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Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a member of the Cas family. Previous studies have revealed that NEDD9 coordinates the focal adhesion kinase and Src signaling cascades that are involved in integrin-dependent adhesion and migration, invasion, cell apoptosis and life cycle, and survival, which may play a role in epithelial-mesenchymal transformation. The aim of this study was to analyze the expression of NEDD9 and E-cadherin in gastric cancer (GC) and evaluate their clinical significance.NEDD9 and E-cadherin expression was analyzed with immunohistochemistry using tissue microarray technique in 435 GC patients who underwent gastrectomy. The NEDD9 expression level was defined by the combination score, which was determined by multiplying the staining intensity score and the proportion score (≥5; NEDD9-high,5; NEDD9-low). E-cadherin loss was defined as a total loss of staining. The clinicopathologic parameters, overall survival, and disease-free survival rates were analyzed according to the NEDD9 and E-cadherin expression status.The combined NEDD9 and E-cadherin expression status correlated with lymphatic invasion (P = 0.001), vascular invasion (P = 0.020), and T stage (P = 0.001). Combined high NEDD9 expression and loss of E-cadherin expression status had a worse overall survival rate (P 0.001) and served as a poor prognostic factor (Hazard ratio 2.49, 95% CI 1.25-5, P = 0.01).Immunohistochemical staining for NEDD9 and E-cadherin may function as a candidate prognostic marker for gastric cancer in everyday practice, especially when applied in combination.

AIM The purpose of the study was to investigate imaging predictors of Kirsten-ras (KRAS) mutations using magnetic resonance imaging (MRI) in patients with rectal cancer. PATIENTS AND METHODS A total of 275 patients with rectal cancer were enrolled. They underwent pretreatment rectal MRI, and then KRAS mutation evaluation following surgery. Two reviewers assessed diverse MRI findings associated with rectal cancer. RESULTS KRAS mutations were detected in 107 (38.9%). KRAS mutations were associated with N stage, gross tumor pattern, axial length of the tumor, and the ratio of the axial to the longitudinal dimensions of the tumor (p=0.0064, p

Background: Due to morphologic similarities between undifferentiated sarcoma (US) and dedifferentiated liposarcoma (DDLPS), some portions of US could be identified as DDLPS. In this study, we applied adipocyte-related antibodies in order to discriminate possible cases of DDLPS from US. Materials and methods: A total of 46 cases, previously diagnosed as US, were examined. Immunohistochemistry for MDM2, CDK4, calreticulin, FABP4, and stathmin were performed. Histological findings were reviewed and clinical data was analyzed retrospectively. Results: MDM2, CDK4, calreticulin, FABP4, and stathmin were positive in 17 (37.0%), 14 (30.4%), 3 (6.5%), 1 (2.2%), and 12 (26.1%) of the total 46 cases, respectively. MDM2/CDK4 positive cases showed more frequent positivity for calreticulin/FABP4/stathmin. Survival analysis, based on staining pattern, revealed a significantly better survival in the group where either MDM2 and CDK4 were positive and at least one of calreticulin, FABP4, or stathmin staining were positive. Conclusions: We conclude that when either MDM2-positive or CDK4-positive cases show any other positive results for calreticulin, FABP4, or stathmin, they have a significantly better survival and the possibility of DDLPS should be considered. Additional use of calreticulin, FABP4, or stathmin immunohistochemistry helps us to narrow the pool for further studies such as molecular analysis for a definite diagnosis.

Objective We report a case of intramural florid cystic endosalpingiosis in the lower uterine segment of the uterus. Case report A 43-year-old female presented with vaginal bleeding. Abdominal computed tomography suggested a leiomyoma with cystic degeneration. A total hysterectomy revealed a 4.0 cm × 3.8 cm cystic mass in the lower uterine segment. The cystic space microscopically was lined with a single layer or stratified layer of ciliated columnar cells that resembled tubal epithelium without cytologic atypia. The glandular spaces were surrounded by normal myometrium with no evidence of periglandular endometrial stroma, which was consistent with the diagnosis of florid cystic endosalpingiosis. Conclusion Florid cystic endosalpingiosis involving the uterus is a rare and clinically unexpected finding; however, it should be considered in the differential diagnosis of a uterine mass.

Perivascular epithelioid cell tumor (PEComa) is a rare collection of tumors arising in a wide array of anatomic locations. It is characterized by the presence of a peculiar population of myomelanocytic marker-positive perivascular epithelioid cells, and is commonly detected in the uterus. The colorectal area is an uncommon site for primary PEComa. In this study, we describe a 17-year-old patient presenting with a rectal polyp. Histologically, the tumor consisted of sheets of round to polygonal epithelioid cells with clear and granular cytoplasm, and a prominent capillary network. Some of the tumor cells were positive for Fontana-Masson staining. Immunohistochemically, the tumor cells were positive for HMB-45, and were negative for cytokeratin, vimentin, S-100 protein, actin, desmin, EMA, CD34, and c-kit. After finding melanosomes or premelanosomes at the ultrastructural level, the diagnosis of PEComa was made. Although PEComa arising within the intestinal tract is unusual and clinically unexpected, PEComa should be considered in the differential diagnosis of rectal polypoid lesions.

Objectives: The trefoil factor family (TFF) is composed of three thermostable, and protease-resistant proteins, named TFF1, TFF2 and TFF3, and plays a role in gastrointestinal mucosal defence and repair. Recently, TFFs have been found to be related to the development of various types of cancer. This study assessed the relationship between the expression of TFF1 and TFF3 and the clinicopathological parameters in gastric carcinoma (GC). Materials and Methods: The expression of TFF1 and TFF3 was analyzed by immunohistochemistry in 292 GCs and 20 normal gastric tissues. Results: All normal gastric tissues expressed TFF1, but 53.8% of GCs showed reduced TFF1 expression. However, TFF3 was not detected in normal gastric tissues and 44.2% of GCs showed a high level of expression. Highly expressed TFF3 was significantly correlated with lymph node metastasis, lymphatic invasion, vein invasion, and advanced stage. The overall survival was shorter in patients with high expression of TFF3 than in those with low expression of TFF3 in 292 GCs and in 125 early GCs (EGCs). Moreover, in patients with EGCs, high expression of TFF3, associated with reduced expression of TFF1, was determined as an independent poor prognostic marker. Conclusions: Reduced expression of TFF1 and increased expression of TFF3 may play a role in the carcinogenesis of gastric cancer. Furthermore, high expression of TFF3 with reduced expression of TFF1 may be a marker of poor prognosis for patients with EGC.

Background: Histone deacetylase inhibitors are a new class of drugs used in treatment of malignant tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma, and it accounts for more than 40% of all B-cell lymphomas. In this study, we aimed to determine the expression patterns of histone deacetylases (HDACs) in DLBCL, to examine whether HDAC expression patterns differ among cases, and to assess whether these findings have clinical significance. Materials and methods: We selected 91 cases of DLBCL diagnosed at St. Vincent Hospital, The Catholic University of Korea, from 2001-2012. We performed a pathology slide review and collected clinical data including age, sex, tumor site, survival time, and mortality. Immunohistochemical analysis was performed using primary antibodies for HDACs, including HDAC1 and 2 of class I, HDAC4 and 5 of class IIa, and HDAC6 of class IIb. Expression site was determined to be nuclear, cytoplasmic, or both. Staining intensities were graded as low and high. We assessed correlations between HDAC expression levels and clinical data and survival analysis. Results: Of the 91 cases examined, 46 (50.5%) were men and 45 (49.5%) were women. Most of the patients were elderly, and 74 (81.3%) cases were older than 46 y. Forty-six (50.5%) cases showed lymph node involvement, and 45 (49.5%) cases showed lymphoma at extranodal sites. In nodal lymphoma, staining was strongly positive for HDAC2, whereas staining was weak or negative for HDAC4; however, there was no significant correlation with survival. But nodal lymphoma cases with high nuclear expression of HDAC2 and nodal lymphoma cases with high nuclear expression of HDAC2 and low nuclear expression of HDAC4 showed significantly shorter survival times compared with other cases. Conclusions: High nuclear expression of HDAC2 may play an important role in survival of DLBCL patients, especially in those with nodal lymphoma, which is associated with a shorter survival time. Our results may have important implications for treatment of DLBCL by epigenetic regulation.

Objectives: Tumor hypoxia confers poor prognosis of a wide range of solid tumors due to increased malignancy, increased likelihood of metastasis and treatment resistance. The aim of this study was to assess the significance of the expression of HIF-1α and HIF-1α-inducible proteins in gastric cancer and their impact on prognosis. Materials and Methods: The expression of HIF-1α, GLUT-1, CA-9, and iNOS proteins was analyzed by immunohistochemistry in 193 gastric adenocarcinomas (GAs) and 20 normal gastric mucosa. Results: HIF-1α, GLUT-1, CA-9 and iNOS were expressed in 52.3%, 43.0%, 57.0%, and 43.0% of GAs, respectively, which are higher than the normal counterparts except for CA-9. HIF-1α expression was positively correlated with the expression of GLUT-1, CA-9 and iNOS. GLUT-1 expression was higher in the intestinal type (p = 0.012); however, iNOS expression was higher in the less-differentiated type and the diffuse type (p = 0.006, p = 0.032, respectively). The expression of HIF-1α and GLUT-1 was significantly correlated with lymph node metastasis (p = 0.009, p = 0.008, respectively), while the expression of GLUT-1 and iNOS was significantly correlated with the depth of invasion and advanced stage (p = 0.044, p = 0.004; p = 0.009, p = 0.008, respectively). Overall survival was shorter in patients with GLUT-1 expression than in those without GLUT-1 expression, which was statistically significant by univariate analysis (p = 0.042). On multivariate analysis, however, stage was determined as the only independent prognostic marker (p < 0.001). Conclusions: Our data suggest that overexpression of HIF-1α, GLUT-1, and iNOS may play an important role in gastric cancer progression. GLUT-1 is a potential candidate for predicting patient survival.

Recently, as the use of ultrasonographic examination has increased, the possibility of incidental findings of thyroid nodules has also increased. In Korea, the prevalence of thyroid nodules detected by an ultrasonogram is approximately 19-67%.1,2 The fine needle aspiration cytology (FNAC) of the thyroid gland is an important and definitive method for the diagnosis of thyroid nodules.3,4 Follicular neoplasm (FN) and Hurthle cell neoplasm (HCN) are relatively rare diseases and their cytologic diagnosis is difficult when compared with papillary carcinoma (PC) which shows a cytologic accuracy of more than 90%. In addition, cytologic differentiation between benign and malignant tumors is not possible in FN and HCN cases. When the histologic correlation is made, the diagnostic accuracy and predictive malignancy rate of FN and HCN are much lower compared with PC. According to the guidelines for the treatment of thyroid nodules provided by the Korean Thyroid Association, surgery is recommended for patients when FN or HCN is diagnosed by FNAC because the possibility of malignancy in this case is not known until the histologic diagnosis is made from the lobectomy or total thyroidectomy specimen.1,3 In contrast, guidelines for the treatment of PCs are relatively well established according to the categories of cytologic diagnosis. FN and HCN are still rare FNAC findings. Follicular carcinoma (FC) comprises approximately 5% of thyroid cancers,5 and because the number of FN cases is limited and FC cannot be distinguished from benign follicular adenoma (FA) on the basis of cytologic findings, describing FN cytologically in an ambiguous manner may be inevitable. Therefore, more cytologic information regarding FN and HCN are required not only for the cytologic diagnosis but also for the development of appropriate treatment guidelines. In this study we evaluated the FNAC accuracy in FN cases based on the histologic diagnosis and investigated the cytologic findings to increase the probability of a correct cytologic FN diagnosis.

Benign metastatic leiomyomatosis (BML) is a rare disease characterized by smooth muscle cell proliferation in extrauterine sites including the lung, abdomen, pelvis, and retroperitoneum. Depending on location, BML is classified as intravenous leiomyomatosis and diffuse peritoneal leiomyomatosis. Pathogenesis of BML can be iatrogenic after previous myomectomy or hysterectomy, hormonal, or coelomic metaplasia. Treatment options are observation, hormonal suppression, and/or surgical debulking via laparotomy or laparoscopy. Laparoscopic surgery is gaining in popularity in the gynecologic field compared to laparotomic surgery and single-port laparoscopy has the benefits of cosmesis and early tissue extraction by transumbilical morcellation. We report a 39-year-old woman with BML who underwent single-port laparoscopy debulking surgery.

The hedgehog (Hh) signaling pathway was first discovered as a primary regulator of embryonic development.1 Mammalian Hh signal transduction involves three Hh homologues: sonic (Shh), Indian, and Desert. The Hh signaling cascade is initiated as the Hh binds to the twelve transmembrane proteins patched 1 (Ptch). This internalizes the Ptch and relieves the suppression of the smoothened (Smo), which allows for the activation of the glioma-associated oncogene (Gli) transcription factor. The Gli transcription factor exists in three forms, Gli-1, Gli-2, and Gli-3.2,3 Although the detailed mechanism of this pathway is yet to be understood, a full-length Gli-3 is transported into the nucleus in order to activate the Hh target genes.4 Gli-1, one of the Hh target genes that functions only as a transactivator, is considered to be a marker of the Hh pathway activation.4,5 Recent studies have demonstrated that carcinomas of various organs, such as the skin, cerebellum, lungs, stomach, pancreas, prostate, uterine cervix, and breasts, harbor the ligand-dependent activation of the Hh signaling pathway.2,6,7 Shh, Ptch, and Gli-1 have been reported to be overexpressed in breast carcinomas.2 In addition, a positive correlation between the estrogen receptor (ER) status and Gli-1 nuclear translocation has been reported and further studies indicated that estrogen-induced Shh expression activated the Hh pathway and increased cell proliferation.2,8 Breast cancer is one of the most heterogeneous types of tumor with various histology, phenotype, and clinical behavior. In general, systemic therapy recommendations follow the subtype classification, which is determined by hormone receptor status, human epidermal growth factor receptor 2 (HER2) expression and Ki-67 labeling index. The purpose of this study was to evaluate Hh signaling protein expression in breast carcinoma according to immunohistochemical subtypes, correlate the expression with known clinicopathologic parameters, and compare the overall survival rates.

Background: The microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, α-tubulin, and βIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment. Methods: Immunohistochemical expressions of Tau, α-tubulin, and βIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival. Results: Tau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p = .003 and p < .001, respectively). Loss of α-tubulin was significantly correlated with distant metastasis (p = .034). Loss of βIII-tubulin was correlated with lymph node metastasis and ER positivity (p = .004 and p < .001, respectively). In taxanetreated cases, Tau expression and loss of α-tubulin and βIII-tubulin expression were related to disease progression (p = .001, p = .028, and p = .030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p = .049). Conclusions: Tau expression and loss of α-tubulin and βIII-tubulin expression were correlated with aggressive behavior in taxane-treated breast cancer. Further evaluation of Tau, α-tubulin and βIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer.

Sclerosing mesenteritis is a rare benign disease originated from the mesenteries. It can be related to autoimmune disease, vasculitis, ischemia, infection, trauma and operation, but most of cases are idiopathic. The overall prognosis of sclerosing mesenteritis is usually good with benign, course. However, no consensus of treatment has yet been established. We report a case of spontaneous partial regression of sclerosing mesenteritis presented as a huge mass and diagnosed by finding of contrast enhanced abdominal computed tomography and percutaneous ultrasonography guided needle biopsy.

A 50-year-old female patient presented with anorexia and weight loss. Pelvic computed tomography revealed a 12.5× 7.3 cm heterogeneous mass in the left ovary. About 30% of the tumor was occupied by a mature cystic teratoma. The remaining solid portion was composed of fibrous and histiocytic elements, arranged in storiform patterns admixed with bizarre giant cells. The mitotic index was 8 per 10 high power fields, including atypical mitoses. The only immunopositivity was for vimentin. The tumor was diagnosed as a malignant fibrous histiocytoma arising in a mature cystic teratoma. To the best of our knowledge, this is only the third such case in the English language literature.

Background : To determine the most effective method for detecting mycobacteria in formalin-fixed paraffin-embedded (FFPE) tissue, we compared the results of Ziehl-Neelsen stain (ZNS) and mycobacterial culture with those of polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR). Methods : We analyzed 54 cases diagnosed as chronic granulomatous inflammation. In all cases, ZNS and nested PCR using three different primers, IS6110, Mpb64 and IS6110/Rpo b were done. RQ-PCR with the IS6110/Rpob primer was done in 51 cases. Results : Mycobacteria were identified by ZNS in 15/54 (27.8%) cases. RQ-PCR had the highest sensitivity (80.0%) compared to PCR with IS6110 (73.3%), Mpb64 (60.0%) and IS6110/Rpo b (73.3%). Specificity was higher in all PCR experiments (79.582.1%) than in RQ-PCR (69.4%) experiments. The false negative rate was lowest for RQPCR (20.0%) than for PCR with IS6110 (26.7%), Mpb64 (40.0%) and IS6110/Rpob (26.7%). The false positive rate was highest for RQ-PCR (30.6%) compared to PCR with IS6110 (20.5%), Mpb64 (17.9%) and IS6110/Rpob (20.5%). Conclusions : RQ-PCR had the highest sensitivity, and the lowest false negative rate, but it also had a higher false positive rate than PCR for detection of mycobacteria in FFPE tissues.

Calcifying fibrous tumor (CFT) is a recently recognized rare benign lesion characterized by dense hyalinized collagenous tissue with interspersed spindle cells and a lymphoplasmocytic infiltrate. Calcification is the hallmark of CFT and may present in the form of psammomatous bodies or dystrophic calcifications. CFT of the intestinal tract is uncommon and rectal CFT has never been reported. Recently, we experienced a case of CFT found in the rectum of a 36-year-old man. In this study, we described the characteristic histopathological findings with a review of the relevant literature. Although CFT of the intestinal tract as an intrinsic visceral lesion is unusual and clinically unexpected, CFT should be considered in the differential diagnosis of rectal submucosal tumor.