Clinicopathological and immunohistochemical studies of thymic-related tumours in thyroid gland: report of five cases.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
J Y Ro
Publications and source records attributed to J Y Ro.
Assessing abnormal gene promoter methylation in paraffin-embedded sputum from patients with NSCLC.
Aberrant methylation of CpG islands is an important pathway for regulation of gene expression. Recent data suggest that epigenetic abnormalities may occur very early in lung carcinogenesis. We studied the promoters of the four genes, HOX A9, p16(INK4a) (p16), MAGE A1 and MAGE B2 by methylation-specific PCR in matched normal tissue, tumour, and cytological negative sputum samples obtained from 22 patients with non-small cell lung cancer (NSCLC). We further report methylation abnormalities in sputum samples from 56 smokers with differential cytology readouts (negative, inflammatory changes, suspicious, and cancer). Our method was successfully performed on formalin-fixed and paraffin-embedded (FFPE) samples, and was fit to study only few cells obtained by a convenient non-invasive sputum collection and handling. The promoters of MAGE A1 and MAGE B2 had abnormal methylation patterns in, respectively, 50% and 41% of the cytologically negative sputum samples from NSCLC patients, whereas methylation abnormalities of p16 was observed in 27% of negative sputum samples. Interestingly, 95.5% (21 of 22) of the cytologically negative sputum samples from NSCLC patients had abnormal methylation in at least one of the four genes indicating a high sensitivity of this marker system. Moreover, a higher frequency of methylation abnormalities was observed in sputum samples from smokers with high cytological grade compared to low cytological grade. We conclude that the identification of abnormal gene methylation of a limited number of markers in FFPE sputum samples is feasible and may be investigated as a potential system for population-based screening of early stages of lung cancer.
Aged↗
Adenomatoid tumor of the adrenal gland: a clinicopathologic study of 3 cases.
Adenomatoid tumors are relatively uncommon benign neoplasms of mesothelial origin, usually occurring in the male and female genital tracts. Rare extragenital adenomatoid tumors have been identified in the adrenal glands, heart, mesentery, pleura, and lymph nodes. In the adrenal gland, adenomatoid tumors may pose a diagnostic challenge. The differential diagnosis includes adrenocortical carcinoma and metastatic carcinoma, especially signet ring cell carcinoma. Because of its glandular pattern, an adenomatoid tumor may be confused with an adenocarcinoma. We present 3 cases of adrenal adenomatoid tumors, including one with a concurrent large hemorrhagic vascular adrenal cyst. The adenomatoid tumors were unilateral, appeared solid and white, and varied from 1.7 to 4.2 cm in diameter. They occurred in 3 male patients aged 33, 33, and 46 years. One patient presented with abdominal pain due to the presence of a concurrent large adrenal cyst. The tumor was an incidental radiological finding in another case and was discovered during the course of a workup for hypertension in the third case. The light microscopic appearances were consistent with those of typical adenomatoid tumors. Immunohistochemical stains for calretinin and cytokeratin 5/6 were positive, confirming the tumors' mesothelial origin. Ultrastructural studies performed in 2 cases revealed microvilli and desmosomes. Follow-up showed no evidence of recurrence or metastasis. In our experience, the key to the diagnosis of this rare benign tumor is to consider adenomatoid tumor in the differential diagnosis of any glandular tumor occurring in the adrenal gland.
Adenocarcinoma↗
Signal pathway of cytokines produced by reactive oxygen species generated from phorbol myristate acetate-stimulated HMC-1 cells.
The relationship of cytokine production and reactive oxygen species (ROS) generated in mast cells has not been reported yet. This study aimed to examine the signal pathway in the production of cytokines [interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha)] by ROS generated from phorbol myristate acetate (PMA)-stimulated human mast cell line-1 cells (HMC-1). HMC-1 cells were stimulated with 25 ng/ml of PMA. The ROS generation and production of cytokines (IL-8 and TNF-alpha) were measured by fluorescence-activated cell sorter and enzyme-linked immunosorbent assay method, respectively. Phosphorylation of mitogen-activated protein kinase family (extracellular signal-regulated kinase, p38 and c-Jun N-terminal kinase) was detected by the Western blotting method. The expression of cytokine's mRNA was measured by reverse transcriptase--polymerase chain reaction, and the DNA-binding activity of the transcription factors [nuclear factor-kappaB (NF-kappaB) and activator protein-1] was detected by electrophoretic mobility shift assay. PMA-stimulated HMC-1 cells immediately generated ROS, and the generated ROS was inhibited by 1,3-dimethyl-2-thiourea (DMTU), but partially inhibited by catalase or N-acetyl-L-cysteine. The production of cytokines in PMA-stimulated HMC-1 cells reached the maximum at 3-5 h and was inhibited by DMTU and specific kinase inhibitor for p38, SB203580. DMTU and SB203580 also inhibited the expressed cytokine's mRNA level and the increased DNA-binding activity of transcription factors, NF-kappaB in PMA-stimulated HMC-1 cells. These data suggest that intracellular ROS generated from PMA-stimulated HMC-1 cells contributes to the production of inflammatory cytokines via p38 kinase/NF-kappaB.
Antioxidants↗
Contribution of peripheral N-methyl-D-aspartate receptors to c-fos expression in the trigeminal spinal nucleus following acute masseteric inflammation.
In this study, we examined the contribution of N-methyl-D-aspartate (NMDA) receptors on c-fos expression in the trigeminal brainstem nuclei following acute muscle inflammation. Mustard oil (MO; 20%, 30 microL) injected into the masseter muscle induced extensive peripheral edema and Fos-like immunoreactivity (Fos-LI) in several trigeminal brainstem areas including the subnucleus caudalis of the trigeminal spinal nucleus (Vc), the ventral and dorsal regions of the Vc/subnucleus interpolaris transition zone, and the paratrigeminal nucleus. In order to assess the effect of antagonizing NMDA receptors on MO-induced Fos-LI, rats were pre-treated with two different doses of i.v. MK-801 (0.3 mg/kg, 3 mg/kg), a non-competitive NMDA receptor antagonist, 30 min prior to MO injection. Additional groups of rats received MK-801 (0.3 mg/kg) directly in the masseter muscle or in the biceps muscle 5 min prior to MO injection. A higher dose of i.v. MK-801 (3 mg/kg) and MK-801 given locally into the masseter muscle (0.3 mg/kg) produced a significant reduction in total number of MO-induced Fos-LI. Further analyses revealed that pre-treatment with MK-801 (3 mg/kg i.v.) significantly reduced the Fos-LI all throughout the Vc. Only at the caudal Vc, there was a dose-dependent reduction of MO induced Fos-LI. Pre-treatment with masseteric MK-801 also significantly reduced the Fos-LI in the caudal Vc, with the effect greater than that produced by the same dose of MK-801 given intravenously. These results suggest that peripheral NMDA receptors contribute to nociceptive processing from craniofacial muscles.
Animals↗
Allergen-specific immunosuppression by ovalbumin fused with diphtheria toxin in mice sensitized with albumins of different origin.
BACKGROUND: We previously reported that ovalbumin-diphtheria toxin (OVA-DT) fusion protein eliminates mast cells bearing OVA-specific IgE and protects OVA-sensitized mice from fatal anaphylaxis induced by OVA challenge. OBJECTIVE: To prove the specificity of therapeutic effect of OVA-DT to allergy induced by OVA only and not by other allergens such as human serum albumin (HSA), and to examine the cytotoxic effect of OVA-DT on B cells bearing OVA-specific IgE. METHODS: Mice were sensitized with two different antigens, OVA and HSA, and then treated with OVA-DT. The therapeutic effect of OVA-DT on the allergy response to each of allergen was evaluated by anaphylactic test. The effect of OVA-DT on the production of allergen-specific Ig isotypes of the sensitized mice and the cytotoxic effect of OVA-DT on B cells expressing OVA-specific IgE were examined. RESULTS: OVA-DT suppressed only OVA-induced allergy but not HSA-induced allergy in mice sensitized with a mixture of OVA and HSA. The suppression was prolonged even to the mice boosted with the same allergen 14 days after last treatment of OVA-DT. In addition, when the sensitized mice were boosted with the same allergens 14 days after last treatment of OVA-DT, the mice showed to increase the production of OVA-specific IgG2a/IgG3 and decreased that of OVA-specific IgE. OVA-DT targeted B cells bearing OVA-specific IgE, and killed them by DT-mediated cytotoxicity. CONCLUSION: The therapeutic effect of OVA-DT was specific to OVA-induced allergy and the suppression of OVA-induced allergy was continuously shown in the mice boosted with the same allergens. This is considered to be caused by the increase of OVA-specific IgG2a and IgG3, and because of the decrease of OVA-specific IgE by killing of B cells bearing OVA-specific IgE.
Albumins↗
p57kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles.
AIMS: To determine the utility of p57kip2 in the diagnosis of hydatidiform mole. p57kip2 protein is a cyclin-dependent kinase inhibitor (CDKI) and is strongly paternally imprinted, being expressed from the maternal allele. It has been hypothesized that complete mole (CHM) with only the paternal genome would display reduced or nearly absent expression of p57kip2 compared to partial mole (PHM) having both paternal and maternal genomes. METHODS AND RESULTS: The immunohistochemical expression of p57kip2 protein was investigated using paraffin-embedded tissue sections in histologically unequivocal cases of CHM (n = 51), PHM (n = 7), invasive mole (n = 1), and hydropic miscarriage (n = 2), as well as in histologically undetermined cases (n = 9). In the histologically unequivocal complete and invasive moles, expression of p57kip2 was absent except for one case in which villous cytotrophoblast covering the villous stroma was positive (51/52) as well as villous stromal cells (51/52). In contrast, it was strongly and continuously expressed in both villous cytotrophoblast and stromal cells in all cases of PHM and hydropic miscarriage. Among the nine histologically undetermined cases, five cases showing p57kip2 immunopositivity and hyperploid DNA were classified as PHMs, two cases showing p57kip2 immunonegativity and hyperploidy as CHMs, and two cases with p57kip2 immunopositivity and diploid DNA as hydropic miscarriage and diploid PHM, respectively, upon review of the histopathological findings. Intermediate trophoblast forming trophoblastic columns or anchoring villi and extravillous trophoblast at the implantation site showed variable expression of p57kip2 in all gestational conditions. Maternal decidua showed diffuse and strong p57kip2 expression, whereas syncytiotrophoblast was completely negative in all cases regardless of the diagnosis. CONCLUSIONS: In summary, p57kip2 immunostaining results correlated well with morphological features of molar pregnancies and were helpful in determining histologically equivocal cases.
Adolescent↗
Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC.
PURPOSE: We conducted a phase III trial to investigate the timing of chemotherapy with respect to surgery for patients with resectable but high-risk urothelial cancer. The trial was also designed to evaluate the accuracy of clinical staging in patients with locally advanced cancer and the prognostic significance of chemotherapy-induced downstaging. PATIENTS AND METHODS: A total of 140 uniformly evaluated patients with locally advanced urothelial cancer were studied. Planned treatment was five cycles of chemotherapy (M-VAC: methotrexate, vinblastine, doxorubicin, and cisplatin) plus radical cystectomy and pelvic lymph node dissection. Patients were randomly assigned to receive either two courses of neoadjuvant M-VAC followed by surgery plus three additional cycles of chemotherapy, or, alternatively, to have initial cystectomy followed by five cycles of adjuvant chemotherapy. RESULTS: There were no significant differences in outcome between the two groups. By intent-to-treat, 81 patients (58%) remain disease-free, with median follow-up of 6.8 years. We confirmed a high rate of clinical understaging in this cohort, especially among patients showing lymphovascular invasion on biopsy. Patients with no residual muscle-invasive disease at cystectomy after neoadjuvant chemotherapy were likely to be cured. CONCLUSION: These results lend further support to the impression from small randomized trials that, in a high-risk cohort, there is an improved cure fraction by the combination of multiagent chemotherapy and surgery, although we found no preferred sequence. Importantly, it is possible to select appropriate patients for such therapy on the basis of clinical staging information. These results establish a benchmark of outcome for this cohort.
Adult↗
Genetic mapping and DNA sequence-based analysis of deleted regions on chromosome 16 involved in progression of bladder cancer from occult preneoplastic conditions to invasive disease.
Histologic and genetic mapping with 30 hypervariable markers mapped to chromosome 16 were performed on 234 DNA samples of five cystectomy specimens from patients with invasive bladder cancer. Allelic losses of individual markers were related to microscopically identified precursor conditions in the entire bladder mucosa and invasive cancer. Their significance for the development and progression of neoplasia from in situ preneoplastic conditions to invasive disease was analysed by the nearest neighbor algorithm and binomial maximum likelihood analysis. Using this approach we identified five distinct regions of allelic losses defined by their flanking markers and predicted size as follows. p13.3(D16S418-D16S406, 1.2 cM), p13.1(D16S748-D16S287, 12.9 cM), q12 1(D16S409-D16S514, 24.0 cM), q22.1 (D16S496-D16S515, 5.4 cM), and q24 (D16S507-D16S511, 5.9 cM and D16S402-D16S413, 17.4 cM). The regions mapping to p13.1 and q24 were involved in early intraurothelial phases of bladder neoplasia such as mild to moderate dysplasia. On the other hand the deleted region mapping to p13.3 was involved in progression of severe dysplasia/carcinoma in situ to invasive bladder cancer. Testing of markers that exhibited statistically significant LOH in relation to progression of neoplasia from precursor conditions to invasive cancer on 28 tumors and voided urine samples from 25 patients with bladder cancer revealed that q12.1 showed LOH in 46.4% of tumor and 32.0% of voided urine samples. The LOH of a single marker D16S541 could be detected in approximately 28% of tumors and 20% of voided urine samples of patients with bladder cancer. These data imply that the deleted region centered around marker D16S541 spanning approximately 10 cM and flanked by D16S409 and D16S415 contains a novel putative tumor suppressor gene or genes playing an important role in the development of human bladder cancer. To facilitate more precise positional mapping and identification of pathogenetically relevant genes, we analysed of human genome contig and sequence databases spanning the deleted regions. Multiple known candidate genes and several smaller gene-rich areas mapping to the target regions of chromosome 16 were identified.
Aged↗
Long-term impact of smoking on lung epithelial proliferation in current and former smokers.
BACKGROUND: Lung cancer risk remains elevated for many years after quitting smoking. To assess using proliferation indices in bronchial tissues as an intermediate endpoint biomarker in lung cancer chemoprevention trials, we determined the relationship between the extent, intensity, and cessation of tobacco smoking and proliferative changes in bronchial epithelial biopsy specimens. METHODS: Bronchial biopsy specimens were obtained from up to six epithelial sites in 120 current smokers (median pack-years, 42) and 207 former smokers (median pack-years, 40; median quit-years, 8.1). Sections from the paraffin-embedded specimens were stained with hematoxylin--eosin to determine the metaplasia index and with an antibody to Ki-67 to determine the proliferative (labeling) index for the basal and parabasal (Ki-67 PLI) layers. All statistical tests were two-sided. RESULTS: Biopsy sites with metaplasia had statistically significantly higher Ki-67-labeling indices than those without metaplasia (P<.001) in both current and former smokers. Increased proliferation was observed in multiple biopsy sites, with the average Ki-67 PLI of the subject strongly correlating with the metaplasia index (r =.72 for current smokers; P<.001), even in sites without metaplasia (r =.23 for current smokers; P<.001). In current smokers, the Ki-67 PLI was associated with the number of packs smoked/day (P =.02) but not with smoking years or pack-years. In subjects who had quit smoking, the Ki-67 PLI dropped statistically significantly within 1 year (P =.008) but remained detectable for more than 20 years, even in the absence of squamous metaplasia. CONCLUSION: Smoking appears to elicit a dose-related proliferative response in the bronchial epithelia of active smokers. Although the proliferative response decreased gradually in former smokers, a subset of individuals had detectable proliferation for many years and may benefit from targeted chemoprevention. Bronchial epithelial proliferation, measured by Ki-67, may provide a useful biomarker in the assessment of lung cancer risk and in the response to chemopreventive interventions.
Adult↗
CpG island methylation in premalignant stages of gastric carcinoma.
There are limited reports on methylation analysis of the premalignant lesions of gastric carcinoma thus far. This is despite the fact that gastric carcinoma is one of the tumors with a high frequency of CpG island hypermethylation. To determine the frequency and timing of hypermethylation during multistep gastric carcinogenesis, non-neoplastic gastric mucosa (n = 118), adenomas (n = 61), and carcinomas (n = 64) were analyzed for their p16, human Mut L homologue 1 (hMLH1), death-associated protein (DAP)-kinase, thromobospondin-1 (THBS1), and tissue inhibitor of metalloproteinase 3 (TIMP-3) methylation status using methylation-specific PCR. Three different classes of methylation behaviors were found in the five tested genes. DAP-kinase was methylated at a similar frequency in all four stages, whereas hMLH1 and p16 were methylated in cancer samples (20.3% and 42.2%, respectively) more frequently than in intestinal metaplasia (6.3% and 2.1%, respectively) or adenomas (9.8% and 11.5%, respectively). However, hMLH1 and p16 were not methylated in chronic gastritis. THBS-1 and TIMP-3 were methylated in all stages but showed a marked increase in hypermethylation frequency from chronic gastritis (10.1% and 14.5%, respectively) to intestinal metaplasia (34.7% and 36.7%, respectively; P < 0.05) and from adenomas (28.3% and 26.7%, respectively) to carcinomas (48.4% and 57.4%, respectively: P < 0.05). The hMLH1, THBS1, and TIMP-3 hypermethylation frequencies were similar in both intestinal metaplasia and adenomas, but the p16 hypermethylation frequency tended to be higher in adenomas (11.5%) than in intestinal metaplasia (2.1%; P = 0.073). The average number of methylated genes was 0.6, 1.1, 1.1, and 2.0 per five genes per sample in chronic gastritis, intestinal metaplasia, adenomas, and carcinomas, respectively. This shows a marked increase in methylated genes from non-metaplastic mucosa to intestinal metaplasia (P = 0.001) as well as from premalignant lesions to carcinomas (P = 0.002). These results suggest that CpG island hypermethylation occur early in multistep gastric carcinogenesis and tend to accumulate along the multistep carcinogenesis.
Adaptor Proteins, Signal Transducing↗
Comparison of neuronal firing rates in somatosensory and posterior parietal cortex during prehension.
To evaluate their functional roles during prehension, single-unit recordings were made in the hand area of primary somatosensory areas 3b, 1 and 2 (S-I) and posterior parietal areas 5 and 7 (PPC) of the same animal. Response profiles of mean firing rate during performance of a multistage reach, grasp, and lift task were analyzed to determine the period(s) of peak firing and to measure statistically significant rises or falls in rate compared with baseline. We used the peak firing stage(s) to subdivide the population into classes tuned to single actions or two successive stages, or into multiaction groups that had sustained facilitation (BT) or inhibition (GI) during hand-object interactions. Four times as many neurons fired at peak rates during acquisition stages (approach, contact, grasp) than upon release, and their firing rates were higher. Grasping evoked the strongest responses, as grasp-tuned neurons had the highest peak rates in the population; BT, contact-grasp, and grasp-lift cells also fired maximally in the grasp stage. Grasping also coincided with maximal inhibition of GI cells, as well as of neurons tuned to approach or relaxation of grasp. Holding evoked the lowest mean rates, and had the fewest tuned cells. S-I and PPC showed significant differences in behaviors evoking peak firing as well as facilitation and inhibition; these correlated with input modalities in each area. Hand contact with the object and positioning of the fingers for grasp was the most strongly represented behavior in anterior S-I, where 61% received tactile inputs from glabrous skin. Nearly 60% were facilitated at contact, 38% fired at peak rates, and 10% were inhibited; release of grasp evoked peak firing in only 5% of 3b-1 neurons. In posterior S-I, where proportions of tactile and deep inputs were similar, positioning and grasping elicited peak responses in 38% and 31%, respectively; 80% were facilitated or inhibited during grasping. During lift and hold, inhibition rose to 43%, while excitation declined under 10%. PPC had the highest proportions firing at peak rates during hand preshaping before contact (28%) and had the most facilitated responses (38%) in this stage. Only 10% fired at peak rates during grasping. During later manipulatory actions, proportions of facilitated and inhibited responses in PPC were similar to those in posterior S-I. The data support models in which PPC plans hand movements during prehension rather than guiding their execution. Sensory monitoring of hand-object interaction occurs in S-I, where cells sense specific hand behaviors, signal stage completion, enable error correction, and may update grasp programs formulated in PPC. The results are discussed in relation to those obtained from lesion studies in humans.
Animals↗
Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline.
Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty-five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 microl) of either 5% hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.
Animals↗
Mapping and genome sequence analysis of chromosome 5 regions involved in bladder cancer progression.
We studied the evolution of allelic losses on chromosome 5 by whole-organ histologic and genetic mapping in 234 mucosal DNA samples of 5 cystectomy specimens with invasive bladder cancer and preneoplastic changes in adjacent urothelium. The frequency of alterations in individual loci was verified on 32 tumors and 29 voided urine samples from patients with bladder cancer. Finally, deleted regions on chromosome 5 were integrated with the human genome contigs and sequence-based databases. Deleted regions on chromosome 5 involved in intraurothelial phases of bladder neoplasia defined by their nearest flanking markers and predicted size were identified as follows: q13.3-q22 (D5S424-D5S656; 38.8 centimorgan [cM]); q22-q31.1 (D5S656-D5S808; 19.2 cM), q31.1-q32 (D5S816-SPARC; 11.5 cM), and q34 (GABRA1-D5S415; 6.4 cM). The two most frequently deleted neighbor markers (D5S2055 and D5S818) mapping to q22-q31.1 defined a 9 cM region, which may contain genes that play an important role in early phases of urinary bladder carcinogenesis. Human genome database analysis provided an accurate map of deleted regions with positions of 138 known genes and revealed several smaller gene-rich areas representing putative targets for further mapping. The strategic approach presented here, which combines whole-organ histologic and genetic mapping with analysis of the rapidly emerging human genome sequence database, facilitates identification of genes potentially involved in early phases of bladder carcinogenesis.
Aged↗
Methylation of the hMLH1 promoter in multiple gastric carcinomas with microsatellite instability.
Hypermethylation of the hMLH1 promoter is observed in the majority of sporadic gastric carcinomas with high frequency microsatellite instability (MSI), and it contributes to the genesis of MSI-positive gastric carcinoma. Multiple gastric carcinoma is known to have a higher frequency of MSI positivity than single gastric carcinoma. However, the molecular basis of MSI in these tumors remains obscure. We investigated the role of hMLH1 promoter hypermethylation in the genesis of multiple gastric carcinoma with MSI. We analyzed 33 tumors from 15 patients with multiple gastric carcinoma (12 double tumors and three triple tumors) for MSI, expression of hMLH1 and hMSH2, and hypermethylation of hMLH1 and hMSH2 promoters. High frequency MSI was found in seven out of 33 tumors (21%) in five out of 15 patients (33%). All of the tumors with high frequency MSI had a lack of hMLH1 expression, with the presence of hMSH2 expression, while all the tumors with no MSI or low frequency MSI were positive for both hMLH1 and hMSH2. All of the tumors with no expression of hMLH1 had hMLH1 hypermethylation, whereas hMLH1 hypermethylation was observed in two out of 26 (8%) tumors with no or low frequency MSI. None of the tumors showed hMSH2 hypermethylation. These results suggest that epigenetic changes in the hMLH1 promoter account for the genesis of multiple gastric carcinoma with high frequency MSI.
Adaptor Proteins, Signal Transducing↗
Ciliated epithelia in the urethra: case report and literature review.
The presence of ciliated epithelial cells in the urethra has not been well recognized. Only two reports in the literature, both of which used scanning microscopy studies, have described this phenomenon. In this report, we illustrate the presence of scattered, ciliated epithelial cells in penile urethral biopsy specimens from a 38-year-old man with a history of bladder calculi and hematuria, by both light and transmission electron microscopy studies. The cilia in the urethra showed typical light microscopic and ultrastructural features of those seen in other organs. These ciliated cells are present in association with urothelial papilloma, condyloma acuminatum and acute inflammation of the urethra. These findings suggest that ciliated cells in the penile 0 urethra might be a consequence of metaplastic change of the urothelium, secondary to local stimulation or irritation.
Adult↗
Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature.
Lymphoepithelioma-like carcinoma (LELC) is a rare form of lung cancer, usually encountered in Chinese patients. Similar to nasopharyngeal carcinoma, LELC of the lung is strongly associated with Epstein-Barr virus (EBV) infection in Asian patients, but there is controversy over whether an association exists in patients from Western countries. To determine whether such a relationship exists, we retrospectively studied 6 cases of primary LELC of the lung, all of which were in Western patients. There were 4 men and 2 women, ranging in age from 49 to 75 years. The tumors ranged from 1 to 4.5 cm in diameter. Four patients had stage I disease, 1 had stage IIb disease, and 1 had stage IIIa disease. All patients are alive without evidence of disease with a follow-up of 18 to 30 months. Formalin-fixed, paraffin-embedded tissue was stained with hematoxylin-eosin for routine evaluation and immunostained for keratin and leukocyte common antigen (LCA). LCA staining was performed to exclude large-cell lymphoma. Immunoperoxidase staining (1:500 clone CS1-4; Dako, Carpinteria, CA) and in situ hybridization were performed to detect EBV. Tumors consisted of solid nests of undifferentiated tumor cells in a syncytial arrangement surrounded by heavy lymphoplasmacytic infiltrate. Tumor cells stained positively for keratin but negative for LCA. All 6 cases were negative for EBV, suggesting no association between EBV and LELC in the Western population.
Aged↗
Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases.
Sarcomatoid renal cell carcinoma is not a distinct histologic entity and represents high-grade transformation in different subtypes of renal cell carcinoma. It is not known whether any particular histologic type has a predilection for sarcomatoid change or whether the primary histologic type of renal carcinoma undergoing sarcomatoid change affects prognosis. Of 952 consecutively histologically subtyped renal cell carcinomas, the incidence of sarcomatoid differentiation was 8% in conventional (clear cell) renal carcinoma, 3% in papillary renal carcinoma, 9% in chromophobe renal carcinoma, 29% in collecting duct carcinoma, and 11% in unclassified renal cell carcinoma. One hundred one renal cell carcinomas with sarcomatoid change were studied, and clinicopathologic parameters were correlated with outcome. The mean age of patients was 60 years (range, 33-80 years), and the male-to-female ratio was 1.6:1. The median tumor size was 9.2 cm (range, 3-25 cm). The primary histologic subtype of the carcinoma component was conventional (clear cell) renal carcinoma in 80 cases, papillary renal carcinoma in eight, chromophobe renal carcinoma in seven, collecting duct carcinoma in two, and unclassified renal cell carcinoma in four. The sarcomatoid component resembled fibrosarcoma in 54 cases, malignant fibrous histiocytoma in 44, undifferentiated sarcoma (not otherwise specified) in three with focal rhabdomyosarcomatous component in two of them. The spindled elements accounted for 1% to 99% of the sampled tumor (median, 40%; mean 45%). The histologic grade of the spindled elements was intermediate to high in 92 cases and low in nine cases. Most cases were TNM stages III and IV (seven stage I, six stage II, 63 stage III, and 25 stage IV). Follow-up was available in 88 patients; 61 (69%) patients died of disease and had a median survival time of 19 months. Distant metastases, most frequently to the lungs, were documented in 51 (66%) of 77 patients who had available clinical information regarding distant metastasis. The disease-specific survival rate was 22% and 13% after 5 and 10 years, respectively, compared with a cohort of renal cell carcinomas without sarcomatoid change with a 5-and 10-year disease-specific survival of 79% and 76%, respectively. Kaplan-Meier survival analysis showed that tumors with high TNM stage (p = 0.0027), at least 50% sarcomatoid component (p = 0.0453), and angiolymphatic invasion (p = 0.0282) were associated with decreased survival rates. The primary histologic subtype of the carcinoma component and the type and grade of the sarcomatoid component did not affect survival. In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable in predicting outcome among renal cell carcinomas with sarcomatoid change (p = 0.018; risk ratio, 6.984 and 8.439). Compared with a cohort of renal cell carcinomas without sarcomatoid change, sarcomatoid tumors tended to present at a more advanced stage (p = 0.0001). Also, when adjusted for stage, necrosis, and tumor size, patients with tumors with sarcomatoid differentiation had a worse prognosis than did patients with tumors without sarcomatoid change (p = 0.0001). In conclusion, sarcomatoid change in renal cell carcinoma portends a worse prognosis. Because tumors with even a small component of sarcomatoid change may have an adverse outcome, this finding, when present, should be noted in the surgical pathology report.
Adenocarcinoma↗