[Show abstract][Hide abstract]ABSTRACT: Leiomyosarcoma of the uterus is an extremely rare but highly aggressive tumor that accounts for only 1–2 % of uterine malignancies, and is usually associated with a dismal outcome.
The authors present an unusual case of pedunculated subserosal leiomyosarcoma of the uterus mimicking ovarian carcinoma. A 57-year-old postmenopausal woman presented with progressive low abdominal pain and urinary frequency. Pelvic magnetic resonance imaging revealed a large adnexal mass with carcinomatosis peritonei. Laboratory examination revealed an elevated serum CA-125 level (398.4 U/ml). The patient underwent exploratory laparotomy under suspicion of ovarian malignancy. Frozen section indicated malignancy originating from the uterus, and thus, total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymph node dissection, and mass excision were performed. Subsequent histopathologic examination resulted in a final diagnosis of leiomyosarcoma of the uterus. The patient’s postoperative course was uneventful, and gemcitabine and docetaxel adjuvant chemotherapy was administered.
The authors report an unusual case of pedunculated subserosal leiomyosarcoma of the uterus mimicking ovarian carcinoma.
Full-text available · Article · Dec 2016 · Journal of Ovarian Research
[Show abstract][Hide abstract]ABSTRACT: Background
Pseudocarcinomatous hyperplasia of the fallopian tube is a rare, benign disease characterized by florid epithelial hyperplasia. Case presentationThe authors present the history and details of a 22-year-old woman with bilateral pelvic masses and a highly elevated serum CA-125 level (1,056 U/ml). Ultrasonography and magnetic resonance imaging (MRI) of the pelvis showed bilateral adnexal complex cystic masses with a fusiform or sausage-like shape. Contrast-enhanced fat-suppressed T1-weighted images showed enhancement of papillary projections of the right adnexal mass and enhancement of an irregular thick wall on the left adnexal mass, suggestive of tubal cancer. Based on MRI and laboratory findings, laparotomy was performed under a putative preoperative diagnosis of tubal cancer. The final pathologic diagnosis was pseudocarcinomatous hyperplasia of tubal epithelium associated with acute and chronic salpingitis in both tubes. Conclusion
The authors report a rare case of pseudocarcinomatous hyperplasia of the fallopian tubes mimicking tubal cancer.
Full-text available · Article · Dec 2016 · Journal of Ovarian Research
[Show abstract][Hide abstract]ABSTRACT: Gastric cancers have recently been classified into several types on the basis of molecular characterization, and the new taxonomy has shown to have clinical relevance. However, the technology required for thorough molecular classification is complicated and expensive, currently preventing widespread use. We aimed to reproduce the results of molecular classification using only simple techniques, that is, immunohistochemical analysis and in situ hybridization. We classified a cohort of 349 successive gastric adenocarcinomas into 5 subtypes, on the basis of protein or mRNA expression of MLH1, E-cadherin, p53, and Epstein-Barr virus. We observed that the subtypes presented distinct clinicopathologic characteristics and corresponded to the molecular classifications previously reported. Epstein-Barr virus -positive tumors were more common in male individuals and in the body of the stomach. Microsatellite-unstable (MSI) tumors, which showed aberrant MLH1 expression, were correlated with increased age and intestinal histology. Both types showed better overall survival than the other types. Gastric cancers with reduced expression of E-cadherin, corresponding to the epithelial to mesenchymal transition or genome stable subtypes, showed the poorest overall survival, with a high prevalence of poorly cohesive carcinoma (ie, diffuse type, of the Lauren classification system). In conclusion, we were able to reproduce a previously reported molecular classification of gastric cancers using immunohistochemical analysis and in situ hybridization. We verified the effectiveness and applicability of this method, which shows promise for use in a clinical setting in the foreseeable future.
Article · Nov 2016 · American Journal of Surgical Pathology
[Show abstract][Hide abstract]ABSTRACT: The metaphyseal locations of tubular bones with osteoid mineralization in young patients are important diagnostic radiologic features of osteosarcoma. The pelvic bones are an unusual location of osteosarcoma. Although osteosarcoma occurring in pelvic bones is not common, the osteoid matrix may be a critical finding for differentiating osteosarcoma from other common pelvic bone tumors. Therefore, the possibility of osteosarcoma in pelvic bones may be considered in the presence of osteoid matrix even in the old age group.
[Show abstract][Hide abstract]ABSTRACT: Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in developed countries. Chronic endogenous sterile pro-inflammatory responses are strongly linked to EOC progression and chemoresistance to anti-cancer therapeutics. In the present study, the activity of epithelial NF-κB, a key pro-inflammatory transcription factor, was enhanced with the progress of EOC. This result was mechanistically linked with an increased expression of NSAID-Activated Gene 1 (NAG-1) in MyD88-positive type I EOC stem-like cells, compared with that in MyD88-negative type II EOC cells. Elevated NAG-1 as a potent biomarker of poor prognosis in the ovarian cancer was positively associated with the levels of NF-κB activation, chemokines and stemness markers in type I EOC cells. In terms of signal transduction, NAG-1-activated SMAD-linked and non-canonical TGFβ-activated kinase 1 (TAK-1)-activated pathways contributed to NF-κB activation and the subsequent induction of some chemokines and cancer stemness markers. In addition to effects on NF-κB-dependent gene regulation, NAG-1 was involved in expression of EGF receptor and subsequent activation of EGF receptor-linked signaling. The present study also provided evidences for links between NAG-1-linked signaling and chemoresistance in ovarian cancer cells. NAG-1 and pro-inflammatory NF-κB were positively associated with resistance to paclitaxel in MyD88-positive type I EOC cells. Mechanistically, this chemoresistance occurred due to enhanced activation of the SMAD-4- and non-SMAD-TAK-1-linked pathways. All of the present data suggested NAG-1 protein as a crucial mediator of EOC progression and resistance to the standard first-line chemotherapy against EOC, particularly in MyD88-positive ovarian cancer stem-like cells.
[Show abstract][Hide abstract]ABSTRACT: Purpose:
The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here, we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)-positive breast cancers.
Materials and methods:
Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR-/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin-stained full face sections, and MxA expression was evaluated by immunohistochemistry with a tissue microarray.
MxA protein expression was significantly higher in tumors with high histologic grade (p= 0.023) and high levels of TILs (p = 0.002). High levels of TILs were correlated with high histological grade (p = 0.001), negative lymphovascular invasion (p = 0.007), negative lymph node metastasis (p = 0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p = 0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR-/HER2+ breast cancers. However, MxA was not a prognostic factor.
High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value. .
Article · Jul 2016 · Cancer Research and Treatment
[Show abstract][Hide abstract]ABSTRACT: Leiomyomas and schwannomas of the gastrointestinal tract (GIT) are mainly comprised of spindle-shaped tumor cells and should always be differentiated from gastrointestinal stromal tumors (GISTs). Mast/stem cell growth factor receptor Kit (KIT) and discovered on GIST-1 (DOG1) are well-known diagnostic markers for the detection of a GIST by immunohistochemical staining. The aim of the present study was to assess the prevalence and significance of spindle cell tumors of the GIT with KIT- or DOG1-positive spindle-shaped cells, presumed to be interstitial cells of Cajal (ICCs), other than GISTs. A total of 71 leiomyomas and 35 schwannomas were examined and clinicopathological information was obtained. KIT and DOG1 immunostaining was performed to determine the proportions of positive cells. Mutation screening of KIT exons 9, 11, 13 and 17, and platelet-derived growth factor receptor α (PDGFRA) exons 12 and 18 was performed in cases with a relatively high proportion of either KIT- or DOG1-positive cells. The frequency of leiomyomas and schwannomas with KIT- and DOG1-positive ICCs was 35.2% (25/71 cases) and 5.7% (2/35 cases), respectively. Among the esophageal leiomyomas with KIT- and DOG-positive ICCs (14/25; 56.0%), 5 leiomyomas involved the muscularis mucosa and 9 leiomyomas involved the muscularis propria. All gastric leiomyomas with KIT- and DOG1-positive ICCs (11/25; 44%) involved the muscularis propria. All schwannomas with an increased proportion of KIT- or DOG1-positive ICCs were of gastric origin. No KIT or PDGFRA mutations were detected in 7 leiomyomas and 2 schwannomas. In conclusion, the majority of leiomyomas and the minority of schwannomas in the GIT had a significant portion of KIT- and DOG1-positive cells. All of the tumors were located in the upper GIT, and could be present in the muscularis propria or muscularis mucosa. The tumors represented a non-neoplastic proliferation of KIT- and DOG1-positive cells in the GIT. Careful evaluation of KIT- or DOG1-positive cells in spindle cell tumors of the GIT can assist in forming the correct diagnosis by differentiation from a GIST.
Full-text available · Article · Jun 2016 · Oncology letters
[Show abstract][Hide abstract]ABSTRACT: Ovarian cancer shows high mortality due to development of resistance to chemotherapy and relapse. Cancer stem cells (CSCs) have been suggested to be a major contributor in developing drug resistance and relapse in ovarian cancer. In the present study, we isolated CSCs through sphere culture of A2780, SKOV3, OVCAR3 epithelial ovarian cancer cells and primary ovarian cancer cells from patients. We identified heat-stable factors secreted from ovarian CSCs stimulated migration and proliferation of CSCs. Mass spectrometry and ELISA analysis revealed that lysophosphatidic acid (LPA) was significantly elevated in CSC culture media compared with non-CSC culture media. Treatment of CSCs with LPA resulted in augmented CSC characteristics such as sphere-forming ability, resistance to anticancer drugs, tumorigenic potential in xenograft transplantation, and high expression of CSC-associated genes, including OCT4, SOX2, and aldehyde dehydrogenase 1. Treatment of CSCs with LPA receptor 1-specific inhibitors or silencing of LPA receptor 1 expression abrogated the LPA-stimulated CSC properties. Autotaxin, an LPA-producing enzyme, is highly secreted from ovarian CSCs, and pharmacological inhibition or knockdown of autotaxin markedly attenuated the LPA-producing, tumorigenic, and drug resistance potentials of CSCs. Clinicopathological analysis showed a significant survival disadvantage of patients with positive staining of autotaxin. In addition, we further identified that AKT1 activity was up-regulated in ovarian CSCs through an LPA-dependent mechanism and silencing of AKT1 expression led to suppression of CSC characteristics. These results suggest that autotaxin-LPA-LPA receptor 1-AKT1 signaling axis is critical for maintaining CSC characteristics through an autocrine loop and provide a novel therapeutic target for ovarian CSCs. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract]ABSTRACT: Ovarian hemangiomas are usually of the cavernous type, and are rarely encountered. A 73-year-old woman presented with lower abdominal discomfort. Subsequent physical examination depicted a palpable mass in the lower abdomen. Abdominopelvic computed tomography (CT) revealed a well-circumscribed mass with thin septa measuring 12.1 × 9.0 cm in the right ovary. Levels of the tumor markers cancer antigen (CA)-125 and CA 19-9 were within the normal range. At laparoscopy, the tumor was found to be confined to the right ovary and to have a smooth surface. The final histopathological result was ovarian cavernous hemangioma. Microscopically, the mass consisted of multiple, dilated, blood-filled vascular channels separated by loose connective tissue, and all were lined by a single layer of flattened endothelium. The authors present a case of ovarian cavernous hemangioma presenting as a large growing mass in a postmenopausal woman and review previously published literature.
[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.
Full-text available · Article · Apr 2015 · Oncology letters
[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.
Full-text available · Article · Nov 2014 · Oncology letters
[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.
Full-text available · Article · Aug 2014 · The Korean Journal of Pathology
[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.
Full-text available · Article · Jul 2014 · World Journal of Surgical Oncology
[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.
Full-text available · Article · Feb 2014 · The Korean Journal of Parasitology
[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.
Article · Dec 2013 · Journal of the neurological sciences