ALCL than in primary cutaneous ALCL (P = 0.046). Diffuse large B-cell lymphomas with a germinal center B-like subgroup exhibited TUBB3 expression more frequently than non À GCB-like subgroup (P = 0.01). Otherwise, none of the 18 angioimmunoblastic T-cell lymphomas; 18 peripheral T-cell lymphomas, not otherwise specified; 12 follicular lymphomas; 62 marginal zone lymphomas; 7 mantle cell lymphomas; 8 small lymphocytic lymphomas; or 2 FDC sarcomas expressed TUBB3. In angioimmunoblastic T-cell lymphoma and Castleman disease, TUBB3 was positive in immunoblasts corresponding to Epstein-Barr virus-infected or Kaposi sarcoma herpes virusinfected cells. A variety of neoplastic and non-neoplastic lymphoproliferative disorders exhibited characteristic TUBB3 expression patterns; these results suggest potential for diagnostic utility, some insight into the pathobiology of TUBB3 expression, and potential therapeutic implications.
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