Hirokazu Taniguchi

National Cancer Center, Japan, Edo, Tōkyō, Japan

Are you Hirokazu Taniguchi?

Claim your profile

Publications (112)405.83 Total impact

  • Pathology International 12/2014; · 1.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A field for cancerization, or a field defect, is formed by the accumulation of genetic and epigenetic alterations in normal-appearing tissues, and is involved in various cancers, especially multiple cancers. Epigenetic alterations are frequently present in chronic inflammation-exposed tissues, but information on individual genes involved in the formation of a field defect is still fragmental. Here, using non-cancerous gastric tissues of cancer patients, we isolated 16 aberrantly methylated genes, and identified chromatin remodelers ACTL6B and SMARCA1 as novel genes frequently methylated in non-cancerous tissues. SMARCA1 was expressed at high levels in normal gastric tissues, but was frequently silenced by aberrant methylation in gastric cancer cells. Moreover, somatic mutations of additional chromatin remodelers, such as ARID1A, SMARCA2, and SMARCA4, were found in 30% of gastric cancers. Mutant allele frequency suggested that the majority of cancer cells harbored a mutation when present. Depletion of a chromatin remodeler, SMARCA1 or SMARCA2, in cancer cell lines promoted their growth. These results showed that epigenetic and genetic alterations of chromatin remodelers are induced at an early stage of carcinogenesis and are frequently involved in the formation of a field defect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Cancer Letters 11/2014; · 5.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We here report on two rare cases of intrafollicular classical Hodgkin lymphoma (CHL). Case 1 was a 34-year-old man who underwent left supraclavicular lymph node biopsy. Case 2 was a 28-year-old woman who underwent surgical resection of an anterior mediastinal mass. The histology and microenvironment of both specimens resembled those of nodular lymphocyte predominant Hodgkin lymphoma. Nodular architecture was observed, which comprised normal-appearing small lymphocytes and scattered lymphocyte predominant (LP)-like cells. CD23(+) follicular dendritic cell meshworks were present in the nodules, surrounded by a mantle zone containing IgD(+) B cells. The LP-like cells were ringed by CD3(+) and PD-1(+) T cells, and numerous CD20(+) B cells were present in the background. However, the immunophenotypes of the LP-like cells resembled those of Hodgkin/Reed-Sternberg cells of CHL; they were positive for CD15, CD30, and PAX5, and negative for CD20, Bcl6, Oct2, and Bob1. These histopathological findings indicate that CHL can be derived from the germinal center.
    Pathology International 11/2014; · 1.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT This study aimed to indicate the patients' outcomes and pathological characteristics of follicular lymphoma (FL) with peripheral blood (PB) involvement. Of 533 patients with FL, 56 (11%) had PB involvement. Of the patients treated with rituximab, 39 patients with PB involvement had significantly shorter progression-free survival than 107 patients with stage IV disease without PB involvement (P = .021), but the overall survival was not different (P = .804). The histopathology of the primary sites was usually nodal (95%) low-grade (86%) FL with IGH/BCL2 fusion (75%). Flow cytometric and immunohistochemical analyses revealed that the incidence of CD10 positivity was lower in the bone marrow (55% and 58%) and PB (41% and not available) than in the primary site (86% and 93%) (P = .004 and P = .0001, respectively). Therefore, even if small lymphoma cells in the bone marrow and PB are negative for CD10, FL cannot be ruled out.
    Leukemia and Lymphoma 10/2014; · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and study aims: Compared with any other location in the gastrointestinal tract, the duodenum presents the most challenging site for endoscopic resection. The aim of this study was to analyze the clinical outcomes of duodenal endoscopic resection and to assess the feasibility of the technique as a therapeutic procedure. Patients and methods: A total of 113 consecutive patients with 121 nonampullary duodenal tumors underwent endoscopic resection by endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), or polypectomy between January 2000 and September 2013. Long-term outcomes were investigated in patients with more than 1 year follow-up. Results: The median tumor size was 12 mm (range 3 - 50 mm). Lesions consisted of 63 adenocarcinomas/high-grade intraepithelial neoplasias (53 %) and 57 adenomas/low-grade intraepithelial neoplasias (48 %). Endoscopic resection included 106 EMRs (87 %), 8 ESDs (7 %), and 7 polypectomies (6 %). En bloc resection was achieved in 77 lesions (64 %), and 43 lesions (35 %) underwent piecemeal resection; one procedure was discontinued due to perforation. There were 14 cases of delayed bleeding after EMR (12 %), 1 perforation (1 %) during ESD, and 1 delayed perforation (1 %) after ESD, which required emergency surgery. Of the 76 patients who were followed for more than 1 year, none of the patients died from a primary duodenal neoplasm, and there were no local recurrences during the 51-month median follow-up period (range 12 - 163 months). Conclusions: Duodenal endoscopic resection was feasible as a therapeutic procedure, but it should only be performed by highly skilled endoscopists because of its technical difficulty. Piecemeal resection by EMR is acceptable for small lesions, based on these excellent long-term outcomes.
    Endoscopy 10/2014; · 5.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms of borderline malignancy that generally affect children and young adults.1 IMTs most commonly occur in the lung, mesentery, and retroperitoneum.1 Gastric IMTs are extremely rare, with less than 10 cases reported in English-language literature.2This article is protected by copyright. All rights reserved.
    Histopathology 10/2014; · 3.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We recently reported that the presence of a papillary adenocarcinoma (pap) component was an independent risk factor for lymphatic involvement in endoscopically resected early gastric cancer (EGC). This study aimed to investigate the potential association between the presence of a pap component in EGC and lymph node metastasis (LNM).
    Journal of Gastroenterology 08/2014; · 4.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the clinicopathological and prognostic significance of a nodular pattern and immunophenotypes in primary mediastinal large B-cell lymphoma (PMBL), histopathological features, including a nodular pattern and immunophenotypes, were analyzed in 58 Japanese PMBL patients. The patients were 23 men and 35 women with a median age of 31 years. The 4-year progression free survival (PFS) rate was 78%, and the 4-year overall survival (OS) rate was 89%. Among the histopathological and immunohistochemical features, Bcl6+ (P = 0.013), MUM1+ (P = 0.091), and pale cytoplasm (P = 0.064) were favorable prognostic indicators of PFS, and Bcl6+ (P = 0.051) and MUM1+ (P = 0.07) were favorable prognostic indicators of OS. Patients with Bcl2 negativity (n = 11) had 4-year PFS and OS rates of 100%. Histologically, a nodular pattern, resembling nodular sclerosis classical Hodgkin lymphoma (CHL), was observed in 22 patients (38%). However, this was not a significant prognostic indicator. In conclusion, Bcl6+, MUM1+, Bcl2-, and pale cytoplasm are candidate favorable prognostic indicators for PMBL and should be further examined in larger studies. We suggest that PMBL with a nodular pattern may belong to the same histological spectrum as nodular sclerosis CHL.
    Pathology International 08/2014; 64(8). · 1.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pathological response rate (pathRR) is a common endpoint used to assess the efficacy of preoperative therapy for gastric cancer. PathRR is estimated based on the percentage of the residual tumor area in the primary tumorous bed. Various cutoff definitions used in previous trials (e.g., 10, 33, 40, 50, 67 %) often impair the comparability of pathRRs between trials.
    Gastric Cancer 06/2014; · 4.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: HER2 protein overexpression and gene amplification are important biomarkers for identifying gastric cancer patients who may respond to HER2-targeted therapy using trastuzumab. The aim of this study was to evaluate the concordance between HER2 protein expression and gene amplification in both surgically resected tumors and matched biopsy specimens of gastric cancer. Formalin-fixed, paraffin-embedded sections of 207 surgically resected tumors and 158 biopsy specimens from 207 cases of invasive intestinal-type gastric cancer were analyzed. Protein expression was assessed using immunohistochemistry and graded by the modified scoring criteria for gastric cancer. Gene amplification was evaluated by fluorescence in situ hybridization (FISH). HER2 overexpression was observed in 17 % of both surgically resected tumors (35/207) and biopsy specimens (26/158). HER2 gene amplification was detected in 31 % (61/200) of surgically resected tumors and 32 % (47/147) of biopsy specimens. Except for immunohistochemistry (IHC) equivocal (2+) cases, the concordance rates between IHC and FISH was 90.9 % in surgically resected tumors and 90.2 % in biopsy specimens. In IHC 2+ cases, the rate of HER2 gene amplification was 56 and 38 % in surgically resected tumors and biopsy specimens, respectively. IHC-FISH discordance was mainly due to intratumoral heterogeneity and low-level gene amplification. The concordance rate of IHC results between surgically resected specimens and the corresponding biopsy specimen was 57.0 % (κ = 0.224), and in discordant cases, HER2 positivity in biopsies and HER2 negativity in surgically resected tumors were most common. The concordance rate of FISH results between surgically resected tumors and biopsy specimens was 72.7 % (κ = 0.313). Polysomy 17 was detected in 5.5 and 7.5 % of surgically resected tumors and biopsy specimens and significantly correlated with IHC score, but polysomy 17 could explain one IHC score 3+ and FISH-negative tumor only. Although high concordance rates between HER2-protein expression and gene amplification were observed in both surgically resected tumors and biopsy specimens, the agreement levels were evaluated to be fair. Polysomy 17 was infrequent and seemed to have limited impact on gastric HER2 testing. Further investigations are required for an appropriate biopsy method to reduce false results of HER2 testing and to clarify the clinical significance of intratumoral heterogeneity in HER2 status.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 06/2014; · 2.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biomarkers associated with anti-EGFR antibodies therapy have been investigated in metastatic colorectal cancer (CRC). We conducted this study to evaluate the clinical utility of a combined assessment of EGFR status and genomic mutations of the EGFR downstream signal pathway in predicting the efficacy of anti-EGFR antibody treatment. We collected formalin-fixed paraffin-embedded tumor tissues and evaluated the EGFR status by immunohistochemistry (IHC), dual color in situ hybridization (DISH) and genomic analyses of KRAS, BRAF, PIK3CA and NRAS by direct sequencing. A total of 129 patients were evaluated in our study. Among KRAS wild-type patients, EGFR DISH positivity was associated with a higher response rate than DISH negativity (56.3 vs. 21.1%, p = 0.011). A subgroup with EGFR DISH positivity plus IHC3+ and wild-type of EGFR downstream gene mutations achieved higher response rate and disease control rate. EGFR DISH positivity, KRAS codon 146 mutation and NRAS codon 61 mutation were prognostic factors in both progression-free survival and overall survival by multivariate analyses. Combined assessment of DISH plus IHC and EGFR downstream gene mutations was useful to predict the response to anti-EGFR antibodies treatment in metastatic colorectal cancer patients in our study.
    Archives of medical research 05/2014; · 1.88 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-161-S-162. · 13.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: c-MET is implicated in the pathogenesis and growth of a wide variety of human malignancies, including colorectal cancer (CRC). The aim of the present study was to clarify the association between c-MET expression and tumor recurrence in CRC patients after curative liver resection, and to evaluate concordance in c-MET expression and various mutations of KRAS, BRAF, and PIK3CA between primary CRC and paired liver metastases. A cohort of patients was tested for c-MET immunoreactivity (ie, immunohistochemistry; IHC) and KRAS, BRAF, and PIK3CA mutations. Analyses were performed both on primary tumors and paired liver metastases, and the association between IHC and mutations results were assessed. A total of 108 patients were eligible. A total of 53% of patients underwent simultaneous resection of primary tumors and metastases, and the others underwent metachronous resection. Levels of concordance between primary tumors and metastases were 65.7%, 87.7%, 100%, and 95.2% for c-MET, KRAS, BRAF, and PIK3CA, respectively. High levels of c-MET expression (c-MET-high) in the primary tumors were observed in 52% of patients. Relapse-free survival (RFS) was significantly shorter for patients with c-MET-high primary tumors (9.7 months) than for those with c-MET-low primary tumors (21.1 months) (p=0.013). These results suggest that a high level of genetic concordance in KRAS, BRAF, and PIK3CA between primary tumors and liver metastases, and c-MET-high in the primary tumors was associated with shorter RFS after hepatic metastasectomy.This article is protected by copyright. All rights reserved.
    Cancer Science 05/2014; · 3.53 Impact Factor
  • Takahiro Fujii, Takahisa Matsuda, Yasushi Sano, Shin-Ei Kudo, Yasushi Oda, Kazuhiro Kaneko, Kinichi Hotta, Tadakazu Shimoda, Yutaka Saito, Nozomu Kobayashi, [......], Yuichiro Yamaguchi, Kiwamu Hasuda, Tomoaki Shinohara, Hideki Ishikawa, Yoshitaka Murakami, Hirokazu Taniguchi, Takahiro Fujimori, Yoichi Ajioka, Daizo Saito, Shigeaki Yoshida
    Gastrointestinal Endoscopy 05/2014; 79(5):AB582. · 4.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: RAS-RAF-MEK-ERK and PI3K-AKT pathways form a significant cascade for potential molecular target therapy in advanced cancer. The clinical significance of mutations in these genes in advanced gastric cancer (AGC) is uncertain. We collected formalin-fixed, paraffin-embedded and fresh frozen tumor samples from AGC patients and analyzed the KRAS, NRAS, BRAF and PIK3CA mutations by direct-sequencing. We retrospectively investigated the clinicopathological features of these mutations in AGC patients, and selected patients with metastatic gastric cancer. Among 167 AGC patients, mutations of KRAS codons 12/13 (N = 8/164, 4.9%), PIK3CA (N = 9/163, 5.5%), and NRAS codon 12/13(N = 3/159, 1.9%) were detected. Comparison of the clinicopathological features of the mutated KRAS, PIK3CA, NRAS genes with an all-wild type of these genes showed that the frequency of the intestinal type was significantly higher in patients whose tumor tissue contained KRAS mutations (P = 0.014). Among 125 patients with metastatic gastric cancer, patients with NRAS codon 12/13 mutations in their tumors had shorter overall survival compared with NRAS wild-type patients (MST: 14.7 vs 8.8 months, P = 0.011). By multivariate analyses, NRAS codon 12/13 mutation was an indicator for poor prognosis in patients with metastatic gastric cancer (adjusted HR 5.607, 95% CI: 1.637-19.203). Our study indicated that mutations of KRAS, PIK3CA and NRAS were rare in AGC. NRAS mutations were likely to associate with poor prognosis in metastatic state of AGC patients, but further validation of other research is required.
    BMC Research Notes 04/2014; 7(1):271.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and study aims: After noncurative endoscopic submucosal dissection (ESD) for differentiated-type early gastric cancer (EGC), close observation is often preferred when a cancer-positive lateral margin is the only noncurative factor. However, sometimes recurrence is found during the observation period. This study aimed to examine risk factors for recurrent cancer based on the long-term clinical outcomes after noncurative ESD in which the only noncurative factor was a cancer-positive lateral margin. Patients and methods: Among 3784 EGCs (3316 patients) treated by ESD between 1997 and 2010, 77 noncurative differentiated-type EGCs (75 patients) were retrospectively analyzed after meeting the following inclusion criteria: 1) the only noncurative factor was a cancer-positive lateral margin; 2) close observation was selected after the ESD; and 3) > 1 year follow-up after ESD. Results: Locally recurrent cancer was found in 10 lesions within a median follow-up period of 59.8 months; no metastasis or gastric cancer-related death occurred. The cumulative incidence of local recurrence 5 years after ESD was 11.9 %. All locally recurrent cancers were mucosal differentiated-type adenocarcinomas. Multivariate analysis indicated that a cancer-positive lateral margin length of ≥ 6 mm was significantly associated with local recurrence (hazard ratio 20.8; 95 % confidence interval 5.2 % - 82.9 %; P < 0.001). The cut-off value of 6 mm was determined by the receiver operating characteristic curve; the sensitivity and specificity for 5-year risk of developing local recurrence were 66.7 % and 95.6 %, respectively. Conclusions: A cancer-positive lateral margin length of ≥ 6 mm was an independent risk factor for local recurrence, and this may be a useful criterion for selecting high-risk cases for stricter management.
    Endoscopy 02/2014; · 5.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Currently in Japan, differentiated-type gastric submucosal invasive cancers <500 μm with negative lymphovascular involvement are included in expanded pathological criteria for curative endoscopic treatment. This categorization is based on a retrospective examination of surgical resection cases in which patients suitable for such expanded criteria were determined to have a negligible risk of lymph node metastasis. We performed endoscopic submucosal dissection on a 66-year-old man with early gastric cancer in June 2004, and pathology revealed a well-differentiated adenocarcinoma, 16 × 8 mm in size, minute submucosal invasion depth (100 μm), and negative lymphovascular invasion or ulceration as well as tumor-free margins, so the case was diagnosed as a curative resection. In this case, however, local recurrence and distant metastasis resulted in August 2011. The patient received systemic chemotherapy but died of gastric cancer 23 months after recurrence.
    Gastric Cancer 01/2014; · 4.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal villous adenoma is thought to be associated with a high risk of progression to adenocarcinoma. To better characterize the genetic alterations involved in colorectal carcinogenesis related to villous adenoma, we analyzed mutations in APC, BRAF, KRAS, TP53, and GNAS in 12 colorectal adenocarcinomas associated with villous adenomas. APC, KRAS, and BRAF mutations were identified in five, 11, and one lesion, respectively, and most of these mutations were shared between the villous adenoma and the adenocarcinoma components in the respective lesions, except in one lesion with APC mutations and in two lesions with KRAS mutations. TP53 mutations were observed exclusively in four adenocarcinoma components, consistent with their role in the progression from adenoma to adenocarcinoma. Activating GNAS mutations were found in nine villous adenomas; however, unexpectedly, these mutations were shared only in three associated adenocarcinomas. Notably, all six adenocarcinomas with discordant GNAS mutation statuses were nonmucinous type, whereas all the other adenocarcinomas, including three adenocarcinomas associated with GNAS wild-type villous adenomas, were mucinous type. The current study suggests that GNAS-mutated villous adenomas may not necessarily be direct precursors of associated adenocarcinomas. At the same time, our observations support the role of activating GNAS mutations in increased mucin production in colorectal neoplasms. © 2014 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 01/2014; 53(4). · 3.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the HER2 amplification status and HER2 overexpression status in neuroendocrine carcinomas (NECs) of the stomach. We analyzed 51 gastric NECs, including 15 pure NECs and 36 NECs associated with adenocarcinoma and/or dysplasia, for HER2 amplification by dual-color chromogenic in situ hybridization and for HER2 expression by immunohistochemistry. HER2 amplification was observed in 3 NECs (8%) and in 7 (19%) adenocarcinoma/dysplasia associated with NECs. Immunohistochemically, all the NECs, including those showing HER2 amplification, invariably lacked HER2 expression. On the other hand, 3+/positive and 2+/equivocal HER2 overexpression was observed in 3 (8%) and 6 (17%) adenocarcinoma/dysplasia associated with NEC, respectively. HER2 expression is consistently absent in gastric NECs, regardless of the HER2 amplification status or association with HER2-positive adenocarcinoma/dysplasia components. Accordingly, HER2 is unlikely to be a valid therapeutic target in gastric NECs. Also, the absence of HER2 expression in NECs could be one of the causes of intratumoral heterogeneity of HER2 expression in gastric cancers. This article is protected by copyright. All rights reserved.
    Histopathology 12/2013; · 3.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and study aim: Endoscopic resection has been favored for the management of intramucosal adenocarcinoma of the esophagogastric junction (AEGJ) over standard treatment with surgical resection. Several previous studies have reported only short-term outcomes. The aim of the present study was to report the long-term follow-up and outcomes of endoscopic submucosal dissection (ESD), a representative endoscopic resection method, for the management of superficial AEGJ. Patients and methods: A retrospective cohort study included 53 consecutive patients with superficial AEGJ who underwent ESD between 2001 and 2007 at the National Cancer Center Hospital, Tokyo, Japan. Rates of overall survival, recurrence-free survival, and cause-specific survival of patients with AEGJ after endoscopic resection were analyzed. Results: The 5-year overall, recurrence-free, and cause-specific survival rates in the 53 patients were 94.2 %, 92.3 % and 96.1 %, respectively. The median follow-up was 6.1 years. En bloc, R0, and curative resection rates were 100 %, 79 %, 68 %, respectively. In 36 patients with curative resection, the cause-specific survival rate was 100 % and no recurrence or metastases were detected. In 17 patients with non-curative resection, recurrence was found in three patients (17 %); two of the three patients died of their disease whilst one patient received chemotherapy. Conclusions: Superficial AEGJ can be well controlled by ESD when curative resection is achieved.
    Endoscopy 12/2013; 45(12):992-6. · 5.20 Impact Factor

Publication Stats

684 Citations
405.83 Total Impact Points


  • 2007–2014
    • National Cancer Center, Japan
      • • Endoscopy Division
      • • Center for Cancer Control and Information Services
      Edo, Tōkyō, Japan
  • 2008–2012
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
  • 2007–2010
    • Clinical Research Hospital, Tokyo
      Edo, Tōkyō, Japan