[Show abstract][Hide abstract] ABSTRACT: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of α-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor α, causing cells to be prone to tumorigenesis.
This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs), using a pentose nucleic acid clamping method and direct sequencing.
We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results.
This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs.
[Show abstract][Hide abstract] ABSTRACT: Raf-1 kinase inhibitory protein (RKIP), an endogenous inhibitor of the extracellular signal-regulated kinase (ERK) pathway, suppresses metastasis in a number of cancer types, including colorectal carcinoma (CRC); thus, RKIP downregulation significantly contributes to CRC invasiveness and metastatic potential. However, our previous study demonstrated that RKIP-positive tumors in CRC patients are predictive of hepatic colorectal metastases (HCMs). Based on the previous finding that the ERK pathway can be activated independently of RKIP, we hypothesized that RKIP-expressing HCMs may express significant levels of phosphorylated ERK (pERK). Thus, the present study evaluated the expression of RKIP and pERK in 68 HCM tissue samples using immunohistochemistry. RKIP expression was positive in 22 (32.4%) of the 68 samples, seven (31.8%) of which exhibited nuclear pERK immunoreactivity exclusively at the invasive tumor front. Furthermore, pERK expression at the invasive front was significantly associated with recurrent HCM following hepatic resection, and pERK expression observed at the invasive front of RKIP-expressing HCMs indicated that the activation of the ERK pathway may also be involved in the invasive process of these tumors, despite the presence of RKIP. A strong association between pERK expression and the presence of recurrent HCM may indicate that the ERK pathway is important in the metastatic recurrence of RKIP-positive HCM.
[Show abstract][Hide abstract] ABSTRACT: An epidermoid cyst of the cecum is extremely rare; only eight cases have been reported in the literature. A 63-year-old woman was admitted to Kyung Hee University Medical Center with a colonic mass that had been discovered incidentally during a regular health check-up. The radiographic impression was that this mass was a gastrointestinal stromal tumor. During surgery, an exophytic mass in the cecal wall was resected by using an ileocecectomy. Based on the macroscopic and the microscopic findings, this case was identified as an epidermoid cyst of the cecal wall. We report this case to discuss the origin of this entity and the unusual nature of our case.
Annals of Coloproctology 02/2015; 31(1):37-9. DOI:10.3393/ac.2015.31.1.37
[Show abstract][Hide abstract] ABSTRACT: An enteric duplication cyst presenting as enterocolic intussusception is an exceptional clinical entity. We herein report a rare case of an ileal duplication cyst that manifested as an ileocolic intussusception. A 19-year-old woman was hospitalized due to right upper quadrant pain. Colonoscopy revealed a polypoid mass protruding into the colonic lumen. Ultrasonography demonstrated intussusception with a teardrop-shaped cystic mass at the tip. Computed tomography also showed ileocolic intussusception with a 2.5 cm-sized round cystic mass at the tip of intussusceptum. Microscopically, the cystic wall consisted of a well-defined smooth muscle coat and heterotopic gastric mucosa, consistent with an enteric duplication cyst. This case highlights an ileal duplication cyst as an uncommon cause of adult ileocolic intussusception. To the best of our knowledge, this is the first case of enteric duplication cyst identified as a pathological lead point for enterocolic intussusception in an adult. Enteric duplication cysts should be included in the differential diagnosis of cystic-leading lesions for adult intussusceptions.
The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 12/2014; 25(Suppl 1):S196-S198. DOI:10.5152/tjg.2014.4011 · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Beclin-1 induces autophagy, which is known to be involved in many physiopathological processes such as cell development, aging, stress response, immune response and cancer. Several studies showed that Beclin-1 expression is associated with several prognostic factors of gastric carcinomas. Recently, the connection between autophagy and the hedgehog (HH) signaling pathway has been studied. Here, we investigated the relationship between the autophagy and hedgehog (HH) signaling pathways in gastric adenocarcinoma. We evaluated Beclin-1 and Gli2 expression in 108 gastric adenocarcinoma tissues via immunohistochemical analysis, using a tissue microarray, in relation to survival and other prognostic factors. Our results show that increased Beclin-1 expression is correlated with favorable clinicopathological variables including histologic grade, tumor size, primary tumor (T) stage, lymph node metastasis, lymphatic invasion, neural invasion, and tumor recurrence. Furthermore, increased Gli-2 expression was correlated with several favorable clinicopathological variables including primary tumor (T) stage, lymphatic invasion, and tumor recurrence. Increased Beclin-1 expression was significantly correlated with increased Gli2. Univariate analyses for disease-free survival and overall survival revealed that the higher Beclin-1 and Gli2 expression group had a more favorable prognosis compared with the lower Beclin-1 and Gli2 expression group. Our results suggest that progressively increased Beclin-1 and Gli2 expression contributes to the inhibition of tumor growth and metastasis in gastric adenocarcinoma and Beclin-1 acts as a tumor suppressor by regulating the HH signaling pathway through Gli2 expression in gastric adenocarcinoma.
Pathology - Research and Practice 11/2014; 211(4). DOI:10.1016/j.prp.2014.11.005 · 1.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autophagy plays critical roles in both cell survival and cell death. Beclin-1, a key modulator of autophagy function, is considered a haploinsufficient tumor suppressor. The role of Beclin-1 expression in cancer is still controversial. Some studies favor the idea that autophagy suppresses tumor development, whereas other researchers suggest that autophagy enhances tumorigenesis. The expression and function of Beclin-1 in gallbladder cancer (GBCA) remain largely unknown.
Methodology: We performed immunohistochemical staining for Beclin-1 in 119 GBCA cases, and investigated whether Beclin-1 expression correlated with clinicopathologic characteristics and prognosis of patients.
Beclin-1 was expressed in the cytoplasm of cancer cells with occasional nuclear staining in 53 (44.5%) of the 119 cases of GBCA with no expression in adjacent normal epithelial cells. Increased expression of Beclin-1 was significantly associated with longer survival rate of patients with GBCA in univariate (p=0.006) and multivariate analyses (p=0.005). There is no association between Beclin-1 expression and clinicopathologic characteristics.
Beclin-1 was highly expressed in GBCA, and positive expression in cancer cells was significantly related with favorable prognosis in GBCA patients. Our results suggest that the expression of Beclin-1 may be an independent predictive marker of favorable prognosis in GBCA.
[Show abstract][Hide abstract] ABSTRACT: The occurrence of idiopathic pulmonary lesions in laboratory rats, characterized by lymphohistiocytic interstitial pneumonia with dense perivascular lymphoid cuffs, has been reported over the past decade. Although the term rat respiratory virus (RRV) was adopted to confer a putative viral etiology to the idiopathic pulmonary lesions, the etiology of this disease remains to be elucidated. Recently, inflammatory lesions have been observed in the lungs of immunocompetent laboratory rats similar to those previously described. Based on the latest evidence indicating that Pneumocystis carinii (P. carinii), and not putative RRV, causes infectious interstitial pneumonia in laboratory rats, the present study investigated whether the pulmonary lesions observed were caused by P. carinii infection. Male Sprague-Dawley rats, free of known pathogens, were introduced into a rat colony positive for RRV-type lesions. Routine histopathological examinations were performed on the rat lung tissues following exposure. The presence of Pneumocystis organisms was confirmed using Grocott's methenamine silver (GMS) staining. At week 3 following introduction, a few small lymphoid aggregates were located adjacent to the edematous vascular sheath. By week 5, foci of dense perivascular lymphoid cuffing were observed. Multifocal lymphohistiocytic interstitial pneumonia and prominent lymphoid perivascular cuffs were observed between week 7 and 10. GMS staining confirmed the presence of Pneumocystis cysts. Thus, the results of the present study demonstrated that P. carinii caused lymphohistiocytic interstitial pneumonia in a group of laboratory rats. The observations strongly support the conclusion that P. carinii infection in immunocompetent laboratory rats causes the lung lesions that were previously attributed to RRV.
Experimental and therapeutic medicine 08/2014; 8(2):442-446. DOI:10.3892/etm.2014.1732 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The current study presents a rare case of intradermal melanocytic nevus with lymphatic nevus cell embolus. A 26-year-old male presented with a slowly enlarging, pigmented nodule on the back, measuring 1 cm in diameter. Histological observations of the lesion were typical of an intradermal melanocytic nevus. The most notable feature of this nevus, however, was an aggregate of nevus cells within a lymphatic vessel of the upper dermis. The nevus cells observed within the lymphatic lumen demonstrated characteristic morphological features of type A nevus cells. The cells were round-to-cuboidal, exhibited abundant cytoplasm with well-defined cell borders and formed nests. In addition, the nevus cell aggregate was lined by flattened endothelial cells. Nevus cell aggregates occur in the collagenous framework of lymph nodes, however, the mechanism by which nevus cells are deposited in lymph nodes has been a source of interest and controversy. The histological observation presented may be regarded as support for the mechanical transport or benign metastasis theories, which posit transfer of nevus cell emboli, via lymphatics, from a cutaneous nevus to the draining regional lymph node. Due to its rarity, a lymphatic nevus cell embolus creates diagnostic and management issues for pathologists and clinicians. This observation must not be interpreted as evidence of malignancy, but must be assessed in context with the associated histological features of the lesion.
[Show abstract][Hide abstract] ABSTRACT: Chemokines are a family of peptide mediators that play an essential role in cellular migration and intracellular communication in tumor cells as well as immune cells. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in Ewing sarcoma (ES) family tumor (ESFT) progression. Using real-time quantitative reverse transcription-polymerase chain reaction, we investigated the mRNA expression of CXCL16, CXCR6, and ADAM 10 in various cell lines. We also investigated the expression of CXCL16, CXCR6, ADAM 10, and ADAM 17 in tissue samples from 61 ESFT patients using immunohistochemistry. The mRNA expression levels of CXCL16 and CXCR6 in the ES cell line were higher than those in the other cell lines. Immunohistochemical staining revealed that CXCL16 and CXCR6 were highly expressed in tumor cells of ESFT and showed a positive correlation between them. The expression of CXCL16 and CXCR6 was associated with the occurrence of lung metastasis. Univariate analysis revealed that CXCL16 or CXCR6 expression was associated with worse prognosis of ESFT patients. In addition, CXCL16 and CXCR6 expression was associated with shorter overall survival irrespective of other prognostic factors. Our results suggest that the CXCL16/CXCR6 axis appears to be important in the progression of ESFT, resulting in more aggressive clinical behavior. Furthermore, there may be a decrease in the overall survival in ESFT patients who have tumors that stain strongly for CXCL16 and CXCR6.
Human pathology 11/2013; 45(4). DOI:10.1016/j.humpath.2013.09.017 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: FOXP3 is a transcription factor and a well-known hallmark of immune suppressive T regulatory cells. Recent studies indicate that in tumor cells, FOXP3 plays an important role in tumor development in addition to its well-established Treg function in the immune system. We investigated tumoral FOXP3 expression in breast carcinoma, and the relationships between tumoral FOXP3 expression and p53, HER-2/ErbB2, Ki67, infiltrated Tregs, and other clinicopathological variables. Tissue samples from 272 cases of breast carcinoma were used. We assessed tumoral FOXP3, p53, HER-2/ErbB2, Ki67, and infiltrated Tregs using immunohistochemical staining. Positive expression of tumoral FOXP3 was observed in 38.6% (105/272) of breast carcinomas. Positive tumoral FOXP3 expression was significantly related with positive p53 and higher Ki67 expression. Higher histological grade was significantly correlated to increased tumoral FOXP3 expression. Tumoral FOXP3 expression was positively correlated with infiltrated FOXP3-expressing Tregs. From these data, we argue that tumoral FOXP3 has a potential oncogenic function in conjunction with the p53 tumor suppressor protein and infiltrated Tregs in human breast carcinomas.
Pathology - Research and Practice 09/2013; 209(12). DOI:10.1016/j.prp.2013.08.010 · 1.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Detection of proximal serrated polyps (PSPs) is increasingly recognized as a new qualitative target for colonoscopy. The aims of this study were to assess the detected prevalence of PSPs and synchronous adenomas in an asymptomatic average-risk screening cohort and to evaluate potential factors associated with detection of PSPs.
The study included 1,375 asymptomatic average-risk Korean patients (aged 50 years or older) who underwent screening colonoscopy. In total, 1,710 polyps were evaluated pathologically.
The overall PSP detection rate (PSPDR) was low at 3.1%, despite high polyp (54.0%) and adenoma detection rates (ADRs, 43.5%). ADR did not correlate with PSPDR, but it was strongly correlated with PDR (r=0.810; p<0.001). Patients with PSPs were more likely to have longer withdrawal time and more proximal colon adenomas than patients without PSPs (adjusted odds ratio [OR], 1.19; 95% confidence interval [CI], 1.09 to 1.31; p<0.001) (adjusted OR, 2.03; 95% CI, 1.06 to 3.88; p=0.031, respectively).
The detected prevalence of PSPs was low (<5%) in an asymptomatic average-risk screening Korean population, despite the high prevalence of conventional adenomas. A longer mucosal inspection of the proximal colon may serve as a practical method to enhance detection of PSPs.
Gut and liver 09/2013; 7(5):524-31. DOI:10.5009/gnl.2013.7.5.524 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peritoneal loose bodies (PLBs) are usually discovered incidentally during laparotomy or autopsy. A few cases of giant PLBs presenting with various symptoms have been reported in the literature. Here, we describe a case of a giant PLB incidentally found in the pelvic cavity of a 50-year-old man. Computed tomography revealed a free ovoid mass in the pelvic cavity that consisted of central dense, heterogeneous calcifications and peripheral soft tissue. The mass was an egg-shaped, hard, glistening concretion measuring 7.5×7.0×6.8 cm and weighing 160 g. This concretion consisted of central necrotic fatty tissue surrounded by concentrically laminated, acellular, fibrous material. Small PLBs usually do not require any specific treatment. However, if PLBs cause alimentary or urinary symptoms due to their large size, surgical removal may be recommended. It is essential for clinicians to be aware of this entity and its characteristic features to establish the correct diagnosis.
The Korean Journal of Pathology 08/2013; 47(4):378-82. DOI:10.4132/KoreanJPathol.2013.47.4.378 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gallbladder carcinoma (GBCA) is one of the most aggressive malignancies. It is usually diagnosed at an advanced stage, and prognosis remains poor despite advances in imaging techniques and aggressive surgical treatment. Overexpression of multidrug resistance-associated proteins (MRPs) in tumor cells is a major cause of the intrinsic multidrug resistance phenotype. Despite the documented importance of MRP expression in many carcinomas, the prognostic significance of MRP2 expression in primary GBCA is not known. Immunostaining for MRP2 was performed on tissue samples obtained from 143 patients with GBCA. We examined the association between MRP expression and clinicopathological characteristics and outcome of patients with GBCA. GBCA demonstrated MRP2 immunoreactivity in the apicolateral membranes of epithelial cells. MRP2 expression was positive in 53.1% (76/143) of GBCA samples. Positive MRP2 expression was significantly associated with the presence of local recurrence (P = 0.038), lymphatic invasion (P = 0.038), vascular invasion (P = 0.023), and perineural invasion (P = 0.006). In addition, the median survival time of patients with MRP2-positive GBCA (15 months) was significantly shorter than that of patients with MRP2-negative GBCA (85 months, P = 0.011). We found that the expression of MRP2 in GBCA contributed to aggressive tumor behavior and poor prognosis, suggesting that MRP2 expression can be used as a potential prognostic biomarker of GBCA.
[Show abstract][Hide abstract] ABSTRACT: There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients.
We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report.
Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms.
A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.
The Korean Journal of Pathology 06/2013; 47(3):227-37. DOI:10.4132/KoreanJPathol.2013.47.3.227 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: MicroRNAs (miRNAs) play important roles in the development, differentiation, and function of different cell types and in the pathogenesis of various human diseases. miRNAs are differentially expressed in normal and cancer cells. The investigation of miRNA expression between healthy subjects and patients with osteosarcoma is crucial for future clinical trials. We performed miRNA microarray analysis on 8 formalin-fixed, paraffin-embedded osteosarcoma tissue samples. We confirmed the results of the microarray analysis using reverse transcription polymerase chain reaction. miRNA profiling of osteosarcoma tissue samples showed that expression of 10 miRNAs had increased 10-fold compared with normal controls. Among the 10 miRNAs, 3 miRNAs (miR-199b-5p, miR-338-3p, and miR-891a) were confirmed to have been up-regulated by reverse transcription polymerase chain reaction. After transfection of 4 osteosarcoma cell lines with miR-199b-5p inhibitor, the expression of Notch pathway components in the transfected cell lines was changed. These results revealed that miR-199b-5p plays a role in Notch signaling in osteosarcoma. Recently, the inhibition of Notch and HES1 signaling has been suggested as a potential therapeutic strategy to prevent metastasis in human osteosarcoma. Taken together with our results, we suggest that miR-199b-5p inhibitor may also be a therapeutic option for osteosarcoma.
Human pathology 04/2013; 44(8). DOI:10.1016/j.humpath.2013.01.016 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is a rare variant of PTC. The term 'PTC with fibromatosis-like stroma' has been used as a synonym to describe this variant. It is characterized by extensive proliferation of fibroblasts and myofibroblasts in the tumor stroma, which occurs in up to 80% of the tumors. We herein describe a case of PTC-NFS which developed in a 49-year-old woman with the demonstration of findings of ultrasonography, fine needle aspiration cytology and histological examination of the lesion. To characterize the stromal components, we investigated the expression of several immunohistochemical markers which have been shown to be expressed differently in nodular fasciitis (NF) and fibromatosis (FM). The immunostaining results demonstrated nuclear and cytoplasmic accumulation of β-catenin, cytoplasmic transforming growth factor-β expression and nuclear Smad expression in the stromal cells, suggesting that the stromal cells in this case have similar molecular profiles to those of FM rather than NF.
The Korean Journal of Pathology 04/2013; 47(2):167-71. DOI:10.4132/KoreanJPathol.2013.47.2.167 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peritoneal serous papillary carcinoma (PSPC), a rare primary malignancy arising from the abdominal and pelvic peritoneum, is characterized by peritoneal carcinomatosis with ascites and a histological pattern similar to that of papillary serous ovarian carcinoma. We herein describe a rare case of PSPC with unusual clinical presentations involving a single primary tumor originating from the peritoneal lining of the sigmoid colon with no evidence of intraperitoneal spread, pelvic lymph node involvement or distant metastasis. Awareness of such unusual presentations of PSPC should assist in the diagnosis of this disease, thereby improving the management of patients with this condition.
Internal Medicine 01/2013; 52(2):227-32. DOI:10.2169/internalmedicine.52.8541 · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study assessed selective dermal rejuvenation using sequential intradermal injections of carbon dioxide and hyaluronic acid as a treatment of facial wrinkles. An injection device was designed. After topical anesthesia, 0.1-mL carbon dioxide was gently injected intradermally so as to spread diffusely. A volume of 0.01- to 0.02-mL diluted hyaluronic acid was sequentially injected until the skin rose slightly. Overlapping injections were performed at 3 to 5 mm intervals. This process was repeated until the wrinkles were smoothened. This study included 36 cases of facial wrinkles in 34 patients. The follow-up period was 3 to 11 months. Temporary adverse effects were injection-site pain, mild edema, and redness. Most cases showed obvious improvement in skin thickness, elasticity, and smoothening. Complications included irregularities and hyperpigmentation in 3 cases, and 91% were highly satisfied with the antiwrinkle treatment. This method was a safe, economical, and clinically effective antiwrinkle treatment.
Annals of plastic surgery 12/2012; 70(6). DOI:10.1097/SAP.0b013e31823fa958 · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: : NF-E2-related factor 2 (Nrf2) is involved in defence against oxidative stress in human cells. Nrf2 is over-expressed in many types of cancers suggesting that it plays a role in carcinogenesis and chemoresistance. We examined Nrf2 expression in osteosarcoma to determine its prognostic significance.
: Nrf2 expression was assessed using immunohistochemistry in 58 specimens from patients with osteosarcoma. We investigated whether Nrf2 expression was associated with clinicopathological parameters.
: Nrf2 was positively expressed in 19 (32.8%) of 58 specimens. Nrf2 expression in osteosarcoma indicated a poor prognostic outcome (p = 0.0074), and correlated with worse disease-free survival (p = 0.0279). Nrf2 expression had a significant relationship with histological subtype (osteoblastic versus non-osteoblastic, p = 0.042); the non-osteoblastic subtype showed a higher rate of Nrf2 expression (50.0%) than the osteoblastic subtype (23.7%). Nrf2 expression showed no significant relationship with response to neoadjuvant chemotherapy (p = 0.115). Other clinicopathological parameters had no relationship with Nrf2 expression.
: Increased expression of Nrf2 is associated with a poor outcome and disease-free survival in osteosarcoma. Our results suggest that Nrf2 is a possible marker of poor prognosis in osteosarcoma.