Kazuo Shimozato

National Center for Geriatrics and Gerontology, Ōbu, Aichi-ken, Japan

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Publications (34)77.66 Total impact

  • Article: Genotypes of Candida albicans isolated from healthy individuals and their distribution in patients with oral candidiasis.
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    ABSTRACT: For the study of Candida albicans genotypes involved in development of candidiasis, Candida albicans isolates were collected from healthy volunteers and patients with oral candidiasis and genotyped on the basis of 25S rDNA and microsatellite polymorphisms. In the microsatellite analysis using two microsatellite markers (CDC3 and CAI), 63 healthy volunteer isolates were classified into 35 genotypes (allelic relations to CDC3 alleles 1:2/CAI alleles 1:2), among which genotypes II (115:119/23:23), III (115:123/18:27), and V (123:127/32:41) were found at frequencies of 12.7 %, 7.9 %, and 7.9 %, respectively. In 68 oral candidiasis isolates classified into 39 genotypes, genotypes II and III were identified in 4.4 % and 20.6 % of the isolates, respectively. The frequency of genotype III was higher in the candidiasis isolates than in the healthy isolates (p < 0.05). These results suggest that genotype III C. albicans assigned by CDC3/CAI is related to the development of oral candidiasis.
    Journal of Infection and Chemotherapy 06/2013; · 1.80 Impact Factor
  • Article: Effects of medullary lesions on conditional pacemaker activity of neonatal rat hypoglossal motoneurons in vitro.
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    ABSTRACT: N-methyl-D-aspartate (NMDA) has been demonstrated to induce rhythmic activity in various neurons, including hypoglossal motoneurons (XIIms) and converts them to conditional pacemakers. Using whole-cell patch clamp recording in a slice preparation from neonatal rats, we confirmed that some XIIms act as conditional pacemakers, with TTX-insensitivity and a burst period that is voltage-dependent during NMDA application. Other XIIms in this study only fired tonically with NMDA application. Effects of medullary structures on conditional pacemaker XIIms were assessed using lesioned preparations. As a result, NMDA-induced rhythm (NIR) in the XIIm was observed with ventral lesions (excluding inspiratory neurons) and with dorsal lesions (excluding the swallowing center located in the nucleus of the solitary tract). The NIR was also observed with lateral lesions, but with a significantly decreased burst period. These data suggest that NMDA receptor activation selects a subset of XIIms and changes them to pacemakers whose properties can be altered by their excitability. The data also demonstrate that structures fundamental to the NIR are located within the area near the XII nucleus, indicating that the NIR is distinct from inspiratory and swallowing activities. The lateral medulla is considered to be a source of modulation of the excitability of XIIms.
    Neuroscience Research 03/2013; · 2.25 Impact Factor
  • Article: Endoscopic-assisted resection of peripheral osteoma using piezosurgery.
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    ABSTRACT: Endoscopic-assisted surgery has gained widespread popularity as a minimally invasive procedure, particularly in the field of maxillofacial surgery. Because the surgical field around the mandibular angle is extremely narrow, the surrounding tissues may get caught in sharp rotary cutting instruments. In piezosurgery, bone tissues are selectively cut. This technique has various applications because minimal damage is caused by the rotary cutting instruments when they briefly come in contact with soft tissues. We report the case of a 33-year-old man who underwent resection of an osteoma in the region of the mandibular angle region via an intraoral approach. During surgery, the complete surgical field was within the view of the endoscope, thereby enabling the surgeon to easily resection the osteoma with the piezosurgery device. Considering that piezosurgery limits the extent of surgical invasion, this is an excellent low-risk technique that can be used in the field of maxillofacial surgery.
    Oral surgery, oral medicine, oral pathology and oral radiology. 01/2013; 115(1):e16-e20.
  • Article: Morphologic features of the mandibular ramus associated with increased surgical time and blood loss in sagittal split-ramus osteotomy.
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    ABSTRACT: To determine whether specific morphologic features of the mandibular ramus can predict increased surgical time and blood loss in sagittal split-ramus osteotomy (SSRO). The clinical and morphologic features of the mandibular ramus, obtained from computed tomographic images (n = 50), were analyzed to predict the surgical time, the time required for ablation of the medial mandibular ramus, and the time required for sectioning of the mandible in performing a modified Obwegeser SSRO. Significant factors associated with surgical time were an anterior border of the ramus at least 10.5 mm wide, a maximal length of the thickened ramus of at least 8.5 mm, and a distance from the mandibular incisor to the posterior border of the mandible of at least 97.5 mm. There were significant differences in blood loss between the 2 axial aspects of the medial ramus. The greater protrusion of the medial oblique ridge, thickened ramus, and longer distance from the mandibular incisors to the posterior border of the mandible may increase the surgical time and blood loss in patients undergoing classic SSRO. When planning or performing an SSRO, the morphologic features obtained from computed tomographic images may help surgeons gain a better understanding of the potential difficulties when the surgical site involves the medial aspect of the ascending ramus of the mandible.
    Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 01/2013; 71(1):e31-41. · 1.58 Impact Factor
  • Article: Clinicopathological Significance of MAML2 Gene Split in Mucoepidermoid Carcinoma.
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    ABSTRACT: CRTC1-MAML2 and CRTC3-MAML2 fusions have been associated with favorable clinicopathological features of mucoepidermoid carcinoma. However, significance of MAML2 gene split has not been fully clarified. Ninety-five mucoepidermoid carcinomas (paraffin-embedded materials) were analyzed for CRTC1-MAML2 and CRTC3-MAML2 fusions by the reverse transcription polymerase chain reaction (RT-PCR) and for the MAML2 gene split by fluorescence in situ hybridization (FISH). Quantitative RT-PCR for the CRTC1-MAML2 transcript was performed in selected cases. MLL gene involvement, which has been reported in some leukemia cases, was examined by FISH in fusion partner-unknown cases. CRTC1-MAML2 and CRTC3-MAML2 fusions were detected in 37 and six cases, respectively. The MAML2 gene split was detected in 62 cases, which included all CRTC1/3-MAML2 fusion-positive cases. The level of CRTC1-MAML2 transcript expression was highly variable, and its clinicopathological impact was unclear. The MLL gene split was not detected. Mucoepidermoid carcinomas negative for CRTC1/3-MAML2 and positive for the MAML2 gene split (n=19) showed favorable clinicopathological tumor features similar to those positive for CRTC1/3-MAML2 fusions. As compared with negative cases (n=33), mucoepidermoid carcinomas positive for the MAML2 split (n=62) showed a lower patients' age, a mild female predilection, a smaller tumor size, less frequent nodal metastasis, a lower clinical stage, a lower histological grade, and a longer overall and disease-free survival. The MAML2 gene split emerged as an independent prognostic factor for both overall and disease-free survival in multivariate prognostic analysis. The presence of the MAML2 gene split defines a distinct mucoepidermoid carcinoma subset that is associated clinicopathologically with favorable tumor features.
    Cancer Science 10/2012; · 3.33 Impact Factor
  • Article: Factors predictive of pterygoid process fractures after pterygomaxillary separation without using an osteotome in Le Fort I osteotomy.
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    ABSTRACT: OBJECTIVE: This study demonstrated pterygomaxillary disjunction patterns and elucidated factors related to unfavorable pterygomaxillary junction fractures in Le Fort I osteotomy without using an osteotome. STUDY DESIGN: Clinical and anatomical data obtained from computed tomography images (100 sides) were analyzed for their ability to predict patterns of pterygomaxillary disjunction. RESULTS: Separation of the pterygomaxillary junction was most frequently performed at the maxillary tuberosity (48.0%). Twenty-eight pterygoid plates were fractured. Male gender, increased age, thickness of the pterygomaxillary junction, and length of the maxillary tuberosity were significant risk factors for pterygoid process fractures. We also identified that a pterygomaxillary junction thickness less than 2.6 mm and a maxillary tuberosity length of more than 11.5 mm indicated a statistically significant risk of pterygoid process fractures. CONCLUSIONS: Prediction of frangible pterygoid plates by preoperative quantitative evaluation of morphometric values provides useful information for selecting safe procedures.
    Oral surgery, oral medicine, oral pathology and oral radiology. 08/2012;
  • Article: Magnetic resonance imaging assessment of tumorous lesions in the floor of the mouth: case reports and review of the literature
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    ABSTRACT: ObjectivesMagnetic resonance (MR) imaging may provide some information as to the extent and tissue characteristics of a cancerous mass, but the imaging features of lesions in the floor of the mouth have not been sufficiently clarified. MR imaging features of tumescent lesions in this region were characterized, and the differential diagnoses are discussed. MethodsMR images of 12 patients with tumescent lesions in the floor of the mouth (three patients with squamous cell carcinoma, two with adenoid cystic carcinoma, one with hemangioma, one with schwannoma, one with lipoma, and four with ranula) were reviewed. The literature on the imaging features of tumescent disease in the floor of the mouth was searched using the Medline database. ResultsSix types of tumescent lesions in the floor of the mouth are presented. The differential diagnosis through a review of the references is discussed. Malignant tumors were demonstrated as ill-defined masses. MR images were good at showing the internal structures, such as fluid, hemorrhage, fat, nerves, calculus (phlebolith), cholesterol, and keratin, as different signal intensities. Therefore, MR images gave clues for the differential diagnosis. ConclusionMR images presented the distinctive features or the extent of the lesions and were therefore considered useful for a more accurate diagnosis prior to treatment.
    Oral Radiology 04/2012; 22(1):18-26. · 0.27 Impact Factor
  • Article: Computed tomographic anatomy of the mandibular first and second molars and their surrounding structures in the spread of odontogenic infection
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    ABSTRACT: ObjectivesThe purposes of this study were to analyze the CT anatomy of the mandibular first and second molars in uninfected subjects and to clarify the pathway of odontogenic infection originating from the mandibular first and second molars. MethodsCT anatomies, especially for bucco-lingual aspects and the surrounding soft tissues, were investigated in 100 uninfected subjects and 17 infected patients. ResultsAt the level of bifurcation, disappearance of the cortical plates was frequently observed on the buccal and lingual sides of the first molars, and it was reduced on the buccal side in the second molar. In the first molar, the bony width was thinner on the buccal than the lingual side. The lingual cortices were thinner in the second molar. All medial pterygoid and 88% of masseter muscles were situated posteriorly, without horizontally overlapping the second molar, whereas the mylohyoid muscle (MhM) overlapped horizontally with the first and second molars. The MhM was positioned superior to the root apices in 10 and 39% of first and second molars, respectively. All patients with first molar infection showed involvement of buccal structures, and one showed lingual side involvement. In contrast, six of nine patients with second molar infection showed involvement on the lingual side. ConclusionsInfection originating from the second molar was more likely to spread to the lingual side than infection originating from the first molar. CT anatomy surrounding the causal teeth supported the spread pathways of mandibular first and second molar infection.
    Oral Radiology 04/2012; 25(2):99-107. · 0.27 Impact Factor
  • Article: CT analyses of the location of the maxillary third molar in relation to panoramic radiographic appearance
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    ABSTRACT: ObjectiveWe compared the relationship between anatomical structures analyzed by panoramic radiographs and CT images of uninfected impacted maxillary third molars and investigated the pathway of infection originating from pericoronitis of maxillary third molars. MethodsPatients (n=62) with uninfected impacted maxillary third molars and patients (n=8) with odontogenic infection originating from pericoronitis of the maxillary third molars were selected from an image database. CT and panoramic images were evaluated separately by an oral surgeon and a radiologist for the vertical position of the tooth, the presence of bone around the crown, proximity to the maxillary sinus, visibility of masticatory muscles, and mesiodistal and buccopalatal inclinations. ResultsIn uninfected patients, a significant correlation was observed between the vertical positions evaluated by the two methods. Of the third molars, 79 (63.7%) were identified as vertical type on both panoramic and CT images. Regarding the maxillary sinus, of the 19molars classified as the separate type on panoramic images, 2 (10.5%) were identified as the close type on CT. CT examination revealed the involvement of buccal cortical plates and the buccal space in the majority of infected patients. ConclusionsCT images revealed that 94molars (75.8%) showed vertical type on the buccopalatal inclination and that 45 impacted molars (36.3%) showed bone defects in the buccal area. Infections originating from pericoronitis of the maxillary third molar showed involvement of the buccal cortical plates, the buccal space, and other spaces, which were clearly depicted on CT images.
    Oral Radiology 04/2012; 25(2):108-117. · 0.27 Impact Factor
  • Article: Computer-based videofluorographic analysis of posterior pharyngeal wall movement during swallowing in patients with head-and-neck cancer
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    ABSTRACT: ObjectivesWe sought to develop a method for evaluating dysphagia using videofluorography (VF) by analyzing the time course of changes in pharyngeal wall movement and to assess patients with head-and-neck cancer before and after surgery. MethodsThe subjects were 14 patients diagnosed with head-and-neck cancer. We obtained VF images before and after surgery and analyzed them with two-dimensional video measurement software. Then, we calculated dysfunction scores based on the remaining or aspiration amount of sample by interpreting the VF images. ResultsWe found dysmotility of the posterior pharyngeal wall in some postoperative cases. Inter- and intrarater reproducibility was high in the evaluation of posterior pharyngeal wall movements. A significant difference was found in the scores between the patients showing dysmotility of the posterior pharyngeal wall and no dysmotility. ConclusionsWe developed a reproducible method for evaluating movements of the posterior pharyngeal wall during swallowing using VF. This may become a useful tool for objectively evaluating VF data.
    Oral Radiology 04/2012; 25(2):123-128. · 0.27 Impact Factor
  • Article: Impact of CRTC1/3-MAML2 fusions on histological classification and prognosis of mucoepidermoid carcinoma.
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    ABSTRACT: The aim of study was to evaluate the impact of CRTC1-MAML2 and CRTC3-MAML2 fusions on the histological classification of mucoepidermoid carcinoma (MEC) of the salivary glands and on the prognosis of patients. MEC cases (n = 111) were screened for CRTC1-MAML2 and CRTC3-MAML2 fusions by reverse transcription polymerase chain reaction. We developed a system of 'molecular Armed Forces Institute of Pathology (AFIP) classification' that combined the AFIP histological classification proposed by Goode et al. and the presence of CRTC1-MAML2 or CRTC3-MAML2 fusions. MEC cases positive for CRTC1-MAML2 or CRTC3-MAML2 fusion formed a favourable tumour subset that was distinct from fusion-negative cases. When positive for the fusions, 'high-risk' patients, including those with a higher histological grade or an advanced clinical stage, showed an excellent prognosis. For overall survival, 'molecular AFIP classification' was selected as a powerful independent prognostic factor (P=0.0038), as was the clinical stage (P =0.0032). For disease-free survival, 'molecular AFIP classification' was also selected as an independent prognostic factor (P = 0.0006). Molecular AFIP classification may be useful in predicting the prognosis of patients with MEC.
    Histopathology 06/2011; 59(1):90-7. · 3.08 Impact Factor
  • Article: Impact of CRTC1/3–MAML2 fusions on histological classification and prognosis of mucoepidermoid carcinoma
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    ABSTRACT: Okumura Y, Miyabe S, Nakayama T, Fujiyoshi Y, Hattori H, Shimozato K & Inagaki H (2011) Histopathology59, 90–97Impact of CRTC1/3–MAML2 fusions on histological classification and prognosis of mucoepidermoid carcinomaAims:  The aim of study was to evaluate the impact of CRTC1–MAML2 and CRTC3–MAML2 fusions on the histological classification of mucoepidermoid carcinoma (MEC) of the salivary glands and on the prognosis of patients.Methods and results:  MEC cases (n = 111) were screened for CRTC1–MAML2 and CRTC3–MAML2 fusions by reverse transcription polymerase chain reaction. We developed a system of ‘molecular Armed Forces Institute of Pathology (AFIP) classification’ that combined the AFIP histological classification proposed by Goode et al. and the presence of CRTC1–MAML2 or CRTC3–MAML2 fusions. MEC cases positive for CRTC1–MAML2 or CRTC3–MAML2 fusion formed a favourable tumour subset that was distinct from fusion-negative cases. When positive for the fusions, ‘high-risk’ patients, including those with a higher histological grade or an advanced clinical stage, showed an excellent prognosis. For overall survival, ‘molecular AFIP classification’ was selected as a powerful independent prognostic factor (P = 0.0038), as was the clinical stage (P = 0.0032). For disease-free survival, ‘molecular AFIP classification’ was also selected as an independent prognostic factor (P = 0.0006).Conclusions:  Molecular AFIP classification may be useful in predicting the prognosis of patients with MEC.
    Histopathology 06/2011; 59(1):90 - 97. · 3.08 Impact Factor
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    Article: Clinical and functional data implicate the Arg(151)Ser variant of MSX1 in familial hypodontia.
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    ABSTRACT: Multiple previous reports confirm that several missense alleles of MSX1 exhibit Mendelian inheritance of an oligodontia phenotype (agenesis of more than six secondary teeth besides third molars). However, the extent to which missense MSX1 alleles contribute to common, multifactorial disorders is less certain. It is still not yet clear whether multiple non-synonomous MSX1-coding variants identified among patients with oral clefting are merely neutral polymorphisms or whether any of these might represent real mutations with mild effects. The present work steps toward resolving these issues for at least one MSX1 allele: R151S, previously identified in a single Japanese proband with unilateral cleft lip and palate. Candidate gene sequencing within a patient cohort demonstrating mild tooth agenesis (loss of six or less secondary teeth besides third molars, hypodontia), secondarily identified this same MSX1 variant, functioning as a mildly deleterious, moderately penetrant allele. Four of five heterozygous R151S individuals from one Japanese family exhibited the hypodontia phenotype. The in vitro functional assays of the variant protein display partial repression activity with normal nuclear localization. These data establish that the MSX1-R151S allele is a low-frequency, mildly deleterious allele for familial hypodontia that alone is insufficient to cause oral facial clefting. Yet, as this work also establishes its hypomorphic nature, it suggests that it may in fact contribute to the likelihood of common birth disorder phenotypes, such as partial tooth agenesis and oral facial clefting. Nevertheless, the exact mechanism in which differential pleiotropy is manifested will need further and deeper clinical and functional analyses.
    European journal of human genetics: EJHG 03/2011; 19(8):844-50. · 3.56 Impact Factor
  • Article: Genotypes of Candida albicans involved in development of candidiasis and their distribution in oral cavity of non-candidiasis individuals.
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    ABSTRACT: Genotype characteristics and distribution of commensal Candida albicans should be studied to predict the development of candidiasis, however, extensive genotype analysis of commensal C. albicans has not been made. In this study, 508 C. albicans isolates were collected from patients with/without candidiasis and divided into 4 isolate groups (SG-1, oral cavity of non-candidiasis patients; SG-2, patients with cutaneous candidiasis; SG-3, patients with vaginal candidiasis; SG-4, patients with candidemia). These isolates were characterized to study the relationship between genotypes and pathogenicity using microsatellite analysis. Using CDC3 and CAI, 5 genotypes (I, 111: 115/33: 41; II, 115: 119/23: 23; III, 115: 123/18: 27; IV, 115: 123/33: 40; and V, 123: 127/32: 41) were found in 4.2%, 8.9%, 7.1%, 2.2% and 3.1% of the isolates, respectively. Genotypes II and III were commonly found in all isolate groups. These genotypes were further divided into 28 types by additional HIS3 and CAIII microsatellite markers. In this analysis, C. albicans with type 6 and type 23 was widely distributed as a commensal species in the oral cavity of non-candidiasis patients and found to be related with candidiasis development. Additionally, genotypes I and IV were found in SG-2 and/or SG-4, suggesting that the fungus with those genotypes is also involved in this development. In contrast, genotype V was not identified in any infective isolates.
    Nippon Ishinkin Gakkai Zasshi 01/2011; 52(4):315-24.
  • Article: Two missense mutations of the IRF6 gene in two Japanese families with popliteal pterygium syndrome.
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    ABSTRACT: Mutations in the interferon regulatory factor 6 gene (IRF6) cause either popliteal pterygium syndrome (PPS) or Van der Woude syndrome (VWS), allelic autosomal dominant orofacial clefting conditions. To further investigate the IRF6 mutation profile in PPS, we performed mutation analysis of patients from two unrelated Japanese families with PPS and identified mutations in IRF6: c.251G>T (R84L) and c.1271C>T (S424L). We also found R84L, which together with previous reports on R84 mutations, provided another line of evidence that both syndromes could result from the same mutation probably under an influence of a modifier gene(s). This supports the idea that the R84 residue in the DNA binding domain of IRF6 is a mutational hot spot for PPS. A luciferase assay of the S424L protein in the other family demonstrated that the mutation decreased the IRF6 transcriptional activity significantly to 6% of that of the wild-type. This finding suggests that the C-terminus region of IRF6 could have an important function in phosphorylation or protein interaction. To our knowledge, this is the first report of mutations observed in Japanese PPS patients.
    American Journal of Medical Genetics Part A 09/2010; 152A(9):2262-7. · 2.39 Impact Factor
  • Article: Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12).
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    ABSTRACT: Identification of the breakpoints of disease-associated chromosome rearrangements can provide informative clues to a positional cloning approach for genes responsible for inherited diseases. Recently, we found a three-generation Japanese family segregating balanced chromosome translocation t(9;17)(q32;q12). One of the subjects had cleft lip and palate. We examined whether regions near the breakpoint could be associated with cleft lip and/or palate. We determined the breakpoints involved in the translocation by fluorescence in situ hybridization analysis and subsequent long-range polymerase chain reaction. In order to study the role of these disrupted regions in nonsyndromic cleft lip and/or palate, we performed mutation analysis and a haplotype-based transmission disequilibrium test using tagging single-nucleotide polymorphisms in the flanking regions of the breakpoints in white and Filipino nonsyndromic cleft lip and/or palate populations. Sequence analysis demonstrated that two genes, SLC31A1 (solute carrier family 31 member 1) on chromosome 9 and CCL2 (chemokine ligand 2) on chromosome 17, were rearranged with the breaks occurring within their introns. It is interesting that SLC31A1 lies closed to BSPRY (B-box and SPRY domain), which is a candidate for involvement with cleft lip and/or palate. Some of the variants in BSPRY and CCL2 showed significant p values in the cleft lip and/or palate population compared with the control population. There was also statistically significant evidence of transmission distortion for haplotypes on both chromosomes 9 and 17. The data support previous reports that genes on chromosomal regions of 9q and 17q play an important role in facial development.
    The Cleft Palate-Craniofacial Journal 09/2009; 46(5):532-40. · 0.82 Impact Factor
  • Article: Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma.
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    ABSTRACT: Mucoepidermoid carcinoma is the most common primary malignancy of the salivary gland. We and others showed that CRTC1-MAML2 gene fusion was associated with favorable clinicopathological tumor features. Recently, a novel gene fusion, CRTC3-MAML2, was reported as a rare gene alteration in a case of mucoepidermoid carcinoma. However, its frequency and clinicopathological significance remains unclear. In all, 101 cases of mucoepidermoid carcinoma and 89 cases of non-mucoepidermoid carcinoma of the salivary gland were analyzed, and RNA was extracted from formalin-fixed, paraffin-embedded specimens. In the CRTC family, there have been three genes, CRTC1, CRTC2, and CRTC3. We developed reverse transcription-polymerase chain reaction (RT-PCR) assays for CRTC1-MAML2, CRTC2-MAML2, and CRTC3-MAML2 fusions. Clinicopathological data of the patients were obtained from their clinical records. Of 101 cases of mucoepidermoid carcinoma, 34 (34%) and 6 (6%) were positive for CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts. However, in the 89 cases of non-mucoepidermoid carcinoma, neither transcript was noted. In the former cases, CRTC1-MAML2 and CRTC3-MAML2 fusions were mutually exclusive. The other fusion, CRTC2-MAML2, was not detected. We confirmed that the clinicopathological features of CRTC1-MAML2-positive mucoepidermoid carcinomas indicated an indolent course. CRTC3-MAML2-positive mucoepidermoid carcinomas also had clinicopathologically favorable features; all cases showed a less advanced clinical stage, negative nodal metastasis, no high-grade tumor histology, and no recurrence or tumor-related death after surgical resection of the tumor. It is interesting to note that patients with CRTC3-MAML2-positive tumors (mean 36 years of age) were significantly younger that those with the CRTC1-MAML2 fusion (55 years) and those with fusion-negative tumors (58 years). In conclusion, CRTC3-MAML2 fusion, which is mutually exclusive with CRTC1-MAML2 fusion and specific to mucoepidermoid carcinoma, may be detected more frequently than previously expected. Mucoepidermoid carcinomas possessing CRTC3-MAML2 fusion may be associated with favorable clinicopathological features and patients may be younger than those with CRTC1-MAML2 fusion or those with no detectable gene fusion.
    Modern Pathology 09/2009; 22(12):1575-81. · 4.79 Impact Factor
  • Article: Prognostic significance of p27Kip1, Ki-67, and CRTC1-MAML2 fusion transcript in mucoepidermoid carcinoma: a molecular and clinicopathologic study of 101 cases.
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    ABSTRACT: Mucoepidermoid carcinoma (MEC) is the most frequently detected primary malignancy of the salivary gland and is characterized by a marked variation in prognosis. In the present study, we investigated the prognostic significance of p27Kip1, Ki-67, and CRTC1 (also called MECT1, TORC1, and WAMTP1)-MAML2 fusion in MEC. MEC cases (n = 101) were examined for p27Kip1 and Ki-67 expression using immunohistochemistry and for CRTC1-MAML2 fusion transcript using reverse transcriptase-polymerase chain reaction. p27Kip1, Ki-67, and the CRTC1-MAML2 fusion transcript were expressed in 71, 31, and 34 of the 101 cases, respectively. p27Kip1 and CRTC1-MAML2 fusion were associated with favorable clinicopathologic tumor features and Ki-67 with aggressive clinicopathologic features. Multivariate survival analyses were performed that included the following 10 clinicopathologic factors: age, gender, tumor site, tumor size, nodal metastasis, clinical stage, histologic grade, p27 expression, Ki-67 expression, and CRTC1-MAML2 fusion. For disease-free survival, only p27Kip1 expression was significant as an independent prognostic factor. For overall survival, p27Kip1 expression, CRTC1-MAML2 fusion, and tumor size were significant. In each analysis, p27Kip1 and CRTC1-MAML2 fusion were independent of the clinical stage. Ki-67 expression was not selected in either multivariate analysis. p27Kip1 and CRTC1-MAML2 fusion were associated with favorable clinicopathologic tumor features, and both were useful in predicting the overall survival of patients with MEC. For disease-free survival, p27Kip1 might be the most useful prognostic factor. In contrast, Ki-67 might not be a very powerful prognostic indicator for either survival point.
    Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 08/2009; 67(7):1432-41. · 1.58 Impact Factor
  • Article: Mutations in BMP4 are associated with subepithelial, microform, and overt cleft lip.
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    ABSTRACT: Cleft lip with or without cleft palate (CL/P) is a complex trait with evidence that the clinical spectrum includes both microform and subepithelial lip defects. We identified missense and nonsense mutations in the BMP4 gene in 1 of 30 cases of microform clefts, 2 of 87 cases with subepithelial defects in the orbicularis oris muscle (OOM), 5 of 968 cases of overt CL/P, and 0 of 529 controls. These results provide confirmation that microforms and subepithelial OOM defects are part of the spectrum of CL/P and should be considered during clinical evaluation of families with clefts. Furthermore, we suggest a role for BMP4 in wound healing.
    The American Journal of Human Genetics 03/2009; 84(3):406-11. · 10.60 Impact Factor
  • Article: Prognostic factors for keratocystic odontogenic tumor (odontogenic keratocyst): analysis of clinico-pathologic and immunohistochemical findings in cysts treated by enucleation.
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    ABSTRACT: The purpose of this study was to determine prognostic factors for the recurrence of keratocystic odontogenic tumors (KCOTs) following simple enucleation by examining clinico-pathologic and immunohistochemical findings. Following enucleation, the frequency of recurrence among 32 subjects diagnosed with KCOT was analyzed for tumor site, radiographic and histologic features, and immunopositivity for Ki-67 and p53. Keratocystic odontogenic tumors in four out of 32 subjects (12.5%) recurred during the follow-up period (median: 33 months, range: 7-114 months). Three out of four subjects (75.0%) among recurrent group showed high expression of Ki-67 (LI >10%) in basal layer and four (4/28; 14.3%) among non-recurrence group (P = 0.025). Expression of p53 among non-recurrent group was observed in 11 subjects (11/28; 39.3%), and in three subjects (3/4; 75.0%) among the recurrent group (P = 0.295). Hazard risk for the recurrence of KCOT was 4.02 (95% CI 1.42-18.14) for high Ki-67 expression in the basal layer by the Cox proportional hazard model (P = 0.009). In our study, none of the other clinico-pathologic variables were associated with the recurrence of KCOT. The results suggested that the evaluation of Ki-67 expression in KCOT at the time of pathological diagnosis might be helpful for consideration of appropriate adjunctive surgical procedures to avoid a recurrence and may serve as a prognostic marker.
    Journal of Oral Pathology and Medicine 12/2008; 38(4):386-92. · 1.63 Impact Factor

Institutions

  • 2012
    • National Center for Geriatrics and Gerontology
      Ōbu, Aichi-ken, Japan
  • 2004–2012
    • Aichi Gakuin University
      Nagoya-shi, Aichi-ken, Japan
  • 2006–2009
    • Nagoya City University
      • Department of Pathology
      Nagoya-shi, Aichi-ken, Japan