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• Standardization of CD30 immunohistochemistry staining among three automated immunostaining platforms.

  Masafumi Seki, Akira Satou, Renji Funato, Tomoko Tamaki, Naoki Wada, Norihiro Nakada, Hirofumi Matsumoto, Iwao Nakazato, Eriko Wada, Kaneko Sakurai, Toyonori Tsuzuki, Kennosuke Karube

  Pathology international   74 ( 9 ) 530 - 537   2024.09 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  The identification of CD30 expression by immunohistochemistry is essential for the treatment of lymphomas using an antibody-drug conjugate targeting CD30. However, no standardized protocol for CD30 staining has been available. In this study, we compared three common automated immunostaining platforms {Bond III (B III), Dako Omnis (DO) and Ventana BenchMark ULTRA (VBMU)}. A primary antibody for CD30, the Ber-H2 clone, was diluted 50- to 400-fold for B III and DO, and ready-to-use antibody was used for VBMU. An enhancement step using a linker was introduced in all protocols. First, several candidate dilutions were selected for each platform by staining six cases. These candidate conditions were then confirmed with 60 cases of various types of peripheral T-cell lymphomas (PTCLs). The concordance rates of CD30 expression among platforms differed depending on cutoff values and antibody dilutions, except for anaplastic large cell lymphoma. The concordance rates among three platforms in the evaluation of "positive" or "negative" were 100% and 97% when the cutoff values were 1% and 10% respectively, if using 400-diluted antibody in B III and 100-diluted antibody in DO. This study demonstrated the feasibility of equalizing CD30 staining of PTCLs among different platforms by adjusting protocols.

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• A Case of SMARCB1-Deficient Sinonasal Carcinoma With Clear Cell Morphology.

  Tomoko Tamaki, Kyonosuke Teruya, Hitoshi Hirakawa, Mariko Tomita, Naoki Wada

  Cureus   16 ( 5 ) e59684   2024.05 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  SMARCB1 is a gene known to cause carcinogenesis in many soft tissue tumors, including malignant rhabdoid tumors and epithelioid sarcoma. Since the first report of a subtype of sinonasal carcinoma characterized by a deficiency of the SMARCB1 gene in 2014 to date, fewer than 200 cases have been reported. We report a case of SMARCB1-deficient sinonasal carcinoma with clear cell morphology. In our case, there are no evident basaloid or plasmacytoid/rhabdoid tumor cells, which are typical histopathological features of SMARCB1-deficient sinonasal carcinoma. SMARCB1-deficient sinonasal carcinoma is prone to recurrence and has a very poor prognosis. As the development of molecularly targeted agents progresses, therapeutic efficacy is expected to improve. Simultaneously, the importance of early and accurate diagnosis of SMARCB1-deficient sinonasal carcinoma will increase. With the limited information provided by biopsy specimens, it is necessary to confirm the loss of SMARCB1 expression by immunohistochemistry and investigate the presence of SMARCB1 gene deletion by molecular genetics, considering the possibility of SMARCB1-deficient sinonasal carcinoma even in atypical cases without basaloid or plasmacytoid/rhabdoid cell morphology, as in our case.

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• Effects of low-intensity extracorporeal shock wave therapy on lipopolysaccharide cystitis in a rat model of interstitial cystitis/bladder pain syndrome.

  Naohisa Kusakabe, Tadanobu Chuyo Kamijo, Naoki Wada, Hiroki Chiba, Nobuo Shinohara, Minoru Miyazato

  International urology and nephrology   56 ( 1 ) 77 - 86   2024.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  PURPOSE: To investigate the effect of low-intensity extracorporeal shock wave therapy (LiESWT) on lipopolysaccharide (LPS)-induced cystitis in an animal model of interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: Sprague-Dawley rats were divided into three groups: control, cystitis (LPS group, intravesical injection of LPS (1 mg) twice), and cystitis with LiESWT (LiESWT group). On the third and fourth days, LiESWT was administered (0.12 mJ/mm2, 300 shots each time) on the lower abdomen toward the bladder. On the seventh day, the rats underwent pain assessment and a metabolic cage study. Subsequently, a continuous cystometrogram (CMG) was performed under urethane anaesthesia. Immunohistochemical studies were also performed, including S-100 staining, an immunohistochemical marker of Schwann cells in the bladder. RESULTS: In the LPS group, the pain threshold in the lower abdomen was significantly lower than that in the control group. In the metabolic cage study, the mean voided volume in the LPS group significantly increased. The CMG also revealed a significant decrease in bladder contraction amplitude, compatible with detrusor underactivity in the LPS group. Immunohistochemical studies showed inflammatory changes in the submucosa, increased fibrosis, and decreased S-100 stain-positive areas in the muscle layer of the LPS group. In the LiESWT group, tactile allodynia and bladder function were ameliorated, and S-100 stain-positive areas were increased. CONCLUSION: By restoring nerve damage, LiESWT improved lower abdominal pain sensitivity and bladder function in an LPS-induced cystitis rat model. This study suggests that LiESWT may be a new therapeutic modality for IC/BPS.

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• Intraoperative cone-beam computed tomography-guided curettage for osteoid osteoma.

  Yuichi Tsuha, Hiromichi Oshiro, Kohei Mizuta, Yusuke Aoki, Tomoko Tamaki, Naoki Wada, Yasunori Tome, Kotaro Nishida

  Medicine ( Ovid Technologies (Wolters Kluwer Health) )  102 ( 51 ) e36747-1 - e36747-5   2023.12 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Recently, cone-beam computed tomography (CBCT)-guided surgeries have been developed for bone and soft tissue tumors. The present study aimed to evaluate the efficacy of CBCT-guided curettage for osteoid osteoma. Our study population included 13 patients who underwent primary curettage for osteoid osteoma using intraoperative CBCT in a hybrid operating room between April 2019 and November 2022. We collected the following data: sex, age, follow-up period, symptom onset to time of surgery, tumor size and location, length of skin incision, operating time, radiation dose, recurrence, postoperative complications, and visual analog scale for pain during the last follow-up. There were 10 male and 3 female patients, and the mean age was 25.0 years (range, 9–49 years). The mean follow-up period was 10.6 months (range, 0.4–24.0 months). The locations of the tumors were the proximal femur in 6 patients, the acetabular region in 2 patients, and the ilium, tibial shaft, calcaneus, cuboid, and talus in 1 patient each. The mean time of symptoms onset to surgery was 18.7 months (range, 2.3–69.9 months). The mean maximum diameter of the tumor was 5.9 mm (range, 3.5–10.0 mm). The mean length of the skin incision was 2.2 cm (range, 1.5–3.5 cm). The mean operating time was 96.9 minutes (range, 64–157 minutes). The mean dose of radiation was 193.2 mGy (range, 16.3–484.0 mGy). No recurrences, postoperative complications, and reoperation were observed in this study. All the patients reported 0 mm on the visual analogue scale for pain on the last follow-up. CBCT-guided curettage for osteoid osteoma was minimally invasive and reliable. This procedure can be effective for the treatment of lesions found in deep locations such as the pelvic bone and proximal femur or an invisible lesion that cannot be detected by regular fluoroscopy.

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• p16 Overexpression in Sinonasal Squamous Cell Carcinoma: Association with Human Papillomavirus and Prediction of Survival Outcomes.

  Hitoshi Hirakawa, Taro Ikegami, Masatomo Touyama, Yurika Ooshiro, Tomoyo Higa, Teruyuki Higa, Shinya Agena, Hidetoshi Kinjyo, Shunsuke Kondo, Norimoto Kise, Katsunori Tanaka, Hiroyuki Maeda, Tomoko Tamaki, Naoki Wada, Mikio Suzuki

  Journal of clinical medicine   12 ( 21 ) 6861   2023.10 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  p16 overexpression is often used as a surrogate marker for human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma but remains an uncertain diagnostic tool for HPV-related sinonasal squamous cell carcinoma (SNSCC). Our study involved 79 consecutive SNSCC patients who were treated at a tertiary referral university hospital during 2006-2021. We retrospectively examined their clinical characteristics and conducted p16 immunohistochemistry and HPV detection. We found that 12.7% of the patients exhibited p16 overexpression, which was significantly more common in the nasal cavity and increased from 2015 onward. The HPV was a high-risk type and viral loads ranged from 4.2 to 1.6 × 106 copies/ng DNA with genome integration. Five-year overall survival (OS) and five-year relapse-free survival (RFS) rates were 74.6% and 69.9%, respectively. Our multivariate analysis showed that T category (T1-4a) and hemoglobin levels (≥13.7) were significant favorable prognostic factors for OS, while T category, performance status, and p16 overexpression were significantly associated with RFS. In patients with p16 overexpression, OS was 100% and RFS was 90%. Our findings suggest that p16 overexpression is a reliable surrogate marker for transcriptionally active HPV infection and predicts a favorable prognosis.

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Other Papers 【 display / non-display 】

Other Papers 【 display / non-display 】

• 成人T細胞白血病・リンパ腫(ATLL)の病理組織学的形態および免疫表現型に関する検討(A study on histopathological morphology and immunophenotype of adult T-cell leukemia/lymphoma (ATLL))

  玉城 智子, 加留部 謙之輔, 仲田 典宏, 松本 裕文, 仲里 巌, 和田 直樹

  日本病理学会会誌 ( (一社)日本病理学会 )  112 ( 1 ) 274 - 274   2023.03

   

• Standardization of CD30 immunohistochemical staining on different staining platforms

  関雅文, 佐藤啓, 舩戸連嗣, 玉城智子, 和田直樹, 加留部謙之輔

  日本病理学会会誌   112 ( 1 )   2023

   

  J-GLOBAL

• SDPRは子宮体部類内膜癌においてILKを介してALDH1を制御する

  田原 紳一郎, 野島 聡, 大島 健司, 堀 由美子, 倉重 真沙子, 和田 直樹, 本山 雄一, 奥崎 大介, 池田 純一郎, 森井 英一

  日本癌学会総会記事 ( (一社)日本癌学会 )  79回   YSA - 2   2020.10

   

• 動脈炎におけるステロイド治療が及ぼす組織学的変化(Histological change of Arteritis under steroid treatment)

  田中 さやか, 佐々木 香織, 皆見 勇人, 野浦 郁恵, 小林 郁江, 大畑 麻衣, 和田 直樹, 桑江 優子, 大澤 政彦

  日本病理学会会誌 ( (一社)日本病理学会 )  109 ( 1 ) 459 - 459   2020.03

   

• 肝reactive lymphoid hyperplasiaの1例(A case of reactive lymphoid hyperplasia of the liver)

  野浦 郁恵, 佐々木 香織, 皆見 勇人, 小林 郁江, 大畑 麻衣, 和田 直樹, 田中 さやか, 桑江 優子, 大澤 政彦

  日本病理学会会誌 ( (一社)日本病理学会 )  109 ( 1 ) 350 - 350   2020.03

   

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Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• A study on histopathological morphology and immunophenotype of adult T-cell leukemia/lymphoma (ATLL)

  Tomoko Tamaki, Kennosuke Karube, Norihiro Nakada, Hirofumi Matsumoto, Iwao Nakazato, Naoki Wada

  2023.04  -  2023.04 

• Cytologic Characteristics and Differential Diagnosis of Secretory Carcinoma: An Analysis of 16 Cases

  Kayoko Higuchi, Akihiko Kawahara, Katsuyuki Tsuha, Yuri Kato, Tomoya Minami, Yuko Chibana, Hirofumi Koyama, Naoki Wada, Makoto Urano, Toshitaka Nagao

  第20回日韓細胞診合同会議  (韓国Gunsan city（群山）のGunsan Saemangeum Convention Center(GSCO))  1900.01  -  1900.01 

Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2018.04  -  2021.03 

  Direct: 3,500,000 (YEN)  Overheads: 1,050,000 (YEN)  Total: 4,550,000 (YEN)

• Elucidation of the factor involved in the dynamic differentiation of lymphoplasmacytic lymphoma

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2018.04  -  2021.03 

  Investigator(s): WADA Naoki 

  Direct: 3,500,000 (YEN)  Overheads: 4,550,000 (YEN)  Total: 1,050,000 (YEN)

  　View Summary

  Glutamine (Gln) is important not only for cell proliferation but also for differentiation. Although Gln is essential for plasmacytic differentiation of lymphocytes, no study has been done on the effect of Gln on differentiation of tumor cells, such as lymphoma. Here I examined the effect of Gln on plasmacytic differentiation of lymphoplasmacytic lymphoma (LPL) with its cell line. Gln promoted plasmacytic differentiation of LPL, and p38 MAPK signaling pathway mediated such differentiation. I previously reported that the subpopulation with plasmacytic differentiation was vulnerable to apoptosis in LPL. Although it is difficult to lead these findings to the radical therapy, they might help the treatment of LPL.

• The positive marker identification of tumor-initiating cells and the dynamic analyses of them in lymphoplasmacytic lymphoma (LPL)

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2015.04  -  2018.03 

  Investigator(s): WADA Naoki 

  Direct: 3,800,000 (YEN)  Overheads: 1,140,000 (YEN)  Total: 4,940,000 (YEN)

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  MWCL-1 was established as LPL cell line. MWCL-1 cells were classified into three subpopulations by flow cytometric analyses using anti-CD20 and anti-CD138 antibodies: CD20-CD138-, CD20+CD138-, and CD20+CD138+ cells. We searched for markers preferentially expressed in CD20-CD138- cells of MWCL-1 (the candidates for tumor-initiating cells of LPL), and the chemokine receptor CXCR7 was isolated. We also searched for favorable microenvironments for their proliferation, and we found that hypoxia and CXCL12-CXCR7 signaling appeared to be favorable microenvironments. We then examined the effect of plasma-activated medium (PAM) on LPL cell line, and we found that PAM induced plasma cell (CD138 positive) differentiation, which appeared to be mediated by PRDM1α (the transcription factor promoting plasma cell differentiation).

• The positive marker identification of tumor-initiating cells and the dynamic analyses of them in lymphoplasmacytic lymphoma (LPL)

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2015.04  -  2018.03 

  Investigator(s): WADA Naoki 

  Direct: 3,800,000 (YEN)  Overheads: 4,940,000 (YEN)  Total: 1,140,000 (YEN)

  　View Summary

  MWCL-1 was established as LPL cell line. MWCL-1 cells were classified into three subpopulations by flow cytometric analyses using anti-CD20 and anti-CD138 antibodies: CD20-CD138-, CD20+CD138-, and CD20+CD138+ cells. We searched for markers preferentially expressed in CD20-CD138- cells of MWCL-1 (the candidates for tumor-initiating cells of LPL), and the chemokine receptor CXCR7 was isolated. We also searched for favorable microenvironments for their proliferation, and we found that hypoxia and CXCL12-CXCR7 signaling appeared to be favorable microenvironments. We then examined the effect of plasma-activated medium (PAM) on LPL cell line, and we found that PAM induced plasma cell (CD138 positive) differentiation, which appeared to be mediated by PRDM1α (the transcription factor promoting plasma cell differentiation).

• Dynamic analyses of tumor-initiating cells in lymphoplasmacytic lymphoma (LPL)

  Grant-in-Aid for Young Scientists(B)

  Project Year: 2013.04  -  2015.03 

  Investigator(s): WADA NAOKI 

  Direct: 3,200,000 (YEN)  Overheads: 960,000 (YEN)  Total: 4,160,000 (YEN)

  　View Summary

  MWCL-1 was established as LPL cell line. MWCL-1 cells were classified into three subpopulations using a flow cytometer with anti-CD20 and anti-CD138 antibodies: CD20-CD138-, CD20+CD138-, and CD20+CD138+. When cultured, CD20-CD138- cells yielded all three subpopulations. Compared to the other subpopulations, CD20-CD138- cells possessed the efficient ROS expelling and in vitro colony formation activities, and were resistant to apoptosis. These results suggested that CD20-CD138- cells might be a candidate for tumor-initiating cells in LPL. Low oxygen culture of MWCL-1 induced the production of CD20-CD138- cells, and this result suggested that hypoxia was an advantageous microenvironment for CD20-CD138- cells. CXCR7 mRNA/protein expression was the highest in CD20-CD138- cells. When CXCL12, a ligand of CXCR7, was added, the proportion of CD20-CD138- cells significantly increased. CXCL12-CXCR7 signaling might exert a great influence on CD20-CD138- cells.

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Social Activity 【 display / non-display 】

• 2024.01