Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants.

OBJECTIVE: Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants. METHODS: We investigated clinicopathological features of PLC (n = 11) compared with those of other variants of invasive lobular carcinoma (ILC, non-PLC) (n = 32). Histological variants of the non-PLC group consisted of classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n = 4). A review of cytological reports and fine needle aspiration (FNA) smear samples was performed for the PLC (n = 9) and non-PLC (n = 27) groups. RESULTS: Patients with PLC were older, and had a higher nuclear grade and a higher incidence of axillary lymph node metastasis and triple negative phenotype than non-PLC patients (P = 0.007, P < 0.001, P = 0.02 and P < 0.001, respectively). Cytological findings in PLC included medium- to large-sized nuclei, prominent nucleoli, a moderate-to-severe degree of pleomorphism, apocrine change and background necrosis, none of which were evident in the smears of the non-PLC group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, and P = 0.03, respectively). Despite these differences, patients with PLC and non-PLC showed similar clinical outcomes in our follow-up period. CONCLUSIONS: Based on our results, a cytological diagnosis of PLC should be proposed if there are moderate- to large-sized nuclei, prominent nucleoli, a moderate-to severe degree of nuclear pleomorphism, apocrine change and necrosis in the background in FNA biopsy samples.

Mucinous carcinoma of the breast: a comparative study on cytohistological findings associated with neuroendocrine differentiation.

OBJECTIVE: Mucinous carcinoma (MCA) may show neuroendocrine differentiation (ND), but the cytological features characteristic of ND remains elusive. We compared fine needle aspiration (FNA) findings of MCA between cases with high and low degrees of ND. METHODS: Histological sections of 37 MCA cases were immunohistochemically evaluated for expression of chromogranin A and synaptophysin, and were graded as 0 to 3+ degrees of ND. They were divided into low ND (grade 0 and 1+) and high ND (grade 2+ and 3+) groups. Pre-operative FNA samples of each group were assessed for cytological features. RESULTS: The mean age of the high ND group (n = 18) was higher than the low ND group (n = 19, P = 0.01). In FNA samples of the high ND group, 17 cases showed moderate to severe degrees of discohesiveness, but low ND cases mainly showed no or only mild discohesiveness (P < 0.001). Nine of the low ND cases displayed overlapped, cohesive cell clusters, whereas, in the high ND cases, the cells were arranged in a loose, flat and monolayered pattern (P = 0.045). Fourteen of the high ND cases had round nuclei, but oval nuclei were predominant in the low ND cases (P = 0.027). The nuclei were eccentrically located in 12 of the high ND cases but were centrally located in 14 of the low ND cases (P = 0.01). CONCLUSIONS: Mucinous carcinoma with high ND may be diagnosed by the presence of discohesiveness, a flat, monolayered pattern, and round or eccentrically located nuclei. Features of ND in carcinomas in other organs, such as intracytoplasmic granules and coarse chromatin, may not be reliable cytological features of ND in MCA.

Cellular sources of tenascin-C in canine mammary carcinomas.

Tenascin-C (Tn-C) is an extracellular matrix glycoprotein implicated in the progression of several human cancers. In canine mammary carcinomas, accumulation of Tn-C has been recognized in 3 different areas: regions of proliferating myoepithelial cells in complex carcinoma, basement membrane zone in low-grade simple carcinoma, and reactive stroma in high-grade simple carcinoma. To identify the Tn-C synthesizing cells in these areas, we utilized double-labeling immunohistochemistry, branched DNA in situ hybridization, and in situ hybridization-immunohistochemistry double-labeling techniques. In complex carcinomas, Tn-C was generated by proliferating myoepithelial cells. Tn-C in low-grade simple carcinomas was also derived from myoepithelial cells existing as a basal monolayer. However, stromal Tn-C in high-grade carcinomas was mainly synthesized by fibroblasts/myofibroblasts, similar to human breast cancer. Thus, the origin of Tn-C in canine mammary carcinomas differs between low- and high-grade malignancies. The role of myoepithelial cell-generated Tn-C is not yet understood.

Epithelial splicing regulatory protein 1 is a favorable prognostic factor in pancreatic cancer that attenuates pancreatic metastases.

Epithelial splicing regulatory protein 1 (ESRP1) binds the FGFR-2 auxiliary cis-element ISE/ISS-3, located in the intron between exon IIIb and IIIc, and primarily promotes FGFR-2 IIIb expression. Here we assessed the role of ESRP1 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis was performed using anti-ESRP1, FGFR-2 IIIb and FGFR-2 IIIc antibodies in 123 PDAC cases. ESRP1 expression vector and small interference RNA (siRNA) targeting ESRP1 were transfected into human PDAC cells, and cell growth, migration and invasion were analyzed. In vivo heterotopic and orthotopic implantations using ESRP1 overexpression clones were performed and effects on pancreatic tumor volumes and hepatic and pulmonary metastases determined. ESRP1 immunoreactivity was strong in the nuclei of cancer cells in well-to-moderately differentiated PDACs but weak in poorly differentiated cancers. Well-to-moderately differentiated cancers also exhibited high FGFR-2 IIIb and low FGFR-2 IIIc expression, whereas this ratio was reversed in the poorly differentiated cancers. Increased ESRP1 expression was associated with longer survival in comparison with low ESRP1 expression, and PANC-1 cells engineered to express ESRP1 exhibited increased FGFR-2 IIIb expression and decreased migration and invasion in vitro, whereas ESRP1 siRNA-transfected KLM-1 cells exhibited increased FGFR-2 IIIc expression and increased cell growth, migration and invasion. In vivo, ESRP1-overexpressing clones formed significantly fewer liver metastases as compared with control clones. ESRP1 regulates the expression pattern of FGFR-2 isoforms, attenuates cell growth, migration, invasion and metastasis, and is a favorable prognostic factor in PDAC. Therefore, devising mechanisms to upregulate ESRP1 may exert a beneficial therapeutic effect in PDAC.

Acinar cell cystadenoma of the pancreas in a cat.

Cystic tumours of the pancreas are heterogeneous lesions with a spectrum of morphology and biological behaviour in people. These are poorly characterized in animals. A multicystic tumour of the pancreas was identified in an 11-year-old, female, mixed breed cat. The tumour was 5.5 cm in diameter and the largest cysts were 1.5 cm in diameter. Microscopically, the cysts were lined by single layered or pseudostratified, flat, cuboidal or columnar epithelial cells that occasionally formed papillary structures with a thin fibrous core. The tumour cells had eosinophilic granules in the apical cytoplasm, similar to zymogen granules, and the nuclei were uniform in size and shape. Mitotic figures were not observed. Immunohistochemically, the tumour cells expressed trypsin, but not cytokeratin 7. A diagnosis of acinar cell cystadenoma of the pancreas was made and this is the first report of this tumour in a cat.

CD30-positive diffuse large B-cell lymphoma with microvillous features: so-called microvillous lymphoma.

A case of CD30-positive microvillous lymphoma (MVL) in an 87-year-old man who was encountered generalised lymphadenopathy is presented. Histopathologically, the tumour showed a morphological mimic of anaplastic large cell lymphoma (ALCL) with sinusoidal growth pattern. Immunohistochemically (IHC), the tumour cells were CD30(+), CD20(+), CD45(+), BCL-2(+), BCL-6(+), MUM1(+), Ki-67(+), CD45RO(-), CD3(-), CD10(-), CD15(-), CD56(-), EMA(-), TIA-1(-) and ALK(-). Flow cytometry confirmed the IHC. In situ hybridisation for Epstein-Barr virus RNA was negative. Electron microscopically, the tumour cells were similar to large transformed lymphocytes and had circumferentially profuse microvillous projections resembling those of epithelial mesothelioma cells. In conclusion, CD30-positive MVLs are indistinguishable from ALCLs that have ultrastructural microvillous projections by morphology alone. However, the lack of EMA, TIA-1 and ALK expression in this MVL case facilitated a definite distinction from ALCLs. The results of a panel of three markers (CD10(-), Bcl-6(+) and MUM1(+)) suggested that the present case of CD30-positive MVLs has an activated non-germinal centre B-cell origin.

A non-acromegalic case of multiple endocrine neoplasia type 1 accompanied by a growth hormone-releasing hormone-producing pancreatic tumor.

Cases of acromegaly due to GHRHproducing pancreatic endocrine tumors have been reported. Here we present a case of a 31-yr-old nonacromegalic man with hyperparathyroidism and elevated serum IGF-I with normal serum GH levels. Serum GH was not suppressed below 1 ng/ml by the glucose tolerance test and increased in response to TR H and GHRH administration. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia and an abdominal computed tomography (CT ) scan showed a tumor in the pancreatic tail. Plasma concentration of GHRH was elevated. Based on these clinical data, multiple endocrine neoplasia (MEN) type 1 was suspected. Three enlarged parathyroid glands were removed and a distal pancreatectomy was performed. Pathological examination of the parathyroid glands and pancreatic tumor showed nodular hyperplasia and a well-differentiated endocrine tumor, respectively, both compatible with MEN features. Immunohistochemistry revealed positive immunoreactivity for GHRH, SS , insulin, glucagon, chromogranin A, and pancreatic polypeptide in the pancreatic tumor. After pancreatic surgery, elevated levels of GHRH and IGF-I were normalized and pituitary hyperplasia definitely decreased in size. In cases of pituitary hyperplasia with elevated IGF-I, ectopic GHRH syndrome must be considered even if physical features of acromegaly are absent. It is also important to measure plasma GHRH concentrations in order to give a diagnosis.

Expression of nestin in rat and human glomerular podocytes.

Nestin is a neuroepithelial precursor cell marker expressed in a variety of human cell types during development. However, no information exists on the expression of nestin in mature glomeruli as well as during the glomerular development. Here, we examined nestin expression in rat and human glomerular tissues in quiescent states using RT-PCR and immunohistochemical methods. Nestin mRNA was detected in the rat glomeruli in parallel with its expression in developing rat brains. In the normal mature rat glomeruli, WT-1 positive cells expressed nestin. Co-expression of nestin and vimentin was observed in mature rat podocytes. Immunoelectron microscopy revealed nestin localization in the cell bodies and primary processes of podocytes. A similar expression pattern was observed for vimentin. In matured glomeruli, nestin was not expressed by mesangial and endothelial cells. In the newborn rat, early developing glomeruli (metanephric cap, metanephric vesicle, comma-shaped vesicle and S-shaped body phases) expressed nestin. In the capillary loop stage, Bowman's capsules also expressed nestin. Immunoelectron microscopy demonstrated that developing podocytes and endothelial cells in S-shaped phase glomeruli expressed nestin. Additionally, in immature glomeruli, the mesangial cells in capillary stage of glomerulus also expressed nexin. As in the rat, WT-1 positive cells in human glomeruli also expressed nestin and immunoelectron microscopy confirmed nestin expression in human glomerular podocytes. These results reveal that in normal condition nestin is expressed in several glomerular cell types at early stage of development and becomes confined to podocytes in mature glomeruli, thus implicating nestin in podocyte functions.

Sex differences in mucosal response to Helicobacter pylori infection in the stomach and variations in interleukin-8, COX-2 and trefoil factor family 1 gene expression.

BACKGROUND: Gastric cancer incidence in men is almost double that in women. We investigated mucosal responses in the stomach against Helicobacter pylori (H. pylori) infections to elucidate the interindividual or sex-related differences, which may in turn be associated with gastric cancer incidence, mucosal changes of stomach as measured by the Sydney System, and interleukin-8, cyclooxygenase-2 and trefoil factor family 1 (TFF1) gene expression. METHODS: An age-, sex-, H. pylori status- and disease-matched case-control study was performed in 574 H. pylori-positive and 225 H. pylori-negative patients selected from 4125 patients with a diagnosis of benign disease of the stomach. Levels of acute and chronic inflammations, atrophy and intestinal metaplasia scored according to the Sydney System were compared by stomach site and by sex. Two biopsy specimens (antral and corpus gastric mucosa) from patients with benign gastric diseases (142 patients; 72 men, 70 women) were analysed for interleukin-8, cyclooxygenase-2 and TFF1 mRNA expression as measured by real-time PCR. RESULTS: Inflammation and activity scores in antrum with H. pylori infection were higher in men, but scores declined according to age. Atrophy and intestinal metaplasia scores in corpus with H. pylori infection appeared more severe in men than in women, especially in older patients. In women, atrophy score increased with increasing age, particularly in postmenopausal H. pylori-negative patients. Interleukin-8 mRNA induction was detected in both antrum and corpus mucosa in H. pylori infection, but sex differences were not found. Response of cyclooxygenase-2 mRNA expression against H. pylori infection in the mucosa was higher in men than women. In H. pylori-negative patients, TFF1 mRNA levels in women were significantly higher than in men, and TFF1 mRNA was significantly lower in positive than negative women. CONCLUSIONS: Sex differences in mucosal responses to H. pylori infection in the stomach may be correlated with sex differences in the incidence of stomach cancer.

Effect of general anesthesia on the abnormal immune response in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the influence of mental stress on the neuroendocrine-immune system in patients with rheumatoid arthritis (RA). METHODS: Twenty-four patients with RA and 10 patients with osteoarthritis (OA) who underwent total knee or hip arthroplasty under general anesthesia were enrolled in this study. The blood levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors (TNF-Rs) and other substances related to stress were measured just before administering anesthesia on the day of the operation when the patients lay on the operating table and roughly 30 min later when the patients were under general anesthesia without mental stress. These values were compared with those at the same time on the day before the operation, which were considered as controls. RESULTS: In patients with RA under general anesthesia, the levels of IL-6, TNF-alpha, and TNF-R1 and TNF-R2 in the peripheral blood were significantly decreased compared with the levels before anesthesia (p < 0.01). Before anesthesia the levels of IL-1Ra in the peripheral blood were significantly higher, and the level of IL-1Ra was enhanced after the administration of general anesthesia, when compared with the level on the day before the operation (p < 0.01). Such changes were not apparent in patients with OA. CONCLUSION: In patients with RA, excessive mental stress should be eliminated to modify the interaction between the stress-immune system and stress-endocrine system as a method to better control disease activity.

Fine needle aspiration cytology for soft tissue tumours of the hand.

The purpose of this study was to evaluate the usefulness of fine needle aspiration cytology for the preoperative diagnosis of soft tissue tumours of the hand. Fine needle aspiration cytology was performed on 93 soft tissue tumours of the hand which were classified as malignant, benign or unclassified based on cytological findings. We also attempted to make specific diagnosis by cytology. The cytological diagnosis was then compared with the postoperative histopathological diagnosis. The cytological differentiation between benign and malignant tumours showed neither false-positive nor false-negative results. Of the 47 lesions with sufficient material for cytology and that were postoperatively diagnosed histologically, 35 (including one recurrent lesion) were correctly diagnosed by fine needle aspiration cytology. No complications were encountered. Fine needle aspiration cytology has a high degree of diagnostic accuracy and safety for soft tissue tumours of the hand.

Genetic polymorphisms of aldehyde dehydrogenase 2, cytochrome p450 2E1 for liver cancer risk in HCV antibody-positive japanese patients and the variations of CYP2E1 mRNA expression levels in the liver due to its polymorphism.

BACKGROUND: Hepatocellular carcinoma (HCC) in persons with liver cirrhosis (LC) arises following hepatitis virus infection. Alcohol may accelerate the risk of development of LC and HCC. Cytochrome p450 2E1 (CYP2E1) oxidizes ethanol to form acetaldehyde and aldehyde dehydrogenase 2 (ALDH2) detoxifies acetaldehyde, which is carcinogenic in humans, and both alcohol-metabolizing enzymes show the genetic polymorphisms in a Japanese population. METHODS: Using polymorphism analysis, we studied the frequency of ALDH2 functional deletion due to the G to A single-bp mutation in exon 12 and CYP2E1 polymorphism in the transcriptional region, both associated with higher levels of acetaldehyde, in 135 patients with LC and/or HCC, including 99 with HCC, and 135 non-cancer controls. The mRNA expression levels of CYP2E1 in the liver were also examined in 55 surgical specimens. RESULTS: The allelic frequency of the homozygous ALDH2 2-2 genotype, coding for the enzyme deletion, was significantly higher compared to that of the homozygous or heterozygous ALDH2 1-1 genotypes in cases with HCC (OR = 5.4, 95% CI 2.1-14.0). There were no differences in the frequencies of specific genotypes of CYP2E1 in cases of HCC, but combined analysis of ALDH2 and CYP2E1 revealed that the odds ratio of occurrence of the C1/C1 homozygosity of CYP2E1 and the ALDH2 2-2 homozygosity was as high as 23.0 (2.9-182). The mRNA levels of CYP2E1 were higher in the liver of patients with the C1/C1 homozygosity of CYP2E1 than in those with other genotypes (P < 0.05). CONCLUSIONS: ALDH2 and CYP2E1 polymorphisms may modify the risk of development of HCC against the background of LC in the Japanese. Polymorphism analysis of alcohol-metabolizing enzymes using molecular techniques may be useful in the risk assessment of liver cancer in patients with hepatitis C virus infection.

Expression and localization of basic fibroblast growth factor and its mRNA in solitary fibrous tumor.

Solitary fibrous tumors (SFTs) represent a distinct neoplasm that should be included in the differential diagnosis of spindle-cell neoplasms of the soft tissue. Basic fibroblast growth factor (bFGF or FGF-2) is a mitogenic and angiogenic polypeptide produced by diverse cell types, including the cells derived from normal tissue and neoplastic lesions. In this study, the expression of bFGF, vimentin, CD 34, c-kit (or CD 117), desmin, S-100 protein, and alpha-smooth muscle actin (alpha-SMA) in SFTs, hemangiopericytomas (HPC), gastrointestinal stromal tumors (GIST), and dermatofibrosarcoma protuberans (DFSP) were evaluated to assess their usefulness in the differential diagnosis of these lesions. The expression of bFGF mRNA was also examined in SFTs by in situ hybridization (ISH) using a digoxigenin-labeled bFGF oligonucleotide probe. All the SFTs, GISTs and DFSPs exhibited strong and diffuse immunoreactivity for CD34 and vimentin, and were completely negative for desmin, S-100 protein and alpha-SMA. The HPCs were positive for vimentin, but negative for CD34. In all the SFTs, strong and diffuse nuclear immunostaining was observed with bFGF antibody, contrasting with the negative staining observed in the majority of the HPCs, GISTs, and DFSPs. The bFGF mRNA was also expressed in the SFT cells. The constitutive expression of the bFGF in the SFT widens the spectrum of available markers for these tumors, providing a useful addition to their differential diagnosis in difficult cases, and contributing to the understanding of their histogenesis and molecular pathogenesis.

[Expression and intracytoplasmic signal transduction pathway of fibroblast growth factor (FGF)-10 in human cervical cancer cell lines].

Fibroblast growth factor (FGF) -10 is a new member of the FGF family initially reported in Japan. It is mainly synthesized by mesenchymal cells and acts on epithelial cells in a paracrine manner. FGF-10 actions are dependent on their binding to the iiib form of FGF receptor 2 (FGFR2) iiib, also known as keratinocyte growth factor receptor (KGFR). FGF-10 has high amino acid homology to keratinocyte growth factor (KGF) and plays an important role in fetal limb and lung development and skin wound healing. In the present study, the expression of FGF-10 and FGFR2 iiib messenger RNA (mRNA) in two different human uterine cervical cancer cell lines (CaSki and ME-180) were examined. Both CaSki and ME-180 cells expressed FGFR2 iiib mRNA, while only CaSki cells expressed FGF-10 mRNA and protein. Recombinant FGF-10 (1 ng/ml) increased the growth rate of ME-180 cells and also enhanced mitogen-activated protein kinase (MAPK) phosphorylation of the cells. These data indicate that FGF-10 may directly promote the growth of squamous cell cancer in the uterine cervix via the MAPK pathway.

Hemorrhagic gastric carcinoma in an acromegalic patient.

A rare case of hemorrhagic gastric carcinoma in an acromegalic patient is reported. A 79-year-old Japanese man was referred to our hospital with diagnoses of upper gastrointestinal hemorrhage and angina pectoris. This patient showed typical clinical features of acromegaly, with increased serum growth hormone (GH) and insulin-like growth factor I (IGF-I) level. A high titer of serum anti-Helicobacter pylori (H. pylori) IgG was also observed. After percutaneous transluminal coronary angioplasty treatment for stenosis of the right coronary artery, the patient underwent distal gastrectomy. Gastric cancer was Type 2 macroscopically and was diagnosed histologically as a papillary and well to moderately differentiated tubular adenocarcinoma. Reverse transcription-polymerase chain reaction analysis estimated that the amount of IGF-I receptor mRNA expression in the gastric cancer tissue was 1.6 times higher than that in the adjacent atrophic mucosa, whereas the amount of IGF-I mRNA expression in the cancer tissue was only half that in the atrophic mucosa. Both the stimulatory effects of GH and/or IGF-I on cell proliferation and H. pylori infection in gastric tumorigenesis may have been responsible for the development and growth of gastric carcinoma in this patient.

Immunohistochemical expression of T, Tn and sialyl-Tn antigens and clinical outcome in human breast carcinoma.

BACKGROUND: The extent of expression of reactive T (Thomsen-Friedenreich), Tn and sialyl-Tn antigens has been assumed to predict carcinoma aggressiveness. We studied the expression of T, Tn and sialyl-Tn antigens in a relatively large cohort of breast carcinoma patients with known long-term outcome to assess the clinical and biological significance of these antigens. MATERIALS AND METHODS: T, Tn and sjalyl-Tn antigens were examined in 72 consecutive primary breast carcinomas by immunohistochemistry using well defined monoclonal antibodies and their semiquantitative values were correlated with established clinicopathologic prognostic parameters of the disease to determine their relationship with long-term clinical outcome. RESULTS: Of the 72 carcinomas, 63 (87.5%) each expressed T or Tn antigens, while 16 (22%) expressed sialyl-Tn antigens. Most carcinomas (81%) expressed more than one of the antigens simultaneously, being the most frequent combination T/Tn antigen expression. No significant correlation was noted between the expression of T, Tn and sialyl-Tn antigens (whether individually or in combination) and the prognostic parameters including patient age, disease stage, tumor size, lymph node status, nuclear and histologic grades, histologic types, hormone receptor status and menopausal status. Univariate survival analyses showed that disease stage, tumour size and lymph node metastasis were significant predictors of overall survival. Interestingly, a significant inverse correlation was found between the Tn antigen expression (p = 0.04), as well as the combined T/Tn (p = 0.03) and Tn/sialyl-Tn (p = 0.02) antigen expressions and long-term overall survival. In a multivariate Cox proportional hazard model, disease stage and a negative or low Tn antigen expression emerged as significant predictors of overall survival. CONCLUSION: Our data suggested that the expression of T, Tn and sialyl-Tn antigens does not appear to predict the outcome of patients with breast carcinoma in a long-term run. Moreover, the findings signified a potential value for a negative or low Tn antigen expression in prognostic stratification of breast carcinomas.

Expression of cathepsin B and cystatin C in human breast cancer.

Cathepsin B, which was originally found to be a lysosomal cysteine protease, is also an important matrix protease. In this study, we investigated the expression of cathepsin B and cystatin C, the strongest inhibitor of cathepsin B, and measured the relative amounts of each in human breast cancer tissues. Cystatin C expression relative to cathepsin B expression was found to be decreased. This finding could be associated with the looseness of cancerous interstitial tissue, which might play a role in cancer invasion and metastasis. This report documents the first simultaneous investigation of cathepsin B and cystatin C in breast cancer tissues.

Localization of extracellular matrix and mitogen-activated protein kinase (MAPK) in aorta of streptozotocin treated Mongolian gerbils.

To evaluate the relationship among the extracellular matrix (ECM) and mitogen-activated protein kinase (MAPK) family for the vascular damages in hyperglycemia, we injected Mongolian gerbils intravenously with 150 mg/kg streptozotocin (STZ) and observed over the next one year the resulting aortic changes by immunohistochemical techniques. After STZ treatment, hyperglycemia was confirmed. At 4 weeks after STZ administration morphological observation revealed increased stromal components among the vascular smooth muscle cells (SMCs). Immunohistochemically, extracellular matrices such as fibronectin and laminin were localized in the aorta at 4 weeks and one year after STZ administration. The reaction products of MAPK in vascular SMCs were more increased at one year than at 4 weeks after STZ administration. After STZ administration, the increase of ECM and MAPK was observed in the aorta, which suggests these factors play important roles in the pathogenesis of macrovasculopathy in diabetes mellitus.

Use of electron microscopic evaluation for the diagnosis of adrenal cortical carcinoma in fine needle aspiration cytology: a case report and review of the literature.

Bilateral adrenal tumors were detected in a 72-year-old man who had a history of hepatic inflammatory pseudotumor. Computet tomography (CT)-guided fine needle aspiration cytology (FNAC) of the adrenal glands was performed. The cytologic findings were similar to the previous diagnosis of "inflammatory pseudotumor" in the liver. However, the origin of some aggregated large atypical cells observed in the adrenal FNAC specimens was not known. Immunocytochemically, these large atypical cells were positive for vimentin and negative for cytokeratin and chromogranin A. An electron-microscopic study showed that these large atypical cells contained mitochondria with tubulovesicular cristae and smooth endoplasmic reticulum arranged in whorled and laminated patterns, and these findings confirmed diagnosis of primary adrenal cortical carcinoma. The histopathological diagnosis of the resected bilateral adrenal tumor was adrenal cortical carcinoma. The patient died 7 months after surgery, with recurrence of the bilateral adrenal cortical carcinoma and extensive metastases. A diagnosis of primary adrenal cortical carcinoma with extensive metastases was finally demonstrated by autopsy. Retrospectively, the previous liver tumor was determined to be a metastatic lesion.

Effects of extracellular matrix on phenotype modulation and MAPK transduction of rat aortic smooth muscle cells in vitro.

The transition of arterial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype may play an essential role in the formation of atherosclerotic and restenotic lesions. This process includes a prominent structural reorganization and allows cells to acquire the ability to migrate, proliferate, and secrete extracellular matrix components. According to Western blotting analysis and immunohistochemical and morphological observations, laminin not only retains SMCs in a contractile state but also possibly stimulates cells to transform a synthetic to a contractile phenotype at an early stage, mediated by P38 MAPK signal transduction. However, fibronectin promotes SMCs to transform from a contractile to a synthetic phenotype, mediated by the ERK MAPK signal pathway. The localization of smooth muscle alpha -actin, myosin heavy chain isoform SM2, and vimentin in explant-isolated rat SMCs was affected by a substrate of fibronectin and laminin and also by ERK MAP kinase inhibitor (PD098059) and P38 MAPK inhibitor (SB203580). Furthermore, vimentin may play a much more important role in differentiation than desmin in phenotype modulation in rat aortic smooth muscle cells.