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Shinji Sakurai

Publications and source records attributed to Shinji Sakurai.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic model of stage II non-small cell lung cancer by a discriminant analysis of the immunohistochemical protein expression.

PURPOSE: We aimed to identify the key proteins that influence the prognosis of non-small cell lung cancer (NSCLC) using protein expression profiles of previously known prognostic markers. METHODS: Thirty-one cases of Stage II NSCLC with 5-year follow-up data were selected. Tissue microarrays (TMA) and immunohistochemistry were used to make protein expression profiles of 18 previously reported immunohistochemical prognostic markers and their value in NSCLC was statistically re-evaluated by a discriminant analysis. RESULTS: For the discriminant analysis using marker protein expression profiles, we selected three significant markers, TTF-1, RCAS1 and c-MET, to evaluate each patient's 5-year survival. The requested discriminant function was V = -1.08754 x (RCAS1 score) - 0.83174 x (TTF1 score) + 0.55204 x (cMET score) + 5.46972, and V = 0 served as a cut-off point. The correctness for evaluating a patient's 5-year survival by a discriminant analysis was 87.1%. CONCLUSIONS: A discriminant analysis is thus considered to be a useful statistical method for analyzing the protein expression profiles obtained by combined TMA and immunohistochemical techniques using archival NSCLC tissues. However, the sample size and selection of the marker protein depending on the histology greatly influence the results of a NSCLC study.

Antigens, Neoplasm↗
PubMed2006

High incidence of microscopic gastrointestinal stromal tumors in the stomach.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms with an annual incidence of approximately 10 to 20 per 1 million cases. Although pathologists have often observed incidental small GISTs in the stomach resected from patients with gastric cancer, no report on the real incidence of gastric GISTs is available. In this study, 100 whole stomachs resected from patients with gastric cancer were sectioned at 5-mm intervals and hematoxylin and eosin-stained slides (a mean of 130 slides for each case) were examined for microscopic GISTs. KIT (CD117), CD34, and desmin expression of the incidental tumors was evaluated by immunohistochemistry, and genomic DNA extracted from formalin-fixed and paraffin-embedded tumor tissues was analyzed for c-kit gene mutations in exon 11. In 35 of the 100 whole stomachs, we found 50 microscopic GISTs, all of which were positive for KIT and/or CD34 and negative for desmin. Most microscopic GISTs (45/50, 90%) were located in the upper stomach. Two of the 25 (8%) microscopic GISTs had c-kit gene mutations. Fifty-one leiomyomas with positive expression for desmin were observed in 28 of the 100 stomachs. Both leiomyomas and GISTs were found in 12 stomachs. These results indicate that microscopic GISTs are common in the upper portion of the stomach. Considering the annual incidence of clinical GISTs, only few microscopic GISTs may grow into a clinical size with malignant potential. Further studies are required to clarify the genetic events responsible for the transformation of microscopic GISTs to clinical GISTs.

Aged↗
PubMed2006

Direction of spin axis and spin rate of the pitched baseball.

In this study, we aimed to determine the direction of the spin axis and the spin rate of pitched baseballs and to estimate the associated aerodynamic forces. In addition, the effects of the spin axis direction and spin rate on the trajectory of a pitched baseball were evaluated. The trajectories of baseballs pitched by both a pitcher and a pitching machine were recorded using four synchronized video cameras (60 Hz) and were analyzed using direct linear transform (DLT) procedures. A polynomial function using the least squares method was used to derive the time-displacement relationship of the ball coordinates during flight for each pitch. The baseball was filmed immediately after ball release using a high-speed video camera (250 Hz), and the direction of the spin axis and the spin rate (omega) were calculated based on the positional changes of the marks on the ball. The lift coefficient was correlated closely with omegasinalpha (r = 0.860), where alpha is the angle between the spin axis and the pitching direction. The term omegasinalpha represents the vertical component of the velocity vector. The lift force, which is a result of the Magnus effect occurring because of the rotation of the ball, acts perpendicularly to the axis of rotation. The Magnus effect was found to be greatest when the angular and translational velocity vectors were perpendicular to each other, and the break of the pitched baseball became smaller as the angle between these vectors approached 0 degrees. Balls delivered from a pitching machine broke more than actual pitcher's balls. It is necessary to consider the differences when we use pitching machines in batting practice.

Acceleration↗
PubMed2006

Interobserver variability in histologic recognition, interpretation of KIT immunostaining, and determining MIB-1 labeling indices in gastrointestinal stromal tumors and other spindle cell tumors of the gastrointestinal tract.

The authors studied the concordance among seven pathologists for the histologic diagnosis, interpretation of KIT immunostaining, and determining MIB-1 labeling indices (LI) in 80 adult patients with primary spindle cell tumors, mainly of the gastrointestinal tract, mesentery, retroperitoneum, and pelvis, based on the review of tissue sections using an immunohistochemical panel of antibodies for KIT/CD117, CD34, desmin, smooth muscle actin (SMA), and S-100 protein. Tumors included 30 gastrointestinal stromal tumors (GISTs), 10 leiomyomas, 10 leiomyosarcomas, 10 schwannomas, 10 solitary fibrous tumors, and 10 desmoid-type fibromatoses. The overall concordance with the original diagnosis of each histologic type was 97.9%, the kappa value ranging from 0.95 to 1.00 (mean 0.97), indicating a perfect agreement. The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.3%, the kappa value ranging from 0.77 to 0.90 (mean 0.86). The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.9%, the kappa value ranging from 0.72 to 0.93 (mean 0.85). The overall concordance for determining MIB-1 LI was 90% with the original evaluation, and the overall kappa value ranged from 0.62 to 0.86 (mean 0.77). These results indicate that it is possible to reliably diagnose GIST and other spindle cell tumors of the gastrointestinal tract with the use of an immunohistochemical panel of antibodies for KIT, CD34, desmin, SMA, and S-100 protein. Although there is clearly unavoidable inter-observer and interlaboratory variability in the interpretation of KIT immunostained sections and interobserver variability in the determination of MIB-1 LI, the concordance between observes is very acceptable, and in most instances such variability can be eliminated by careful reviewing of the hematoxylin and eosin and immunostained sections.

Adult↗
PubMed2006

Unique case of pulmonary bronchial gland type tumor with broad spectrum of cell differentiation from the terminal duct-acinar unit to excretory duct.

In the lung, acinic cell carcinoma (ACC) is a rare form of tumor. Reported herein is a unique bronchial gland-type tumor diagnosed as well-differentiated ACC that developed in the B9 bronchus of the left lung. Various immunohistochemical and histochemical staining partly satisfied the diagnosis of ACC. Moreover, this tumor contained various sizes of mucous cysts lined by columnar mucous cells, which produced abundant mucin positive for Alcian blue, which is usually present in mucoepidermoid carcinoma. Therefore, the present case is a unique tumor having a broad spectrum of cell differentiation from the terminal duct--acinar unit to the striated duct and excretory duct. This is the first case of unique bronchial gland-type tumor with mixed histological features of ACC and mucoepidermoid carcinoma.

Carcinoma, Acinar Cell↗
PubMed2005

Cytogenetic confirmation of a gastrointestinal stromal tumor and ewing sarcoma/primitive neuroectodermal tumor in a single patient.

We report a rare case in which two tumor entities, a gastrointestinal stromal tumor (GIST) and Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), with distinct cytogenetic features occurred in a single patient. The patient was a 72-year-old woman. The first tumor was a submucosal gastric tumor and was diagnosed as a low-risk group GIST based on morphological characteristics and the results of an immunohistochemical analysis for c-kit and CD34. Further cytogenetic analysis revealed that this tumor had a point mutation (D842V substitution) in exon 18 of the platelet-derived growth factor receptor alpha gene. The second tumor was found more than 4 years after the appearance of the first tumor. ES/PNET was highly suspected both morphologically and immunohistochemically, and the diagnosis was confirmed by the detection of an EWS rearrangement using a fluorescence in situ hybridization technique. Although the cytogenetic correlations of these two tumors are unclear, accurate histologic recognition is of clinical importance because the treatments for these two tumors differ.

Aged↗
PubMed2005

Epstein-Barr virus-associated gastric carcinoma in the remnant stomach: de novo and metachronous gastric remnant carcinoma.

BACKGROUND: The remnant stomach corresponds to the gastric cardia, but is exposed to a completely different environment. The present study was performed to investigate the role of Epstein-Barr virus (EBV) infection in patients with gastric remnant carcinoma (GRC). METHODS: Clinicopathological features, gastritis, and infection by EBV were investigated in patients with two types of GRC: GRC occurring at an interval of 10 years or longer between operations (de novo GRC group) and GRC occurring within 10 years after the initial operation for gastric carcinoma (metachronous GRC group). RESULTS: EBV involvement in the de novo GRC group (23%) was not significantly different from that in the cardia of non-remnant carcinomas (controls; 18%). EBV involvement showed greater correlations in male patients (18/63; 28%), and in those with gastritis cystica polyposa (GCP; 13/41; 31%), and those with an interval of 20 years or longer (15/50; 30%) than with the other parameters. Multivariate analysis showed a significant correlation between GCP and EBV infection. Histologically, hyperplasia or mild atrophy, and mild lymphocytic infiltration were observed in 56% and 67% of non-neoplastic mucosa of EBV-associated GRC, respectively. In the metachronous GRC group, EBV-encoded mRNA in situ hybridization (EBER-ISH) of 27 pairs of primary gastric carcinomas (GCs) and metachronous GRCs indicated that only six EBV (+) metachronous GRCs were derived from EBV (+) GC. CONCLUSIONS: Epstein-Barr virus infection, together with long-standing inflammation, which causes GCP, may facilitate the development of de novo GRC. Close follow-up of patients treated with distal gastrectomy for EBV-associated GC is necessary to detect metachronous GRC.

Aged↗
PubMed2005

Gastrointestinal stromal tumors of neurofibromatosis type I (von Recklinghausen's disease).

Gastrointestinal stromal tumor (GIST), as well as the hyperplastic lesions of intestinal neural tissue and its supporting structures, is a gastrointestinal complication of type 1 neurofibromatosis (NF1) (von Recklinghausen's disease). In the present study, we analyzed the histologic and immunohistochemical features, and the c-kit and PDGFRA gene mutations of 36 GISTs derived from 9 NF1 patients. Distinctively, multiple GISTs arose preferentially in the small intestine. The histologic features of NF1-associated GISTs are almost similar to those of non-NF1 GISTs, but characteristically most of the NF1-associated GISTs contained skeinoid fibers. Thirty-three GISTs (92%) showed immunoreactivity for KIT, and 23 tumors (64%) showed diffuse or mosaic-like immunoreactivity for S-100 protein. Hyperplasic lesions, which may be the hyperplasia of interstitial cells of Cajal, were observed around some GISTs. Exons 9, 11, 13, and 17 of the c-kit gene and exons 12 and 18 of the PDGFRA gene were amplified and directly sequenced. Point mutations of c-kit gene or PDGFRA gene were identified only in three (8%) and two (6%) tumors, respectively. NF1-associated GISTs, showing the dual differentiation of interstitial cells of Cajal and Schwann cells, develop in close association with the myenteric nerve structure of gastrointestinal tract of NF1 patients. The point mutations of c-kit and PDGFRA gene may play a limited role in the tumorigenesis of NF1-associated GISTs.

Adult↗
PubMed2005

PKC theta, a novel immunohistochemical marker for gastrointestinal stromal tumors (GIST), especially useful for identifying KIT-negative tumors.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the digestive tract and the majority of GIST has characteristic gain-of-function mutations of the c-kit gene, which encodes the KIT receptor for stem cell factor. The present study aimed to establish the usefulness of protein kinase C theta (PKC theta) as an immunohistochemical marker for GIST in comparison with KIT immunohistochemistry. PKC theta immunohistochemistry was carried out not only on 48 cases of GIST and another 40 cases of gastrointestinal mesenchymal tumors, but also on 24 cases of various tumors known to be immunohistochemically positive for KIT. Immunohistochemically, 41 out of 48 cases (85%) of GIST were positive for PKC theta, and its expression was confirmed by Western blot analysis using six cases of surgically resected GIST. In the present study there were six GIST immunohistochemically negative for KIT, which histologically revealed a myxoid epithelioid appearance characteristic to that of GIST with platelet-derived growth factor receptor alpha mutation. All six GIST were immunohistochemically positive for PKC theta. No PKC theta immunoreactivity was observed in other gastrointestinal mesenchymal tumors and various KIT-positive tumors except for three cases (14%) of gastrointestinal schwannomas. The present study revealed that PKC theta is an immunohistochemically novel and useful marker for GIST, especially for GIST negative for KIT.

Biomarkers, Tumor↗
PubMed2004

Development of gastric carcinoma from intestinal metaplasia in Cdx2-transgenic mice.

In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. Many epidemiologic studies have found an association between the formation of intestinal metaplasia and the development of gastric carcinoma. However, there is no direct evidence that shows intestinal metaplasia is a precursor lesion of gastric carcinoma, to date. We periodically examined the intestinal metaplastic mucosa of Cdx2-transgenic mice we have previously generated. Gastric polyps developed from intestinal metaplastic mucosa in all stomachs of Cdx2-transgenic mice examined. These gastric polyps consisted of intestinal-type adenocarcinoma that invaded the submucosa and muscularis propria and occasionally spread into the subserosa. p53 and APC gene mutations were recognized in the adenocarcinomas. The participation of APC and p53 gene mutations in gastric carcinogenesis from the intestinal metaplasia was verified by the Cdx2-transgenic mice, carrying Apc(Min) mutation or p53 deficiency, that developed gastric polyps much earlier than Cdx2 alone. We successfully showed that long-term intestinal metaplasia induces invasive gastric carcinoma. These results indicate that intestinal metaplasia itself plays a significant role in the genesis and progression of gastric carcinoma.

Adenocarcinoma↗
PubMed2004

Gastrointestinal stromal tumor in the jejunum: diagnosis and control of bleeding with electrocoagulation by using double-balloon enteroscopy.

A 43-year-old man presented with gastrointestinal bleeding. A tumor with central ulceration was observed in the jejunum, with the use of a new enteroscopy system called "double-balloon enteroscopy". Bleeding after biopsy sampling of the tumor was controlled endoscopically by using electrocoagulation. Histological findings of the biopsy specimens were consistent with gastrointestinal stromal tumor, and this was surgically resected. Double-balloon enteroscopy was useful for the diagnosis as well as the control of bleeding in this patient.

Adult↗
PubMed2004

Myxoid epithelioid gastrointestinal stromal tumor (GIST) with mast cell infiltrations: a subtype of GIST with mutations of platelet-derived growth factor receptor alpha gene.

We analyzed 30 gastrointestinal stromal tumors (GISTs) that were immunohistochemically weak or negative for KIT. Histologically, all 30 GISTs consisted of epithelioid tumor cells in at least a part of the tumor. The tumor cells showed different morphologies and arranged themselves in different histological patterns. In 20 of the 30 GISTs, round or oval epithelioid tumor cells often showed a less cohesive pattern of growth and showed eosinophilic cytoplasm and peripherally placed nuclei with myxoid stroma, whereas in the remaining 10 cases, tumor cells were arranged in a more cohesive pattern without myxoid stroma. The former type of tumors is called myxoid epithelioid GISTs in this study. Subsequent mutational analyses showed that the platelet-derived growth factor receptor alpha (PDGFRA) gene mutations in exon 12 or exon 18 were identified in 20 (66.7%) of the 30 GISTs, and especially in 18 (90%) of the 20 myxoid epithelioid GISTs. Moreover, 17 (85%) of the 20 myxoid epithelioid GISTs were accompanied by mast cell infiltrations within the tumor nodules. In the remaining cases, 2 (6.7%) of the 30 GISTs had c-kit gene mutations in exon 11, and no mutation was found in 8 (26.7%) of 30 GISTs. None of the patients with myxoid epithelioid GISTs died of disease. These results suggest that myxoid epithelioid GISTs are a distinct subtype of GISTs that are closely correlated with the PDGFRA gene mutation and that recognition of such histological characteristics should be helpful for molecular subclassification of GISTs that are important for molecular targeting therapy by imatinib mesylate (STI571).

Adult↗
PubMed2004

c-kit gene mutations in intracranial germinomas.

Gain-of-function mutations of the c-kit gene and the expression of phosphorylated KIT are found in most gastrointestinal stromal tumors and mastocytosis. Further, almost all gonadal seminomas/dysgerminomas exhibit KIT membranous staining, and several reports have clarified that some (10-25%) have a c-kit gene mutation. But, whether intracranial germinomas also have a c-kit gene mutation remains unsolved. To elucidate the presence, frequency, and location of c-kit gene mutations in intracranial germinomas, we analyzed five mutational hot spots (exons 9, 10, 11, 13, and 17) in the c-kit genomic DNA of 16 germinomas using polymerase chain reaction and direct sequencing. We found c-kit gene mutations at exon 11 (W557C) or 17 (D816V, D820V, and N822Y) in four germinomas (25.0%), although no statistically significant difference in any clinicopathological factor was found between patients with or without mutations. These results are similar to those seen in gonadal seminoma/dysgerminoma patients, and confirm that intracranial germinomas are exact counterparts of gonadal seminomas/dysgerminomas, as would be expected on histological and immunohistochemical grounds. Moreover, molecular targeting drugs such as imatinib mesylate (STI571), which is a selective inhibitor of KIT, might be promising agents for the treatment of intracranial germinomas with c-kit gene mutations.

Adolescent↗
PubMed2003

DNA-based identification resolved suspected misdiagnosis due to contaminated cytological specimens.

We report a clinical mishap based on sample contamination of cytological specimens. Bronchial lavage fluid collected from three male patients was submitted to a pathological institute for cytological diagnosis and to the clinical laboratory in the hospital for tuberculosis screening. Cytological slides of two patients were diagnosed as lung adenocarcinoma and lobectomy was carried out on one patient. However, diagnosis of the surgical specimen was tuberculoma. To resolve the discrepancy, genome DNA was isolated from patients' blood, cytological slide glasses and the mycobacterial culture tubes. Analysis of mitochondrial hyper-variable sequence and microsatellite revealed sample contamination in the cytological slide of the tuberculoma patient. DNA from the mycobacterial culture tubes showed identical results with the cytological slides, suggesting that the contamination occurred at the bed-side. Preservation of part of cytological specimen will be a help to avoid dispute between pathological laboratory and hospital over responsibility of incident.

Adenocarcinoma↗
PubMed2003

Application of the AMeX method to the evaluation of HER-2 status in breast carcinomas: comparison with the results of HercepTest.

The recent development of the recombinant humanized monoclonal antibody against HER-2 oncoprotein requires a simple and accurate method for the evaluation of HER-2 status in patients with breast cancers. We here report that the evaluation of the HER-2 status is improved by the use of the acetone-methanol-xylene (AMeX) method. Compared with an ordinary test of HercepTest, 25 out of 63 cases (39.7%) were scored upwards by the AMeX method. In addition, the HER-2 gene amplification was easily estimated by fluorescence in situ hybridization (FISH) using the AMeX method. Thus, the AMeX method is likely to provide more improved data about the HER-2 status in breast carcinoma specimens.

Breast Neoplasms↗
PubMed2003

Alterations of the c-kit gene in testicular germ cell tumors.

Expression and gain-of-function mutation of the c-kit gene, that encodes a receptor tyrosine kinase (KIT), have been reported in mast cell tumors and gastrointestinal stromal tumors (GISTs). Among human testicular germ cell tumors (GCTs), seminomas and seminoma components of mixed GCTs have also been shown to express KIT, but only one study has found the c-kit gene mutation at exon 17 in seminoma. To elucidate the frequency and location of the c-kit gene mutation of testicular GCTs, we analyzed the whole coding region of the c-kit complementary DNA along with 4 mutational hot spots (exons 9, 11, 13 and 17) of the c-kit genomic DNA by polymerase chain reaction and direct sequencing. Somatic mutations were found in 4 pure seminomas of 34 testicular GCTs (11.8%). One mutation was found in exon 11 (W557R) and the others were observed in exon 17 (D816H and D816V). These types of mutations were reported in GISTs (W557R), seminoma (D816H) and mastocytosis (D816V) and were considered to be gain-of-function mutations, although there were no differences of any clinicopathological factors or outcome between patients with and without mutations. Additionally, we also demonstrated coexpression of Gly-Asn-Asn-Lys510-513 (GNNK) + and GNNK - isoforms of the c-kit gene with dominance of the GNNK - transcript in all testicular GCTs. The mutations and/or preferential expression of GNNK - isoform of the c-kit gene might play an important role in the development of testicular GCTs, and these tumors may also be targets for STI571, which is a promising drug for advanced and metastatic GISTs.

Adult↗
PubMed2002

Clonality and K-ras mutation analyses of epithelia in intraductal papillary mucinous tumor and mucinous cystic tumor of the pancreas.

Histological criteria for subclassification of intraductal papillary mucinous tumor (IPMT) and mucinous cystic tumor (MCT) of the pancreas remain ambiguous in the absence of apparent invasion or metastasis. To elucidate this issue, we evaluated clonality and K- ras mutations in 11 cystic tumors of the pancreas from female patients, including 7 IPMTs and 4 MCTs. The analyses were performed on DNA from laser microdissected epithelia showing different degrees of atypia as well as normal-appearing epithelia (NAE) in the individual tumors. The grades of atypia were classified into three groups on conventional hematoxylin-eosin staining. Clonality was assessed using the methylation-induced polymorphic inactivation of the X-linked phosphoglycerate kinase gene. The incidence of monoclonality increased with the grades of atypia: 27% for NAE, 43% for grade 1, and 100% for grades 2 and 3. In three of four MCTs, foci of NAE were polyclonal, while monoclonality was seen in each one of grades 1 and 2. The frequency of K- ras mutation depended on the grades of atypia: 0% for NAE, 29% for grade 1, 50% for grade 2, and 75% for grade 3. Polyclonal epithelia were devoid of K- ras mutation in 92% of sites, while monoclonality was associated with both wild and mutational types in an approximately equal ratio. Both IPMT and MCT seem to arise from polyclonal epithelia and to be replaced by monoclonal neoplastic cells as they undergo dysplastic changes and K- ras mutation. These data suggest that the monoclonal expansion precedes K- ras mutation.

Adenocarcinoma, Mucinous↗