Faculty Profiles - TANUMA Junichi

Papers - TANUMA Junichi

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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

Low-grade myofibroblastic sarcoma of the tongue with difficulty of diagnosis: a case report and review of the literature. Reviewed

Kawaharada M, Katagiri W, Maruyama S, Nishiyama H, Hayashi T, Kobayashi T, Tanuma J

Journal of Oral and Maxillofacial Surgery, Medicine and Pathology 33 ( 1 ) 93 - 97 2021.1

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

We describe a case of low-grade myofibroblastic sarcoma (LGMS) on the dorsum of the tongue. A 41-year-old Japanese man noticed that a mass on the dorsal surface of the tongue had been present for 8 months. Computed tomography showed a homogeneously enhancing mass measuring 16 x 14 mm in the midline of the tongue. Magnetic resonance imaging showed a homogeneously enhancing mass with an almost clear margin on post-contrast T1-weighted imaging. The lesion was homogeneous with high signal intensity on T2-weighted imaging. The patient underwent excisional biopsy. Histologically, the tumor had an indistinct margin and was composed of spindle-shaped cells arranged in cellular fascicles. The cell nuclei showed signs of mild atypia. Positive staining for desmin and less strong staining for a-smooth muscle actin revealed that the tumor cells were myofibroblasts or smooth muscle cells. The tumor cells were negative for h-caldesmon. The MIB-1 labeling index of the tumor was 4.9 %. Thus, based on the histopathological, immunohistochemical and imaging findings, the tumor was finally diagnosed as LGMS. We reviewed the literature on the immunohistochemistry of LGMS. We suggest that immunohistochemistry is helpful in the differential diagnosis of LGMS.

File： kawaharada.pdf

DOI： 10.1016/j.ajoms.2020.07.011

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Corrigendum to “An ectomesenchymal chondromyxoid tumour on the lateral border of the tongue” [Int J Oral Maxillofac Surg 49 (2020) 1290–1203] (International Journal of Oral … Maxillofacial Surgery (2020) 49(10) (1290–1293), (S0901502720301399), (10.1016/j.ijom.2020.04.010))

K. Sakurai, K. Nakamori, M. Yamazaki, J. I. Tanuma

International Journal of Oral and Maxillofacial Surgery 2021

Language：English Publishing type：Research paper (scientific journal) Publisher：Churchill Livingstone

The authors regret that although we stated “four cases with lesions involving the floor of the mouth and two with lesions involving the hard palate have been reported”, none actually involved the oral floor. We erroneously called the base of the tongue as the floor of the mouth. Therefore, we would like to correct this to “four cases with lesions involving the base of the tongue and two with lesions involving the hard palate have been reported”. The authors would like to apologise for any inconvenience caused.

DOI： 10.1016/j.ijom.2021.05.021

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口腔細胞診のベセスダシステムとLBC法の標本作製 Invited

田沼順一

細胞検査士会報 68 ( 1 ) 3 - 7 2020.12

17年を経過して再減量手術を行った上顎骨線維性異形成症の1例

伊藤元貴, 児玉泰光, 大貫尚志, 高村真貴, 林孝文, 阿部達也, 田沼順一, 小林正治, 高木律男

新潟歯学会雑誌 50 ( 2 ) 79 - 85 2020.12

Language：Japanese Publisher：新潟歯学会

線維性異形成症(FD)は正常な骨組織が線維性結合組織で置換され増殖することを特徴とする非腫瘍性骨病変である。骨格成長後にはFDの増殖が静止するとされているが、成人期でも増大をきたすことがある。今回、上顎骨FDの減量手術後再増大をきたし、再び減量手術が必要となった症例を経験したので報告する。患者は42歳の男性。25歳の時に上顎骨FDの減量手術を施行されるも受診が途絶え、再増大による顔面非対称をきたしたため17年後に当科初診となった。顔面非対称改善と病変増大による機能障害の予防のため、右側上顎骨頬側と口蓋側の2回に分けて減量手術を行った。削除量の目安としてCT画像から3次元実体モデルを利用してサージカルガイドを制作し、術中の対称性確認と手術時間の短縮を行った。術後3年経過した現在、明らかな再増大はない。今回もあくまで減量手術であり、病巣の残遺に伴う病態変化の可能性についての患者教育とともに長期の経過管理が重要と考えられた。(著者抄録)

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Frequent Germline and Somatic Single Nucleotide Variants in the Promoter Region of the Ribosomal RNA Gene in Japanese Lung Adenocarcinoma Patients Reviewed International journal

Riuko Ohashi, Hajime Umezu, Ayako Sato, Tatsuya Abé, Shuhei Kondo, Kenji Daigo, Seijiro Sato, Norikazu Hara, Akinori Miyashita, Takeshi Ikeuchi, Teiichi Motoyama, Masashi Kishi, Tadahiro Nagaoka, Keiko Horiuchi, Atsushi Shiga, Shujiro Okuda, Tomoki Sekiya, Aya Ohtsubo, Kosuke Ichikawa, Hiroshi Kagamu, Toshiaki Kikuchi, Satoshi Watanabe, Jun-Ichi Tanuma, Peter Schraml, Takao Hamakubo, Masanori Tsuchida, Yoichi Ajioka

Cells 9 ( 11 ) 2409 - 2409 2020.11

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

Ribosomal RNA (rRNA), the most abundant non-coding RNA species, is a major component of the ribosome. Impaired ribosome biogenesis causes the dysfunction of protein synthesis and diseases called “ribosomopathies,” including genetic disorders with cancer risk. However, the potential role of rRNA gene (rDNA) alterations in cancer is unknown. We investigated germline and somatic single-nucleotide variants (SNVs) in the rDNA promoter region (positions −248 to +100, relative to the transcription start site) in 82 lung adenocarcinomas (LUAC). Twenty-nine tumors (35.4%) carried germline SNVs, and eight tumors (9.8%) harbored somatic SNVs. Interestingly, the presence of germline SNVs between positions +1 and +100 (n = 12; 14.6%) was associated with significantly shorter recurrence-free survival (RFS) and overall survival (OS) by univariate analysis (p < 0.05, respectively), and was an independent prognostic factor for RFS and OS by multivariate analysis. LUAC cell line PC9, carrying rDNA promoter SNV at position +49, showed significantly higher ribosome biogenesis than H1650 cells without SNV. Upon nucleolar stress induced by actinomycin D, PC9 retained significantly higher ribosome biogenesis than H1650. These results highlight the possible functional role of SNVs at specific sites of the rDNA promoter region in ribosome biogenesis, the progression of LUAC, and their potential prognostic value.

File： cells-09-02409-v2.pdf

DOI： 10.3390/cells9112409

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前舌腺に発生した腺癌NOSの1例

三上俊彦, 船山昭典, 西山秀昌, 山崎学, 田沼順一, 小林正治

日本口腔外科学会雑誌 66 ( 11 ) 553 - 558 2020.11

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

52歳女。舌の違和感を主訴に近医を受診し、右側舌腫瘍を指摘された。他院のMRIで腫瘍性病変を認められ、当科での加療を勧められて来院した。右側舌下面粘膜下に15×15×15mm大の比較的境界明瞭な弾性硬の腫瘤を認めた。画像所見からは腺系腫瘍が示唆され、良悪性を含めた病理組織学的診断目的に生検を行ったが、組織型の確定には至らず、舌癌の診断のもと全身麻酔下に舌部分切除術を施行した。切除標本の病理組織所見は、淡明細胞の胞巣状増殖が主体ながら、粘液産生を示す二相性腺管がわずかに混在していたことから、鑑別疾患として筋上皮癌、上皮筋上皮癌、多型腺癌、明細胞癌が挙げられた。免疫染色によって筋上皮癌、上皮筋上皮癌、多型腺癌は否定され、EWSR1遺伝子のFISH解析によって明細胞癌も否定されたため腺癌NOS(not otherwise specified)と診断した。術後4年の現在まで再発・転移は認めていない。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01073&link_issn=&doc_id=20201130470003&doc_link_id=10.5794%2Fjjoms.66.553&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.66.553&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Rac1-dependent phagocytosis of apoptotic cells by oral squamous cell carcinoma cells: A possible driving force for tumor progression. Reviewed International journal

Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abé, Masayuki Tsuneki, Hiroko Kato, Kenji Izumi, Jun-Ichi Tanuma, Jun Cheng, Takashi Saku

Experimental cell research 392 ( 1 ) 112013 - 112013 2020.7

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

Apoptotic cell death frequently occurs in human cancer tissues including oral squamous cell carcinoma (SCC), wherein apoptotic tumor cells are phagocytosed not only by macrophages but also by neighboring tumor cells. We previously reported that the engulfment of apoptotic SCC cells by neighboring SCC cells frequently occurs at the invading front. Therefore, we hypothesized that the phagocytosis of these apoptotic cells by tumor cells contributes to disease progression. Herein, using cultured oral SCC cells, we aimed to confirm whether tumor cells actually phagocytose apoptotic cells and to examine whether cellular activities are regulated by the phagocytosis of apoptotic cells. Co-culture experiments showed that living cells could ingest apoptotic cells into phagolysosomes. NSC23766, an inhibitor of Rac1, which is a key regulator of phagocytic cup formation in professional phagocytes, dramatically suppressed the phagocytosis of apoptotic cells by living cells. Additionally, cell migration and the secretion of DKK1, a tumor-promoting protein, were enhanced by co-culture with apoptotic cells, whereas NSC23766 inhibited these effects. These results show that tumor cells can actively phagocytose apoptotic neighbors in a Rac1-dependent manner and that such activity increases their migration. The regulation of apoptotic cell phagocytosis thus represents new directions for therapeutic intervention for oral cancer.

File： 1-s2.0-S0014482720302354-main.pdf

DOI： 10.1016/j.yexcr.2020.112013

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An ectomesenchymal chondromyxoid tumour on the lateral border of the tongue. Reviewed International journal

K Sakurai, K Nakamori, M Yamazaki, J-I Tanuma

International journal of oral and maxillofacial surgery 2020.5

Language：English

Ectomesenchymal chondromyxoid tumour (ECT) is an extremely rare intraoral mesenchymal tumour. Most of these tumours have been identified on the anterior aspect of the dorsal surface of the tongue. ECT is difficult to diagnose because of its rarity. We report a case of ECT arising on the lateral border of the tongue in a 67-year-old woman. The tumour, measuring 20 × 10 mm in size, was surgically removed. Histopathologically, the tumour was composed of small polygonal cells arranged in sheets, with a myxoid or hyalinized stroma. The tumour boundary was clear; however, the tumour showed a multinodular structure expanding along the tongue surface without obvious capsule. Careful examination revealed the tumour nodule to be spreading in a skip lesion-like fashion away from the main part of the tumour in the striated muscle layer. Although there was no evidence of recurrence at 18 months after the surgery, our observations suggest that surgery for ECT resection with a safety margin is more appropriate than enucleation.

File： 1-s2.0-S0901502720301399-main.pdf

DOI： 10.1016/j.ijom.2020.04.010

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The usefulness of oral LBC for oral disease-Fast, cheap, and accurate of oral cytology- Invited Reviewed

Jun-ichi Tanuma

Niigata Dental Journal 50 ( 1 ) 1 - 6 2020.1

Masseter muscle hypertrophy: A case report Reviewed

Masayuki Tsuneki, Satoshi Maruyama, Manabu Yamazaki, Kanae Niimi, Tadaharu Kobayashi, Hideyoshi Nishiyama, Takafumi Hayshi, Jun-ichi Tanuma

JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY 31 ( 6 ) 428 - 431 2019.12

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

Masseter muscle hypertrophy is defined as the unilateral or bilateral expansion of the masseter muscle, and little is known about its etiology. Here we report a case of masseter muscle hypertrophy in a female patient in her 20 s who complained of facial asymmetry. Because of the hemifacial overgrowth of the right-side maxillofacial region from birth, she was thought to have congenital hemifacial hyperplasia. After orthodontic treatment and osteotomy, the patient underwent debulking of the right masseter muscle. Histologically, the surgical specimens exhibited thick masseter muscle fibers arranged irregularly. Masseter muscle cells exhibited diameters in the range of 20-60 mu m.

File： 1-s2.0-S2212555819301905-main.pdf

DOI： 10.1016/j.ajoms.2019.08.005

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Cytoplasmic expression of SOX9 as a poor prognostic factor for oral squamous cell carcinoma. Reviewed International journal

Yoshimasa Sumita, Manabu Yamazaki, Satoshi Maruyama, Tatsuya Abé, Jun Cheng, Ritsuo Takagi, Jun-Ichi Tanuma

Oncology reports 40 ( 5 ) 2487 - 2496 2018.11

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

Transcription factor SRY‑box 9 (SOX9) is a key regulator of chondrocyte differentiation and sex determination, and it is also involved in the progression of various types of human cancer. However, its putative association with oral squamous cell carcinoma (OSCC) remains elusive. The aim of the present study was to investigate the expression profiles of SOX9 in various oral epithelial lesions, including OSCC. We performed immunohistochemical analysis of SOX9 expression in surgical specimens of OSCC, which simultaneously exhibited different grades of epithelial lesions, and analyzed the correlation between SOX9 expression and several clinicopathological factors. Moreover, we performed immunofluorescent staining, western blot analysis and real‑time reverse transcription‑polymerase chain reaction to assess SOX9 expression in OSCC HSC‑3 (a metastatic cell line) and HSC‑4 (a non‑metastatic cell line) cell lines. In surgical specimens, SOX9 expression was detected in the nuclei of proliferating cells in areas with epithelial dysplasia and carcinoma in situ, but not in areas with normal epithelia. Nuclear SOX9 expression was observed in most SCC cells. Notably, cytoplasmic SOX9 expression was confirmed only in some SCC cells; however, cytoplasmic SOX9 expression was significantly and positively correlated with poor clinical outcomes. Both protein and mRNA expression of SOX9 were significantly higher in the HSC‑3 cell line than that in the HSC‑4 line. Notably, however, only HSC‑3 cells exhibited cytoplasmic localization of SOX9 expression. Our findings indicate that SOX9 may be involved in the tumorigenesis and progression of OSCC. Furthermore, its cytoplasmic expression represents a potential predictive biomarker for tumor aggressiveness and OSCC prognosis.

File： 2018SOX9 oncology report.pdf

DOI： 10.3892/or.2018.6665

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A case of glandular odontogenic cyst arising in the maxillary premolar region. Reviewed

Tanaka S, Kaneko Y, Inagaki Y, Nagayama M, Tanuma J, Sumitomo S

Jpn. J. Oral Maxillofac. Surg 64 ( 10 ) 577 - 581 2018.10