[Show abstract][Hide abstract] ABSTRACT: Tumor hypoxia is significant in promoting tumor progression and resistance to therapy, and hypoxia-inducible factor 1α (HIF-1α) is essential in the adaptive response of cells to hypoxia. The aim of the present study was to investigate the expression of hypoxic markers and evaluate their prognostic significance in soft tissue sarcoma (STS). A retrospective analysis of 55 patients with STS from Pusan National University Hospital (Busan, Korea) between 1998 and 2007 was conducted, using immunohistochemistry to analyze the expression of HIF-1α, carbonic anhydrase 9 (CA9), glucose transporter-1 (GLUT1) and vascular endothelial growth factor (VEGF). The association between the overexpression of these markers and clinicopathological characteristics, including the overall survival (OS) and progression-free survival (PFS) in cases of STS, were investigated. Overexpression of HIF-1α, CA9, GLUT1 and VEGF was shown in 54.5, 32.7, 52.7 and 25.5% of tumors, respectively, and all exhibited a significant association with high French Federation of Cancer Centers (FNCLCC) grade and high American Joint Committee on Cancer (AJCC) stage. Overexpression of HIF-1α and CA9 was associated with a shorter OS and a shorter PFS. On multivariate analysis, AJCC stage and HIF-1α overexpression had independent prognostic significance. In the group receiving chemotherapy (n=27), HIF-1α overexpression was independently associated with a decreased OS. These results indicate that overexpression of HIF-1α and CA9 is associated with poor prognosis, and that HIF-1α overexpression is an independent unfavorable prognostic factor in STS.
[Show abstract][Hide abstract] ABSTRACT: In a viewpoint of histogenesis, lung adenocarcinoma can be subdivided into 2 groups, terminal respiratory unit (TRU) and non-TRU types. We recently reported a non-TRU type adenocarcinoma designated as ciliated adenocarcinoma (now, we prefer central type adenocarcinoma). We suggest reasons that mucinous adenocarcinoma should encompass central type adenocarcinoma to represent its biologic characteristics as non-TRU type adenocarcinoma.
MUC5AC and MUC5B were more significantly expressed in non-TRU type adenocacinoma (P<0.01). Thirty-five (76.1%) and 45 cases (97.8%) of 46 non-TRU type adenocarcinoma showed positivity for MUC5AC and MUC5B. Twelve (7.6%) and eight (5.1%) cases of 157 TRU type adenocarainoma showed positivity for MUC5B and MUC5AC. NKX2-1 gene expression was measured with qRT-PCR. △△Ct of NKX2-1 gene expression was 6.79 for TRU type adenocarcinoma and 0.6 for non-TRU type adenocarcinoma. Overall survival and disease free survival were poorer in non-TRU type adenoarcinoma (P=0.02 and P=0.03). Multivariate test also showed non-TRU type adenocarcinoma is an independent prognostic factor (P=0.04).
MUC5AC and MUC5B were specific makers for non-TRU adenocarcinoma including both of central type adenocarcinoma and mucinous adenocarcinoma. We suggest that non-TRU type adenocarcinoma presents poorer prognosis so that it should be regarded separately from TRU type adenocarcinoma. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Pure squamous cell carcinoma (SCC) of the stomach is rare and resembles SCC arising elsewhere in the body. The pathogenesis of SCC remains unclear and controversial. At present, <100 cases of primary SCC of the stomach have been reported. The current study presents a case of SCC of the stomach in a 61-year-old male. Total gastrectomy was performed and a 7.0×6.7×4.5-cm tumor with a superiorly located ulcer was identified in the cardia. Upon histological examination, a moderately-differentiated SCC was observed. Tumor cells extended to the serosa, and the perigastric regional lymph node was also involved. No evidence of human papillomavirus (HPV) or Epstein-Barr virus (EBV) infection was identified using a DNA microarray and in situ hybridization, respectively. A post-operative computed tomography scan four months after the gastrectomy revealed tumor recurrence and dissemination of the tumor to the jejunum and pancreas. The patient succumbed to the disease six months later despite the administration of low-dose adjuvant 5-fluorouracil/cisplatin chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Background
Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.
We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.
The expression of TWIST, E-cadherin, HIF1α, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1α expression and reduced E-cadherin expression. The altered HIF1α/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.
Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1α/TWIST/E-cadherin pathway may play an important role in the progression of OEC.
The Korean Journal of Pathology 08/2014; 48(4):283-91. DOI:10.4132/KoreanJPathol.2014.48.4.283 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Soft tissue sarcomas (STS) are rare. We evaluated the WT1 protein expression level in various types of STS and elucidated the value of WT1 as a prognostic factor and a possible therapeutic target.
Immunohistochemical staining for WT1 was performed in 87 cases of STS using formalin-fixed, paraffin-embedded blocks. The correlation between WT1 expression and clinicopathological factors was analyzed. Survival analysis was conducted in 67 patients. We assessed the validity of WT1 immunohistochemistry as an index of WT1 protein expression using Western blot analysis.
WT1 expression was noted in 47 cases (54.0%). Most rhabdomyosarcomas and malignant peripheral nerve sheath tumors showed WT1 expression (91.7% and 71.4%, respectively; P = 0.005). WT1 expression was related to higher FNCLCC histologic grade and AJCC tumor stage. In the group with high grade STS, strong WT1 expression was correlated with better survival (P = 0.025). The immunohistochemical results were correlated quantitatively with the staining score and the concentration of the Western blot band.
This study demonstrates that various types of STS show positive immunostaining for WT1 and that WT1 expression has a prognostic significance. So STS should be considered candidates for WT1 peptide--based immunotherapy.
World Journal of Surgical Oncology 07/2014; 12(1):214. DOI:10.1186/1477-7819-12-214 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The S100A4 protein, a member of the S100 family of calcium-binding proteins, has been considered as a candidate prognostic marker in patients with cancer. The present study was conducted to evaluate the prognostic value of S100A4 and to examine its correlation with the clinicopathological parameters and the overall survival and progression-free survival in patients with endometrial carcinoma (EC). To do this, we performed immunohistochemistry of formalin-fixed tissue sections obtained from 135 cases of EC. In addition, we quantified the level of S100A4 mRNA using the quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The cytoplasmic expression of S100A4 protein was observed in 35 cases (25.9%). There was a significant association between the expression of S100A4 and clinicopathological parameters such as histologic grade, FIGO stage, lymph node metastasis and loss of progesterone receptor (PR). qRT-PCR demonstrated that the level of S100A4 mRNA was significantly higher in ECs as compared with normal endometrium. The cytoplasmic expression of S100A4 had a significant correlation with shorter overall survival and progression-free survival on the Kaplan-Meyer survival analysis. In multivariate analysis, there was a significant correlation between S100A4 expression and a poorer OS. In conclusion, our results indicate that S100A4 may be a biological marker indicating the recurrence and poor prognosis in patients with EC.
[Show abstract][Hide abstract] ABSTRACT: Sparganosis is a parasitic infection caused by the plerocercoid tapeworm larva of the genus Spirometra. Although the destination of the larva is often a tissue or muscle in the chest, abdominal wall, extremities, eyes, brain, urinary tract, spinal canal, and scrotum, intramuscular sparganosis is uncommon and therefore is difficult to distinguish from a soft tissue tumor. We report a case of intramuscular sparganosis involving the gastrocnemius muscle in an elderly patient who was diagnosed using ultrasonography and MRI and treated by surgical excision. At approximately 1 cm near the schwannoma at the right distal sciatic nerve, several spargana worms were detected and removed.
The Korean Journal of Parasitology 02/2014; 52(1):69-73. DOI:10.3347/kjp.2014.52.1.69 · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To diagnose soft tissue tumor, such as lipoma and Schwannoma, magnetic resonance imaging (MRI) is sufficient in most cases. However, various characteristics are found in MRI images of Schwannoma, thus other type of tumors are often misdiagnosed as Schwannoma with MRI images. In this study, we evaluate the diagnostic value of specific MRI findings of Schwannoma.
[Show abstract][Hide abstract] ABSTRACT: The aims of this article are to differentiate soft tissue masses showing low signal intensity on T2-weighted images (T2WIs) according to the histopathologic findings.
[Show abstract][Hide abstract] ABSTRACT: Myolipomas are very rare benign lipomatous soft tissue tumors which are usually located in retroperitoneum, abdominal and pelvic cavity, and the abdominal wall. They can be diagnosed histologically by the presence of irregularly admixed mature adipose tissue and smooth muscle fibers. The correct diagnosis of myolipoma is important, because it should be considered in the differential diagnosis of fat-containing lesions of the soft tissue and should follow a benign clinical course despite its frequently large size and deep location. We report here a case of myolipoma arising in the mesentery of the jejunum.
[Show abstract][Hide abstract] ABSTRACT: Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease that mainly affects renal, extracranial carotid, and vertebral arteries. Intracranial FMD is uncommon unlike extracranial or renal FMD, and the primary manifestation of intracranial FMD is intracranial aneurysm. We report an unusual case of intracranial FMD showing various ocular manifestations, including central retinal artery occlusion, transient monocular blindness, and oculomotor nerve palsy without renal involvement.
Journal of the neurological sciences 12/2013; 337(1-2). DOI:10.1016/j.jns.2013.12.009 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Polycomb group (PcG) genes are evolutionary conserved regulators of gene expression that contribute to normal lymphocyte development, and are involved in malignant transformation of these cells. Recently, BMI1 and EZH2 have been shown to be involved in lymphomagenesis and oncogenesis. We tried to elucidate EZH2 as a prognostic factor for diffuse large B cell lymphoma (DLBCL). High-level expression of EZH2 (EZH≥70%) was associated with superior overall survival (OS) of 85.8%, which compares to those of low expression (EZH2<70%) with OS of 44.5% (p=0.005). Subgroup analysis showed that the ABC subtype with high EZH2 expression had the highest overall survival (p= 0.011). In the analysis of EZH2 expression within the low IPI score, high EZH2 expression had a significant statistical correlation with longer OS (p=0.034). With high IPI scores, high EZH2 expression tended to be associated with longer OS (p=0.130). Our results showed that EZH2 expression had a high prognostic relevance to survival outcomes. We demonstrated that DLBCL was associated with increased expression of the EZH2 PcG protein and Ki67. The distribution of EZH2 expression was wider than that of Ki67. In summary, increased EZH2 expression of tumor cells was associated with improvements in overall survival.
[Show abstract][Hide abstract] ABSTRACT: Anticancer activity of silibinin, a flavonoid, has been demonstrated in various cancer cell types. However, the underlying mechanisms were not elucidated in human ovarian cancer cells. The present study was undertaken to examine the effect of silibinin in vitro and in vivo on tumor growth in human ovarian cancer cells. Silibinin decreased cell viability in a dose- and time-dependent manner. Silibinin caused an increase in reactive oxygen species (ROS) generation and the silibinin-induced cell death was prevented by the antioxidant N-acetylcysteine (NAC). Western blot analysis showed silibinin-induced down-regulation of extracellular signal-regulated kinase (ERK) and Akt. Transfection of constitutively active forms of MEK and Akt prevented the silibinin-induced cell death. Oral administration of silibinin in animals with subcutaneous A2780 cells reduced tumor volume. Subsequent tumor tissue analysis showed that silibinin treatment induced a decrease in Ki-67 positive cells, an increase in TUNEL-positive cells, activation of caspase-3, and inhibition of p-ERK and p-Akt. These results indicate that silibinin reduces tumor growth through inhibition of ERK and Akt in human ovarian cancer cells. These data suggest that silibinin may serve as a potential therapeutic agent for human ovarian cancers.
Journal of Agricultural and Food Chemistry 04/2013; 61(17). DOI:10.1021/jf400192v · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary artery embolism is an infrequent cause of acute myocardial infarction. In addition, native aortic valve thrombosis is a very rare condition. We report a case of native valve thrombosis causing acute ST-elevation myocardial infarction in healthy middle-aged man who has no established cardiovascular risk factor. We diagnosed native aortic valve thrombosis using various imaging techniques and confirmed our diagnosis histopathologically after surgical operation.
Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 01/2013; 22(3). DOI:10.1016/j.carpath.2013.01.001 · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective: To determine whether the levels of inflammatory mediators in gastric fluid (GF) of a premature newborn are associated with those in amniotic fluid (AF) of the newborn's mother. Patients: Twenty-three pairs of pregnant women and their premature newborns <35 weeks gestation, born by Cesarean sections. Methods: Amniotic fluids and newborn gastric fluids were obtained from women during Cesarean section procedure. The mother-premature newborn dyads were retrospectively assessed to analyze the clinical and laboratory data. Concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and mannose-binding lectin (MBL) were compared between amniotic and newborn gastric fluids in each dyad. Results: Premature newborns and their mother with funisitis had significantly higher median AF IL-6 and TNF-α and GF IL-8 concentrations than those without funisitis (p = 0.022 for AF IL-6; p = 0.023 for AF TNF-α; p = 0.022 for GF IL-8). The concentrations of IL-6, IL-8, TNF-α and MBL in newborn GF were significantly correlated with those in AF in each dyad (p = 0.000, r = 0.872 for IL-6; p = 0.000, r = 0.851 for IL-8; p = 0.000, r = 0.768 for TNF-α; p = 0.000, r = 0.845 for MBL, respectively). Conclusion: The levels of inflammatory mediators in GF of a premature newborn immediately after birth are strongly associated with those in AF of the newborn's mother.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 01/2013; 26(11). DOI:10.3109/14767058.2013.767889 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis.
Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC).
CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers.
The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.
The Korean Journal of Pathology 12/2012; 46(6):532-40. DOI:10.4132/KoreanJPathol.2012.46.6.532 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and aimThe biologic behavior of gastrointestinal stromal tumors (GIST) is a topic of continuing controversy. The assessment of accurate mitotic figures is known to be one of the major indicators for patients with GIST. However, it is not always easy to search for mitotic figures (MFs) and count them accurately on hematoxylin and eosin stained (H&E) slides. Methods
In this study, phopho-histone H3 (PHH3), which is a recently described specific mitosis marker, was immunohistochemically examined and compared to the mitotic count on H&E sections (H&E-MI) and Ki-67 expression (Ki-67 PI). A hundred cases of histologically confirmed GISTs were reviewed based on counting MF on H&E slides. PHH3 positive MFs (PHH3-MI) were counted in the same way, and the Ki-67 PI was calculated for each case. ResultsA strong correlation was found between PHH3-MI and H&E-MI. Recurrence-free survival was correlated with risk category by National Institutes of Health (NIH) consensus criteria (P = 0.017), mucosal invasion (P = 0.005), H&E-MI (P = 0.002), Ki-67 PI (P = 0.005), and PHH3-MI (P = 0.000). None of these factors was an independent prognostic factor. Conclusions
Among GISTs, PHH3 staining was primarily found to support grading by facilitating mitotic counting, and it might have a prognostic value in GISTs.
Basic and Applied Pathology 12/2012; 5(4). DOI:10.1111/baap.12003
[Show abstract][Hide abstract] ABSTRACT: Baker's cysts are one of the most common cystic lesions around the knee joint and mainly caused by fluid distension of the gastrocnemius-semimembranous bursa that is situated along the medial side of the popliteal fossa. Typically, a Baker's cyst extends along the intermuscular planes around the knee joint and may enlarge any direction. However, it is mostly located in the inferomedial or superficial layers of the knee joint and less commonly extends laterally or proximally. Expansion of the cyst tends to respect the intermuscular planes, and Baker's cysts along the intramuscular route have been rarely reported. Thus, we report a case of Baker's cyst with intramuscular extension into the vastus medialis muscle.
[Show abstract][Hide abstract] ABSTRACT: Background
Toll-like receptors (TLR) are a family of pattern recognition receptors that constitutes a major part of the innate immune system. The TLR4/(Myeloid differentiation factor 88 (MyD88) signaling pathway has been shown to have oncogenic effects.
To demonstrate the role of TLR4/MyD88 signaling in ovarian epithelial cancers (OECs), we examined the expression of TLR4, MyD88 and nuclear factor- κB (NF-κB) in OECs. The expression of TLR4, MyD88, and NF-κB was detected by immunohistochemistry, and the relationships between these and clinicopathologic features in 123 cases of OECs were also analyzed.
The expression of TLR4, MyD88, and NF-κB in OECs was observed in 46.3% (57/123), 36.6% (45/123) and 65% (80/123) of OEC cases, respectively. The TLR4, MyD88, and NF-κB expressions were associated with the histologic type of OECs, particularly with the clear cell type of OEC. There was no significant correlation between TLR4 or NF-κB expression and histologic grade, tumor size, mitotic count, FIGO (International Federation of Gynecology and Obstetrics) stage, disease recurrence. However, there was a significant correlation between MyD88 expression and FIGO stage, disease recurrence as well as histologic type. In univariate analysis, the expression of TLR4 and MyD88, and the coexpression of TLR4/MyD88 and TLR4/MyD88/NF-κB had a significant impact on the survival of patients with OECs. Only MyD88 expression had an independent prognostic significance in multivariate analysis.
Our findings suggest that the TLR4/MyD88 signaling pathway is associated with the survival of patients with OECs, and that MyD88 is an independent prognostic predictor in patients with OECs. The TLR4/MyD88 signaling pathway may be a mechanism responsible for poor prognosis in patients with clear cell type of OEC.
World Journal of Surgical Oncology 09/2012; 10(1):193. DOI:10.1186/1477-7819-10-193 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Whereas most carcinomas occur through a sequential step, atypical adenomatous hyperplasia and bronchioloalveolar carcinoma pathway is known for pulmonary adenocarcinoma. This type is known as terminal respiratory unit adenocarcinoma. Based on our observation of transitions from normal ciliated columnar cells to adenocarcinoma via dysplastic mucous columnar cells, we reviewed our archive of pulmonary adenocarcinoma. Terminal respiratory unit type adenocarcinoma was defined as adenocarcinoma with type II pneumocyte, Clara cell, or bronchiolar cell morphology according to previous reports. Among 157 cases, 121 cases have been identified as terminal respiratory unit type adenocarcinoma and 36 cases as non-terminal respiratory unit type adenocarcinoma. Among non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma.
Modern Pathology 05/2012; 25(9):1265-74. DOI:10.1038/modpathol.2012.76 · 6.19 Impact Factor