Targeted Protein Degradation: Principles and Applications of the Proteasome.

The proteasome is a multi-catalytic protease complex that is involved in protein quality control via three proteolytic activities (i.e., caspase-, trypsin-, and chymotrypsin-like activities). Most cellular proteins are selectively degraded by the proteasome via ubiquitination. Moreover, the ubiquitin-proteasome system is a critical process for maintaining protein homeostasis. Here, we briefly summarize the structure of the proteasome, its regulatory mechanisms, proteins that regulate proteasome activity, and alterations to proteasome activity found in diverse diseases, chemoresistant cells, and cancer stem cells. Finally, we describe potential therapeutic modalities that use the ubiquitin-proteasome system.

NY-ESO-1 as a diagnostic and prognostic marker for myxoid liposarcoma.

INTRODUCTION: Myxoid liposarcoma (MLS) is a common lipogenic sarcoma, which is difficult to diagnose in small specimens. New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) is a cancer-testis antigen expressed in neoplastic tissue. In this study, NY-ESO-1 expression was assessed in various soft tissue tumors (STTs), and we also evaluated its diagnostic utility. METHODS: We included 434 cases of STTs for collection of clinicopathological data. Tissue microarrays were designed, and immunostaining for NY-ESO-1 was examined. We investigated the correlation between NY-ESO-1 expression and various clinicopathological parameters. We also evaluated the role of NY-ESO-1 as a diagnostic marker for MLS and its possible use in prognostication. RESULTS: Sixty-four of the 434 STTs (14.75%) were immunoreactive for NY-ESO-1, and the most frequent type of tumor in the NY-ESO-1 positive group was MLS (70.3%, 45/64), followed by synovial sarcoma (17.2%, 11/64). MLS showed 72.6% (45/62) immunopositivity for NY-ESO-1. The sensitivity and specificity of NY-ESO-1 expression for the diagnosis of MLS were 84.4% and 100%, respectively, compared to DDIT3 fluorescence in situ hybridization. When restricting analysis to the MLS (n=62), the NY-ESO-1 positive group had a poor overall survival (OS) rate (P=0.039). CONCLUSION: NY-ESO-1 was substantially and widely expressed in the majority of MLS cases. NY-ESO-1 positivity by IHC staining was also a predictor of a poor OS in patients with MLS. It is possible to use NY-ESO-1 for diagnosis and for predicting a prognosis in patients with MLS, and it may be used as a therapeutic target.

Distinct histologic and genetic characteristics of round cell sarcoma with CIC-DUX4 fusion and comparison with ewing sarcoma.

CIC-DUX4 fusion gene associated sarcoma is a new emerging subgroup of round cell sarcoma with Ewing sarcoma-like morphology. Distinguishing these tumors from Ewing sarcoma family tumors (ESFT) is critical because of the clinical impact but is still challenging due to the overlapped histological and immunohistochemical phenotypes of each subtype. The present study investigated small round cell sarcoma to identify CIC-DUX4 fusion positive sarcoma, examined clinical, histopathologic and immunohistochemical characteristics of CIC-DUX4 sarcoma, and evaluated parameters to differentiate Ewing sarcoma family tumors. Seventy patients with undifferentiated round cell sarcoma or Ewing-like sarcoma were retrieved. Molecular tests including EWSR1, CIC break apart FISH, and RT-PCR for CIC-DUX4 gene fusion were performed and immunohistochemistry was performed. Six cases (8.6%) of CIC-DUX4 sarcomas were detected. Histologically, CIC-DUX4 sarcomas composed of heterogeneous round, plasmacytoid, and spindle cells and more commonly showed cytologic pleomorphism with bizarre nuclei and multinucleated cells and myxoid stoma unlike ESFT. CIC-DUX4 sarcomas didn't show overall survival differences (p = 0.325) compared to ESFT but they demonstrated short disease-free survival (p = 0.034) and poor response to treatment (p = 0.007). Therefore, molecular analysis to detect the distinctive genetic alteration is mandatory in tumors with atypical histologic, immunohistochemical and/or clinical presentation for accurate diagnosis and treatment.

Clinico-cytopathologic analysis of 574 Pericardial Effusion Specimens: Application of the international system for reporting serous fluid cytopathology (ISRSFC) and long-term clinical follow-up.

INTRODUCTION: A pericardial effusion (PE) has a variable etiology and the primary role is diagnosis of metastatic malignancy. We analyzed the PE cytology in a large cohort in accordance with the international system for reporting serous fluid cytopathology (ISRSFC) and evaluated the long-term patient outcomes. METHODS: PE specimens from 2010 to 2014 with an available clinical history, cytologic data, and pericardial biopsy results were collected. RESULTS: A total of 574 PE specimens were obtained from 486 patients, representing 1.5% (574/38,589) of all body fluid specimens. Three hundred and eighty-two (66.6%) cases were "negative," 54 (9.4%) cases were "atypia of undetermined significance," 10 (1.7%) cases were "suspicious for malignancy," and 128 (22.3%) cases were "malignancy". The most common origin for malignant PE was the lung (82.1%), in both men (70.5%) and women (50.6%). Breast cancer (20%) in women and gastric cancer (4.9%) in men were the second most common malignant PE, respectively. The mean interval from the occurrence of malignant PE to death was 10.06 months (range; 0-116.03 months, median 3.5 months), and the 1-year survival rate was 16.7%. In addition, the 1-year survival rates after malignant PE onset were 0% for gastric cancer, 13.9% for lung cancer, 19.8% for breast cancer, and 21.1% for the other cancers (p = 0.011). CONCLUSION: Our present study is the first to our knowledge to classify the pericardial fluid from 574 cases in accordance with the recently published ISRSFC, and to present the long-term outcomes of patients with malignant PE at the same time. Moreover, we report for the first time that it is gastric and not lung cancer patients that have the poorest prognosis after the occurrence of malignant PE.

Hepatoid thymic carcinoma: a case report of a rare subtype of thymic carcinoma.

Hepatoid thymic carcinoma is an extremely rare subtype of primary thymus tumor resembling "pure" hepatoid adenocarcinomas with hepatocyte paraffin 1 (Hep-Par-1) expression. A 53-year-old man presented with voice change and a neck mass. Multiple masses involving the thyroid, cervical and mediastinal lymph nodes, and lung were detected on computed tomography. Papillary thyroid carcinoma was confirmed by biopsy, and the patient underwent neoadjuvant chemoradiation therapy. However, the anterior mediastinal mass was enlarged after the treatment whereas the multiple masses in the thyroid and neck decreased in size. Microscopically, polygonal tumor cells formed solid sheets or trabeculae resembling hepatocytes and infiltrated remnant thymus. The tumor cells showed immunopositivity for cytokeratin 7, cytokeratin 19, and Hep-Par-1 and negativity for α-fetoprotein. Possibilities of germ cell tumor, squamous cell carcinoma, and metastasis of thyroid papillary carcinoma were excluded by immunohistochemistry. This report on the new subtype of thymic carcinoma is the third in English literature thus far.

SILAC-Based Quantitative Proteomic Analysis of Oxaliplatin-Resistant Pancreatic Cancer Cells.

Oxaliplatin is a commonly used chemotherapeutic drug for the treatment of pancreatic cancer. Understanding the cellular mechanisms of oxaliplatin resistance is important for developing new strategies to overcome drug resistance in pancreatic cancer. In this study, we performed a stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative proteomics analysis of oxaliplatin-resistant and sensitive pancreatic cancer PANC-1 cells. We identified 107 proteins whose expression levels changed (thresholds of 2-fold changes and p-value ≤ 0.05) between oxaliplatin-resistant and sensitive cells, which were involved in multiple biological processes, including DNA repair, cell cycle process, and type I interferon signaling pathway. Notably, myristoylated alanine-rich C-kinase substrate (MARCKS) and Wntless homolog protein (WLS) were upregulated in oxaliplatin-resistant cells compared to sensitive cells, as confirmed by qRT-PCR and Western blot analysis. We further demonstrated the activation of AKT and ß-catenin signaling (downstream targets of MARCKS and WLS, respectively) in oxaliplatin-resistant PANC-1 cells. Additionally, we show that the siRNA-mediated suppression of both MARCKS and WLS enhanced oxaliplatin sensitivity in oxaliplatin-resistant PANC-1 cells. Taken together, our results provide insights into multiple mechanisms of oxaliplatin resistance in pancreatic cancer cells and reveal that MARCKS and WLS might be involved in the oxaliplatin resistance.

Clinicopathologic Analysis of Cathepsin B as a Prognostic Marker of Thyroid Cancer.

Thyroid cancer incidence has increased worldwide; however, investigations of thyroid cancer-related factors as potential prognosis markers remain insufficient. Secreted proteins from the cancer secretome are regulators of several molecular mechanisms and are, thereby, ideal candidates for potential markers. We aimed to identify a specific factor for thyroid cancer by analyzing the secretome from normal thyroid cells, papillary thyroid cancer (PTC) cells, and anaplastic thyroid cancer cells using mass spectrometry (MS). Cathepsin B (CTSB) showed highest expression in PTC cells compared to other cell lines, and CTSB levels in tumor samples were higher than that seen in normal tissue. Further, among thyroid cancer patients, increased CTSB expression was related to higher risk of lymph node metastasis (LNM) and advanced N stage. Overexpression of CTSB in thyroid cancer cell lines activated cell migration by increasing the expression of vimentin and Snail, while its siRNA-mediated silencing inhibited cell migration by decreasing vimentin and Snail expression. Mechanistically, CTSB-associated enhanced cell migration and upregulation of vimentin and Snail occurred via increased phosphorylation of p38. As our results suggest that elevated CTSB in thyroid cancer induces the expression of metastatic proteins and thereby leads to LNM, CTSB may be a good and clinically relevant prognostic marker.

Aggressive Paraganglioma of the Urinary Bladder with Local Recurrence and Pelvic Metastasis.

Many pheochromocytoma and extra-adrenal paraganglioma are benign, but some are malignant. Pheochromocytoma of the Adrenal gland Scaled Score analyzed the histological characteristics of the tumor. Tumors with a Pheochromocytoma of the Adrenal gland Scaled Score of 4 or higher have a higher risk of recurrence. This pattern is thought to be applicable to paraganglioma as well, and to future patient follow-up efforts. We report a recurrent and metastatic paraganglioma of the urinary bladder.

Hippo pathway and tumoral FOXP3 expression correlate with tumor growth in squamous cell carcinoma of the lung.

BACKGROUND: Expression of FOXP3 in tumors is associated with proliferation, migration, and invasion, has been implicated in cancer prognosis, and may be related to metastatic potential. The Hippo signaling pathway is known to regulate tissue homeostasis and organ size through cell proliferation and apoptosis. We investigated tumoral FOXP3, Lats2, and YAP expression related to the Hippo pathway in squamous cell carcinoma (SCC) of the lung. METHODS: Between 1983 and 2006, 149 cases of SCC were diagnosed and surgically resected at Kyung Hee University Hospital. Immunohistochemical staining for FOXP3, YAP, and Lats2 was done. RESULTS: Tumor size was inversely correlated with tumoral FOXP3 expression (p = 0.015), Treg count (p < 0.0001), and positive Lats2 expression (p = 0.028). YAP expression was inversely correlated with lymph node metastasis (p = 0.039). Positive tumoral FOXP3 expression was significantly associated with infiltrated Treg count (p = 0.001) and positive Lats2 expression (p = 0.007). CONCLUSION: Tumoral FOXP3 has the potential to suppress tumor function in SCC of the lung. The decrease or loss of FOXP3 expression in cancer cells is thought to contribute to SCC tumorigenesis and progression in the lung. The tumor suppressor function of FOXP3 in SCC of the lung was related to Lats2 and YAP expression in the Hippo pathway.

Clear cell chondrosarcoma of the talus in Von Hippel-Lindau disease: a rare tumor in an unusual location and uncommon co-presentation.

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome. Clear cell chondrosarcoma (CCCS) is a rare variant of chondrosarcoma. Here, we report a case of CCCS in the talus occurring in a patient with VHL disease. A 32-year-old man presented with ankle pain for 2 years. MRI revealed a 4.2 cm mass in the talus, and needle biopsy was performed. The patient underwent curettage but the final diagnosis was CCCS. Adjuvant radiation therapy was performed without additional talectomy and the patient was alive without recurrence for a follow-up period of 2 years. To our knowledge, this is the first case in the English medical literature of a co-presentation of this rare disease and condition: i.e. CCCS with VHL disease in the unusual location of the talus. We cautiously suggest that CCCS may be associated with VHL disease based on their histologic similarity.

Expression of Beclin-1, an autophagy-related protein, is associated with tumoral FOXP3 expression and Tregs in gastric adenocarcinoma: The function of Beclin-1 expression as a favorable prognostic factor in gastric adenocarcinoma.

BACKGROUND: Autophagy, which is stimulated by cellular or environmental stresses, is involved in several distinct biological processes, and the regulation mechanism is complex. Autophagy has been reported to modulate immune system components. In the present study, the expression of Beclin-1 and LC3, an autophagy-related proteins, and its relationship with FOXP3 expression were investigated in gastric adenocarcinoma cells and FOXP3+T cells (regulatory T cells). METHODS: Tissue samples were acquired from 182 cases of gastric adenocarcinoma that were surgically resected at Kyung Hee University Hospital at Gangdong from 2006 to 2012. Immunohistochemical staining for Beclin-1, LC3, FOXP3, and CD8 was performed. RESULTS: Consequently, positive Beclin-1 expression was significantly associated with a smaller tumor size, mixed histologic type, better histologic grade, lower T category, lower N category, lower recurrence rate, less lymphatic invasion, less vascular invasion, and less neural invasion. Positive tumoral FOXP3 expression was significantly associated with a lower T category, lower N category, lower recurrence rate, and less lymphatic invasion. The cases of more infiltrated Tregs (≥ 25/high power field, HPF) significantly correlated with a lower N category, lower recurrence rate, less lymphatic invasion, more infiltrated CD8+T cells, and a higher number of tumor-infiltrating lymphocytes. Beclin-1 and LC3 expression were positively correlated with tumoral FOXP3 overexpression. In addition, Beclin-1 expression was significantly associated with a greater number of infiltrated Tregs in gastric adenocarcinoma. Both the positive Beclin-1 expression and positive tumoral FOXP3 expression cases showed significantly better disease-free and overall survival. In addition, the patients with an increased number of infiltrated Tregs (≥ 25/HPF) showed better disease-free and overall survival rates. CONCLUSION: In conclusion, the autophagic function of Beclin-1 in gastric adenocarcinoma cells was associated with an increased number of infiltrated Tregs and tumoral FOXP3 containing tumor suppressor function. Therefore, the favorable effects of Beclin-1 expression in gastric adenocarcinoma is associated with the regulation of Tregs and tumoral FOXP3 expression.

Proteomic Analysis of Primary Colon Cancer and Synchronous Solitary Liver Metastasis.

BACKGROUND/AIM: Colon cancer is prone to distant metastases to other sites and the risk of recurrence is relatively high. Therefore, the identification of liver metastasis-related factors is important for the diagnosis or treatment of colon cancer. The aim of this study was to identify the metastasis-related factors that are differentially expressed in synchronous solitary liver metastasis compared to primary colon cancer. MATERIALS AND METHODS: Tissues of primary colon cancer and associated with liver metastases of five patients were used for mass spectrometry. Identified proteins were validated by western blotting. The in silico analysis was performed using the STRING database and GeneMANIA. RESULTS: We identified 58 differentially expressed proteins (DEPs), including 51 under-expressed and 7 over-expressed proteins among a total of 164 identified proteins. Major hubs of protein-protein networks were ACTC1, PRDX6, TPI1, and ALDH1A1. DEPs were located in the extracellular region and cytoplasm and were involved in the regulation of enzymatic activity. The metabolic process was significantly enriched in biological processes and an involvement in the KEGG pathway. CONCLUSION: These DEPs can potentially be used as biomarkers for the diagnosis of liver metastasis and they may provide a new strategy for developing anti-metastatic liver drugs in colon cancer patients.

Redox-Mediated Mechanism of Chemoresistance in Cancer Cells.

Cellular reactive oxygen species (ROS) status is stabilized by a balance of ROS generation and elimination called redox homeostasis. ROS is increased by activation of endoplasmic reticulum stress, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family members and adenosine triphosphate (ATP) synthesis of mitochondria. Increased ROS is detoxified by superoxide dismutase, catalase, and peroxiredoxins. ROS has a role as a secondary messenger in signal transduction. Cancer cells induce fluctuations of redox homeostasis by variation of ROS regulated machinery, leading to increased tumorigenesis and chemoresistance. Redox-mediated mechanisms of chemoresistance include endoplasmic reticulum stress-mediated autophagy, increased cell cycle progression, and increased conversion to metastasis or cancer stem-like cells. This review discusses changes of the redox state in tumorigenesis and redox-mediated mechanisms involved in tolerance to chemotherapeutic drugs in cancer.

The expression of C-MYC in gastric adenocarcinoma is associated with PD-L1 and FOXP3 expression: C-MYC overexpression is a good prognostic factor.

BACKGROUND: C-MYC appears to initiate and maintain tumorigenesis through modulation of immune regulatory molecules such as PD-L1. The aim of our research was to evaluate the clinical implication of C-MYC expression in gastric adenocarcinoma in relation to the expression of the immune regulatory molecules PD-L1 and FOXP3. METHODS: Tissue samples were acquired from 182 cases of gastric adenocarcinoma that were surgically resected at Kyung Hee University Hospital at Gangdong from 2006 to 2012. Immunohistochemical staining for C-MYC, PD-L1, CD8 and FOXP3 was done. RESULTS: C-MYC overexpression showed a significant correlation with smaller tumor size, lower T category, lower N category, lower recurrence rate, and less lymphatic invasion. And C-MYC overexpression was negatively correlated with PD-L1 expression. The tumoral FOXP3 was positively correlated with C-MYC overexpression and Tregs count. PD-L1 expression was positively correlated with Tregs, CD8 + T cells, and tumor infiltrating lymphocytes (TIL). Tregs count was positively correlated with CD8 + T cells and TIL. CD8 + T cells was positively correlated with TIL. CONCLUSION: We discovered that the immune regulatory effect of C-MYC and PD-L1, and the tumor suppressor function of tumoral FOXP3 had a significant influence on the tumor microenvironment (Tregs, CD8 + T cells, and tumor infiltrating lymphocytes) in a complex manner. The C-MYC overexpression is a good prognostic factor in gastric adenocarcinoma.

Application of MDM2 Fluorescence In Situ Hybridization and Immunohistochemistry in Distinguishing Dedifferentiated Liposarcoma From Other High-grade Sarcomas.

Distinguishing dedifferentiated liposarcoma (DDLPS) from other high-grade spindle and pleomorphic sarcomas is important because of better prognosis in case of DDLPS. MDM2 amplification, a genetic abnormality of well-differentiated liposarcoma, is known to be present not only in DDLPS, but also in some other sarcomas. To differentiate DDLPS, we investigated MDM2 amplification and expression in high-grade spindle sarcomas. Eighty-five cases of nonlipogenic high-grade sarcomas, diagnosed between 2008 and 2011, were investigated. Tissue microarray, immunohistochemistry, and fluorescence in situ hybridization for MDM2 were performed. Forty-one of 85 cases (48.2%) showed MDM2 amplification and expression. Cases of MDM2 amplification were reclassified based on histology, immunophenotype, and clinical data. Thirty-nine of 41 cases, including those originally diagnosed as DDLPS (n=30), undifferentiated pleomorphic sarcoma (n=7), myxofibrosarcoma (n=1), and pleomorphic liposarcoma (n=1) could be reclassified as DDLPS. In addition, MDM2 immunohistochemistry and MDM2 fluorescence in situ hybridization showed an excellent correlation (P<0.001, sensitivity 92.7%, specificity 100%). MDM2 amplification and expression are potentially very useful in distinguishing between DDLPS and other undifferentiated high-grade spindle and pleomorphic sarcomas, even though a few other sarcomas also showed MDM2 amplification and expression.

Efficacy and safety of everolimus and sunitinib in patients with gastroenteropancreatic neuroendocrine tumor.

PURPOSE: Efficacy of targeted agents, such as everolimus and sunitinib, has been demonstrated in prospective trials on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Considering the heterogeneous clinicopathological characteristics of neuroendocrine tumors (NETs), evaluation of treatment outcomes in a real-world setting is necessary. METHODS: Clinical records of 44 patients with GEP-NET who were treated with everolimus or sunitinib between March 2007 and October 2014 were retrospectively reviewed. Considering the distinct characteristics of pancreatic NETs (pNETs) and non-pancreatic gastrointestinal NETs (GI-NETs), efficacy analysis was performed separately. RESULTS: Pancreas was the most common primary site (n = 28, 64%), followed by rectum (n = 10, 23%) and stomach (n = 3, 7%). Sunitinib and everolimus were administered in 27 (61%) and 17 (39%) patients, respectively. In patients with pNET, median progression-free survival (PFS) with everolimus and sunitinib was 16.6 months (95% CI 8.0-25.1) and 8.0 months (95% CI 0.0-17.4), respectively (p = 0.51). Among non-pancreatic GI-NET patients, median PFS with everolimus and sunitinib was 14.7 months (95% CI 2.4-27.0) and 1.7 months (95% CI 0.5-3.0), respectively (p = 0.001). Compared to patients treated with everolimus, tumor grade 3 (30 vs. 0%) and history of prior cytotoxic chemotherapy (70 vs. 50%) were more common in patients treated with sunitinib. CONCLUSIONS: Both everolimus and sunitinib were effective in GEP-NET patients. Outcomes of everolimus therapy in GEP-NETs were consistent with those reported elsewhere. Poor efficacy of sunitinib in non-pancreatic GI-NETs may be attributable to the baseline characteristics associated with poor clinical outcomes.

Superior Cervical Sympathetic Ganglion: Normal Imaging Appearance on 3T-MRI.

OBJECTIVE: To identify superior cervical sympathetic ganglion (SCSG) and describe their characteristic MR appearance using 3T-MRI. MATERIALS AND METHODS: In this prospective study, we recruited 53 consecutive patients without history of head and neck irradiation. Using anatomic location based on literature review, both sides of the neck were evaluated to identify SCSGs in consensus. SCSGs were divided into definite (medial to internal carotid artery [ICA] and lateral to longus capitis muscle [LCM]) and probable SCSGs based on relative location to ICA and LCM. Two readers evaluated signal characteristics including intraganglionic hypointensity of all SCSGs and relative location of probable SCSGs. Interrater and intrarater agreements were quantified using unweighted kappa. RESULTS: Ninety-one neck sites in 53 patients were evaluated after exclusion of 15 neck sites with pathology. Definite SCSGs were identified at 66 (73%) sites, and probable SCSGs were found in 25 (27%). Probable SCSGs were located anterior to LCM in 16 (18%), lateral to ICA in 6 (7%), and posterior to ICA in 3 (3%). Intraganglionic hypointensity was identified in 82 (90%) on contrast-enhanced fat-suppressed T1-weighted images. There was no statistical difference in the relative location between definite and probable SCSGs of the right and left sides with intragnalionic hypointensity on difference pulse sequences. Interrater and intrarater agreements on the location and intraganglionic hypointensity were excellent (κ-value, 0.749-1.000). CONCLUSION: 3T-MRI identified definite SCSGs at 73% of neck sites and varied location of the remaining SCSGs. Intraganglionic hypointensity was a characteristic feature of SCSGs.

Prognosis of Pregnancy-Associated Gastric Cancer: An Age-, Sex-, and Stage-Matched Case-Control Study.

BACKGROUND/AIMS: Pregnancy-associated gastric cancer is a rare condition. This case-control study was performed to identify the clinicopathological features and prognostic factors of pregnancy-associated gastric cancer. METHODS: All consecutive patients who presented to our tertiary referral hospital with pregnancy-associated gastric cancer from 1991 to 2012 were identified. Two age-, sex-, and stagematched controls for each case were also identified from the records. Clinicopathological, gynecological, and oncological outcomes were recorded. Immunohistochemical staining was performed for estrogen receptor, progesterone receptor, epidermal growth factor receptor, human epidermal growth factor receptor, and E-cadherin. Fluorescence in situ hybridization was performed for fibroblast growth factor receptor 2. RESULTS: The median overall survival rates of the pregnancyassociated gastric cancer and control groups were 7.0 months and 15.0 months, respectively (p=0.189). Poor prognostic factors included advanced stage and tumor location in the corpus or the entire stomach but not pregnancy status or loss of E-cadherin. Pregnancy-associated gastric cancer was associated with a longer time from diagnosis to treatment (21 days vs 7 days, p=0.021). The two groups did not differ in the expression of the receptors or E-cadherin. CONCLUSIONS: The dismal prognosis of pregnancy-associated gastric cancer may related to the tumor stage and location rather than to pregnancy itself.

Primitive Neuroectodermal Tumor of the Stomach: A Case Report.

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is a highly aggressive small round cell tumor that mainly occurs in the bone or soft tissue of children or young adults but is extremely rare in the stomach. A 55-year-old man presented with melena and anemia. On endoscopy, an ulcerofungating mass was observed in the high body and total gastrectomy was performed. Histologically, the mass consisted of small round cells with scanty cytoplasm and inconspicuous nucleoli. They often formed perivascular pseudorosettes and multinucleated giant cells were frequently observed. The tumor cells strongly expressed CD99, FLI1, and chromogranin and weakly expressed synaptophysin and CD56. EWS-FLI1 fusion transcript was confirmed by reverse transcription-polymerase chain reaction. ES/PNET is frequently misdiagnosed because of its similarity with small cell carcinoma. Although gastric ES/PNET is very rare, it should be included in differential diagnoses of small round cell tumor in the stomach.