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M Fukayama

Publications and source records attributed to M Fukayama.

At least 55 records · Page 3Linked to original sources
PubMed1999

p16 inactivation in small-sized lung adenocarcinoma: its association with poor prognosis.

p16, an inhibitor of cell cycle machinery, is frequently inactivated in non-small cell carcinoma of the lung (NSCCL). To clarify the significance of p16 inactivation in the progression of lung adenocarcinoma, we immunohistochemically evaluated p16 protein status and Rb, p53 and cyclin D1 expression in 51 surgically resected adenocarcinomas that were less than 3 cm in diameter (median follow-up period: 52.5 months). Twenty-one of 51 adenocarcinomas showed negative immunostaining for p16. Twenty adenocarcinomas were also negative for Rb, while 31 and 13 were positive for p53 and cyclin D1, respectively. Loss of p16 expression was significantly correlated with scar grade, lymphatic permeation, lymph node metastasis and clinical stage. Rb protein expression was also inversely correlated with scar grade, pleural involvement and vascular invasion. When the cases were stratified according to the expression of both proteins, the Rb-/p16- subset (7/51) consisted of poorly differentiated adenocarcinoma with a higher grade of invasion. While Rb, p53 and cyclin D1 protein status showed no significant correlations with prognosis, p16 inactivation was significantly correlated with poor prognosis, and the prognosis of Rb-/p16- was the worst among the 4 subsets. Inactivation of p16 may play a role in accelerating scar formation and lymph node metastasis, and may contribute through these mechanisms to poor prognosis in patients with small-sized lung adenocarcinoma.

Adenocarcinoma↗
PubMed1999

New DNA polymorphisms of human MMH/OGG1 gene: prevalence of one polymorphism among lung-adenocarcinoma patients in Japanese.

MMH/OGG1 is an 8-hydroxyguanine-specific DNA glycosylase/AP-lyase, one of the mutator enzymes for the excision repair of 8-hydroxyguanine. DNA polymorphisms in human MMH/OGG1 gene were newly identified and analyzed to examine a possible association with lung-cancer risk by a population-based study. Polymorphic allele 3 in hMMH/OGG1 exon 1 was significantly prevalent among Japanese patients with adenocarcinoma of the lung [odds ratio (OR): 3.152, 95% confidence interval (CI): 1.266-7.845], indicating that the excision repair of 8-hydroxyguanine may play a role in predisposition to lung cancer.

Adenocarcinoma↗
PubMed1999

Granulocytic sarcoma of the thymus in a nonleukaemic patient.

We report a case of granulocytic sarcoma arising from the thymus in a 17-year-old nonleukaemic patient. The patient presented with an anterior mediastinal tumour and underwent surgical resection. Histological examination showed a diffuse infiltrate of immature round cells in the thymus. Tumour cells were diffusely peroxidase positive, but naphthol AS-D chloroacetate esterase negative. Immunohistochemical staining revealed expression of CD34 and terminal deoxynucleotidyl transferase (TdT), but not of CD13 and CD33. Ultrastructurally, electron-dense or medium-density granules were present in the cytoplasm. Four months after successful autogenic bone marrow transplantation, pleural and pericardial fluid contained tumour cells with azurophilic granules, which expressed CD13 and CD33, but not CD34 and TdT. The patient died of the disease 18 months after clinical manifestation, but still without developing leukaemia. The granulocytic sarcoma in the present case may have originated from myeloid precursors in the thymus and remained within the extramedullary site despite the differentiation into a more committed myeloid lineage at the relapse.

Adolescent↗
PubMed1999

Embryonic form of smooth muscle myosin heavy chain (SMemb/MHC-B) in gastrointestinal stromal tumor and interstitial cells of Cajal.

Myosin heavy chain (MHC) isoform expression was evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) to clarify a possible link between gastrointestinal stromal tumor (GIST) and interstitial cells of Cajal (ICCs) in the gastrointestinal (GI) tract. Using monoclonal antibodies against MHC isoforms, 18 of 27 GISTs (67%) showed immunoreactivity for non-smooth-muscle myosin or the embryonic form of MHC (SMemb), but only one tumor showed immunoreactivity for smooth muscle cell (SMC)-specific isoforms (SM1 and SM2). Co-expression of KIT or CD34, which is also expressed in GIST and ICCs, was demonstrated in 18 (100%) and 16 SMemb-positive tumors (89%), respectively. Otherwise, the expression of SMemb in GIST was not correlated with the patient's age or sex, tumor size, histological grade of GIST, or expression of mesenchymal cell markers, such as alpha-smooth muscle actin (alpha-SMA) or S100 protein. By double-fluorescence immunostaining of the tunica muscularis of the GI tract wall, co-expression of KIT, CD34, and SMemb was demonstrated in ICCs, which were negative for SM1 and SM2. RT-PCR analysis confirmed that GIST expressed SMemb-mRNA, which lacked neuronal cell-specific inserts of 30 bp. These facts further strengthen the current hypothesis that GIST is a tumor of ICCs.

Adult↗
PubMed1999

Polymerase chain reaction screening of immunoglobulin heavy chain and T cell receptor gamma gene rearrangements: a practical approach to molecular DNA analysis of non-Hodgkin's lymphoma in a surgical pathology laboratory.

Characterization of the clonality of non-Hodgkin's lymphoma (NHL) by the rearranged segments of immunoglobulin heavy chain (Ig(H)) or T cell receptor (TCR) genes is not only useful in the confirmation of the diagnosis but also for the future assessment of how a secondary lymphoma, such as a recurrence or another primary lymphoma, occurs. As a practical approach to obtaining and registering this information in a surgical pathology laboratory, FR3 and FR1 regions of Ig(H) gene and TCRgamma gene were concurrently amplified by polymerase chain reaction (PCR) using each pair of consensus primers and the same PCR protocol. Examined samples consisted of 134 primary NHL (phenotypically, 108 B cell and 26 T cell NHL), 19 reactive lymphadenopathies, as well as five secondary lymphomas whose primary lesions were included in this study. Among the primary NHL, the combined PCR analysis disclosed the clonality in 103 of 134 NHL (77%), by FR3 PCR in 77 B cell and two T cell NHL, by FR1 PCR in 59 B cell and one T cell NHL, and by TCRgamma PCR in 11 B cell and 17 of 26 T cell NHL, but in none of the reactive lymphadenopathies. Among the secondary lymphomas, the same pattern of PCR analysis was obtained in two cases (the durations between first and second lymphomas; 6 and 10 months), which suggested recurrence. In contrast, different results were obtained in three cases (17-37 months), which indicated another primary or emergence of the subclones. The results of Southern blot analysis were concordant with the PCR results of the first and the secondary lymphomas. Although the combined PCR analysis cannot replace Southern blot hybridization because of its lower detection rate, it can select those cases suitable for further Southern blot analysis thus reducing the number of unnecessary examinations by nearly 75%. This approach may also be useful in the comparative evaluation of primary and secondary lymphomas.

Biomarkers, Tumor↗
PubMed1999

MEN1 gene mutations in sporadic neuroendocrine tumors of foregut derivation.

Foregut-derived neuroendocrine (NE) tumors occur sporadically or in association with multiple endocrine neoplasia type 1 (MEN1) syndrome. Thirty-nine sporadic NE tumors of foregut derivation (six thymic, 21 bronchial, three gastric, and nine pancreatic tumors) as well as two hindgut-derived rectal carcinoids for somatic MEN1 gene mutation were analyzed by direct sequencing analysis. Five tumors showed mutations: nonsense mutations (Q393X and R98X) in thymic and pancreatic NE tumors, respectively, a 4 b.p. deletion (357del4) in a gastric NE carcinoma, and missense mutations (D172Y and S178Y) in pancreatic NE tumors. No mutation was identified in pulmonary or rectal NE tumors. In a patient with a pancreatic NE tumor (D172Y), the corresponding germline DNA showed the same mutation, suggesting that sporadic MEN1 syndrome was masked in this case. Somatic MEN1 gene mutations and deletions may play a crucial role in the tumorigenesis of a subset of foregut-derived NE tumors. Sporadic MEN1 syndrome may occur as a sporadic NE tumor of the pancreas.

Adult↗
PubMed1999

Pulmonary fibrosis and lung carcinoma: a comparative study of metaplastic epithelia in honeycombed areas of usual interstitial pneumonia with or without lung carcinoma.

Usual interstitial pneumonia (UIP), or idiopathic pulmonary fibrosis, has been considered to be associated with a high risk for lung carcinoma. To investigate this well-known but still equivocal relationship, we reviewed the clinical features of UIP autopsy cases with or without lung carcinoma (n = 32 and 38, respectively), and compared the morphology and cell kinetics of metaplastic epithelia in the honeycombed areas (n = 11, each group). Thirty-two of 70 UIP autopsy cases showed lung carcinomas. Clinically, UIP with lung carcinoma showed a male predominance (P = 0.001), a higher rate of smoking history (P = 0.001) and a later onset of UIP (P = 0.02), compared with UIP without lung carcinoma. Most of the carcinomas were peripheral in origin (90%), and 65% were topographically associated with honeycombed areas or the border between honeycombing and non-fibrotic areas. Quantitative assessment of the metaplastic epithelia in the honeycombed areas revealed that squamous metaplasia, but not cuboidal cell metaplasia or bronchial cell metaplasia, occurred more frequently in UIP with lung carcinoma than in UIP without lung carcinoma (P = 0.02). There were no significant differences between the two groups with regard to the labeling indexes of Ki-67 and p53 in the metaplastic epithelia, including squamous metaplasia. The degree of atypical squamous metaplasia was not different between the two groups. The quantitative predominance of squamous metaplasia in the honeycombed areas may not be a precursor for lung carcinoma, but might reflect a constitutional susceptibility of UIP patients to develop a lung carcinoma.

Adenocarcinoma↗
PubMed1999

Regional proliferation of HMB-45-positive clear cells of the lung with lymphangioleiomyomatosislike distribution, replacing the lobes with multiple cysts and a nodule.

The authors report a case of a localized lesion of the lung presenting as multiple cysts and as a tumor in the right upper and middle lobes, consisting of a diffuse proliferation of clear cells with intralysosomal glycogen granules and human melanin black (HMB)-45 immunoreactivity. A 33-year-old woman complained of dyspnea because of the enlargement of bullae in the right upper and middle lung fields without stigmata of tuberous sclerosis. Resection showed multiple, various-size air-filled cysts and a tumor. The cysts in the resected lungs were reminiscent of lymphangioleiomyomatosis (LAM), accompanied by the diffuse proliferation of clear cells in the interstitium. The tumor, 1.8 cm in diameter, resembled a clear cell tumor of the lung (CCTL) and showed proliferation of clear cells with sinusoidlike vascular spaces. Both forms of proliferation were continuous spatially, and both constituent cells showed diffuse HMB-45 immunoreactivity. The cells that comprised a nodule revealed ultrastructurally abundant cytoplasmic glycogen, which was in the form of free and membrane-bound glycogen granules. This case may represent a particular pulmonary lesion consisting of CCTL-LAM hybrid cells, which share the cytologic features with CCTL cells on one hand, and the proliferative pattern and potential with LAM cells on the other.

Adenocarcinoma, Clear Cell↗
PubMed1999

C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the GI tract, and expresses KIT and CD34 in most cases. Gain-of-function mutation of the c-kit proto-oncogene has been described, but its significance in GIST has not yet been fully evaluated. Mutation in exon 11 of the c-kit gene was determined by both polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing in primary and metastatic GISTs and esophageal leiomyomas in Japanese subjects. C-kit gene mutation was identified in 15 of 48 primary GISTs (31%), four of seven metastatic GISTs, but none of the leiomyomas. Three mutations were mis-sense point mutations, and 16 were in-frame deletions of 3-48 bp. C-kit gene mutation was observed equally in low- and high-risk groups, and was not related to any clinical and pathologic factors, phenotypes or Ki-67 labeling index (LI) of tumor cells. In five of 15 deletion mutations (four in primary tumors and one in a metastatic tumor), the mutations were present at the distal location of exon 11 of the c-kit gene, which was a minor mutation in previous reports from Finland and the USA. C-kit gene mutations in GIST are not always related to a poor prognosis, but further comparative studies are necessary in Western and Japanese populations.

Adult↗
PubMed1999

[Levofloxacin-induced neurological adverse effects such as convulsion, involuntary movement (tremor, myoclonus and chorea like), visual hallucination in two elderly patients].

Levofloxacin-induced-neurological adverse events such as convulsion, involuntary movement (tremor, myoclonus and chorea-like) and visual hallucination in two elderly patients are reported. A 67-year-old man with minor alcoholism and a past-history of gastrectomy and cholecystectomy was given 300 mg/day of oral levofloxacin and fulfenamic acid for an upper respiratory infection. On the 4th day, he reported gradual exacerbation of hand tremor which resembled chorea-like involuntary movement and gait disturbance. He also experienced visual hallucinations. On the 7th day, he suffered generalized convulsions and was admitted. Serum concentration of levofloxacin at this time (3 hours after last administration of a 100 mg tablet of levofloxacin) was 3.6 micrograms/ml. Cessation of the agents promoted complete recovery of these neurological adverse effects within a week. Another 85-year-old man with chronic bronchitis and slight renal impairment received long term administration of 200 mg/day of levofloxacin. On the 68th day of administration, gradual exacerbation of gait disturbance, dysarthria and chorea-like involuntary movement occurred. On the day of admission, 76 days after the start of administration, the serum level of levofloxacin was 2.55 micrograms/ml and that of spinal fluid was 1.12 micrograms/ml (3 hours after the last administration of a 100 mg tablet of levofloxacin). Cessation of the agents promoted complete recovery of these neurological adverse effects within the next two weeks. Both patients had no apparent neurological disorders except age-related brain atrophy. Age-related renal and brain impairment might have contributed to the neurological adverse effects of levofloxacin.

Aged↗
PubMed1999

[Evaluation of antimycotics in the elderly].

Incidence and risk factors were analyzed in elderly patients with deep-seated mycosis. Twenty cases with candidiasis or aspergillosis were found in 1,663 autopsy cases. Intravascular catheters and administration of antibiotics were prominent risk factors for candidiasis as was steroid therapy. Leukocytopenia due to anti-cancer drugs caused aspergillosis. Preventive use of AMPH in patients with hematological malignancies or with steroid therapy was effective against mycosis. Although AMPH is also effective for almost all kinds of deep-seated mycosis, we rarely administered it to elderly patients because of its nephrotoxicity. The safe use of antimycotics requires checking drug sensitivity of causative fungi in a laboratory, and establishing the optimal dosage for patients with impaired renal function.

Aged↗
PubMed1999

[Mucosa-associated lymphoid tissue lymphoma with Sjögren's syndrome].

A 68-year-old woman presented with Sjögren's syndrome. Chest X-ray films disclosed consolidated shadows in the right S2 and an infiltration shadow in the right S8 with small nodules. Pathological examination of transbronchial lung biopsy (TBLB) specimens revealed lymphocytic infiltrations that stained positive with UCHL-1 and L 26 in immunohistochemical studies. Lung tissue specimens obtained by video-assisted thoracic surgery showed lympho-epithelial lesions with dense lymphocytic infiltration. Southern blot hybridization and polymerase chain reaction (PCR) assays demonstrated monoclonality and immunoglobulin heavy chain gene rearrangement. These findings yielded a diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. The detection of rear-ranged genes encoding for immunoglobulin heavy chains is useful for the diagnosis of primary pulmonary lymphoproliferative disorders, especially malignant lymphomas.

Aged↗
PubMed1999

Microsatellite instability and loss of heterozygosity in primary and secondary proliferative lesions of the parathyroid gland.

Clonality and genetic abnormalities were evaluated to characterize proliferative lesions of the parathyroid gland. Fourteen lesions from patients with single-gland proliferation (adenomas [PA]), 6 lesions from patients with multiple-gland proliferation (primary hyperparathyroidism [PHPT]), and 47 lesions from 16 patients with secondary hyperparathyroidism (SHPT) were examined. Based on the X chromatin inactivation pattern, which was revealed by a HUMARA assay of lesions from female patients (n = 34; 24 informative cases), monoclonality was demonstrated in 6 of 10 PA (60%), 2 of 5 PHPT (40%), and 6 of 9 SHPT lesions (14 of 27 lesions, 52%). By PCR analysis using 17 microsatellite markers on eight chromosomes (chromosomes 1, 2, 3, 5, 6, 11, 13, and 17), loss of heterozygosity was sporadically observed in 4 of 14 PA, 3 of 6 PHPT, and 7 of 47 SHPT lesions, in most cases on a single locus of chromosome 11. On the other hand, microsatellite instability was observed more frequently: ie, in six PA, five PHPT, and nine SHPT lesions. The profile of microsatellite instability depended on the type of proliferation: microsatellite instability (MI) seemed to cluster in the region of chromosome 11 in PA. Microsatellite instability on TP53 was observed in 3 of 6 PHPT lesions and in 2 of 47 SHPT lesions but in no PA lesions. Microsatellite instability on Mfd47 was observed in only some cases of SHPT. Although no significant correlation was identified among histologic features, clonality, and genetic abnormalities in cases of primary proliferation, genetic abnormalities were more frequently observed in SHPT lesions that lacked fat tissues. Thus, genetic instability might be important in proliferative disorders of the parathyroid gland, either with or without uremia. However, genetic instability seems to be induced by different mechanisms in the three types of proliferation studied. In SHPT, the absence of fat tissues may indicate that the proliferation is accompanied by genetic changes.

Adenoma↗
PubMed1998

Telomerase activity in gastrointestinal stromal tumors.

BACKGROUND: Telomerase activity has been observed in 80-90% of carcinomas derived from various organs. However, to the authors' knowledge this report is the first assessment of telomerase activity in gastrointestinal stromal tumors (GISTs). METHODS: Telomerase activity was analyzed by the telomerase repeat amplification protocol assay in 29 tumors from 26 patients (23 primary tumors from 22 patients, 1 pair of primary and metastatic tumors from 1 patient, and 4 metastatic tumors from 3 patients). Phenotypes, tumor cell proliferation, and overexpression of p53 protein were evaluated immunohistochemically. RESULTS: Seven of 24 primary tumors (29%) and 5 of 5 metastatic tumors (100%) showed telomerase activity. Telomerase activity positive (+) GISTs were significantly larger (P < 0.05) and showed a significantly higher rate of proliferation than telomerase activity negative (-) tumors (P < 0.0001). All telomerase activity (+) GISTs were classified histologically as high risk tumors. Conversely, 15 of the 17 telomerase (-) GISTs were classified histologically as low risk tumors (P < 0.0001). With regard to p53 immunoreactivity, two and seven telomerase activity (+) tumors showed diffuse and sporadic positivity, respectively, whereas only five telomerase activity (-) tumors showed only focal or sporadic positivity. Telomerase activity was correlated significantly with poor prognosis (P < 0.05) in the patients in whom the primary GISTs were evaluated (n = 23). CONCLUSIONS: Telomerase activity may be a useful marker for evaluating the malignant potential of GIST. A distinct subgroup of GISTs is a target for therapy with a telomerase inhibitor.

Adult↗
PubMed1998

High frequency of fibroblast growth factor (FGF) 8 expression in clinical prostate cancers and breast tissues, immunohistochemically demonstrated by a newly established neutralizing monoclonal antibody against FGF 8.

Fibroblast growth factor (FGF) 8, also known as androgen-induced growth factor, was originally isolated from an androgen-dependent mouse mammary Shionogi carcinoma SC-3 cell line, in which it was shown to have androgen-regulated properties. We previously demonstrated that Fgf 8 transcripts were detected in several human prostate and breast cancer cell lines and that recombinant FGF 8 was mitogenic to an androgen-sensitive prostate cancer LNCaP cell line. In this study, to characterize the roles of FGF 8 in clinical hormone-responsive cancers, we established a monoclonal antibody against FGF 8. In Western blots, this antibody specifically interacted with a FGF 8b isoform that was identical between mouse and human but was not identical to other murine 8a and 8c isoforms. In a cell growth assay using SC-3 cells, the newly established anti-FGF 8 antibody blocked androgen- and FGF 8-stimulated growth but not basic FGF-stimulated growth. Immunohistochemical analyses by use of the established anti-FGF 8 antibody demonstrated that FGF 8 was frequently expressed in human prostate cancers, appearing in 40 of 43 cases (93%), whereas both prostatic hyperplasia specimens and normal prostate tissues included in biopsy specimens were negative for FGF 8 expression. On the other hand, FGF 8 was detected in normal ductal and lobular epithelial cells in breast tissues. FGF 8 was also frequently expressed in various breast diseases, including fibroadenomas (5 of 5 cases, 100%), intraductal papillomas (3 of 3 cases, 100%), ductal hyperplasias (3 of 6 cases, 50%), and breast cancers (8 of 12 cases, 67%). Androgen receptors were also immunohistochemically detected in FGF 8-positive prostate cancers (40 of 40 cases, 100%) and FGF 8-positive breast diseases (17 of 19 cases, 89%). These findings strongly suggest that FGF 8 is involved in hormone-related tumorigenesis of the prostate and breast.

Animals↗
PubMed1998

Neuroendocrine differentiation in thymic epithelial tumors with special reference to thymic carcinoma and atypical thymoma.

To determine the neuroendocrine (NE) features of thymic epithelial tumor, immunohistochemistry and electron microscopy studies were performed on eight NE tumors (thymic carcinoids) and 26 non-NE tumors (nine thymic carcinomas, five atypical thymomas, and 12 thymomas other than lymphocytic thymoma). Immunohistochemical studies were performed with antibodies against general markers for NE cells (synaptophysin, alpha subunit of a guanine nucleotide-binding protein, Go, and small-cell lung carcinoma cluster 1 antigen), and a broad panel of antibodies for hormonal substances. Thymic carcinoid showed synchronous diffuse immunoreactivity for the three NE markers and contained cells that were positive for a variety of hormonal products: human chorionic gonadotropin (hCG) alpha-subunit (eight of eight), hCG beta-subunit (three of eight), adrenocorticotropic hormone (ACTH) (three of eight), calcitonin (two of eight), calcitonin gene-related peptide (two of eight), and serotonin (one of eight). Conversely, although positivity for NE markers was neither synchronous nor diffuse in non-NE tumors, seven of nine thymic carcinomas, three of five atypical thymomas (focal or dispersed distribution), and none of the five thymomas were positive for at least two of these NE markers. A small number of neoplastic cells were positive for hCGalpha-subunit or ACTH in three thymic carcinomas and one atypical thymoma. Ultrastructurally, dense core granules (DCG) were much more frequent in thymic carcinoid, but several DCG-like granules were identified in 12 of 13 non-NE tumors with or without immunoexpression of NE markers. The presence of focal or dispersed NE cells in thymic carcinoma and atypical thymoma may reflect multidirectional differentiation within the tumor, which, like cytological atypia, epithelial CD5 expression, and lack of immature T cell infiltration, may be another feature of this group at thymic tumors.

Adenocarcinoma↗
PubMed1998

Analysis of K-ras oncogene mutation directly applied to atypical cell clusters on cytologic smear slides of bile and pancreatic juice.

To develop an objective reference for the cytological evaluation of atypical cells in bile and pancreatic juice, we analyzed K-ras oncogene mutation in atypical cell clusters, which were collected directly from cytological smear slides; 50 samples (cell clusters) from 31 smear slides of 21 patients with carcinomas of the pancreatic head region, and nine samples from eight cases of benign disease. These cell clusters (5-1000 cells/cluster) were selectively suspended in buffer containing proteinase K, and subjected to DNA extraction. K-ras codon 12 mutation was determined by polymerase chain reaction amplification, followed by digestion with BstNI. The K-ras gene was amplified in 20 of 21 cases with carcinoma (34/50 samples), and in seven of eight cases with non-neoplastic disease (8/9 samples). Among the cases of which primary tumors showed K-ras mutation, amplification was successful in 10 of 11 cases; mutation was demonstrated in three of seven cases with cytologically atypical cells (4/11 samples), and in three of three cases with cytologically malignant cells (5/7 samples). No mutation was identified in the 10 cases of carcinoma without K-ras mutation (0/15 samples), or in eight cases of non-neoplastic disease (0/8 samples). Cytological details could be comparatively evaluated between atypical cell clusters with or without mutation on the same smear slides in two cases. This type of direct analysis of atypical cell clusters may be useful in the self-assessment of cytological diagnosis of bile and pancreatic juice.

Adenocarcinoma↗