Faculty Profiles - TANUMA Junichi

Papers - TANUMA Junichi

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Masticatory muscle tendon-aponeurosis hyperplasia that was initially misdiagnosed for polymyositis: a case report and review of the literature Reviewed

Wataru Katagiri, Daisuke Saito, Satoshi Maruyama, Makiko Ike, Hideyoshi Nisiyama, Takafumi Hayashi, Jun-ichi Tanuma, Tadaharu Kobayashi

Maxillofacial Plastic and Reconstructive Surgery 45 ( 18 ) 2023.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Background

Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a relatively newly identified clinical condition that manifests as trismus with a square-shaped mandible. Herein, we report a case of MMATH that was initially misdiagnosed for polymyositis due to trismus and simultaneous lower limb pain, with literature review.

Case presentation

A 30-year-old woman had a history of lower limb pain after exertion for 2 years. Initial physical examination had been performed at the Department of General Medicine in our hospital. There was also redness in the hands and fingers. Although polymyositis was suspected, it was denied. The patient visited our department for right maxillary wisdom tooth extraction.

Clinical examination revealed that the patient had a square-shaped mandible. The maximal mouth opening was 22 mm. There was no temporomandibular joint pain at the time of opening. Furthermore, there was awareness of clenching while working. Panoramic radiography revealed developed square mandibular angles with flattened condyles. Computed tomography showed enlarged masseter muscles with high-density areas around the anterior and lateral fascia. Magnetic resonance imaging also showed thickened tendons and aponeuroses on the anterior surface and inside bilateral masseter muscles. Finally, the patient was diagnosed with MMTAH. Bilateral aponeurectomy of the masseter muscles with coronoidectomy and masseter muscle myotomy was performed under general anesthesia. The maximum opening during surgery was 48 mm. Mouth opening training was started on day 3 after surgery. Histopathological examination of the surgical specimen showed that the muscle fibers were enlarged to 60 μm. Immunohistochemistry testing for calcineurin, which was associated with muscle hypertrophy due to overload in some case reports, showed positive results. Twelve months after surgery, the mouth self-opening and forced opening were over 35 mm and 44 mm, respectively.

Conclusions

Herein, we report a case of MMATH. Lower limb pain due to prolonged standing at work and overload due to clenching were considered risk factors for symptoms onset of MMATH.

File： Masticatory.pdf

DOI： 10.1186/s40902-023-00386-6

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Other Link： https://link.springer.com/article/10.1186/s40902-023-00386-6/fulltext.html

Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma Invited Reviewed

Nyein Nyein Chan, Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abé, Kenta Haga, Masami Kawaharada, Kenji Izumi, Tadaharu Kobayashi, Jun-ichi Tanuma

International Journal of Molecular Sciences 24 ( 7 ) 6035 2023.3

Liquid‐based cytology for differentiating two cases of pemphigus vulgaris from oral squamous cell carcinoma Reviewed International journal

Maruyama S, Yamazaki M, Abé T, Kato Y, Kano H, Sumita Y, Tomihara K, Tanuma J

Diagnostic Cytopathology 51 ( 5 ) 1 - 6 2023.2

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Pemphigus vulgaris (PV) is a rare autoimmune disease characterized by blisters on the skin and mucous membrane. Since it often appears in the oral mucosa first, it may be diagnosed by oral mucosal cytology. Although the cytologic finding is characterized by acantholytic cells, that is, Tzanck cells, it is important to distinguish PV from neoplastic lesions of the oral mucosal epithelium, including differentiation from atypical parabasal/basal cells, which appear in squamous cell carcinoma (SCC). In this study, we examined the cellular findings in two cases of PV and a case of well-differentiated SCC with loss of epithelial cell cohesion. The samples were prepared using liquid-based cytology, which showed small round-shaped and deeply stained atypical, orangeophilic keratinocytes not only in SCC but also in PV, which made differentiation between the two difficult. However, Tzanck cells found in PV differ from the deep atypical parabasal/basal cells of SCC, suggesting that the cell outline is indistinct and small protrusions and brush-like structures are observed. This feature of Tzanck cells may be useful in cytological judgment.

File： Diagnostic Cytopathology - 2023 - Maruyama - Liquid%E2%80%90based cytology for differentiating two cases of pemphigus vulgaris from.pdf

DOI： 10.1002/dc.25117

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口底部に生じた異所性胃腸管嚢胞の1例

齋藤直朗, 丸山智, 加藤祐介, 竹内涼子, 田沼順一, 小林正治

日本口腔外科学会雑誌 69 ( 1 ) 27 - 31 2023.1

Language：Japanese Publisher：(公社)日本口腔外科学会

4歳5ヵ月女児。既往として出生前診断で指摘されていた口底部の嚢胞様病変に対し、生後3日に開窓術が施行され、病理組織学的に類表皮嚢胞と診断された。今回、3歳9ヵ月時に開窓部からの出血を主訴に当科へ受診となった。数日後に出血が治まったため、いったん終診となったが、4歳2ヵ月頃より唾仙痛様症状が出現したため再診した。口腔内所見および画像所見を踏まえて、開窓術後の変化を伴う口底部類表皮嚢胞と診断され、5歳時に全身麻酔下で嚢胞摘出術が行われた。その結果、病理組織学的に異所性胃腸管嚢胞と確定診断された。術後3年経過現在、再発なく、経過良好である。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01073&link_issn=&doc_id=20230201450005&doc_link_id=10.5794%2Fjjoms.69.27&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.69.27&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Adenosquamous Carcinoma with the Acantholytic Feature in the Oral Cavity: A Case Report and Comprehensive Literature Review Reviewed

Tatsuya Abé, Manabu Yamazaki, Satoshi Maruyama, Nobuyuki Ikeda, Yoshimasa Sumita, Kei Tomihara, Jun-ichi Tanuma

diagnotics 12 ( 2398 ) 2398 - 2398 2022.12

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Adenosquamous carcinoma (ASC) is an aggressive subtype of squamous cell carcinoma (SCC). Due to its poor prognosis, a precise pathological diagnosis of ASC is essential but challenging because its pathological criteria are still unclear. Here, we present a rare case of oral ASC accompanied by acantholytic features. The tumor was raised in the mandibular gingiva and recurred locally approximately 13 months after the initial surgery with cervical lymph node metastasis. Pathological specimens of the primary lesion showed acantholysis in a large area of the SCC. Mucous cells, the characteristic finding indicating glandular differentiation, were imperceptible in the initial surgical specimen but increased in the locally recurrent and metastatic lymph node specimens. In a comprehensive literature review of oral ASC cases, the present case was the only case of ASC with acantholytic features. We reconfirmed that ASC has poor prognoses, such as low 5-year overall survival and disease-free survival, high locoregional recurrence, and high distant metastasis rates. A precise diagnosis of ASC is required for estimating prognosis and undergoing close follow-up, even if the adenocarcinomatous component is limited to a small area in the lesion.

File： diagnostics-12-02398.pdf

DOI： 10.3390/diagnostics12102398

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Clinicopathologic factors influencing the screening accuracy of oral cytology: A retrospective cohort study Reviewed International journal

MASAMI KAWAHARADA, SATOSHI MARUYAMA, MANABU YAMAZAKI, TATSUYA ABÉ, NYEIN NYEIN CHAN, AKINORI FUNAYAMA, ATSUSHI UENOYAMA, TOSHIYUKI AKIMORI, KEI TOMIHARA, JUN-ICHI TANUMA

Oncology letters 24 ( 385 ) 385 - 385 2022.10

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Cytology is a simple and non-invasive screening method for oral cancer. However, this method is not yet routinely used by clinicians because of its high false negative rate (FNR) and due to lack of sufficient studies examining the factors for high FNRs. The present retrospective study aimed to compare the screening performance of conventional cytology (CC) and liquid-based cytology (LBC) through histological validation, and to elucidate factors inducing false negative screening in oral cytology. Cytological specimens with histological examination and intraoral digital images of the lesion were retrospectively collected between January 2017 and December 2018 for CC and between October 2019 and September 2021 for LBC. Oral cytological screening was conducted based on the oral Bethesda system for oral cytology. Clinical subtypes were re-evaluated using intraoral digital images. The screening accuracy of oral cytology was calculated considering the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting the malignant transformation of oral lesions. No statistically significant difference was noted in the inadequate rate between CC and LBC groups. For CC and LBC, the sensitivities were 60.9 and 59.2%, the specificities were 87.3 and 79.1%, the PPVs were 85.8 and 76.2%, and the NPVs were 63.9 and 63.2%, respectively. Thus, the screening accuracy was similar between methodologies. Among the clinicopathological factors investigated, histological diagnosis and cellularity contributed to false negative results. Homogeneous findings of oral epithelial dysplasia and the superficial growth of carcinoma in situ/squamous cell carcinoma resulted in false negative findings for CC and LBC. Furthermore, LBC samples with a lower cell number (<2,000 squamous cells) exhibited statistically significantly increased FNRs. The present study found that the cytological methods did not affect the inadequate rate and screening accuracy, whereas clinical subtype and cellularity decreased screening accuracy. Therefore, cytological screening and subsequent follow-up should be performed while considering clinical findings and the cellularity of cytology smears.

File： ol_24_5_13505_PDF.pdf

DOI： 10.3892/ol.2022.13505

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Oral cytology can easily spot serious diseases Invited

Dental Outlook 140(3) ( 9 ) 500 - 508 2022.9

Metastasis of pulmonary adenocarcinoma to the oral cavity: A case report and literatures review of the last 30 years Reviewed

Masami Kawaharada, Satoshi Maruyama, Tatsuya Abé, Takafumi Hayashi, Tadaharu Kobayashi, Jun‐ichi Tanuma

Oral Science International 1 - 6 2022.9

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

File： Oral Science International - 2022 - Kawaharada - Metastasis of pulmonary adenocarcinoma to the oral cavity A case report.pdf

DOI： 10.1002/osi2.1130

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/osi2.1130

Rosai-Dorfman disease of the maxilla: A rare case report and literature review Reviewed

Takahiro Nagai, Manabu Yamazaki, Atsushi Nishikawa, Yasumitsu Kodama, Hideyoshi Nishiyama, Takafumi Hayashi, Jun-ichi Tanuma, Ritsuo Takagi, Kei Tomihara

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 34 ( 5 ) 665 - 671 2022.9

Novel cytological model for the identification of early oral cancer diagnostic markers: The carcinoma sequence model. Invited Reviewed International journal

Masami Kawaharada, Manabu Yamazaki, Satoshi Maruyama, Tatsuya AbÉ, Nyein Nyein Chan, Taiichi Kitano, Tadaharu Kobayashi, Takeyasu Maeda, Jun-Ichi Tanuma

Oncology letters 23 ( 3 ) 76 2022.3

Language：English Publishing type：Research paper (scientific journal)

Most oral squamous cell carcinomas (OSCCs) arise from a premalignant lesion, oral epithelial dysplasia; however, useful markers for the early detection of OSCC are lacking. The present study aimed to establish a novel experimental model to observe changes in the sequential expression patterns of mRNAs and proteins in a rat model of tongue cancer using liquid-based cytology techniques. Cytology specimens were collected at 2, 5, 8, 11, 14, 17 and 21 weeks from rats treated with 4-nitroquinoline 1-oxide to induce tongue cancer. The expression of candidate biomarkers was examined by performing immunocytochemistry and reverse transcription-quantitative PCR. The percentage of positively stained nuclei was calculated as the labeling index (LI). All rats developed OSCC of the tongue at 21 weeks. The mRNA expression levels of bromodomain protein 4 (Brd4), c-Myc and Tp53 were upregulated during the progression from negative for intraepithelial lesion or malignancy to squamous cell carcinoma (SCC). Brd4- and c-Myc-LI increased in low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion and SCC specimens. p53-LI was significantly increased in SCC specimens. This novel experimental model allowed the observation of sequential morphological changes and the expression patterns of mRNAs and proteins during carcinogenesis. Combining immunocytochemistry with cytology-based diagnoses may potentially improve the diagnostic accuracy of OSCC.

File： ol_23_3_13196_PDF.pdf

DOI： 10.3892/ol.2022.13196

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口腔上皮の反応異型と上皮内扁平上皮癌

田沼順一

病理と臨床 40 ( 3 ) 281 - 283 2022.3

Melanotic neuroectodermal tumor of infancy in the mandible: A case report. Reviewed International journal

Ryoko Takeuchi, Akinori Funayama, Yohei Oda, Tatsuya Abé, Manabu Yamazaki, Satoshi Maruyama, Takafumi Hayashi, Jun-Ichi Tanuma, Tadaharu Kobayashi

Medicine 100 ( 50 ) e28001 2021.12

Language：English Publishing type：Research paper (scientific journal)

RATIONALE: Melanocytic neuroectodermal tumor of infancy (MNTI) is a rare benign pigmented neoplasm that arises from the neural crest and has an aggressive growth pattern. It is predominantly seen in infants under 1 year of age, and the most common site of involvement is the maxilla. The currently accepted treatment is removal by surgical resection. Herein, we report a case of MNTI that involved the anterior alveolar ridge of the mandible in a 6-month-old infant. PATIENT CONCERNS: A case of a 6-month-old male child with a huge mass in the anterior alveolar ridge of the mandible. DIAGNOSIS: The tumor was diagnosed using histopathological and immunohistochemical techniques on the biopsy specimen obtained following incisional biopsy. Based on the findings, a final diagnosis of MNTI was established. INTERVENTIONS: Radical resection of the tumor was performed, after determining the extent of resection by referring to the mandibular 3D model created using the pre-operative CT data. OUTCOMES: The postoperative course was uneventful, and no recurrence has been observed to date for more than 4 years after surgery. LESSONS: This case emphasizes that early diagnosis and radical surgery are critical to the effective treatment, as MNTI exhibits rapid and destructive growth. It also requires careful and close follow-up because of high recurrence rates.

File： Melanotic_neuroectodermal_tumor_of_infancy_in_the.24.pdf

DOI： 10.1097/MD.0000000000028001

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Other iatrogenic immunodeficiency-associated lymphoproliferative disorders in the oral cavity: a clinicopathologic study of 4 cases and literature review Reviewed

Masami Kawaharada, Satoshi Maruyama, Tatsuya Abé, Manabu Yamazaki, Akira Kurokawa, Wataru Katagiri, Ritsuo Takagi, Takafumi Hayashi, Tadaharu Kobayashi, Jun-ichi Tanuma

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 132 ( 6 ) 687 - 697 2021.12

Crosstalk between oral squamous cell carcinoma cells and cancer-associated fibroblasts via the TGF-β/SOX9 axis in cancer progression Reviewed International journal

Kenta Haga, Manabu Yamazaki, Satoshi Maruyama, Masami Kawaharada, Ayako Suzuki, Emi Hoshikawa, Nyein Nyein Chan, Akinori Funayama, Toshihiko Mikami, Tadaharu Kobayashi, Kenji Izumi, Jun-ichi Tanuma

Translational Oncology 14 ( 12 ) 101236 - 101236 2021.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

Cancer-associated fibroblasts (CAFs) have important roles in promoting cancer development and progression. We previously reported that high expression of sex-determining region Y (SRY)-box9 (SOX9) in oral squamous cell carcinoma (OSCC) cells was positively correlated with poor prognosis. This study developed three-dimensional (3D) in vitro models co-cultured with OSCC cells and CAFs to examine CAF-mediated cancer migration and invasion in vitro and in vivo. Moreover, we performed an immunohistochemical analysis of alpha-smooth muscle actin and SOX9 expression in surgical specimens from 65 OSCC patients. The results indicated that CAFs promote cancer migration and invasion in migration assays and 3D in vitro models. The invading OSCC cells exhibited significant SOX9 expression and changes in the expression of epithelial-mesenchymal transition (EMT) markers, suggesting that SOX9 promotes EMT. TGF-β1 signalling inhibition reduced SOX9 expression and cancer invasion in vitro and in vivo, indicating that TGF-β1-mediated invasion is dependent on SOX9. In surgical specimens, the presence of CAFs was correlated with SOX9 expression in the invasive cancer nests and had a significant impact on regional recurrence. These findings demonstrate that CAFs promote cancer migration and invasion via the TGF-β/SOX9 axis.

File： 1-s2.0-S193652332100228X-main.pdf

DOI： 10.1016/j.tranon.2021.101236

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Response to Letter to the Editor “Ectomesenchymal chondromyxoid tumour on the lateral border of the tongue: some historical and clinical considerations”

K. Sakurai, K. Nakamori, M. Yamazaki, J.-i. Tanuma

International Journal of Oral and Maxillofacial Surgery 2021.10

Spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis: a case report. International journal

Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abé, Yoshimasa Sumita, Yuji Katsumi, Yutaka Nikkuni, Takafumi Hayashi, Jun-Ichi Tanuma

Journal of medical case reports 15 ( 1 ) 438 - 438 2021.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Spindle cell squamous cell carcinoma is an uncommon variant of squamous cell carcinoma; its diagnosis is sometimes challenging because it histopathologically resembles neoplastic or reactive spindle cell lesions of mesenchymal origins. Here, we report a rare case of spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis. CASE PRESENTATION: A 69-year-old Japanese man presented with pain and a polypoid mass on the lower left gingiva. He had received chemoradiotherapy for squamous cell carcinoma of the buccal mucosa 15 years prior to this consultation. In addition, he was treated for mandibular osteonecrosis 6 years after chemoradiotherapy without evidence of cancer recurrence. A biopsy revealed atypical spindle or pleomorphic cells scattered in the edematous and fibrin-rich stroma; however, no malignant squamous components were apparent. These atypical cells frequently contained neutrophils within their cytoplasm that formed cell-in-cell figures. Immunohistochemically, the atypical cells were negative for cytokeratins, epithelial membrane antigen, and E-cadherin, but positive for p63, vimentin, and p53. Although these findings suggested spindle cell squamous cell carcinoma, it was difficult to reach a definitive diagnosis. Based on a clinical diagnosis of a malignant tumor, the patient underwent a hemimandibulectomy. The surgically resected specimen had a typical spindle cell squamous cell carcinoma histology consisting of biphasic spindle cells and conventional squamous cell carcinoma components. Moreover, the surgical specimen also exhibited spindle tumor cells that frequently included neutrophils, around which intense staining for lysosomal-associated membrane protein 1 and cathepsin B was observed. This suggested that the cell-in-cell figures represent active neutrophil phagocytosis by tumor cells, and not emperipolesis. CONCLUSION: The presence of neutrophil phagocytosis may be a potent indicator of malignancy.

File： s13256-021-03066-z.pdf

DOI： 10.1186/s13256-021-03066-z

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Central mucoepidermoid carcinoma arising directly from a glandular odontogenic cyst of the mandible: a case report. Reviewed International journal

Satoshi Maruyama, Taisuke Mori, Manabu Yamazaki, Tatsuya Abé, Eijitsu Ryo, Hiroyuki Kano, Go Hasegawa, Jun-Ichi Tanuma

Diagnostic pathology 16 ( 1 ) 61 - 61 2021.7

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Central mucoepidermoid carcinoma (MEC) is a rare salivary gland tumor that affects the jawbone. Glandular odontogenic cyst (GOC) is also a rare odontogenic developmental cyst with glandular differentiation. GOC shares some histological features with central MEC, and a pre-existing GOC can develop into central MEC. Here, we present a rare case of central MEC developed directly from a pre-existing GOC of the mandible. CASE PRESENTATION: A 67-year-old Japanese man presented with a cystic lesion in the right third molar region. Histologically, the biopsy specimen demonstrated both typical findings of a GOC component lined with non-keratinized squamous epithelium and a recognizable component of central MEC consisting of polycystic nests with mucous cells, intermediate cells, and epidermoid cells in the cyst wall. The results from the immunohistochemistry for cytokeratin (CK) profiling demonstrated that, while both central MEC and GOC expressed CKs 7, 14, 18, and 19, CK13 was interestingly exclusively expressed in GOC. Fluorescence in-situ hybridization (FISH) revealed the rearrangement of the Mastermind like (MAML)-2 gene in both the MEC and GOC components. CONCLUSIONS: Our case suggests that central MEC and GOC may be in the same spectrum of diseases caused by the rearrangement of the MAML-2 gene. However, given that the expression profile of CK13 was completely different between central MEC and GOC, they can be considered as separate tumors. Overall, we demonstrated a rare case in which central MEC may have originated directly from the GOC.

File： maruyama.pdf

DOI： 10.1186/s13000-021-01124-0

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A comparative study between CT, MRI, and intraoral US for the evaluation of the depth of invasion in early stage (T1/T2) tongue squamous cell carcinoma Reviewed

Masaki Takamura, Taichi Kobayashi, Yutaka Nikkuni, Kouji Katsura, Manabu Yamazaki, Satoshi Maruyama, Jun-ichi Tanuma, Takafumi Hayashi

Oral Radiology 38 ( 1 ) 114 - 125 2021.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

<title>Abstract</title><sec>
<title>Objectives</title>
This study aimed to clarify the accuracy of intraoral ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) in preoperative image depth of invasion (DOI) measurement of T1/T2 tongue cancer through comparison with histopathological measurements.

</sec><sec>
<title>Methods</title>
Imaging of the primary lesions was performed at our hospital; the lesions were classified into T1 and T2 based on the 8th edition of the AJCC/UICC, and surgery performed. There was histopathological confirmation of lesions as squamous cell carcinoma in 48 patients with tongue cancer. T3 and T4 cases, cases in which preoperative chemotherapy and radiation therapy were performed, and cases where biopsy was performed before imaging were excluded. The radiological DOI in US, CT, and MRI and the histopathological DOI as base were comparatively investigated and statistical analyses were performed by Bland–Altman analysis and Spearman's rank correlation coefficient.

</sec><sec>
<title>Results</title>
Bland–Altman analysis showed that the US radiological DOI was overestimated by an average of 0.2 mm compared to the histopathological DOI, while CT and MRI radiological DOI were overestimated by an average of 2–3 mm. The comparison of CT and MRI revealed that the difference between the MRI and histopathological DOI, as well as the 95% limit of agreement, were smaller than those of the CT radiological DOI.

</sec><sec>
<title>Conclusions</title>
US is the most accurate preoperative diagnostic tool for T1 and T2 squamous cell carcinoma; CT and MRI tend to have an overestimation of about 2–3 mm and so caution is required.

</sec>

File： Takamura2021_Article_AComparativeStudyBetweenCTMRIA.pdf

DOI： 10.1007/s11282-021-00533-7

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Other Link： https://link.springer.com/article/10.1007/s11282-021-00533-7/fulltext.html

Identification and characterization of R2TP in the development of oral squamous cell carcinoma. International journal

Tetsuo Kiguchi, Yoshito Kakihara, Manabu Yamazaki, Kouji Katsura, Kenji Izumi, Jun-Ichi Tanuma, Takashi Saku, Ritsuo Takagi, Makio Saeki

Biochemical and biophysical research communications 548 161 - 166 2021.4

Language：English Publishing type：Research paper (scientific journal)

R2TP is a well-conserved molecular chaperone complex, composed of Pontin, Reptin, RPAP3, and PIH1D, in eukaryotes. Recent studies have suggested an involvement of R2TP in cancer development. However, it remains unclear if it is related to the development of oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer. Here, we identify and investigate the function of R2TP in OSCC development. Immunohistochemical analysis reveals that all of the R2TP components are strongly expressed in normal oral epithelia and OSCC tissues, where actively proliferating cells are abundant. Co-immunoprecipitation assay identifies that R2TP components form a protein complex in OSCC-derived HSC4-cells. Knockdown experiments show that all R2TP components, except for RPAP3, are required for the cell proliferation and migration of HSC-4 cells. Furthermore, we reveal that Pontin contributes to a gain-of-function (GOF) activity of mutp53-R248Q in HSC-4 cells by regulating phosphorylation levels of mutp53 at Ser15 and Ser46. To our knowledge, this study is the first to report the functional involvement of R2TP and its components in the malignant characteristics of OSCC cells.

DOI： 10.1016/j.bbrc.2021.02.074

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Bethesda system for oral cytology：differentiation points for NILM, LSIL, HSIL and SCC Invited Reviewed

Jun-ichi Tanuma

38 ( 2 ) 136 - 145 2021.4

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