RESUMEN

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated tumor with a high incidence in Asian countries. NPC is a type of squamous cell carcinoma originating from the nasopharyngeal mucosa. Although rare, NPCs show some uncommon histologic variants; these variations remain to be understood. We described the cytologic characteristics of a rare NPC variant with abundant intracytoplasmic mucin. A 37-year-old Japanese man presented to our hospital with bilateral ear discomfort and palpable lymph nodes. Nasopharyngeal biopsy showed tumor cells with abundant intracytoplasmic, Alcian blue-PAS-positive mucin. Immunohistochemical analysis demonstrated that the tumor cells were positive for p40 and p53. Epstein-Barr encoding region (EBER) in situ hybridization (ISH) showed EBV infection of the tumor cells. Fluorescence in situ hybridization (FISH) using MAML2 break-apart probes did not show split signals. Fine needle aspiration biopsy (FNAB) cytology of the metastatic lymph nodes was also performed. Smear samples had a necrotic and inflammatory background with both lymphocyte and neutrophil infiltration. Highly cellular tumor clusters and dispersed cells with naked nuclei were observed. The tumor cells showed a clear cytoplasm with distinct cell borders. Intracytoplasmic mucin pushing the nucleus to the periphery was observed in the scattered tumor cells in a liquid-based cytology sample. Given these findings, the final diagnosis was advanced nasopharyngeal carcinoma; cisplatin-based chemoradiation therapy was performed as the first-line treatment. The tumor recurred 8 months after completing the treatment. The recurrent nasopharyngeal tumor was a typical non-keratinizing NPC and lacked intracytoplasmic mucin.

Asunto(s)

Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Humanos , Hibridación Fluorescente in Situ , Mucinas , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico

RESUMEN

OBJECTIVE: Atypical polypoid adenomyomas (APAs) are uncommon tumours consisting of atypical endometrioid glands and fibromyomatous stroma. Identifying the biphasic nature of atypical glandular components and spindle mesenchymal components without atypia is crucial for the cytological diagnosis of APA. We investigated the utility of lesion-targeted cytology (LTC) to directly collect firm spindle components. METHODS: We recruited seven consecutive surgical patients who underwent cytological examinations before surgery and were diagnosed with APA on postoperative histological examinations. Cytological smears were obtained by routine sampling in five cases and by targeted sampling using transvaginal ultrasonography, that is, LTC, in two cases. We retrospectively analysed the cytological findings from our cases and compared them to those of APA cases previously reported in the English literature. RESULTS: Among 5/7 cases that involved routine cytological sampling, normal cytological findings were found in 2 and atypical glandular cells were found in 3, but spindle cells from mesenchymal components were not detected. In contrast, among 2/7 cases in which sampling involved LTC, spindle cells without atypia, in addition to atypical glandular cells were found. CONCLUSIONS: Lesion-targeted cytology is useful to assess mesenchymal components of APAs and may improve the cytological diagnosis of APA.

Asunto(s)

Adenomioma/diagnóstico , Citodiagnóstico , Neoplasias Endometriales/diagnóstico , Leiomioma/diagnóstico , Neoplasias Uterinas/diagnóstico , Adenomioma/patología , Adulto , Neoplasias Endometriales/patología , Endometrio/diagnóstico por imagen , Endometrio/patología , Femenino , Humanos , Leiomioma/patología , Manejo de Especímenes , Ultrasonografía/normas , Neoplasias Uterinas/patología , Útero/diagnóstico por imagen , Útero/patología , Frotis Vaginal/normas

RESUMEN

OBJECTIVES: To investigate the use of imaging methods for predicting carcinogenesis in lobular endocervical glandular hyperplasia (LEGH). METHODS: We retrospectively analyzed preoperative images on transvaginal sonography and magnetic resonance imaging (MRI) in 23 cases with histologically diagnosed LEGH. RESULTS: Shape of cervical multicystic lesions on MR images could be divided into two types the flower-type with many small cysts surrounded by larger cysts, and the raspberry-type with many tiny, closely aggregated cysts. Six (46%) of 13 cases had raspberry-type lesions that were not detected on transvaginal sonography but were seen on MRI. Adenocarcinoma in situ (AIS) was identified in 4 postmenopausal women with raspberry-type lesions during the follow-up periods. In these cases, cytologic examination by targeted endocervical sampling using sonography enabled early detection of AIS. CONCLUSIONS: MRI and cytologic examination by targeted endocervical sampling may be very useful for predicting carcinogenesis in LEGH.

Asunto(s)

Adenocarcinoma in Situ/diagnóstico por imagen , Carcinogénesis , Cuello del Útero/diagnóstico por imagen , Imagen por Resonancia Magnética , Neoplasias del Cuello Uterino/diagnóstico por imagen , Adenocarcinoma in Situ/patología , Adulto , Anciano , Cuello del Útero/patología , Femenino , Humanos , Hiperplasia , Persona de Mediana Edad , Ultrasonografía , Neoplasias del Cuello Uterino/patología

RESUMEN

IgG4-related disease (IgG4-RD) can affect various organs, and the pancreas and salivary gland are representative examples. We report a rare case of IgG4-RD of the paratestis. A 74-year-old man presented with left scrotal swelling. Scrotopuncture drainage and cytology confirmed a clear, yellow retention liquid (130 mL) with many small, similar lymphocytes and a few plasmacytes. Many lymphoid cells were immunopositive for CD3 on a cell block section, indicating that a predominant type of lymphoid cells was T cell. There were also some CD20 immunopositive cells and a few IgG4 immunopositive cells. Two months later the left scrotal swelling had returned, and he underwent radical inguinal orchiectomy. Microscopically, there was considerable lymphoplasmacytic inflammatory infiltration, fibrosis and abundant IgG4 immunopositive cells in the paratesticular region. The histopathologic and immunohistochemistry findings were consistent with IgG4-RD. However, the abundant T cells in the scrotal fluid complicated the cytological diagnosis in our case.

Asunto(s)

Enfermedades Autoinmunes/patología , Enfermedad Relacionada con Inmunoglobulina G4/patología , Inmunoglobulina G/inmunología , Células Plasmáticas/patología , Anciano , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Biopsia/métodos , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/inmunología , Inmunohistoquímica/métodos , Masculino , Glándulas Salivales/patología

RESUMEN

OBJECTIVES: Early detection of endocervical adenocarcinoma is especially important for cancers that are human papillomavirus (HPV) negative. We investigated the clinicopathologic significance of yellow gastric-type mucin observed on Papanicolaou smears. METHODS: We described "atypical endocervical cells with gastric-type mucin" (AEC-GAM) when yellow mucin was observed in endocervical cells. We retrieved AEC-GAM samples from 58,752 cervical smears performed at Yamanashi University Hospital during our study period and reviewed clinical, cytologic, and pathologic features. RESULTS: We detected AEC-GAM in 172 (0.29 %) smears from 65 patients, and 41 of these 65 patients were histologically diagnosed with lobular endocervical glandular hyperplasia (LEGH) (43%) or pyloric gland metaplasia (20%). The prevalence of adenocarcinoma was 25% (7/28) in LEGH cases and 11% (7/65) in AEC-GAM smears. CONCLUSIONS: Yellow mucin is a diagnostic clue for endocervical glandular lesions with gastric differentiation. We recommend describing AEC-GAM on cytologic reports to improve cytologic screening for HPV-negative cervical cancers.

RESUMEN

We report a case of minimal deviation adenocarcinoma (MDA) of the uterine cervix showing varicolored cytopathologic features on Papanicolaou (Pap) smear, which may indicate features suggestive of lobular endocervical glandular hyperplasia (LEGH)-adenocarcinoma sequence. A 57-year-old woman presented with a profuse amount of watery vaginal discharge. Gynecological examination revealed a cervical mass with involvement of the right parametrium. Conventional Pap smear showed hypercellularity consisting of approximately 4 types of clusters as follows: (1) clusters showing a monolayered honeycomb sheet of endocervical cells with golden-yellow mucin and bland nuclei, (2) three-dimensional clusters showing varicolored mucin and irregular nuclear overlapping, (3) irregularly shaped clusters showing distorted chicken-wire-mesh appearance with noticeable protrusions of the nuclei and clear or faint varicolored cytoplasm, and (4) crowded clusters showing scarce mucin and nuclear atypia. The surgically resected uterus revealed LEGH-mimicking lesion with fused papillae and a cribriform pattern in the endocervix and many glands exhibiting gastric differentiation that invaded deeper areas of the stroma with a subtle stromal reaction. Compared with histologic findings, two types of clusters, the crowded cluster with scarce mucin and the cluster with distorted chicken-wire-mesh-type appearance, were considered as adenocarcinoma, and the latter was interpreted as a gastric-type adenocarcinoma. Three-dimensional varicolored type clusters showed atypical features, but insufficient atypical features compared with those of adenocarcinoma. Detection of clusters with varicolored mucin on conventional Pap smear may provide a clue for the early recognition of the malignant potential of LEGH on cytology. The chicken-wire-mesh type clusters may be a characteristic cytologic finding of MDA.

Asunto(s)

Adenocarcinoma/patología , Neoplasias del Cuello Uterino/patología , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Prueba de Papanicolaou

RESUMEN

We report a rare case of extranodal NK/T-cell lymphoma, nasal type of the uterine cervix that showed cytologic features mimicking cervical cancer. A 65-year-old woman presented with vaginal bleeding. Gynecological examination revealed a bulky tumor of the cervix. A conventional Papanicolaou-stained cervical smear showed hypercellularity consisting of numerous variably sized cohesive clusters that mimicked epithelial tumors, with a necrotic and inflammatory background. A small number of individually scattered cells were also identified. These scattered cells showed pleomorphic, often cleaved, or horseshoe-shaped nuclei and pale cytoplasm. Biopsy specimens revealed a diffuse growth of atypical cells with an angiocentric pattern. Extensive necrosis and infiltration of inflammatory cells were present. There were numerous mitotic figures. The tumor cells were positive for CD45RO, CD3ε, CD56, granzyme B, TIA-1, CD7, and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization, and negative for cytokeratin, chromogranin A, synaptophysin, CD4, CD5, CD8, CD20, and CD30. Based on these findings, this tumor was diagnosed as extranodal NK/T-cell lymphoma, nasal type of the uterine cervix.

Asunto(s)

Linfoma Extranodal de Células NK-T/patología , Neoplasias del Cuello Uterino/patología , Anciano , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Linfoma Extranodal de Células NK-T/metabolismo , Prueba de Papanicolaou , Neoplasias del Cuello Uterino/metabolismo , Frotis Vaginal

RESUMEN

Adult granulosa cell tumor (AGCT) is an uncommon neoplasm of the ovary with potential for aggressive behavior and late recurrence. The most important prognostic factor for AGCT is tumor stage. Thus, cytological assessment of pleural or ascitic fluids is crucial for initial staging and subsequent patient management. We report herein two cases of ovarian AGCT presenting with exfoliated tumor cells in pleural and ascitic fluid. The first case involved a 61-year-old woman who presented with stage Ic (a) AGCT. Seven years after initial diagnosis, pleural effusion and pleural dissemination were identified. The second case involved a 50-year-old woman who presented with stage IV AGCT with massive ascites and right pleural effusion. Fluid cytology from both cases showed cohesive or loose clusters of small uniform neoplastic cells with round-to-oval nuclei, coffee-bean-shaped nuclear grooves, small nucleoli, and scant cytoplasm. Call-Exner bodies were also observed in these cytologic specimens. In the differential diagnosis of small monomorphic tumor cells in pleural effusion or ascites, coffee-bean-shaped nuclear grooves and cell clusters forming Call-Exner bodies are diagnostic clues of AGCT.

Asunto(s)

Líquido Ascítico/patología , Tumor de Células de la Granulosa/diagnóstico , Ovario/patología , Derrame Pleural/diagnóstico , Líquido Ascítico/química , Femenino , Tumor de Células de la Granulosa/patología , Histocitoquímica , Humanos , Persona de Mediana Edad , Cavidad Pleural/patología , Derrame Pleural/patología

RESUMEN

We present an unusual case of papillary thyroid carcinoma in a 47-year-old Japanese woman. The tumor, 0.8 cm in diameter, was located in the upper left lobe of the thyroid. Histologically, we observed a microfollicular-like and trabecular arrangement of the tumor cells with marked hyalinized stroma and hyaline globules. Immunohistochemically, tumor cells were positive for thyroglobulin and thyroid transcription factor 1. Hyaline stroma and globular bodies were immunopositive for laminin and type IV collagen. MIB-1 index was approximately 1% without membranous immunoreactivity. Under the electron microscope, hyaline stroma and globules showed electron-dense, complex meshwork structures composed of granular and fibrous elements similar to the structure of the lamina densa. Genetic analysis demonstrated a BRAF(V600E) mutation. Based on these findings, we diagnosed the present tumor as a rare morphological variation of papillary thyroid carcinoma with excessive hyaline globules consisting of basal membrane materials.

Asunto(s)

Matriz Extracelular/ultraestructura , Hialina/ultraestructura , Neoplasias Primarias Secundarias/ultraestructura , Neoplasias de la Tiroides/ultraestructura , Adenocarcinoma Bronquioloalveolar/patología , Neoplasias de la Mama/patología , Carcinoma , Carcinoma Ductal de Mama/patología , Carcinoma Papilar , Matriz Extracelular/metabolismo , Femenino , Humanos , Hialina/metabolismo , Inmunohistoquímica , Neoplasias Pulmonares/patología , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Mutación , Neoplasias Primarias Secundarias/metabolismo , Proteínas Proto-Oncogénicas B-raf/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo

RESUMEN

Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare tumor, defined in the 2005 WHO classification as a primary salivary duct tumor. Previously, the neoplasm had been recognized as a variant of salivary duct carcinomas. A 56-year-old Japanese woman noticed a mass in the left subaural region. On radiological examinations, a multicystic tumor was seen in the left parotid gland. Fine-needle aspiration biopsy was performed. The smears revealed several characteristic cytologic features. The tumor cells were arranged in irregular overlapping and showed inconspicuous nuclear atypia with variable-sized and irregularly shaped cytoplasmic vacuoles. Based on these findings, a cystic tumor with uncertain malignancy was diagnosed. A parotidectomy was performed, because the tumor was slowly growing and contained solid components on the radiological images. Based on the histologic findings, along with immunohistochemistry, LGCCC was diagnosed based on resemblance to breast low-grade ductal carcinoma in situ and intraductal proliferation of tumor cells. This is the first report of the cytomorphological findings of LGCCC.

Asunto(s)

Cistadenocarcinoma/patología , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/patología , Biopsia con Aguja Fina , Cistadenocarcinoma/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de las Glándulas Salivales/diagnóstico por imagen , Sialografía , Coloración y Etiquetado , Tomografía Computarizada por Rayos X

RESUMEN

We immunochemically studied p16(INK4a) expression in 116 urine cytologic samples and compared results with 190 histologic samples. The cytologic samples were classified into 4 groups: 1, mild cellular atypia; 2, moderate cellular atypia; 3, severe cellular atypia; and 4, malignancy. Overexpression of p16(INK4a) was detected in none of 32 cases in group 1, 8 (16%) of 50 cases in group 2, 5 (42%) of 12 cases in group 3, and 11 (50%) of 22 cases in group 4. In addition, by histologic analysis, p16(INK4a) overexpression was not detected in nonneoplastic urothelium, except for a few cases of reactive atypia, but it was detected in about 50% of urothelial carcinomas. In particular, a high incidence (16/20 [80%]) of p16(INK4a) overexpression in high-grade carcinomas was noted in cytologic samples. Immunocytologic analysis of p16(INK4a) expression in cytologic samples is a useful ancillary tool for detection of urothelial carcinoma with infiltrating potential.

Asunto(s)

Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Neoplasias de la Vejiga Urinaria/patología , Anciano , Carcinoma de Células Transicionales/metabolismo , Técnicas Citológicas , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Neoplasias de la Vejiga Urinaria/metabolismo

RESUMEN

BACKGROUND: Among the combinations of coamplified genes, Myc and ERBB2 or EGFR have attracted much attention for their relevance to cytogenetics, carcinogenesis and cancer therapy. MATERIALS AND METHODS: Gene amplification of Myc, ERBB2 and EGFR were examined on 97 formalin-fixed and paraffin-embedded gallbladder carcinomas, by fluorescence in situ hybridization (FISH). RESULTS: FISH revealed three tumors had Myc amplification. By dual color FISH, one of these three tumors had two populations of tumor cells with the coexistence of amplified Myc and ERBB2, and Myc and EGFR. The second tumor had a high level of amplification of Myc without amplification of ERBB2 or EGFR. The third tumor had a low level of coamplification of Myc and ERBB2. A case of polysomy 8 also demonstrated amplification of ERBB2 and EGFR. CONCLUSION: The present study shows that genomic instability due to Myc amplification may cause specific amplification of EGFR and/or ERBB2.

Asunto(s)

Adenocarcinoma/genética , Receptores ErbB/genética , Neoplasias de la Vesícula Biliar/genética , Genes myc , Receptor ErbB-2/genética , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Receptores ErbB/biosíntesis , Femenino , Neoplasias de la Vesícula Biliar/enzimología , Neoplasias de la Vesícula Biliar/patología , Amplificación de Genes , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Receptor ErbB-2/biosíntesis

RESUMEN

The present study used immunohistochemical staining and in situ hybridization (ISH) to examine whether progression of cervical intraepithelial neoplasia, grade 2 (CIN 2) can be predicted by p16INK4a immunoexpression and high-risk human papilloma virus (HPV) ISH signal types. We studied 52 cases histologically diagnosed with CIN 2: dysplasia regressed in 28 cases; 13 cases progressed to CIN 3; and CIN 2 persisted in 11 cases. Expression of p16INK4a and high-risk HPV signal both related to grade of CIN. Stronger p16INK4a immunoexpression and a higher frequency of expression of a punctate nuclear signal were observed in CIN 2 lesions before progression compared with those before regression. CIN 2 cases in which moderate to strong immunoexpression of p16INK4a and a punctate signal were observed simultaneously progressed to CIN 3 in 10 (91%) of 11 cases. CIN 2 cases with moderate to strong immunoexpression of p16INK4a and a high-risk HPV punctate signal should be treated because of the great risk of progression.

Asunto(s)

Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Papillomaviridae/aislamiento & purificación , Displasia del Cuello del Útero/mortalidad , Neoplasias del Cuello Uterino/mortalidad , Adulto , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Persona de Mediana Edad , Pronóstico , Neoplasias del Cuello Uterino/química , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/química , Displasia del Cuello del Útero/virología

RESUMEN

OBJECTIVES: The aim of this study was to investigate differences in the process of carcinogenesis between adenocarcinoma coexistent with LEGH and conventional adenocarcinoma. And we intend to describe appropriate treatment plans for LEGH in this study. METHODS: Using the surgical pathology files of patients who visited the University of Yamanashi Hospital, Yamanashi Central Hospital and Kofu Municipal Hospital between 1996 and 2005, pathological diagnoses were reevaluated based on criteria for the diagnosis of LEGH by Nucci et al. As for the cases including adenocarcinoma with LEGH: (a) we created a map showing position of the LEGH component and adenocarcinoma component and squamo-columnar junction (SCJ) in HE-stained specimens, (b) immunohistochemical staining was performed using antibodies to CEA, HIK1083 and p53, and (c) detection of HPV DNA was performed using PCR and in situ hybridization (ISH). RESULTS: Endocervical adenocarcinoma was observed coexistent with LEGH in 5 cases (19.2%). (a) LEGH was located in a remote place from the SCJ. Sizes of lesions in the 5 cases ranged from 18 to 35 mm in width and 7 to 16 mm in depth. (b) HIK1083 was diffusely immunopositive in the cytoplasm of LEGH component and focal immunopositive in 4 cases with adenocarcinoma component. Immunopositivity for CEA was seen in the cytoplasm of adenocarcinoma component in 4 cases. Immunopositivity for p53 was seen in adenocarcinoma component nuclei in 2 cases. (c) HPV DNA was not detected using PCR and ISH in either LEGH or adenocarcinoma components. CONCLUSIONS: The present study suggests that clear differences exist in the process of carcinogenesis between adenocarcinoma associated with LEGH and conventional adenocarcinoma. LEGH may represent a precursor of cervical adenocarcinoma independent of HPV infection. As LEGH displays characteristics of precancerous mucinous adenocarcinoma, surgical treatment should be considered for LEGH growing beyond a certain size.

Asunto(s)

Adenocarcinoma/patología , Cuello del Útero/patología , Neoplasias Glandulares y Epiteliales/patología , Lesiones Precancerosas/patología , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/virología , Adulto , Anciano , Alphapapillomavirus/genética , Cuello del Útero/virología , ADN Viral/aislamiento & purificación , Femenino , Humanos , Hiperplasia , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/patología , Lesiones Precancerosas/virología , Neoplasias del Cuello Uterino/virología

RESUMEN

BACKGROUND: Porphyromonas gingivalis has been implicated as an important pathogen in the development of adult periodontitis, and its colonization of subgingival sites is critical in the pathogenic process. We recently reported the construction and characterization of human immunoglobulin G isotype clones, which were specifically reactive with recombinant (r) 40-kDa outer membrane protein (OMP) of P. gingivalis. The aim of this study was to investigate the efficacy of human monoclonal antibody (hMAb) against r40-kDa OMP of P. gingivalis to the protection alveolar bone loss by P. gingivalis in rats. METHODS: The role of 40-kDa OMP in the adherence of P. gingivalis to human gingival epithelial cells (HGECs) was examined by preincubating with r40-kDa OMP hMAb before adding the HGECs. Moreover, we used a rat model to examine the effect of the anti-r40-kDa OMP hMAb in alveolar bone loss by oral infection. Forty-six days after the last infection, the periodontal bone level was assessed morphometrically on defleshed rat jaws. RESULTS: The adherence to HGECs was reduced by 84% compared to adherence levels without the antibody. P. gingivalis could not be detected from rats in a P. gingivalis-non-infected group and a group that was administered the anti-r40-kDa OMP hMAb. The bone loss in P. gingivalis-infected animals that were administered the anti-r40-kDa OMP hMAb was significantly lower than that of P. gingivalis-infected rats. CONCLUSIONS: Our results suggest that transchromosomic mouse-derived hMAb against r40-kDa OMP of P. gingivalis protects against periodontal bone loss. This newly constructed anti-r40-kDa OMP hMAb was used to protect against periodontal diseases caused by P. gingivalis infection.

Asunto(s)

Pérdida de Hueso Alveolar/prevención & control , Anticuerpos Antibacterianos/inmunología , Anticuerpos Monoclonales/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Infecciones por Bacteroidaceae/complicaciones , Porphyromonas gingivalis/inmunología , Pérdida de Hueso Alveolar/inmunología , Pérdida de Hueso Alveolar/microbiología , Animales , Anticuerpos Antibacterianos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Células Cultivadas , Modelos Animales de Enfermedad , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Encía/citología , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina G/uso terapéutico , Isotipos de Inmunoglobulinas , Masculino , Periodontitis/inmunología , Periodontitis/microbiología , Porphyromonas gingivalis/patogenicidad , Ratas , Ratas Wistar , Proteínas Recombinantes , Estadísticas no Paramétricas

RESUMEN

BACKGROUND: As a safe immunotherapeutic approach, human monoclonal antibody (hMAb) may be effective in clearing periodontopathic bacteria. The trans-chromosomic (TC) technology has recently been applied to construction of the TC mouse, which enables us to incorporate entire human chromosome fragments containing immunoglobulin (Ig) gene cluster. The aim of this study is to establish TC mouse-derived hMAb, and to test the in vitro opsonophagocytic activity. METHODS: Human Ig-producing TC mouse was immunized by recombinant 40-kDa outer membrane protein (r40-kDa OMP) of Porphyromonas gingivalis 381, and the spleen cells were fused with the mouse myeloma cell line. The specificity of antir40- kDa OMP hMAb was evaluated with the enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance assays. Flow cytometric analyses were performed to assess the opsonophagocytic activity. RESULTS: We successfully constructed 99 IgG isotype clones (IgG1: 84; IgG2: 11; IgG4: four clones), which were specifically reactive with r40-kDa OMP. The anti-r40-kDa OMP IgG1 hMAbs promoted phagocytosis of P. gingivalis by neutrophils. Futhermore, an increased opsonophagocytic activitity of anti-r40-kDa OMP IgG1 hMAbs was observed not only in P. gingivalis 381, but also in the W50, W83, and Su63 strains. CONCLUSION: Our results document the TC mouse-derived hMAb to promote neutrophil phagocytosis of P. gingivalis, suggesting an immunotherapeutic option for clearance of P. gingivalis.

Asunto(s)

Anticuerpos Monoclonales/inmunología , Neutrófilos/inmunología , Fagocitosis/inmunología , Porphyromonas gingivalis/inmunología , Animales , Anticuerpos Monoclonales/genética , Reacciones Antígeno-Anticuerpo , Humanos , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Ratones

RESUMEN

Carcinomas of the biliary tract have a poor prognosis. It is important to understand the molecular genetic characteristics of these tumours in order to employ newer effective treatments and to improve patient prognosis. There is increasing evidence that overexpression of tyrosine kinase growth factor receptors such as ErbB-2, epidermal growth factor receptor (EGFR), and Met may play important roles in the development of biliary tract carcinomas. The aim of this study was to assess the potential for novel chemotherapies targeting these receptors. Overexpression of the tyrosine kinase receptor proteins was examined by immunohistochemistry in 221 biliary tract carcinomas, of which 28 were from the intrahepatic bile duct, 78 from the extrahepatic bile duct, 89 from the gall bladder, and 26 from the ampulla of Vater. Positively stained tumours were further examined for gene amplification by fluorescence in situ hybridization. Overexpression of ErbB-2 was found in 15.7%, 11.5%, and 5.1% of carcinomas of the gall bladder, ampulla of Vater, and extrahepatic bile duct, respectively, and gene amplification was present in 79% of these. Overexpression of EGFR was found in 8.1% of tumours with no predominant location and was also associated with gene amplification with high frequency (77%). Met overexpression, most frequent in intrahepatic bile duct carcinomas (21.4%), was not associated with gene amplification. It is proposed that the new adjuvant chemotherapies could be directed to carcinomas of the biliary tract in which ErbB-2 and EGFR are overexpressed.

Asunto(s)

Neoplasias del Sistema Biliar/genética , Receptores ErbB/genética , Genes erbB-2/genética , Proteínas Proto-Oncogénicas c-met/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Extrahepáticos/patología , Conductos Biliares Intrahepáticos/patología , Neoplasias del Sistema Biliar/patología , Neoplasias del Conducto Colédoco/genética , Neoplasias del Conducto Colédoco/patología , Femenino , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/patología , Amplificación de Genes/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética

RESUMEN

The LIM domain is a protein-protein interaction motif critically involved in a variety of fundamental biological processes, including cytoskeletal organization, cell lineage specification, and organ development. In this study we examined the expression of the LIM proteins paxillin and Hic-5 in adult human tissues by immunohistochemistry and immunoblotting. Paxillin expression was widespread and observed both in non-muscle and muscle tissues. Of the latter, paxillin was mainly expressed in multinuclear striated muscle. In contrast, Hic-5 showed restricted expression and was expressed in muscle tissues, mainly in mononuclear smooth muscle. Taken together with previous findings, it appears likely that the counterbalance between paxillin and Hic-5 may be deeply involved in muscle differentiation.

Asunto(s)

Moléculas de Adhesión Celular/metabolismo , Proteínas del Citoesqueleto/metabolismo , Fosfoproteínas/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Adulto , Humanos , Immunoblotting , Inmunohistoquímica , Músculo Esquelético/metabolismo , Músculo Liso/metabolismo , Especificidad de Órganos , Paxillin