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Yasuhiko Kitayama

Publications and source records attributed to Yasuhiko Kitayama.

11 recordsLinked to original sources
PubMed2006

Chromosomal numerical abnormality profiles of gastrointestinal stromal tumors.

BACKGROUND: Biological variations in and the heterogeneity of gastrointestinal stromal tumors (GISTs) are well known, but chromosomal numerical abnormality (CNA) has not been fully examined especially in this context. The aim of this study is to test CNA as a possible biological predictor of biological behavior of GISTs. METHOD: We applied microwave-assisted FISH protocol to pathological archives of GIST tumors displaying different clinical features to characterize the CNA profile of these tumors. A panel of 18 centromere enumeration probes (CEP) and 24 bacterial artificial chromosome (BAC) or P1-derived artificial chromosome (PAC) probes containing genes like Aurora kinases (AURKs) and other candidate genes involved in human carcinogenesis were used. CNA profiles, histopathological risk categorization and Ki-67 labeling indexes of 23 primary and/or metastatic GIST tumors of 12 subjects (both primary and metastatic in 7 subjects) were compared between primary GIST with and without metastases, and between metastatic and primary portions in 7 individuals. RESULTS: CNA in the primary sites was more extensive in the GISTs with recurrence and metastasis than in those without, especially as to the loss of chromosome 20 and genomic imbalance of AURKA-containing BAC probe on 20q in the cases with metastasis. The consistent loss of one allele of chromosome 14q was also noted. Interestingly, both primary and metastatic tumors in identical individuals had similar CNA profiles. CONCLUSION: The extent of CNA differed between GISTS with and without recurrence or metastasis; thus, FISH analysis of specimens from the primary sites may predict the biological behavior of this tumor.

Adult↗
PubMed2006

Chromosomal numerical abnormalities in early stage lung adenocarcinoma.

Chromosomal numerical abnormalities (CNA) are ubiquitous in human cancers. However, the question of when a CNA occurs in the course of tumor generation and progression, is controversial. Recent radiological scrutiny has enabled the identification of small peripheral lesions in the lung. A chromosome-wide investigation encompassing almost all the chromosomal centromeres was performed using modified fluorescence in situ hybridization on the archived pathological samples of 16 atypical adenomatous hyperplasia (AAH) and 30 lung adenocarcioma (AdCa) specimens including those smaller than 1 cm in size. The prevalence of the gain was more extensive in male than in female patients, and in non-smokers than in smokers. It tended to be greater in poorly differentiated AdCa, in moderately differentiated AdCa, and in well-differentiated AdCa cases, in that order. Most AAH had non-specific gains affecting all the examined chromosomes. The prevalence of the gain differed significantly between AAH and bronchioloalveolar carcinoma (BAC) </= 1 cm, but not between BAC < 1 cm and well-differentiated AdCa > 1 cm. It is proposed that the CNA is a distinct phenomenon occurring in the early or premalignant stage of lung AdCa, and that the CNA itself may not be a sequel in the carcinogenetic process, but a driving factor in carcinogenesis.

Adenocarcinoma↗
PubMed2006

Repeated fluorescence in situ hybridization by a microwave-enhanced protocol.

A novel re-hybridization protocol for pathology archive sections that uses microwave-assisted fluorescence in situ hybridization (FISH) is described. Stripping the probe from the pathology archive sections with HCl and re-hybridizing with the next probe by intermittent microwave irradiation generated clear signals without background noise. Repeated stripping and hybridization with numerous bacterial artificial chromosome (BAC)-derived probes would identify the profile of genome-wide changes in small lesions on sections.

Chromosome Aberrations↗
PubMed2005

Modified fluorescence in situ hybridization methods using pathology archives.

Brain tumors, like many other common tumors, are frequently associated with chromosomal numerical abnormalities. However, as the identification of abnormal characteristics by conventional cytogenetic or molecular methods has been hampered by technical difficulties, minimal information has been available about specific chromosomal or locus-specific gene alterations. Recently, fluorescence in situ hybridization (FISH) has emerged as a powerful clinical and research tool for the assessment of genomic instability within interphase nuclei. Here, we developed a modified FISH protocol including short-term microwave treatment to analyze specimens from the pathology archives that had been routinely processed and stored. The FISH signals obtained using this modified method showed a significant improvement compared with those obtained using the standard FISH method. This new technique thus enables the analysis of various paraffin-embedded tissue sections of intracranial tumors obtained under inappropriate fixation conditions. We highlight the advantages of this modified FISH procedure on a tissue microarray of archival materials for current diagnostic and investigative neuropathology applications.

Brain Neoplasms↗
PubMed2005

Simultaneous imaging of membrane antigen and the corresponding chromosomal locus in pathology archives.

A new procedure for the simultaneous staining of membranous antigens, such as tyrosine kinase-type cell surface receptor HER2 (c-erbB2), and the corresponding chromosome (chromosome 17 for c-erbB2) in the same cell for use in examining pathology archives is presented. A multistep procedure involving microwave-assisted fluorescence in situ hybridization and immunofluorescence yielded cell images having c-erbB2 on the membrane and genomic signals from the chromosome 17 centromere and the c-erbB2 locus. Furthermore, a combination of microwave-assisted chromogenic in situ hybridization and immunohistochemistry found colorized signals from both chromosome 17 centromere in the nuclei and c-erbB2 on the membranes of individual cells. Quantitative image analysis further confirmed the presence of a significantly stronger c-erbB2 immunoreactivity on cells containing three or more signals from chromosome 17 than from those with less than three signals. It was possible to extend the constellation of cell surface markers and corresponding chromosomes or locus-specific makers to several other genes including CDH1. In this case, the disappearances of CDH1 expression, a CDH1 locus signal, and a centromere enumeration probe (CEP) 16 signal were simultaneously demonstrated in the less-adhesive tumor cells. Thus, it is believed that this procedure might pave the way for exploiting pathology archives for the genotype-phenotype analysis of individual cells.

Antigens, Surface↗
PubMed2005

Nonrandom chromosomal numerical abnormality as a new molecular cytogenetic tumor marker--a retrospective study of 60 gastric cancer cases.

Chromosomal numerical abnormality (CNA) is one of the distinct characteristics of human cancers, though the mechanisms and tumor specificity of this phenomenon have not been adequately analyzed. Recently, we developed a new sensitive fluorescence in situ hybridization (FISH) method that involves short-term microwave (MW) treatment for hybridization. In this study, we applied this modified FISH technique to investigate the CNA of 60 gastric cancer cases with a panel of 18 chromosome-specific alpha-satellite probes (for chromosome 1-4, 6-12, 15-18, 20, X, and Y) and region-specific probes (c-myc, p53, and Her-2/neu) to enumerate the respective chromosome numbers in interphase nuclei of formalin-fixed paraffin-embedded sections. The numerical aberrations of chromosome 1, 3, 8, 17, 20, and X were frequent regardless of histologic types, whereas aberrations of chromosomes 10, 15, and 18 occurred less frequently (p<0.001). From a histopathological standpoint, the mucocellular type of carcinoma had stable CNA in comparison with the tubular type of carcinoma (21.7+/-9.63% vs. 58.3+/-12.32%, p<0.001) and, of note, there was less extensive CNA in female cases. A dramatic difference in patient outcome was detected according to the involvement of chromosomes 3, 10, 11, 12, 17, and Y; cases with CNA of these chromosomes had a worse prognosis (p<0.001). A two-step analysis of the CNA of 6 chromosomes and locus specific gene abnormalities successfully divided gastric cancer cases into those with a good outcome and those with a poor outcome. This analysis allows one to more accurately predict prognosis than by using a simple classification based on conventional clinicopathological diagnosis.

Adult↗
PubMed2003

Peripheral lung adenocarcinomas: 10 mm or less in diameter.

BACKGROUND: Few reports have been published regarding peripheral lung adenocarcinomas that are 10 mm or less in diameter. This is considered to be the smallest tumor size detectable by present diagnostic modalities. METHODS: Clinicopathologic studies were performed in 57 patients with peripheral lung adenocarcinomas of 10 mm or less in diameter. Outcomes were compared with two other groups that consisted of 32 patients with adenocarcinomas between 11 and 15 mm in diameter and 35 patients with adenocarcinomas between 16 and 20 mm in diameter. Tumors were curatively resected between 1992 and 2002. RESULTS: The mean age was 61.7 years. The following three features were more frequent: female sex (78.9%), nonsmokers (77.2%), and cases with carcinoma detected by computed tomography despite negative chest radiography (96.5%). Negative lymphatic invasion (94.7%) was significantly higher. Three cases showed lymphatic invasion that was classified as types E or F, according to Noguchi's classification. There were no cases of lymph node metastasis, pleural involvement, or intrapulmonary metastasis. Well-differentiated type was in 93.0%. Types A and B, which are noninvasive alveolar replacement-type adenocarcinomas, were significantly dominant (86.0%). The 5-year postoperative survival rate was 97.3%, which was significantly better than in the other two groups (75.5%, 78.1%). CONCLUSIONS: Histopathologic features of most peripheral lung adenocarcinomas of 10 mm or less in diameter were types A and B. Types A and B were considered fundamentally indicated for thoracoscopic wedge resections. However, the other types required the standard operation.

Adenocarcinoma↗
PubMed2003

Multiple (multicentric and multifocal) cancers in the ipsilateral breast with different histologies: profiles of chromosomal numerical abnormality.

BACKGROUND: Chromosomal numerical abnormality (CNA) is a characteristic of breast cancer as with other common solid cancers. Multiple mammary carcinomas are also sometimes encountered in the ipsilateral breast. Deciding whether they are multicentric (arising independently) or multifocal (of the same origin) has been a continued challenge to clinicians and pathologists. METHODS: We experienced two cases of macroscopically distinct double carcinomas in the ipsilateral breast, in which two cancers had a different histopathological morphology. Centromere probes identifying 17 different and specific centromeres were used to obtain the profile of CNA for each tumor, with a microwave-assisted FISH protocol. For comparison, a case of three lesions, two of which had the same and the other different histology was also studied. RESULTS: Contrary to our expectations, in spite of the particular difference in the histopathological picture of these tumors, the CNA profile was the same in one case and different in the other. The gain of chromosome 1 and loss of chromosome 15 are representative features shared by multifocal cases. On the other hand, the multiple cancers with the same histology had mostly the same CNA profile. CONCLUSIONS: CNA profiling is useful to identify the lineage of multiple breast cancers. As shown here, regardless of the histological features, a certain common CNA profile can define the same origin of some multiple cancers.

Adenocarcinoma, Mucinous↗
PubMed2003

Nonrandom chromosomal numerical abnormality predicting prognosis of gastric cancer: a retrospective study of 51 cases using pathology archives.

Chromosomal or centromerical numerical abnormality (CNA) is a well-known characteristic of human cancer, but the extensive and specific documentation of CNA in gastric cancer is still sparse, partly because of difficulty in obtaining cytogenetic information. Taking advantage of a recently developed fluorescence in situ hybridization protocol for formalin-fixed paraffin-embedded tissues, we investigated CNA of 51 gastric cancer cases with a panel of 18 chromosome-specific alpha-satellite probes (for chromosomes 1-4, 6-12, 15-18, 20, X and Y) and region specific probes (c-myc and p53) to enumerate respective chromosome numbers in interphase nuclei. The involved chromosomes exhibiting CNA were nonrandom in gastric cancer. Aberrations of chromosomes 1, 8, 17, 20, and X were frequent regardless of histologic types, whereas aberrations chromosomes 10, 15, and 18 occurred less often (p < 0.001). From a histopathologic standpoint, the mucocellular type had stable CNA in comparison with the tubular type (mucocellular type vs tubular type carcinoma: 21.0 +/- 10.63% vs 62.8 +/- 12.79%, p < 0.001). Interestingly, there was less extensive CNA in women (men vs women: 54.3 +/- 9.49% versus 24.9 +/- 12.23%, p < 0.001). A dramatic difference in the outcome was detected according to the involvement of chromosomes 3, 10, 11, 12, 17, and Y; that is, the cases with CNA of these chromosomes had worse prognosis.

Adenocarcinoma↗
PubMed2002

Centromere numerical abnormality in the papillary, papillotubular type of early gastric cancer, a further characterization of a subset of gastric cancer.

Papillary adenocarcinoma of the stomach is a relatively uncommon histological type, and it is often detected in the early stage. We recently characterized the papillary type of gastric cancer and found frequent microsatellite instability and associated mutations. In this study we analyzed the centromere numerical abnormality (CNA) of 18 chromosomes (chromosomes 1-4, 6-12, 15-18, 20, X, and Y) in the papillary and papillotubular types of gastric cancer by a modified fluorescence in situ hybridization technique with microwave treatment. All 3 cases (100%) of papillary adenocarcinoma had high microsatellite instability (MSI-H), and low CNA, and 41% (7 cases) of the 17 cases of papillotubular adenocarcinoma exhibited MSI-H and all 7 cases had low CNA. Further 8 cases (47%) had extensive CNA. In these 15 cases, all the MSI-H cases had lower CNA, and low microsatellite instability (MSI-L) and MSS cases had higher CNA. The remaining two cases showed low CNA and MSI-L and MSS. These profiles were different from those of tubular type gastric cancer, which always had extensive CNA and no MSI. Although the numbers of the cases in this series are limited, our data may suggest that a modest CNA may be another characteristic of gastric cancer with papillary structure.

Adenocarcinoma, Papillary↗