c-Kit expression as a prognostic molecular marker in patients with basal-like breast cancer.

BACKGROUND: As patients with basal-like breast cancer (BLBC) have a poor prognosis and there is no specifically tailored therapy, molecular biological characterization of BLBC is necessary. c-Kit is a transmembrane receptor tyrosine kinase known to play important roles in various solid cancers. This study classified BLBCs from patients with breast carcinoma, and addressed the significance of c-Kit expression in these tumours. METHODS: Primary breast tumours were stained with antibodies against oestrogen receptor, progesterone receptor, human epidermal growth factor receptor (HER) 2, epidermal growth factor receptor (EGFR), cytokeratin 5/6 and c-Kit. The association between c-Kit, BLBC and survival was analysed. RESULTS: A total of 667 patients with breast cancer were followed up for a median of 39 (range 6-72) months. Some 190 tumours (28·5 per cent) were classified as triple-negative for breast cancer (negative for oestrogen receptor, progesterone receptor and HER2) and 149 (78·4 per cent) had characteristics of BLBC (positive for cytokeratin 5/6 and/or EGFR). c-Kit expression was detected in 111 (16·6 per cent) of 667 tumours. c-Kit-positive tumours were more commonly found among patients with BLBC (42 of 149, 28·2 per cent; P < 0·001) and in patients with nodal metastasis (47 of 216, 21·8 per cent; P = 0·014) than in those without. In patients with BLBC, the prognosis was significantly worse in those with c-Kit expression (P < 0·001). Multivariable logistic regression analysis revealed c-Kit as an independent negative prognostic factor for cancer-specific survival in patients with BLBC (hazard ratio 2·29, 95 per cent confidence interval 1·11 to 4·72). CONCLUSION: c-Kit might be a prognostic marker and possible molecular target for therapy in patients with BLBC.

Late recurrence of malignant melanoma mimicking primary peritoneal cancer.

BACKGROUND: Malignant melanoma is an extremely malignant tumor with an unpredictable metastatic profile with variable periods of remission. CASE: A 41-year-old woman presented with recurrent malignant melanoma which had clinical features of an acute state mimicking primary peritoneal cancer. The case was an unusual recurrence of malignant melanoma occurring seven years after diagnosis and treatment of malignant melanoma in the patient's arm. The diagnosis was established postoperatively by immunohistochemistry. CONCLUSION: A variety of imaging methods and pathological methods, including an exploratory laparotomy, may be necessary in cases of patients suspecting primary peritoneal cancer with a previous history of melanoma with possible metastatic dissemination. Urgent diagnosis and treatment of these patients seems to be critical.

Spontaneously complete regression of pseudolymphoma of the remnant pancreas after pancreaticoduodenectomy.

BACKGROUND: Pancreatic pseudolymphoma is extremely rare. METHOD: We present multiple pseudolymphomas in the head and body of the pancreas. The hypoechoic lesions observed by endoscopic ultrasound were enhanced in late-phase angio-computed tomography and homogeneously hypointensive in T1-weighted magnetic resonance imaging (MRI). (18)F-fluorodeoxyglucose positron emission tomography showed strong accumulation in the lesions. The lesions were suspected to be non-functioning islet cell carcinoma. The intraoperative pathological diagnosis for the specimen obtained by a pylorus-preserving pancreaticoduodenectomy was non-neoplastic lymphoid cells. The remnant lesion in the pancreatic body was preserved. RESULTS: Macroscopically, the mass was well-circumscribed gray-white colored lesion. The pathological diagnosis was pancreatic pseudolymphoma. The lesion in the remnant pancreas spontaneously disappeared within one year after the operation. CONCLUSION: The differential diagnosis of pancreatic pseudolymphoma from malignant tumor is very difficult, however, the image findings demonstrated here may be informative. The spontaneous disappearance of pancreatic pseudolymphoma was firstly observed in the present case.

Fatal BK virus pneumonia following stem cell transplantation.

We report the case of a 39-year-old male patient who died of severe BK virus (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After suffering from BKV-associated late-onset hemorrhagic cystitis (HC) with long-term sustained BKV viremia, he died of rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions were seen in his lungs and bladder. An immunohistochemical examination of his lungs was positive for simian virus 40. Based on these pathological results and the high sustained BKV viral load in his blood, we reached a diagnosis of BKV pneumonia. Viral infection can occasionally become life threatening among HSCT recipients. It is widely known that BKV can cause late-onset HC, but BKV-associated pneumonia is rare. Because of its rapid progression and poor prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A treatment strategy for BKV pneumonia also needs to be formulated. Similar to other viral pathogens, BKV can cause pneumonia and the clinician should therefore be aware of it in immunocompromised patients.

Significance of E-cadherin expression in triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC), a subtype of breast cancer that is oestrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative, has a poor prognosis. Although a correlation between E-cadherin expression level and outcome has been demonstrated among all types of breast cancer, little is known about the significance of E-cadherin expression levels in TNBC. METHODS: A total of 574 patients who had undergone a resection of a primary breast cancer except for invasive lobular carcinomas were enrolled in this study. Expressions of ER, PR, HER2, and E-cadherin were assessed by immunohistochemistry. We examined the association between TNBC and other clinicopathological variables and evaluated the significance of the E-cadherin expression. RESULTS: Among the 574 breast cancer cases, 123 (21.4%) revealed a triple-negative phenotype. Patients with TNBC experienced more frequent lymph node metastasis (P=0.024) and a poorer prognosis (P<0.001) in comparison with non-TNBC patients. Triple-negative breast cancer was an independent prognostic factor. Reduced levels of E-cadherin were observed in 238 (41.5%) of the 574 breast cancer cases. E-cadherin reduction was significantly frequent in cases of TNBC (P<0.001) and lymph node metastasis (P=0.032). Furthermore, in the 123 TNBC cases, the prognosis of patients with an E-cadherin-negative expression was significantly worse than that of E-cadherin-positive patients (P=0.0265), especially for those in clinical stage II (P=0.002). A multivariate logistic regression analysis showed a reduction of the E-cadherin expression to be an independent prognostic factor (P=0.046). CONCLUSION: E-cadherin expression may be a useful prognostic marker for classifying subgroups of TNBC.

Increased risk of bacterial infection after engraftment in patients treated with allogeneic bone marrow transplantation following reduced-intensity conditioning regimen.

Although bacterial infection is a major cause of death even after reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT), little is known about the epidemiology and risk factors. The incidence of bacterial infection in 43 patients who received allogeneic bone marrow transplantation (BMT) using a RIC regimen was compared with that in 68 patients who received BMT using a myeloablative conditioning regimen, and risk factors for bacterial infection were identified. Before engraftment, incidences of febrile neutropenia (FN) and documented infections (DI) were significantly decreased in RIC patients (FN: 59.5% vs. 89.6%, P<0.01, DI: 4.8% vs. 17.9%, P<0.01). However, incidence of bacterial infection was significantly increased in RIC patients in the post-engraftment phase (53.8% vs. 11.1%, log-rank, P<0.01). Blood stream was the most frequent focus of infection in both groups. In multivariate analysis, RIC and acute graft-versus-host disease were revealed to be significant risk factors for bacterial infection in this phase. In summary, risk of bacterial infection after engraftment was significantly higher in RIC patients, although infection was decreased before engraftment, and we need to develop a RIC-specific strategy against bacterial infection after RIC SCT.

Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors.

The pathogenesis of carcinosarcoma is still a subject of controversy. In the present study, molecular techniques were applied to determine the pathogenesis of uterine carcinosarcomas. The patterns of chromosome X inactivation were analyzed, targeting a portion of exon 1 of the human androgen receptor (HUMARA) in malignant epithelial and mesenchymal components. The presence of p53 and K-ras mutations were also analyzed. H&E-stained sections of paraffin-embedded, formalin-fixed tissues were microdissected to obtain both epithelial and nonepithelial lesions from 25 carcinosarcomas, and DNAs were extracted by proteinase K digestion. Following treatment with methylation-sensitive restriction endonuclease (HhaI or HpaII), PCR amplification was performed using nested primers targeted to the HUMARA locus. Mutations in the p53 gene and K-ras gene were found in eight (32%) and six (24%) tumors, respectively. The patterns of chromosome X inactivation were different between the carcinomatous and sarcomatous components of three carcinosarcomas, indicating that these three tumors represent collision tumors. By contrast, the patterns of chromosome X inactivation, K-ras sequence, and p53 sequence were identical in both carcinomatous and sarcomatous components in 21 carcinosarcomas, indicating that these 21 tumors represent combination tumors. One case produced equivocal results that precluded determination of whether it represented a collision or combination tumor. These observations show that although most carcinosarcomas are combination tumors, some develop as collision tumors. The determination of histogenesis in individual cases of carcinosarcoma using molecular markers may be worthwhile, because the result could help predict the prognosis of individual cases and help guide clinical management.

Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma.

Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies including hepatocellular carcinoma (HCC), but little is known about the prognostic value of COX-2 in HCC or its associated nontumor liver tissue. We examined the expression of COX-2 protein by immunohistochemistry in 53 patients with HCCs whose corresponding nontumor tissues were hepatitis C virus-related chronic hepatitis (n = 21) and cirrhosis (n = 32). Samples of nine histologically normal livers and eight precancerous dysplasias were also analyzed. The level of COX-2 increased from normal liver to chronic hepatitis to cirrhosis. The majority of cirrhotic livers (81%) displayed marked COX-2 expression. In dysplasias, COX-2 expression was mainly moderate or strong (88%). In HCC, 17% of samples displayed a high COX-2 expression, and 37% of samples expressed COX-2 at a moderate level. Concordant results were obtained with reverse transcription-PCR and Western blot analyses. Clinicopathological survey indicated a significant correlation between COX-2 expression and differentiated carcinoma (P = 0.019). Although there was no correlation between COX-2 expression in HCC and prognosis, a striking difference was found between COX-2 expression in nontumor tissue and shorter disease-free survival (P = 0.0132). Moreover, high COX-2 expression in nontumor tissue was significantly correlated with the presence of active inflammation (P < 0.0001). The present findings suggest that COX-2 expression in nontumor tissue may play a positive role in relapse of HCC after surgery.

Efficacy of Helicobacter pylori eradication on the chronic mucosal inflammation of the remnant stomach after distal gastrectomy for early gastric cancer.

Although eradication of Helicobacter pylori (Hp) after early gastric carcinoma has been recommended, very limited studies have been reported and the method differs from standard therapy. Here, we attempted the eradication of Hp in the remnant stomach after surgery for primary gastric cancer with the standardized method. We examined efficacy and the safeness of the treatment. Thirty-three H. pylori-positive patients after distal gastrectomy were treated with proton pump inhibitor (PPI)-based triple therapies. After eradication, endoscopic and histological changes were classified on the basis of the Updated Sydney System. The eradication rate in the remnant stomach was 90.9% (30 out of 33 cases) after triple therapy. Temporal minor side effects were notified in 3 cases. After eradication, the remnant stomach showed significant decreases in inflammation- and activity-scores. Moreover, significant improvement in glandular atrophy to normal mucosa was found. In conclusion, PPI-based standard therapy is just as effective for Hp eradication in the remnant stomach than it is in the non-operative stomach. Eradication therapy could be performed safely and resulted in a significant improvement in inflammation and atrophy of the mucosal layer in the remnant stomach after early gastric cancer surgery.

Characterization of three cDNA species encoding plastid RNA polymerase sigma factors in Arabidopsis thaliana: evidence for the sigma factor heterogeneity in higher plant plastids.

By database search analysis, we identified three Arabidopsis EST (Expression Sequence Tag) entries having similarity to eubacterial RNA polymerase sigma factors. cDNA clones corresponding to these partial sequences were isolated, and the complete nucleotide sequences were determined. All three sequences encode proteins highly homologous to cyanobacterial and plastid sigma factors, and the gene products have N-terminal extensions which are assumed to function as plastid-targeting transit peptides. Thus we have concluded that the gene products are RNA polymerase sigma factors of plastids, and named sigA, sigB and sigC, respectively. Expression of these genes was analyzed by RNA gel-blot analysis and shown to be induced by illumination after a short-term dark adaptation. This strongly suggests that light regulation of the nuclear encoded sigma factor genes is involved in light-dependent activation of plastid promoters.

Clonal analysis of hepatocellular carcinoma and dysplastic nodule by methylation pattern of X-chromosome-linked human androgen receptor gene.

To investigate the monoclonality of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) and the origin of multiple lesions, patterns of inactivation of X-linked human androgen receptor gene were studied. Fourteen of 15 patients (93%) were heterozygous in the size of the target, and were informative for clonal analysis. Monoclonal composition was demonstrated in all 17 HCCs and two DNs, whereas all non-cancerous hepatic tissues were polyclonal. Of four patients with more than two lesions of HCC or DN, two patients had two lesions with different patterns of X-chromosome inactivation, indicating that the two lesions were multicentric in origin.

Expression of interferon alpha/beta receptor in human hepatocellular carcinoma.

Interferon-alpha (IFNalpha) plays a crucial role in the antiproliferation and immunoregulatory activity through the specific cell surface receptor, interferon-alpha/beta receptor (IFNalpha/betaR). We examined the immunohistochemical expression of IFNalpha/betaR in 91 hepatocellular carcinoma (HCC), HCV-related chronic hepatitis (n=38) and cirrhosis (n=53), dysplastic nodules (n=5), and normal liver (n=9). The level of IFNalpha/betaR increased in chronic hepatitis and cirrhosis compared with normal liver. All the dysplastic nodules showed moderate or high expression. In HCCs, 26% (24/91) of patients showed high IFNalpha/betaR expression while the remaining 38% (35/91) showed moderate, and 35% (32/91) no or faint expression. Clinicopathological survey demonstrated a significant correlation between IFNalpha/betaR expression and differentiation of carcinoma (P=0.0008) although there was no correlation between IFNalpha/betaR expression in HCC and survival or disease-free survival. Thus, IFNalpha/betaR was expressed not only in chronic hepatitis or liver cirrhosis but in HCC and its expression was significantly correlated with tissue differentiation of carcinoma.

Hepatocellular carcinoma in adenomatous hyperplasia of the liver.

A hepatocellular carcinoma (HCC) measuring 0.2 cm in diameter was found in the center of an adenomatous hyperplasia (AH) measuring 1.7 cm in diameter in a cirrhotic liver. The liver cells of the AH showed a marked fatty change and contained many Mallory bodies. The AH and HCC were studied in relation to liver cell dysplasia in 108 surgically resected livers. The AH was mainly associated with fully developed cirrhosis in 5 (71%) of the 7 cases. The liver cell dysplasia, however was accompanied largely by fibrosis and early-stage incomplete septal cirrhosis in 10 (67%) of the 15 cases. As far as the active inflammatory change was concerned, a fairly active inflammation was found in only 3 (20%) of the 15 livers with liver cell dysplasia, but in 4 (57%) of the 7 livers with AH.

Expression of p57/Kip2 protein in pancreatic adenocarcinoma.

INTRODUCTION: Evaluation of the biologic character of carcinomas requires understanding of cell cycle regulators. AIMS: To investigate p57 expression in human pancreatic adenocarcinoma and cyst adenoma. METHODOLOGY: We examined the expression of p57(Kip2), a member of the Cip/Kip family, in 45 pancreatic adenocarcinomas, 7 cystadenomas, and 7 chronic pancreatitis cases. RESULTS: The p57 labeling index (LI) in duct epithelia in chronic pancreatitis averaged 32.8+/-8.3 and was significantly higher than in normal duct epithelia (18.8+/-6.6; p = 0.0011). For the carcinoma, the LI averaged 46.0+/-20.9, which was significantly higher than that for normal duct epithelia (p < 0.0001) and cystadenoma (16.0 11.2; p = 0.0007). However, it was significantly reduced in cases with stage IV disease (p = 0.0351), lymph node metastasis (p = 0.0003), larger size (p = 0.0094), capsular invasion (p = 0.0462), lymphatic invasion (p = 0.0351), and cell proliferating activity (p = 0.0002). In multivariate analysis, p57 LI in pancreatic adenocarcinoma was independently linked to high proliferating activity (p = 0.0230). CONCLUSION: These results suggest that p57 plays a role in the hyperplastic change of the ducts in chronic pancreatitis and that pS7 overexpression contributes to the downregulation of cell proliferation, and its decreased expression contributes to the progression of pancreatic adenocarcinoma.

Refractive-index-adjustable fillers for visible-light-cured dental resin composites: preparation of TiO2-SiO2 glass powder by the sol-gel process.

New fillers have been prepared for visible-light-cured (VL) dental resin composites with the refractive index adjustable to that of the resin phase. These SiO2 glass powders containing TiO2 up to 20 wt% were formed by heating to 1000 degrees C ground gels made from a mixture of Ti[OCH(CH3)2]4 and Si(OC2H5)4. With increasing TiO2 content, the refractive index of the prepared power increased linearly, while the optical transmittance at 467 nm decreased linearly. The experimentally formulated VL-cured resin composites, consisting of (TEGDMA and Bis-GMA) monomer mixture and TiO2-SiO2 glass filler, had greater transmittance when the refractive index of the filler matched that of the monomer mixture, resulting in a greater degree of monomer conversion upon irradiation with VL.

Analysis of photo-initiators in visible-light-cured dental composite resins.

Seven commercial visible-light-cured (VL) dental composite resins were analytically studied for identification of the photo-initiator consisting of photo-sensitizer and reducing agent. Gas-liquid chromatography (GC) was used for the determination of the dilute components extracted from the composite resin. Mass spectroscopy (GC-MS) was used for confirmation of the qualitative data obtained by GC. The results showed that all composite resins examined included camphorquinone (CQ) as a photo-sensitizer. The concentration of CQ in the resin phase, however, ranged from 0.17 to 1.03% w/w. The composite resin with hybrid-sized filler tended to have a higher concentration of CQ than did the micro-filled composite resin. As for the reducing agent, two out of seven brands contained dimethylaminoethyl methacrylate (DMAEMA), and one included dimethyl-p-toluidine (DMPTI). The mixing ratio between CQ and the amine in these three composite resins also varied. Another four brands did not contain either DMAEMA or DMPTI, and would utilize different reducing agents.

Unusual CT and MR findings of inflammatory pseudotumor in the parapharyngeal space: case report.

Unusual MR and CT findings of an inflammatory pseudotumor in the parapharyngeal space of a 73-year-old woman are reported. The mass was hypointense on T1- and T2-weighted images and demonstrated ring enhancement after contrast medium injection. Punctated calcifications were scattered at the periphery. Inflammatory pseudotumors in the parapharyngeal space are rare, and only three cases have been reported. The possible pathogenesis and varieties of inflammatory pseudotumors are discussed.

The role of diffusion-weighted imaging in patients with brain tumors.

BACKGROUND AND PURPOSE: Diffusion-weighted images (DWIs) have been used to study various diseases, particularly since echo-planar techniques shorten examination time. Our hypothesis was that DWIs and tumor apparent diffusion coefficients (ADCs) could provide additional useful information in the diagnosis of patients with brain tumors. METHODS: Using a 1.5-T MR unit, we examined 56 patients with histologically verified or clinically diagnosed brain tumors (17 gliomas, 21 metastatic tumors, and 18 meningiomas). We determined ADC values and signal intensities on DWIs both in the solid portion of the tumor and in the peritumoral, hyperintense areas on T2-weighted images. We also evaluated the correlation between ADC values and tumor cellularity in both gliomas and meningiomas. RESULTS: The ADCs of low-grade (grade II) astrocytomas were significantly higher (P =.0004) than those of other tumors. Among astrocytic tumors, ADCs were higher in grade II astrocytomas (1.14 +/- 0.18) than in glioblastomas (0.82 +/- 0.13). ADCs and DWIs were not useful in determining the presence of peritumoral neoplastic cell infiltration. The ADC values correlated with tumor cellularity for both astrocytic tumors (r = -.77) and meningiomas (r = -.67). CONCLUSION: The ADC may predict the degree of malignancy of astrocytic tumors, although there is some overlap between ADCs of grade II astrocytomas and glioblastomas.

Evidence of chemical bonding at biomaterial-hard tissue interfaces.

For many years, glass-polyalkenoate cements have been described as possessing the unique properties of self-adherence to human hard tissues, such as bones or teeth. However, direct experimental evidence to prove the existence of chemical bonding has not been advanced. X-ray Photoelectron Spectroscopy (XPS) was used to analyze the chemical interaction of a synthesized polyalkenoic acid with enamel and synthetic hydroxyapatite. For both enamel and hydroxyapatite, the peak representing the carboxyl groups of the polyalkenoic acid was detected to have significantly shifted to a lower binding energy. De-convolution of this shifted peak disclosed two components with a peak representing unreacted carboxyl groups and a peak suggesting chemical bonding to hydroxyapatite. On average, 67.5% of the carboxyl groups of the polyalkenoic acid were measured to have bonded to hydroxyapatite. XPS of hydroxyapatite also disclosed its surface to be enriched in calcium and decreased in phosphorus, indicating that phosphorus was extracted at a relatively higher rate than calcium. Analysis of these data supports the mechanism in which carboxylic groups replace phosphate ions (PO4(3-)) of the substrate and make ionic bonds with calcium ions of hydroxyapatite. It is concluded that an ultrathin layer of a polyalkenoic acid can be prepared on a hydroxyapatite-based substrate by careful removal of non-bonded molecules. With this specimen-processing method, XPS not only provided direct evidence of chemical bonding, but also enabled us to quantify the percentages of functional groups of the polyalkenoic acids that bonded to calcium of hydroxyapatite.

Malignant fibrous histiocytoma of the temporal bone with endocranial extension.

Cranial malignant fibrous histiocytomas are rare tumors. Most are hypervascular, destructive masses that are similar to other malignant lesions and to malignant fibrous histiocytomas found elsewhere in the body. We describe a myxoid malignant fibrous histiocytoma of the temporal bone, possibly of dural origin, with features that more closely resembled a meningioma at CT, MR imaging, and angiography.