The molecular mechanism controlling expression profile of keratin molecules in oral mucosal malignancies

2009 Fiscal Year Final Research Report

• Project/Area Number: 20791372
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Niigata University
• Principal Investigator: TAKANORI Takanori Niigata University, 医歯学総合病院, 医員 (00464016)
• Project Period (FY): 2008 – 2009
• Keywords: 実験腫瘍学

Research Abstract

It is still difficult to distinguish epithelial dysplasia and carcinoma in situ (CIS) of oral mucosa histopathologically. To make reproducible diagnoses for CIS, combined immunohistochemistry directed at the positioning of squamous cell proliferation (Ki-67) and differentiation (keratin (K) 13 and K19) was used, both of which support histological evaluations by providing biological evidence. Normal/hyperplastic epithelia was defined by K19+ cells only in the first basal layer, K13+ cells in the third basal and upper layers, and sporadic Ki-67+ cells in the second basal layer. These profiles indicated that a proliferating center of the oral epithelium is located in the parabasal cell layer, and K19 and K13 can be regarded as markers for basal and prickle cells, respectively. Epithelial dysplasia was characterized by irregular stratification of Ki-67+ cells and the absence of K19/K13 in proliferating cells. Irregular emerging of K19+ and K13+ cells in proliferating foci with unique stratification of atypical Ki-67+ cells indicated CIS. When the definition was applied, surgical margins in 172 recurrent cases were shown to contain CIS and squamous cell carcinoma, indicating that the new diagnostic criteria for CIS reflected clinical behaviors of the cases. The results indicate that oral CIS contain more histological variations, especially those with definite keratinization, than what had been previously defined. Moreover, the mucosal lesions with the orthohyperkeratotic dysplasia (OKD) reached about 30 % in recurrence, and more than 50% in multiple cases, respectively. This result indicated that OKD was significant for a background lesion of the malignant transformation, and the presence of the OKD was effective as a prognostication factor.

Research Products

• [Journal Article] Histopathological varieties of oral carcinoma in situ: Diagnosis aided by immunohistochemistry dealing with the second basal cell layer as the proliferating center of oral mucosal epithelia (2010)
  • Author(s): Kobayashi T, Maruyama S, Cheng J, Ida-Yonemochi H, Yagi M, Takagi R, Saku T
  • Journal Title: Pathology International 60 Pages: 156-166
  • Peer Reviewed
• [Journal Article] The absence of significant mutational events of the p53 gene in the only two salivary gland tumors possessing radiation-related development risks, Mucoepidermoid carcinoma and Warthin tumor (2009)
  • Author(s): Abe M, Maruyama S, Yamazaki M, Kobayashi T, Al-Eryani K, Shahidul AM, Tsuneki M, Syafriadi M, Saku T, Cheng J
  • Journal Title: Oral Medicine & Pathology 13 Pages: 151-158
  • Peer Reviewed
• [Journal Article] Nerve sheath myxoma of the tongue: report of a case and review of the literature (2009)
  • Author(s): Al-Eryani K, Sawair FA, Maruyama S, Watanabe M, Kawahara R, Yokobayashi T, Kobayashi T, Kundu S, Syafriadi M, Cheng J, Saku T
  • Journal Title: Oral Medicine & Pathology 13 Pages: 105-110
  • Peer Reviewed
• [Journal Article] Tetraspanin gene expression levels as potential biomarkers for malignancy of gingival squamous cell carcinoma (2009)
  • Author(s): Hirano C, Nagata M, Noman AA, Kitamura N, Ohnishi M, Ohyama T, Kobayashi T, Suzuki K, Yoshizawa M, Izumi N, Fujita H, Takagi R
  • Journal Title: International Journal of Cancer 124(12) Pages: 2911-2916
  • Peer Reviewed
• [Journal Article] Matrix meralloproteinase 7 and perlecan in oral epithelial dysplasia and carcinoma in situ: an aid for histopathologic recognition of their cell proliferation centers (2009)
  • Author(s): Tilakaratne WM, Kobayashi T, Ida-Yonemochi H, Swelam W, Yamazaki M, Mikami T, Alvarado CG, Shahidul AM, Maruyama S, Cheng J, Saku T
  • Journal Title: Journal of Oral pathology & Medicine 38 Pages: 348-355
  • Peer Reviewed
• [Journal Article] 顎骨骨折患者の長期臨床統計-過去32年間について- (2009)
  • Author(s): 小山貴寛、飯田明彦, 児玉泰光, 小林孝憲, 福田純一, 高木律男
  • Journal Title: 新潟歯学会雑誌 39 Pages: 49-54
  • Peer Reviewed
• [Journal Article] Diagnostic value of ITGA3, ITGB4 and ITGB5 expression levels for the clinical outcome of tongue squamous cell carcinoma (2008)
  • Author(s): Kurokawa A, Nagata M, Kitamura N, Noman AA, Ohnishi M, Ohyama T, Kobayashi T, Shingaki S, Takagi R
  • Journal Title: Cancer 112 Pages: 282-285
  • Peer Reviewed
• [Journal Article] Lateral periodontal cyst: a clinicopathological study of 23 cases and an immunohistochemical analysis of its characteristic epithelial plaque in the lining (2008)
  • Author(s): Tsuneki M, Cheng J, Yamazaki M, Maruyama S, Kobayashi T, Ida-Yonemochi H, Suzuki M, Saku T
  • Journal Title: Oral Medicine & Pathology 12(3) Pages: 89-96
  • Peer Reviewed
• [Presentation] 下顎腫瘍 (2009)
  • Author(s): 小林孝憲
  • Organizer: 第20回日本臨床口腔病理学会
  • Place of Presentation: 札幌市
  • Year and Date: 20090729-20090731
• [Presentation] 口唇腫瘍 (2009)
  • Author(s): 小林孝憲
  • Organizer: 第68回日本病理学会東北支部学術集会
  • Place of Presentation: 仙台市
  • Year and Date: 20090214-20090215
• [Presentation] 正角化型異型上皮:新しい診断概念の確立とその意義 (2008)
  • Author(s): 小林孝憲
  • Organizer: 第19回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 東京
  • Year and Date: 20080820-20080822
• [Presentation] Central carcinoma associated with odontogenic cysts (2008)
  • Author(s): Kobayashi T
  • Organizer: The 14th International Congress of Oral Pathology and Medicine
  • Place of Presentation: San Francisco
  • Year and Date: 20080621-20080626
• [Presentation] 口腔粘膜扁平上皮癌・上皮内癌の再発に関する臨床病理学的検討 (2008)
  • Author(s): 小林孝憲
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢市
  • Year and Date: 20080515-20080517