Biomedical subjects

H Kumamoto

Publications and source records attributed to H Kumamoto.

At least 19 recordsLinked to original sources

PubMed2006

Molecular pathology of odontogenic tumors.

Odontogenic tumors are lesions derived from the elements of the tooth-forming apparatus and are found exclusively within the jawbones. This review represents a contemporary outline of our current understanding of the molecular and genetic alterations associated with the development and progression of odontogenic tumors, including oncogenes, tumor-suppressor genes, oncoviruses, growth factors, telomerase, cell cycle regulators, apoptosis-related factors, regulators of tooth development, hard tissue-related proteins, cell adhesion molecules, matrix-degrading proteinases, angiogenic factors, and osteolytic cytokines. It is hoped that better understanding of related molecular mechanisms will help to predict the course of odontogenic tumors and lead to the development of new therapeutic concepts for their management.

Apoptosis↗

PubMed2006

Immunohistochemical detection of MT1-MMP, RECK, and EMMPRIN in ameloblastic tumors.

BACKGROUND: To evaluate the roles of matrix-degrading proteinase regulators in progression of odontogenic tumors, expression of membrane-bound matrix metalloproteinase (MMP) MT1-MMP, MMP inhibitor RECK and MMP inducer EMMPRIN was analyzed in ameloblastic tumors as well as in tooth germs. METHODS: Tissue specimens of 11 tooth germs, 40 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with the use of antibodies against MT1-MMP, RECK, and EMMPRIN. RESULTS: Immunohistochemical reactivity for MT1-MMP, RECK and EMMPRIN was detected predominantly in odontogenic epithelial cells near the basement membrane in tooth germs and benign and malignant ameloblastic tumors. The level of immunoreactivity for MT1-MMP was slightly higher in benign and malignant ameloblastic tumors than in tooth germs. RECK expression was lower in ameloblastomas than in tooth germs. Follicular ameloblastomas showed significantly lower expression of RECK than plexiform ameloblastomas, and immunoreactivity for RECK in acanthomatous ameloblastomas was slightly lower than that in other cellular variants. CONCLUSION: Expression of MT1-MMP, RECK and EMMPRIN in tooth germs and ameloblastic tumors suggests that these normal and neoplastic epithelial components control MMP-dependent extracellular matrix (ECM) degradation during tooth development and tumor progression via epithelial-mesenchymal interactions.

Ameloblastoma↗

PubMed2006

Expression of bone morphogenetic proteins and their associated molecules in ameloblastomas and adenomatoid odontogenic tumors.

OBJECTIVE: To further clarify the roles of regulators of embryonic development, bone morphogenetic protein (BMPs) and their associated molecules, in oncogenesis and cytodifferentiation of odontogenic tumors, the expression of these regulator molecules were analyzed in epithelial odontogenic tumors as well as in tooth germs. MATERIALS AND METHODS: Tooth germs, ameloblastomas, adenomatoid odontogenic tumors, and malignant ameloblastomas were examined by RT-PCR and immunohistochemistry for detection of BMP-2, -4, -7, BMP receptors I and II (BMPR-I, BMPR-II), core-binding factor alpha1 (CBFA1), and osterix. RESULTS: mRNA expression of BMPs, BMPRs, CBFA1, and osterix was detected in all odontogenic tissues. Immunohistochemical reactivity for BMPs, BMPRs, and CBFA1 was detected in both epithelial and mesenchymal cells of tooth germs and epithelial odontogenic tumors. BMPs and BMPRs were evidently expressed in odontogenic epithelial cells in tooth germs and epithelial odontogenic tumors. Acanthomatous ameloblastomas showed increased BMP-7 reactivity in keratinizing cells. Nuclear CBFA1 expression was detected scatteredly in odontogenic epithelial cells in normal and neoplastic odontogenic tissues, as well as in some mesenchymal cells in tooth germs and in some stromal cells in epithelial odontogenic tumors. Ameloblastic carcinomas showed low reactivity for BMPs, BMPRs, and CBFA1. CONCLUSION: BMPs and their associated molecules might play a role in cytodifferentiation of normal and neoplastic odontogenic epithelium via epithelial-mesenchymal interactions.

Ameloblastoma↗

PubMed2005

Immunohistochemical analysis of apoptosis-related factors in lining epithelium of radicular cysts.

BACKGROUND: Some studies suggest that apoptosis-related factors are involved in the inflammatory processes of marginal periodontal lesions. However, the role of apoptosis in periapical inflammatory lesions remains unclear. We investigated the possible role of apoptotic cell death in periapical inflammatory lesions by means of immunohistochemical analysis of apoptosis-related factors and use of a cell proliferation marker. METHODS: Paraffin-embedded sections of 19 radicular cysts (RCs), and five residual radicular cysts (RRCs) and control specimens of normal gingivae excised from seven cadavers were prepared and examined immunohistochemically with the use of monoclonal antibodies or polyclonal antisera against single-stranded DNA (ssDNA), p53, Bax, Bcl-2, caspase-3, Fas, Fas ligand (Fas-L), and Ki-67 antigen. RESULTS: Epithelium of gingiva, RCs, and RRCs showed expression of ssDNA in suprabasal and superficial epithelial cells and Ki-67 reactivity in basal and parabasal cells. Expression of Ki-67 and ssDNA in RCs and RRCs was slightly higher than that in gingiva. Both Ki-67 and ssDNA reactivity in RCs with intense inflammatory reactions or with thick lining epithelium were significantly stronger than those in RCs with less inflammatory reactions or with thin lining epithelium. Reactivity for p53 was noted sporadically in epithelium of gingiva, RCs, and RRCs, and p53 expression in RCs was significantly greater than that in gingiva. Ki-67 and ssDNA reactivity in RCs increased parallel to the degree of p53 expression. Bax and Bcl-2 were detected in some basal epithelial cells in RCs and RRCs as well as in gingiva. The ssDNA reactivity significantly increased parallel to Bax expression and slightly decreased parallel to Bcl-2 expression in lining epithelium of RCs. Caspase-3 was detected in superficial epithelial cells of both gingiva and lining epithelium of RCs and RRCs, and the distribution of these cells was compatible with the expression of ssDNA. Expression of Ki-67 and ssDNA in caspase-3-positive fields was significantly higher than that in caspase-3-negative fields in RCs. There was very limited expression of Fas and Fas-L in lining epithelium of RCs and RRCs as well as in gingiva. CONCLUSIONS: These data suggest that apoptosis-related factors are involved in the pathophysiologic activity of periapical inflammatory lesions. Such factors may be affected by the structure of lining epithelium and the degree of inflammatory change.

Adult↗

PubMed2005

Immunohistochemical detection of beta-catenin and adenomatous polyposis coli in ameloblastomas.

BACKGROUND: To clarify the roles of the Wnt signaling pathway in oncogenesis and cytodifferentiation of odontogenic tumors, expression of beta-catenin and adenomatous polyposis coli (APC) was analyzed in ameloblastomas as well as in tooth germs. METHODS: Tissue specimens of 10 tooth germs, 40 benign ameloblastomas, and five malignant ameloblastomas were examined immunohistochemically with the use of antibodies against beta-catenin and APC. RESULTS: Immunohistochemical reactivity for beta-catenin was detected in the cell membrane and cytoplasm of most odontogenic epithelial cells in tooth germs and ameloblastomas. Nuclear beta-catenin expression was recognized in nine of 40 ameloblastomas and two of five malignant ameloblastomas, but not in tooth germs. APC was evidently expressed in odontogenic epithelial cells neighboring the basement membrane in tooth germs and ameloblastomas, and the reactivity was significantly lower in benign and malignant ameloblastomas than in tooth germs. Follicular ameloblastomas and acanthomatous ameloblastomas tended to show high nuclear beta-catenin expression and low APC reactivity, as compared with other ameloblastoma variants. CONCLUSION: Expression of beta-catenin and APC in tooth germs and ameloblastomas suggests that aberration of the Wnt signaling pathway might play a role in oncogenesis and cytodifferentiation of odontogenic epithelium via deregulation of cell proliferation.

Adenomatous Polyposis Coli Protein↗

PubMed2004

PTC gene mutations and expression of SHH, PTC, SMO, and GLI-1 in odontogenic keratocysts.

The Patched (PTC) gene is responsible for basal cell nevus syndrome (BCNS) accompanied by multiple odontogenic keratocysts (OKCs), and its product plays a role in the Sonic hedgehog (SHH) signaling pathway involving smoothened (SMO) and GLI-1. To clarify the role of SHH signaling in OKCs, the expression of SHH, PTC, SMO, and GLI-1 and mutations of PTC were examined in 18 sporadic, 4 BCNS-associated OKCs and 7 control gingivae. SHH, PTC, SMO, and GLI-1 were detected in all OKC and gingiva samples by reverse transcriptase-polymerase chain reaction (RT-PCR). Immunoreactivity for SHH and GLI-1 was markedly higher in epithelial components than in subepithelial cells, while immunoreactivity for PTC and SMO was similar in epithelial components and subepithelial cells in OKCs. The positive rate of PTC and SMO expression in subepithelial cells of OKCs was significantly higher than that in gingivae. The positive rate of GLI-1 expression in subepithelial cells of BCNS-associated OKCs was significantly higher than that in primary OKCs. These results suggest that the SHH signaling might be involved in the pathophysiologic nature of OKCs. While mutations of the PTC gene could not be detected in 4 BCNS-associated OKCs by direct DNA sequencing, 3 of 5 primary and 4 of 4 recurrent OKCs had several mutations of this gene. These results suggest that PTC mutations are probably related not only to BCNS-associated OKCs but also to sporadic OKCs.

Basal Cell Nevus Syndrome↗

PubMed2004

Adenovirus-mediated CTLA4 immunoglobulin G gene therapy in cardiac xenotransplantation.

BACKGROUND: CTLA4 immunoglobulin (CTLA4 Ig), which binds with high affinity to B7-1 and B7-2, interrupts T-cell activation by inhibiting the costimulatory signal. CTLA4Ig has been used to achieve antigen-specific tolerance induction in cardiac allografts. On the other hand, we have shown that short-term administration of deoxyspergualin (DSG) and daily cyclosporine (CsA) induces long-term survival of cardiac xenotransplants. We hypothesized that the combination therapy of DSG and adenovirus-mediated CTLA4IgG might induce long-term, survival or tolerance in cardiac xenotransplantation. OBJECTIVES: Syrian hamster hearts were transplanted heterotopically into Lewis rats. We compared the survival time and immunopathology of the following five groups: (1) no treatment; (2) DSG (5 mg/kg per day intramuscularly [IM], days -1 to +7) alone; (3) CsA (15 mg/kg per day IM, day 0 to rejection) plus DSG; (4) AdexLacZ (LacZ-adenovirus 1 x 10(9) (PFU intravenously [IV], day -7) plus DSG; and (5) AdexCTLA4IgG (CTLA4IgG-adenovirus 1 x 10(9) PFU IV, day -7) plus DSG. RESULTS: The survival times were: (1) no treatment, 3.7 days; (2) DSG alone, 12.4 days; (3) CyA plus DSG, >100 days; (4) AdexLacZ plus DSG, 11.0 days; and (5) AdexCTLA4IgG plus DSG, 23.6 days. Adenovirus-mediated CTLA4IgG therapy with DSG prolonged survival time significantly compared with DSG alone or AdexLacZ plus DSG, but CTLA4IgG therapy was not as effective as CsA. Immunopathology showed the deposition of C3 and IgM on the endothelium in the AdexCTLA4IgG plus DSG group. CONCLUSIONS: We showed that the effectiveness of adenovirus-mediated CTLA4IgG gene therapy in cardiac xenotransplantation in less than that of CsA. Combination therapy with inhibition of the B7/CD28 constimulatory signal and DSG administration might not be sufficient for long-term survival or tolerance in cardiac xenotransplantation.

Abatacept↗

PubMed2003

Sebaceous adenoma in the retromolar region: report of a case with a review of the English literature.

This paper reports a rare case of sebaceous adenoma on the right mandibular retromolar mucosa in a 73-year-old Japanese man, with a review of the English literature of sebaceous adenomas of salivary gland origin. A painless and yellowish polypoid lesion in the retromolar mucosa was histologically a relatively well-circumscribed neoplastic mass composed of well-differentiated sebaceous cells with cystic and duct-like structures, and was considered to be a true sebaceous gland neoplasm arising from the minor salivary gland tissue.

Adenoma↗

PubMed2002

Intramucosal naevus with pseudoepitheliomatous hyperplasia in the gingiva: a case report.

This article describes the unusual case of an intraoral pigmented naevus with pseudoepitheliomatous hyperplasia of the gingiva. A 62-year-old man presented with an almost coal-black pigmented and partly white, spotted, dome-shaped swelling on the lingual gingiva of the mandible. Histologically, the lesion consisted of clusters of round-shaped naevus cells containing melanin granules, reactive with both S-100 immunohistochemical stain and Masson-Fontana silver stain, and pseudoinvasive squamous nests, reactive with cytokeratin. The pathogenesis of the present lesion and problems encountered in its differential diagnosis are discussed.

Basal Cell Carcinoma↗

PubMed2001

Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells: implications for long-term graft patency.

BACKGROUND: Serotonin can induce proliferation of vascular smooth muscle cells. We assessed the ability of a specific serotonin receptor antagonist, sarpogrelate, to inhibit proliferation of cultured porcine coronary artery smooth muscle cells. METHODS: Cell proliferation and mitotic activity were measured using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide. To determine the effect of sarpogrelate on DNA (deoxyribonucleic acid), RNA (ribonucleic acid), and protein synthesis, radioactive incorporation of 3H-thymidine, 3H-uridine, and 3H-phenylalanine, respectively, was used. Synthesis of DNA was also assessed by flow cytometry with propidium iodide as a fluorochrome. RESULTS: Serotonin, platelet-derived growth factor, endothelin, and angiotensin II all induced proliferation of porcine coronary artery smooth muscle cells. Sarpogrelate specifically inhibited the serotonin-induced cytokine trigger but did not influence platelet-derived growth factor-, endothelin-, or angiotensin II-induced cell proliferation. Sarpogrelate inhibited the serotonin-induced increase in intracellular free ionized calcium concentration, prevented mitogen-activated protein kinase activation, and down-regulated expression of the protooncogenes c-fos and c-jun. Sarpogrelate acted at the G1 phase of the cell cycle. CONCLUSIONS: These data suggest that sarpogrelate could be used as a therapeutic agent to inhibit serotonin-induced neointimal hyperplasia and improve patency of coronary artery bypass grafts.

Animals↗

PubMed2001

Telomerase activity and telomerase reverse transciptase (TERT) expression in ameloblastomas.

Telomerase activity is believed to be crucial for cell immortalization and cancerization, and is proven to be induced by c-myc protein. Telomerase reverse transcriptase (TERT) has been recently identified as a catalytic subunit of telomerase, whose expression is closely correlated with telomerase activity. We estimated telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and examined the immunohistochemical expression of TERT and c-myc protein in 21 ameloblastoma tissues. All ameloblastoma samples were positive for telomerase activity, and TERT expression was detected in the nuclei of neoplastic cells but not in those of stromal cells. Numerous peripheral columnar or cuboidal cells, sporadic central polyhedral cells and some granular cells in ameloblastomas reacted with anti-TERT antibody. These results suggest that telomerase activity is associated with the oncogenesis or proliferative potential of odontogenic epithelium. The expression of c-myc protein showed a similar distribution pattern to that of TERT, suggesting that c-myc protein might induce telomerase activity in ameloblastomas.

Ameloblastoma↗

PubMed2001

Immunohistochemical and ultrastructural investigation of apoptotic cell death in granular cell ameloblastoma.

Apoptotic cell death in granular cell ameloblastomas was examined by immunohistochemistry using anti-single-stranded DNA (ssDNA) antibody and transmission electron microscopy. Routinely prepared sections of granular cell ameloblastomas showed various quantities of granular cells with some apoptotic nuclear fragments. Immunoreactivity for ssDNA was higher in granular cells than in other neoplastic cells. Ultrastructural examination revealed abundant lysosomes in the cytoplasm of granular cells. Numerous apoptotic cell fragments with condensed nuclei in granular cell clusters were phagocytosed by adjacent granular cells. On immunohistochemical characterization of cellular differentiation, granular cells were positive for cytokeratin, CD68, lysozyme and alpha-1-antichymotrypsin, but negative for vimentin, desmin, S-100 protein, neuron-specific enolase and CD15, indicating epithelial origin and lysosomal aggregation. These features suggest that the cytoplasmic granularity in granular cell ameloblastomas might be caused by increased apoptotic cell death of neoplastic cells and associated phagocytosis by neighboring neoplastic cells.

Adult↗

PubMed2001

Detection of cell cycle-related factors in ameloblastomas.

To determine whether cell cycle regulation or alteration plays a role in oncogenesis and cytodifferentiation of odontogenic epithelium, cell cycle-related factors, including cyclin D1, p16INK4a, p21(WAF1/Cip1) and p27Kip1 proteins, DNA topoisomerase IIalpha and histone H3 mRNA, were examined in 8 tooth germs and 31 ameloblastomas. Cyclin D1 was expressed in epithelial cells near the basement membrane in tooth germs and ameloblastomas, suggesting that this protein participates in cell proliferation in odontogenic epithelium. Immunoreactivity for p16 protein was observed in most epithelial cells in tooth germs and ameloblastomas. Expression of p21 protein was detected in most epithelial cells in tooth germs and ameloblastomas, but not in keratinizing or granular cells in variants of ameloblastomas. Expression of p27 protein was chiefly found in central polyhedral cells and keratinizing cells in tooth germs and ameloblastomas. These cyclin-dependent kinase inhibitors were well preserved in ameloblastomas as compared with tooth germs, suggesting that the odontogenic epithelium is strictly regulated by these factors. The cell cycle phase/cellular proliferation markers, DNA topoisomerase IIalpha and histone H3 mRNA, were localized in scattered epithelial cells attached to the basement membrane in tooth germs and ameloblastomas.

Ameloblastoma↗

PubMed2001

Immunohistochemical analysis of cell-cycle- and apoptosis-related factors in lining epithelium of odontogenic keratocysts.

We examined the immunohistochemical expressions of cell-cycle- and apoptosis-related factors to investigate the possible role of these factors in odontogenic keratocyst (OKC). Expression of cyclin D1 and p16 protein was detected in the basal and parabasal cells in lining epithelium of OKCs and was found more frequently in basal cell nevus syndrome (BCNS)-associated OKCs than in primary or recurrent OKCs. Positivity for p21 protein was detected in basal to superficial cells, whereas that for p27 protein was detected in parabasal to superficial cells in lining epithelium of OKCs. DNA topoisomerase IIalpha reacted with nuclei in basal and parabasal cells of the lining epithelium of OKCs, and positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. Expression of Fas in suprabasal to superficial cells and expression of Fas-L in basal and parabasal cells were detected in lining epithelium of OKCs. Immunoreactivity for caspase-3 was detected in basal to suprabasal or superficial cells in lining epithelium of OKCs. Single stranded (ss)DNA-positive nuclei were detected in superficial cells in lining epithelium of OKCs. Fas was more broadly distributed in BCNS-associated OKCs than in primary OKCs, and ssDNA-positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. These results suggest that BCNS-associated OKCs might be a distinguishable entity from solitary OKCs.

Adult↗

PubMed2001

Histopathological and immunohistochemical analysis of calcifying odontogenic cysts.

METHOD AND RESULTS: Calcifying odontogenic cysts (COCs) were examined histopathologically and immunohistochemically to characterize the histological and cytological properties of these lesions. Histopathologically, COCs showed thin or thick lining epithelium with ghost cells. COCs were classified according to proliferative type or nonproliferative type lining epithelium, the presence or absence of ameloblastomatous appearance, and the presence or absence of odontoma in the cyst walls. Immunohistochemically, amelogenin protein was expressed chiefly in ghost cells, whereas cytokeratin 19 (CK19) and bcl-2 proteins were expressed chiefly in lining epithelial cells. The proportion of cases positive for bcl-2 protein was slightly higher in COCs with odontoma than in those without odontoma. Lining epithelial cells sporadically showed positive reactions for Ki-67 antigen. Mean Ki-67 labeling index was slightly greater in COCs with proliferative type lining epithelium, COCs with ameloblastomatous appearance of the cyst walls, and COCs with odontoma of the cyst walls than in COCs without these histological features. Our results suggest that ghost cells or lining epithelial cells show ameloblastic cytodifferentiation or odontogenic epithelial characteristics, that bcl-2 protein is associated with survival of lining epithelial cells in COCs, and that high proliferation potential is associated with ameloblastomatous proliferation or combined odontoma. COCs exhibited various histological features with several transitional forms, and immunohistochemical examinations revealed little or no difference in cytodifferentiation and cellular activity among COCs. CONCLUSION: We conclude that COCs with various histological features have neoplastic potential and may not be separate entities within the same histological spectrum.

Adolescent↗

PubMed2001

Immunohistochemical analysis of apoptosis-related factors (Fas, Fas ligand, caspase-3 and single-stranded DNA) in ameloblastomas.

BACKGROUND: To clarify the possible role of apoptotic cell death in oncogenesis and cytodifferentiation of odontogenic epithelium, apoptosis-related factors--Fas, Fas ligand (FasL), caspase-3 and single-stranded DNA (ssDNA)--were analyzed in ameloblastomas as well as in tooth germs. METHODS: Specimens of 5 tooth germs, 29 benign ameloblastomas and 5 malignant ameloblastomas were examined by immunohistochemistry using anti-Fas, FasL, caspase-3 and ssDNA polyclonal antibodies. RESULTS: Immunoreactivity for Fas and FasL was detected in normal and neoplastic odontogenic epithelial cells. Fas expression in ameloblastomas was slightly lower than that in tooth germs, whereas FasL expression was similar in tooth germs and ameloblastomas. Malignant ameloblastomas showed downregulation of Fas expression and upregulation of FasL expression, as compared with benign ameloblastomas, indicating escape from cell death attack by immune cells. Immunoreactivity for caspase-3 was detected chiefly in cells neighboring the basement membrane in tooth germs and ameloblastomas. Expression of caspase-3 and Fas tended to be low in basal cell ameloblastomas and high in desmoplastic ameloblastomas, as compared with other variants of ameloblastomas. Caspase-3 expression was more intense in malignant ameloblastomas than in tooth germs and benign ameloblastomas. Apoptotic bodies reactive with anti-ssDNA antibody were detected in normal and neoplastic odontogenic epithelial cells detached from the basement membrane. Keratinizing cells in acanthomatous ameloblastomas and granular cells in granular cell ameloblastomas showed increased numbers of apoptotic bodies and increased expression of Fas and caspase-3, as compared with other neoplastic cells. Apoptotic reactions in malignant ameloblastomas were less frequent than in benign ameloblastomas, indicating abnormal regulation of cell turnover in odontogenic epithelial cells. CONCLUSION: These apoptosis-related factors were detected in various patterns in normal and neoplastic odontogenic epithelium, suggesting that these factors might be associated with oncogenesis and cytodifferentiation of epithelial odontogenic tumors.

Ameloblastoma↗

PubMed2001

Immunohistochemical analysis of CD1a-labeled Langerhans cells in human dental periapical inflammatory lesions--correlation with inflammatory cells and epithelial cells.

OBJECTIVE: Distribution and density of CD1a-labeled Langerhans cells (LCs) were examined in human dental periapical inflammatory lesions, and compared with inflammatory cell infiltration or epithelial cell proliferation. MATERIALS AND METHODS: Eighty three periapical lesions (26 apical granulomas (AGs), 8 epitheliated granulomas (EGs), 34 radicular cysts (RCs), 15 residual radicular cysts (RRCs)) were collected. As control, specimens of periodontal ligaments including Malassez epithelial rests were curetted from 21 teeth. LC densities were measured and various degrees of inflammatory cell infiltration were examined immunohistochemically. Labeling indices for the cellular proliferation markers Ki-67 antigen and DNA topoisomerase II alpha were calculated in the epithelial components. RESULTS: LCs were found in all periapical lesions but not in Malassez epithelial rests. LCs were more abundant in epithelial components than in subepithelial layers. Intraepithelial LCs were more frequent in RCs than in RRCs, whereas subepithelial LCs were less frequent in RRCs than in AGs and EGs. T lymphocytes consistently outnumbered macrophages, plasma cells and B lymphocytes. The range of the CD4/CD8-positive cell ratio differed according to the lesions. Increased LC density was associated with the severity of CD3-positive cell infiltration. Ki-67- and Topo II-LI showed various degrees of epithelial immunoreactivity. There was a significant correlation between LC density and proliferative potential of the epithelium in periapical lesions. CONCLUSION: These findings suggested that LCs appeared to be associated with T lymphocyte infiltration and proliferative potential of the epithelial tissue in periapical lesions.

Adult↗

PubMed2001

Chromogenic in situ hybridization analysis of HER-2/neu status in breast carcinoma: application in screening of patients for trastuzumab (Herceptin) therapy.

Evaluation of HER-2/neu status is important in the management of patients with breast carcinoma, especially in determining the possible application of trastuzumab, a humanized anti-HER-2/neu monoclonal antibody. Chromogenic in situ hybridization (CISH) detection of the HER-2/neu oncogene is a newly developed in situ hybridization method that utilizes a robust and unique-sequence DNA probe labeled with digoxygenin, and sequential incubations with antidigoxygenin fluorescein, antifluorescein peroxidase, and diaminobenzidine. In this study, we examined 20 archival specimens of human breast carcinoma using CISH, and we correlated findings with immunohistochemical findings for HER-2/neu. HER-2/neu immunohistochemistry was carried out with HercepTest, a standardized immunohistochemical examination system for HER-2/neu overexpression in surgical pathology specimens. CISH analysis could be done in 18 out of 20 cases examined. Gene copy signals for HER-2/neu were recognized as intranuclear brown dots in both neoplastic and non-neoplastic cells. Seven carcinomas showed an increased number or size of signals and were interpreted as being positive for HER-2/neu amplification. Eight cases were positive with the HercepTest. Seven out of eight carcinoma cases found to overexpress immunoreactive HER-2/neu also demonstrated HER-2/neu gene amplification following CISH analysis. There was a significant correlation between immunohistochemical and CISH analyses (P < 0.001). We found that CISH was a specific, sensitive and easily applicable method for the detection of HER-2/neu gene amplification, which may be used together with immunohistochemical examination for the evaluation of patients with breast carcinoma.

Adenocarcinoma↗