Biomedical subjects

Masazumi Tsuneyoshi

Publications and source records attributed to Masazumi Tsuneyoshi.

At least 55 records · Page 3Linked to original sources

PubMed2006

Aneurysmal bone cyst of the capitate: case report and a review emphasizing local recurrence.

We herein report the case of a 15-year-old boy with cystic lesion of the capitate. Magnetic resonance imaging showed that the lesion demonstrated homogenous low-intensity on T1-weighted imaging and homogenous high intensity on T2-weighted imaging. The lesion was treated by curettage and autologous bone-grafting. The histological specimen from the cystic wall showed loose fibrous tissue with capillary vessels and extravasated red blood cells. The cystic lesion was filled with blood, suggesting that the cystic lesion was actually an aneurysmal bone cyst. The present case is the second reported case of aneurysmal bone cyst of the capitate. No recurrence has been observed during the 4 years since operation. We also review the literature related to ABCs of the hand with special emphasis on local recurrence.

Adolescent↗

PubMed2005

Noninvasive mapping of reactive oxygen species by in vivo electron spin resonance spectroscopy in indomethacin-induced gastric ulcers in rats.

Reactive oxygen species (ROS) are thought to be involved in the gastric ulcer formation induced by indomethacin, a typical nonsteroidal anti-inflammatory drug. However, the location and the time course of ROS generation remain unknown. To assess the sites of ROS generation, we applied the noninvasive measurement of ROS to indomethacin-treated rats. By giving orally a membrane-permeable or impermeable probe, the spectra were collected as a function of time by in vivo 300-MHz electron spin resonance (ESR) spectroscopy. The ESR signal-decay rates of membrane-permeable probes, hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl, in the gastric mucosal region were significantly enhanced 1 h after indomethacin treatment, and they both caused the protection of ulcer formation; however, membrane-impermeable probes, carboxy- and trimethylammonium-TEMPO, which did not exhibit the enhanced signal decay, had no effect on ulcer formation. The enhanced signal decay in the gastric mucosa was suppressed by coadministration of the antioxidants tiron or dimethylthiourea with the nitroxyl probe. The results suggest that the enhanced signal-decay rates in the gastric ulcers observed by in vivo ESR are associated with protective effects. The enhanced signal decay caused by ROS generation in stomach, contributing to the ulcer formation induced by indomethacin, is also suggested to occur at the gastric mucus layer or the interface or the intracellular compartment of epithelial cells. Overall, these results show the potentials of noninvasive assessment of ROS production and the sites of damage by in vivo ESR using nitroxyl probes directed to specific subcellular regions.

Animals↗

PubMed2005

Significance of the relationship between irregular regeneration and two hepatocarcinogenic pathways: "de novo" and so-called "dysplastic nodule-hepatocellular carcinoma" sequence.

BACKGROUND AND OBJECTIVES: Irregular regeneration of hepatocytes has been reported as an important factor in the hepatocarcinogenesis, so we studied the relationship between irregular regeneration and two hepatocarcinogenic pathways, "de novo" and "dysplastic nodule-hepatocellular carcinoma sequence." METHODS: Liver tissue was obtained from surgically resected 112 specimens, early well differentiated hepatocellular carcinomas and non-cancerous tissue. Hepatocellular carcinomas were divided into two groups; carcinoma with dysplastic area (type A) and without dysplastic area (type B) and were compared with irregular regeneration of hepatocytes in the non-cancerous tissue. RESULTS: Eighty-eight of 112 cases were judged to have irregular regeneration, such as anisocytosis, pleomorphism, bulging and map-like distribution. The degree of irregular regeneration was not correlated to the type of early well differentiated hepatocellular carcinomas. However, the existence of pleomorphism, map-like distribution and bulging are significantly correlated with type A. CONCLUSION: Type A might be more frequently occurring in a carcinogenic liver showing some kinds of irregular regeneration.

Carcinoma, Hepatocellular↗

PubMed2005

Renal cancer treatment with low levels of mixed chimerism induced by nonmyeloablative regimen using cyclophosphamide in mice.

Recently, much attention has been paid to nonmyeloablative allogeneic stem cell transplantation for the treatment of metastatic renal cancer. Mature donor T cells cause graft-versus-host disease (GVHD) although they are also the main mediators of the beneficial graft-versus-tumor activity associated with this treatment. Hence, the segregation of the graft-versus-tumor activity from GVHD is an important challenge in managing the clinical course of treatment. We previously reported a series of studies regarding the allograft tolerance induced by allogeneic spleen cells (with bone marrow cells) and cyclophosphamide in mice. Here, we show a modified cyclophosphamide-induced tolerance system for the treatment of murine renal cell carcinoma, RENCA, by shifting the equal balance between graft-versus-host and host-versus-graft reactions toward graft-versus-host reaction with donor lymphocyte infusion. Our results clearly show the antitumor activity against RENCA with only low levels of mixed chimerism in the periphery and the in vivo and in vitro acquired immunity against RENCA even when mixed chimerism is almost undetectable. Because the withdrawal of mixed chimerism reduces the risk of GVHD, the antitumor activity is thus sequentially segregated from the initial GVHD in our model. We believe that this is the first unique model system of nonmyeloablative allogeneic hemopoietic cell transplantation to ever be reported for the treatment of renal cancer.

Animals↗

PubMed2005

The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target.

Recent microarray analyses showed that the S100 family contains members that are candidate diagnostic markers or therapeutic targets. In the present study, to evaluate the involvement of S100A6 in pancreatic cancer and its clinical usefulness for diagnosis, we examined S100A6 mRNA expression in pancreatic tissues and pancreatic juice from patients with different pancreatic diseases. To investigate the role of S100A6 in carcinogenesis of pancreatic cancer and the potential of S100A6 as a diagnostic marker for early detection of pancreatic cancer, we did immunohistochemistry and microdissection-based mRNA analysis of pancreatic normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. We also used in vitro experiments and microarray analysis with RNA interference to evaluate the functional role of S100A6 and its potential as a therapeutic target for pancreatic cancer. S100A6 mRNA levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. In pancreatic juice, there was a significant difference in S100A6 expression between patients with carcinoma and those with nonneoplastic disease. Receiver operating characteristic curves revealed that S100A6 might be a useful marker for diagnosis of pancreatic cancer. Immunohistochemistry and microdissection-based analysis showed differential expression of S100A6 among normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. In vitro data showed that inhibition of S100A6 decreased proliferation and invasiveness of cancer cells, and these findings were supported by microarray data. Our present results suggest that quantitation of S100A6 mRNA is a promising tool for diagnosis of pancreatic cancer, and that S100A6 may be a promising therapeutic target for pancreatic cancer.

Biomarkers, Tumor↗

PubMed2005

ATP-binding cassette superfamily transporter gene expression in human soft tissue sarcomas.

The phenomenon of multidrug resistance (MDR) in various malignant neoplasms has been reported as being caused by one or multiple expressions of ATP-binding cassette (ABC) superfamily protein, including P-glycoprotein/multidrug resistance (MDR) 1 and the MDR protein (MRP) family. However, their expression levels and distribution within soft tissue sarcomas remain controversial. In 86 cases of surgically resected soft tissue sarcoma, intrinsic mRNA levels of MDR1, MRP1, MRP2 and MRP3 were assessed using a quantitative reverse transcriptase-PCR (RT-PCR) method. Moreover, immunohistochemical protein expressions of P-glycoprotein (P-gp), MRP1, MRP2, MRP3 and p53 protein were evaluated in concordant paraffin-embedded material. The mRNA expression and immunohistochemical expression of ABC superfamily transporters were compared to clinicopathologic parameters and proliferative activities as evaluated by the MIB-1-labeling index (LI). Among the various histologic types, malignant peripheral nerve sheath tumor (MPNST) showed significantly high levels of MDR1 (p=0.017) and MRP3 (p=0.0384) mRNA expression, compared to the other tumor types. When the immunohistochemical method was compared to the RT-PCR technique to assess ABC transported expression at the protein and mRNA levels, a significantly close relationship was found between the 2 methods (p<0.05). P-gp expression was significantly correlated with large tumor size (> or =5 cm, p=0.041) and high AJCC stage (stages III and IV) (p=0.0365). Furthermore, cases with nuclear expression of p53 revealed significantly higher levels of MDR1 mRNA expression, compared to those with negative immunoreaction for p53 (p=0.0328). Our results suggest that MDR1/P-gp expression may have an important role to play in tumor progression in the cases of soft tissue sarcoma, and p53 may be one of the active regulators of the MDR1 transcript. In addition, the high levels of both MDR1 and MRP3 mRNA expression in MPNST may help to explain the poor response of this tumor to anticancer-drugs.

ATP-Binding Cassette Transporters↗

PubMed2005

Frequent alteration of p16(INK4a)/p14(ARF) and p53 pathways in the round cell component of myxoid/round cell liposarcoma: p53 gene alterations and reduced p14(ARF) expression both correlate with poor prognosis.

In myxoid/round cell liposarcoma (MLS/RCLS), the presence of a round cell (RC) component has been reported to correlate with a worse prognosis for the patients. However, little is known about the molecular genetic differences between conventional myxoid (MX) components and RC components in this tumour. The aim of this study was to investigate the possible implications of molecular alterations of G1 to S-phase check-point genes, especially in the RC component. We evaluated the immunohistochemical expression of p53, MDM2, p14 and p16 protein and assessed proliferative activities using MIB-1 in 29 RC components and 81 MX components from 90 cases. Mutation of the p53 gene, amplification of the MDM2 gene, homozygous deletion, methylation status and mutation of the p16(INK4a)/p14(ARF) genes were also investigated, using concordant paraffin-embedded and frozen material. The data were analysed together with clinicopathological factors to assess their prognostic implications in MLS/RCLS. Immunohistochemically, the over-expression of p53 protein (p = 0.01366) and the reduced expression of p14 (p < 0.0001) and p16 (p < 0.0001) proteins were significantly more frequently observed in RC components than in MX components. Reduced expression of p14 protein correlated significantly with hypermethylation of the p14(ARF) gene promoter (p = 0.0176) and over-expression of p53 protein (p = 0.00837). By univariate analysis, reduced expression of p14 and p53 missense mutation were found to reduce the rate of survival significantly (p < 0.05). Multivariate analysis, including clinicopathological factors, revealed that tumour site (p = 0.0251), the presence of an RC component (p = 0.0113), high MIB-1 labelling index (p = 0.0005) and p53 missense mutation (p = 0.0036) were adverse prognostic factors. In MLS/RCLS, reduction of p14 protein expression and p53 mutation were related to poor prognosis. Accordingly, the p14(ARF)/p53 pathway may contribute to the presence of an RC component and malignant progression in this tumour.

Adolescent↗

PubMed2005

Five-year evolution of a telangiectatic osteosarcoma initially managed as an aneurysmal bone cyst.

We present the clinical, radiographic, and pathologic features of a telangiectatic osteosarcoma (TOS) of the right femoral neck in a 20-year-old man which was initially diagnosed and managed as an aneurysmal bone cyst (ABC). The lesion recurred twice. At the second recurrence TOS was diagnosed. The first local recurrence was recognized 4 years 8 months after the first operation. The clinical diagnosis for the recurrent lesion was recurrent ABC, and curettage and bone graft with internal fixation were performed. The second local recurrence was observed 8 months after the second surgery. The right lesser trochanter appeared destroyed on the radiograph, and a large medial soft tissue mass was demonstrated by computed tomography. The patient underwent wide resection of the tumor with prosthetic replacement of the right proximal femur. The histologic section for this lesion showed a blood-filled cystic lesion, and its wall contained sarcomatous cells with atypical mitoses and tumor osteoid. The histologic diagnosis for the second recurrent lesion was high-grade TOS. The retrospective review of the histologic section for the primary lesion showed similar features to ABC except for a few bizarre cells without mitosis in the tissue of cystic wall. The patient demonstrates no evidence of disease 13 months after the last surgery without adjuvant therapy (he declined chemotherapy).

Adult↗

PubMed2005

Relationship between biological behavior and phenotypic expression in undifferentiated-type gastric carcinomas.

BACKGROUND: It has been proved that some differentiated-type gastric carcinomas have a gastric phenotype. Similarly, it can be conjectured that some undifferentiated-type gastric carcinomas have an intestinal phenotype and that there are biological differences between undifferentiated-type gastric carcinomas with a gastric phenotype and those with an intestinal phenotype. We classified the phenotypes of early undifferentiated-type gastric carcinomas and investigated the relationship between their biological behavior and the phenotypes. METHODS: Sixty lesions of intramucosal undifferentiated-type gastric carcinoma were classified into four phenotypes; gastric type, incomplete-intestinal type, complete-intestinal type, and unclassified type, according to the expression of CD10, MUC2, small-intestinal mucinous antigen (SIMA), human gastric mucin (HGM), or concanavalin A (ConA). RESULTS: The incidence of gastric-type carcinoma, incomplete-intestinal-type carcinoma, and complete-intestinal-type carcinoma was 33% (20 cases), 65% (39 cases), and 2% (1 case), respectively. There was no significant difference in any of the clinicopathological factors examined between the 20 gastric-type carcinomas and the 40 intestinal-type carcinomas, but there were significant differences in the morphological findings. Intestinal-type carcinomas had a glandular structure more frequently than the gastric-type carcinomas. The spreading pattern of gastric-type carcinomas showed a middle-layer type more frequently than the intestinal-type carcinomas. CONCLUSION: Undifferentiated-type gastric carcinomas frequently expressed an intestinal phenotype. There were differences in the growth patterns between undifferentiated-type gastric carcinomas with a gastric phenotype and those with the intestinal phenotype.

Adenocarcinoma↗

PubMed2005

Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas.

The PTEN/MMAC1 ( PTEN ) gene was identified as a tumor suppressor gene encoding a cytoplasmic protein that controls cellular processes. To investigate the potential role and the alteration of the PTEN gene in soft tissue sarcomas (STSs), we searched for homozygous deletion and promoter hypermethylation in a series of 48 STSs that was composed of malignant fibrous histiocytoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, including 2 cases with a mutation that we previously reported; differential polymerase chain reaction and methylation-specific polymerase chain reaction, respectively, were used for the analyses. Furthermore, to determine whether PTEN gene alterations are involved in the down-regulation of PTEN expression, we examined the expression of PTEN protein in 38 cases in which paraffin-embedded tissues were available for immunohistochemical analysis. In addition to our previous results showing that 2 (4%) of 51 cases had a PTEN mutation, promoter methylation was recognized in 6 (13%) of 48 cases, and homozygous deletion was detected in 1 (2%) of 48 cases in the current study. Of 6 cases with promoter methylation of PTEN gene, 5 were malignant peripheral nerve sheath tumor. Decreased expression of PTEN protein was recognized in 11 (29%) of 38 STS cases. Of 9 cases with PTEN alterations (6 cases with promoter methylation, 2 with mutation, and 1 with homozygous deletion), 3 (33%) showed decreased expression of PTEN protein. Furthermore, decreased expression of the PTEN gene showed a statistically significant correlation with high MIB-1 labeling index in 38 STS cases examined ( P = .0441). In conclusion, promoter methylation and homozygous deletion of the PTEN gene were found to be relatively rare events in cases of STS, as is mutation of the gene. Of 9 cases with a PTEN alteration, 3 (33%) showed a decrease in PTEN expression, indicating that PTEN gene alterations seem to play a minor role in the inactivation of PTEN in these tumors. Furthermore, although a further detailed analysis of a larger number of cases is still necessary, the present results suggest that PTEN expression may be a useful indicator of cell proliferation in patients with STS.

Adolescent↗

PubMed2005

Overexpression of laminin-5 gamma2 chain and its prognostic significance in urothelial carcinoma of urinary bladder: association with expression of cyclooxygenase 2, epidermal growth factor receptor [corrected] and human epidermal growth factor receptor [corrected] 2.

Laminin-5 (LN-5) and cyclooxygenase 2 (COX-2) play important roles in many kinds of cancers. Recently, it has been reported that epidermal growth factor receptor [corrected] (EGFR) and/or human epidermal growth factor receptor [corrected] 2 (HER2) expressions are associated with LN-5 and/or COX-2 expressions in a few carcinoma cell lines and human tumor tissue. LN-5, COX-2, EGFR, and HER2 expressions were examined immunohistochemically in 67 patients with urothelial carcinomas (UCs), and associations among these 4 biomarkers and clinicopathologic characteristics were investigated. Patients were classified into transurethral resection group and cystectomy group based on clinical end points, and prognostic significances of increased expressions were evaluated. Overexpression of LN-5, COX-2, EGFR, and HER2 was observed in 16 (23.9%), 34 (50.7%), 42 (62.7%), and 15 (22.4%) of 67 patients, respectively. LN-5 overexpression was associated high-grade (P = .002), invasive (pTa+1 versus pT2-4, P = .011), and nonpapillary (P = .027) UCs. Concerning EGFR and HER2, high-grade (EGFR, P = .0009; HER2, P = .003) and nonpapillary (EGFR, P = .016; HER2, P = .0002) UCs had a significantly higher overexpression rate. UCs penetrating basal membrane (pT1-4) showed significantly higher overexpression rates than pTa UCs on all biomarkers. In transurethral resection group, LN-5 overexpression could be proved as an independent prognostic parameter for intravesical recurrence (P = .007), whereas in cystectomy group, nodal involvement was an independent prognostic parameter for cause-specific survival (P = .025). The current study showed that the 4 biomarkers were associated with aggressive behaviors of UCs. Above all, LN-5 overexpression was considered to play an important role in intravesical recurrence of superficial UCs.

Adult↗

PubMed2005

Prognostic significance of expressions of cell-cycle regulatory proteins in gastrointestinal stromal tumor and the relevance of the risk grade.

Gastrointestinal stromal tumors (GISTs) have a wide spectrum of biologic behavior ranging from benign to malignant. Risk grading based on tumor size and mitotic counts has been proposed in an effort to predict the adverse outcome of GIST in the literature so far. Recent molecular studies have reported the prognostic values of several parameters, including alteration of cell-cycle regulators. The aim of this study was to elucidate the prognostic values of risk grade and alterations of cell-cycle-related proteins, including Ki-67, cyclin A, cyclin B1, cyclin D1, cyclin E, p16, p21, p27, p53, cdc2, and cdk2, in addition to the conventional factors. Eighty cases of primary c-kit-positive GISTs were classified into 2 cases of very-low-risk grade, 20 cases of low-risk grade, 25 cases of intermediate-risk grade, and 33 cases of high-risk grade. The risk grade was correlated with the presence of metastases and/or recurrence. A high level of Ki-67 and cyclin A expression was correlated with risk grade (P = .0027 and .0441, respectively). Overexpression of G2-M regulators, such as cyclin A, cyclin B1, and cdc2, was associated with the Ki-67 labeling index (LI) (P = .0007, .0475, and .0040, respectively). According to univariate analysis, tumor grade (high risk), tumor size (> or =5 cm), mitotic counts (> or =5/50 high-power fields), Ki-67 LI (> or =4.92%), cyclin A LI (> or =1.61%), and cdc2 LI (> or =1.25%) were all found to be significantly associated with a shorter period of disease-free survival (P = .0001, .0270, .0004, .0001, .0001, and .0011, respectively). According to multivariate analysis, both high Ki-67 LI and high-risk grade were found to be significantly associated with a shorter period of disease-free survival (P = .0083 and .0246, respectively). In conclusion, our results strongly support the hypothesis that Ki-67 LI and risk grade are useful for predicting the aggressive biologic behavior of GISTs. Furthermore, alteration of G2-M regulators, such as cyclin A, cyclin B1, and cdc2, is also a useful marker for predicting aggressive behavior and play an important role, at least in part, in the cell proliferation of GIST.

Aged↗

PubMed2005

Histogenesis of intralesional fibrous septum in chordoma.

Intralesional fibrous septum (IFS), a histologic architecture that is typical of chordoma, consists of proliferating spindle-shaped, fibroblast-like cells with an abundance of collagen fibers. However, the histogenesis of IFS is still controversial. In a series of 122 chordomas, special emphasis was placed on the morphology of host tissues involved in IFS and on a transition between IFS and neighboring tissues. In 23 lesions, IFS was also characterized both histochemically and immunohistochemically. IFS was observed in 79 (64.8%) lesions. Occasionally, IFS contained bone fragments and hyalinized matrix with no lining of osteoblastic cells, suggesting degenerated rather than metaplastic bone tissue. Moreover, IFS occasionally showed a direct transition to host bone trabeculae. Histochemically and immunohistochemically, IFS included calcium deposits positive for Alizarin red S staining and expressed both type I and type III collagen. In extraosseous lesions extending to the adjacent soft tissues, IFS frequently involved muscle fibers or peripheral nerve fibers and displayed a smooth transition to neighboring soft tissues. We believe that IFS is induced by a tumor-host interaction that is based on the host bone trabeculae in intraosseous lesions or on soft tissues in extraosseous lesions.

Adolescent↗

PubMed2005

Alterations of the RB1 gene in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma is a malignant adipocytic neoplasm containing a non-lipogenic sarcoma of variable histological grade that arises against the background of a pre-existing well-differentiated liposarcoma. The phenomenon of dedifferentiation is considered to be time-dependent, but the mechanism is not well known. The retinoblastoma protein, encoded by the RB1 gene located at 13q14, is a key regulator of proliferation, development, and differentiation of certain cell types, including adipocytes. In the current study, we investigated the genetic alterations of the RB1 gene, such as mutation (the essential promoter region and the protein-binding pocket domain; exons 20-24) and methylation of the promoter region, in addition to pRB expression and loss of heterozygosity (LOH) status, in two morphologically distinct areas (non-lipogenic dedifferentiated and well-differentiated components) in 27 patients. As a control, 11 undifferentiated high-grade pleomorphic sarcoma/pleomorphic malignant fibrous histiocytoma samples and 11 well-differentiated liposarcoma samples were also evaluated. Dedifferentiated components showed LOH (15/25; 60%) and abnormal retinoblastoma protein expression (18/27; 66.7%) more frequently than noted in the well-differentiated components (3/24; 12.5% and 9/27; 33.3%, respectively). Five and four out of the 27 dedifferentiated components harbored mutations and promoter methylation, respectively, whereas none of these alterations were seen in the well-differentiated components. These results suggest that retinoblastoma protein has a major role to play in dedifferentiation and that a 'two-hit' mechanism is involved in the altered retinoblastoma protein expression in dedifferentiated liposarcoma.

Adult↗

PubMed2005

Intralesional fibrous septum in chordoma: a clinicopathologic and immunohistochemical study of 122 lesions.

Intralesional fibrous septum (IFS) generally is considered a reactive tissue in chordoma; however, little is known about its significance. We studied 122 chordomas for IFS using immunohistochemical techniques and compared IFS and lobular growth patterns (LGPs) formed by IFS with clinicopathologic parameters. Seventy-nine tumors (64.8%) revealed IFS. However, IFS frequently was infiltrated and interrupted by tumor cells with increased expression of proteases; only 33 (42%) of 79 tumors had LGP. In non-skull base chordomas, IFS and LGP were associated with nuclear pleomorphism, a previously described prognostic indicator, mitosis, and the MIB-1 labeling index, indicating a role of IFS and LGP in tumor growth or progression. Paradoxically, patients without LGP tended to have a worse prognosis than those with LGP. We believe that IFS exerts diverse influences on chordoma; however, invasion of IFS leading to loss of the LGP indicates advanced stages of tumor development, possibly predicting an unfavorable prognosis in chordoma.

Bone Neoplasms↗

PubMed2005

Microsatellite instability and hMLH1 and hMSH2 expression analysis in soft tissue sarcomas.

Alterations of the size of microsatellite DNA sequences, namely microsatellite instability (MSI), have been demonstrated in some types of malignancies. We analyzed the MSI of five microsatellite markers in 40 cases of soft tissue sarcoma (STS) using high resolution fluorescent microsatellite analysis. In addition, we examined the expression of hMLH1 and hMSH2 proteins of DNA mismatch repair (MMR) genes by immunohistochemistry, and promoter methylation of the hMLH1 gene by methylation-specific PCR (MSP). MSI was recognized in 10 of 40 STS cases (25%), which consisted of 2 MSH-high (MSI-H) tumors and 8 MSI-low (MSI-L) tumors. A loss of hMLH1 expression was recognized in 7 of 40 STS cases (18%), and loss of hMSH2 expression was recognized in 3 of 40 STS cases (8%). One case showed a loss of both hMLH1 and hMSH2 expression. Promoter hypermethylation of the hMLH1 gene was detected in only 3 of 40 STS cases (8%). Of 10 cases with MSI, 5 (50%) showed a loss of hMLH1 and/or hMSH2 expression. There was a statistically significant correlation between MSI-positive tumors and the loss of hMLH1 and/or hMSH2 expression (p=0.0286). Although the frequency of MSI (25%) or a loss of hMLH1 and/or hMSH2 expression (23%) was relatively low in STS cases, a loss of hMLH1 and/or hMSH2 was recognized in 5 out of 10 MSI-positive cases (50%). These findings suggest that the inactivation of MMR gene expression might be the cause of MSI in STS cases.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Multiple gastric carcinoids and endocrine cell micronests in type A gastritis: Nuclear morphometric and immunohistochemical analysis.

While the hyperplasia-neoplasia sequence of enterochromaffin-like (ECL) cells has been proposed in the pathogenesis of type I gastric carcinoids, the criteria for distinction between hyperplastic endocrine cell micronest (ECM) and neoplastic ECM have not been established. The aims of this study were to clarify differences between the hyperplasia and neoplasia of ECL cells and determine the optimal classification system for gastric ECL cell proliferations in type A gastritis. Endocrine cell lesions (n=531) from 8 surgically-resected stomachs with type A gastritis were reclassified as either atrophic ECM (n=333), hyperplastic ECM (n=168), neoplastic ECM (all ECM > or =0.1 mm in size, n=15), or typical carcinoid (n=15). Hematoxylin and eosin-stained sections were semiautomatically analyzed by nuclear morphometry. Immunohistochemical expression of bcl-2, p53 and Ki-67 was also investigated. As the histologic grade of histology advanced, the morphometric values of area, circumference and largest diameter of the nuclei significantly increased (p<0.0005), while the frequency of diffuse expression of bcl-2 significantly decreased (p<0.0001). Significant differences were also observed in all morphometric parameters and in bcl-2 positivity between the hyperplastic ECM and neoplastic ECM group. There was no expression of p53 in any of the lesions. The Ki-67 index did not differ between the neoplastic ECM and typical carcinoid groups. These results suggest that our system of classification for gastric endocrine cell proliferations in type A gastritis is appropriate. Nuclear morphometry and bcl-2 immunoexpression are useful parameters for the distinction of neoplastic ECMs from hyperplastic ECMs.

Adult↗

PubMed2005

Microsatellite instability and proliferating activity in sinonasal carcinoma: molecular genetic and immunohistochemical comparison with oral squamous cell carcinoma.

Sinonasal carcinomas arise from the respiratory epithelium that lines the nasal and paranasal cavities, and are histologically composed of either squamous or cylindrical cell carcinoma. However, molecular analysis with the purpose of distinguishing sinonasal carcinomas from other head and neck squamous cell carcinomas (HNSCCs), which arise from squamous epithelium, has been limited. Moreover, a wide range of frequency of microsatellite instability (MSI) in HNSCC has been reported. Using high-resolution fluorescent microsatellite analysis (HFRMA), we studied microsatellite alterations in 34 patients with sinonasal carcinoma. As a control, 24 oral squamous cell carcinomas were used. MSI was detected in 14 patients with sinonasal carcinoma (41%), but not in any with oral squamous cell carcinoma (p=0.002). Furthermore, in sinonasal carcinoma, 11 out of 17 (65%) T1-T3 sinonasal carcinomas demonstrated MSI, whereas only 3 out of 15 (20%) T4 tumors demonstrated MSI. Immunohistochemically, sinonasal carcinoma showed a higher MIB-1-labeling index and more frequently showed cytokeratin 18 expression when compared with oral squamous cell carcinoma. These findings suggest that sinonasal carcinoma and HNSCC have quite different molecular backgrounds regarding carcinogenesis, and the role of MSI is relatively minor in cases of advanced sinonasal carcinoma.

Adult↗