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Primary gastric choriocarcinoma-a rare and aggressive tumor with multilineage differentiation: A case report

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World Journal of Clinical Cases 2019年第14期7卷 1837-1843页

作者： Simona Gurzu Constantin Copotoiu Alexandra Tugui Cedric Kwizera Rita Szodorai ioan jung Department of Pathology University of MedicinePharmacySciences and TechnologyTargu Mures 530149Romania Research Center (CCAMF) University of MedicinePharmacySciences and TechnologyTargu Mures 540139Romania Department of Surgery University of MedicinePharmacySciences and TechnologyTargu Mures 530149Romania

BACKGROUND Primary choriocarcinoma of the stomach (PCCS) is a rare tumor, with fewer than 60 cases published in the English-language literature up to December 2018. In this paper, we present the complex immunoprofile of one PCCS and a hypothesis regarding its histogenesis. CASE SUMMARY A 66-year-old previously healthy male underwent an emergency palliative gastrectomy for a gastric obstructive tumor. The histologic examination and immunoprofile of tumor cells showed a mixed tumor that consisted of choriocarcinoma (90%) and moderate differentiated adenocarcinoma (10%), with hepatic metastases (Stage pT2NxM1L1V1R0) and microsatelite stable status. The patient died one month after surgery. The tumor cells showed focal positivity for CDX2 (adenocarcinoma component), HCG (choriocarcinoma) and CD138 (plasmacytoid carcinoma component) and were negative for HER-2,α- fetoprotein, VEGF, maspin and markers of epithelial-mesenchymal transition. The gastric mucosa cells displayed positivity for CDX2, Hepar A and CD138. The complex immunoprofile and literature data synthesis prove that the gastric mucosa cells can present a multilineage differentiation. CONCLUSION PCCS should be considered as an aggressive variant of microsatellite stable gastric adenocarcinoma of an epithelial type, and not a germ cell tumor.

关键词： Choriocarcinoma Stomach Gastrointestinal Immunohistochemistry Maspin Case report

Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer

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World Journal of Gastroenterology 2016年第30期22卷 6764-6775页

作者： Simona Gurzu Camelia Silveanu Annamaria Fetyko Vlad Butiurca Zsolt Kovacs ioan jung Department of Pathology University of Medicine and Pharmacy of Tirgu-Mures Department of Surgery University of Medicine and Pharmacy of Tirgu-Mures Departments of Genetics and Biochemistry University of Medicine and Pharmacy of Tirgu-Mures

Epithelial-to-mesenchymal transition(EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer(CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical(IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapyor radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMTangiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.

关键词： Angiogenesis Colorectal cancer Budding Epithelial-mesenchymal transition Chemoresistance

Interaction of arylsulfatases A and B with maspin: A possible explanation for dysregulation of tumor cell metabolism and invasive potential of colorectal cancer

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World Journal of Clinical Cases 2019年第23期7卷 3990-4003页

作者： Zsolt Kovacs ioan jung Krisztina Szalman Laura Banias Tivadar Jr Bara Simona Gurzu Department of Pathology University of MedicinePharmacySciences and Technology“George Emil Palade”Targu Mures 530149Romania Department of Internal Medicine University of MedicinePharmacySciences and Technology“George Emil Palade”Targu Mures 530149Romania Department of Surgery University of MedicinePharmacyScience and Technology“George Emil Palade”Tirgu Mures 530149Romania Research Center(CCAMF) University of MedicinePharmacySciences and TechnologyTargu Mures 540139Romania

BACKGROUND Although it has been shown that arylsulfatases are lost in colorectal cancer(CRC)cell lines,their exact role in the carcinogenesis and behavior of this cancer was not *** data about the correlation between serum and immunohistochemical(IHC)level of arylsulfatases(ARSA,ARSB)in patients with CRC were published *** To evaluate the possible prognostic value of ARSA and/or ARSB in CRC,at circulating and protein *** The present study included 45 consecutive patients who were prospectively diagnosed with *** IHC stains(protein expression)ARSA,ARSB and maspin expression were *** these markers,cytoplasmic expression was taken into *** gene expression study,circulating mRNA was isolated from all patients,before surgery.A group of 45 healthy patients without inflammatory or tumor pathologies was used as control *** transcription and Taqman Gene Expression Array were used for ARSB gene *** The preoperative circulating RNA level of the ARSB gene was significantly decreased in patients with CRC(RQ1).A more significant decrease(RQ<0.5)occurred in ulcero-infiltrative maspinpositive adenocarcinomas,with a higher degree of tumor budding,diagnosed in locally advanced stages(pT3/4).ARSA/maspin immunopositivity indicated a higher risk for lymph node metastasis,while triple positivity for maspin/ARSA/ARSB and ARSB gene expression level<0.5 were indicators of CRC aggressive behavior,independent of lymph node *** The significant independent negative prognostic factors of CRC are the ulceroinfiltrative aspect,high budding degree,triple positivity for maspin,ARSA and ARSB,and low ARSB gene expression.

关键词： Arylsulfatase Maspin Colorectal cancer ARSB gene Blood Tissue

Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update

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World Journal of Clinical Cases 2015年第5期3卷 393-404页

作者： Simona Gurzu Sabin Turdean Attila Kovecsi Anca Otilia Contac ioan jung Department of Pathology University of Medicine and Pharmacy of Tirgu-Mures540139 Tirgu MuresRomania

Epithelial-to-mesenchymal transition(EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis(type 1 EMT), wound healing and/or fibrosis(type 2 EMT) and malignant tumors(type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition(MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelialto-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail.

关键词： Gastrointestinal stromal tumor Carcinoma Gastrointestinal cancer Hepatic cancer Sarcoma

Paradoxical expression pattern of the epithelial mesenchymal transition-related biomarkers CD44, SLUG, N-cadherin and VSIG1/Glycoprotein A34 in gastrointestinal stromal tumors

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World Journal of Gastrointestinal Oncology 2017年第11期9卷 436-443页

作者： Attila Kovecsi Simona Gurzu Zoltan Szentirmay Zsolt Kovacs Tivadar Jr Bara ioan jung Department of Pathology University of Medicine and Pharmacy Research Center University of Medicine and Pharmacy Department of Pathology National Institute of Oncology Department of Biochemistry University of Medicine and Pharmacy Department of Surgery University of Medicine and Pharmacy

AIM To evaluate the immunohistochemical(IHC) expression of five biomarkers, commonly involved in epithelial mesenchymal/mesenchymal epithelial transition(EMT/MET), in gastrointestinal stromal tumors(GISTs). METHODS In 80 consecutive GISTs the IHC examinations were performed using the EMT-related antibodies E-cadherin,N-cadherin, SLUG, V-set and immunoglobulin domain containing 1(VSIG1) and CD44. RESULTS The positivity rate was 88.75% for SLUG, 83.75% for VSIG1, 36.25% for CD44 and 10% for N-cadherin. No correlation was noted between the examined markers and clinicopathological parameters. Nuclear positivity for SLUG and VSIG1 was observed in all cases with distant metastasis. The extra-gastrointestinal stromal tumors(e-GISTs) expressed nuclear positivity for VSIG1 and SLUG, with infrequent positivity for N-cadherin and CD44. The low overall survival was mainly dependent on VSIG1 negativity(P = 0.01) and nuclear positivity for SLUG and/or CD44. CONCLUSION GIST aggressivity may be induced by nuclear upregulation of SLUG and loss or cytoplasm-to-nuclear translocation of VSIG1. SLUG and VSIG1 may act as activated nuclear transcription factors. The CD44, but not N-cadherin, might also have an independent prognostic value in these tumors. The role of the EMT/MET-related transcription factors in the evolution of GISTs, should be revisited with a larger dataset. This is the first study exploring the IHC pattern of VSIG1 in GISTs.

关键词： SLUG Glycoprotein A34 N-cadherin V-set and immunoglobulin domain containing gastrointestinal stromal tumors

Tuberculosis terminal ileitis:A forgotten entity mimicking Crohn's disease

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World Journal of Clinical Cases 2016年第9期4卷 273-280页

作者： Simona Gurzu Calin Molnar Anca Otilia Contac Annamaria Fetyko ioan jung Department of Pathology University of Medicine and Pharmacy

Intestinal tuberculosis(TB) is an uncommon lesion for which differential diagnosis can be difficult. We present a case of a 53-year-old male and a systematic review of the literature, from clinical symptoms to differential diagnosis, unusual complications and therapy. The patient was admitted to the hospital with signs of acute abdomen as a result of a perforated terminal ileitis. Based on the skip lesions of the terminal ileum and cecum, Crohn's disease(CD) was clinically suspected. An emergency laparotomy and right colectomy with terminal ileum resection was performed and systematic antibiotherapy was prescribed. The patient's status deteriorated and he died 4 d after the surgical intervention. At the autopsy, TB ileotyphlitis was discovered. The clinical criteria of the differential diagnosis between intestinal TB and CD are not very well established. Despite the large amount of published articles on this subject, only 50 papers present new data regarding intestinal TB. Based on these studies and our experience, we present an update focused on the differential diagnosis and therapy of intestinal TB. We highlight the importance of considering intestinal TB as a differential diagnosis for inflammatory bowel disease. Despite the modern techniques of diagnosis and therapy, the fulminant evolution of TB can still lead to a patient's death.

关键词： Ileitis Autopsy Ileotyphlitis Crohn’s disease Tuberculosis Inflammatory bowel disease Ischemic colitis

Single skip metastasis in sentinel lymph node: In an early gastric cancer

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World Journal of Gastroenterology 2015年第33期21卷 9803-9807页

作者： Tivadar Jr Bara Simona Gurzu ioan jung Zoltan Kadar Haruhiko Sugimura Tivadar Bara Department of Surgery University of Medicine and Pharmacy Department of Pathology University of Medicine and Pharmacy Department of Tumor Pathology Hamamatsu UniversitySchool of Medicine

Lymph node status is considered a key prognostic and predictive factor in patients with gastric cancer(GC).Although there is a practical approach to the intraoperative detection of sentinel lymph nodes(SLNs),such a procedure is not included in the European surgical *** this report,we present a practical approach to SLN mapping in a representative case with early gastric cancer(EGC).A 74-year-old female was hospitalized with an endoscopically observed,superficially ulcerated tumor located in the antral *** gastrectomy with D2 lymphadenectomy and SLN mapping was performed by injecting methylene blue dye into the peritumoral submucosal *** incidentally detected blue-stained lymph node located along the middle colic artery was also *** was detected 40 min after injection of the methylene *** examination showed a p T1b-staged well-differentiated HER-2-negative *** of the 41 LNs located at the first,third,and fifth station of the regional LN compartments were found to be free of tumor *** only lymph node with metastasis was located along the middle colicartery and was considered a non-regional lymph *** incidentally identified skip metastasis indicated stage Ⅳ GC.A classic chemotherapy regimen was given,and no recurrences were observed six months after *** this representative case,low-cost SLN mapping,with a longer intraoperative waiting time,totally changed the stage of the tumor in a patient with EGC.

关键词： Early gastric cancer Sentinel lymph node Lymph nod

Cystic jejunal duplication with Heinrich's type Ⅰ ectopic pancreas, incidentally discovered in a patient with pancreatic tail neoplasm

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World Journal of Clinical Cases 2016年第9期4卷 281-284页

作者： Simona Gurzu Tivadar Bara Jr Tivadar Bara Annamaria Fetyko ioan jung Department of Pathology University of Medicine and Pharmacy Department of Surgery University of Medicine and Pharmacy

The aim of this study was to present a case of enteric duplication cyst and criteria for a proper differential diagnosis. A 51-year-old male was hospitalized for pancreatic tail neoplasm and distal pancreatectomy with splenectomy was performed. During surgery, a jejunal cystic lesion was incidentally detected and jejunectomy was performed. Microscopically, the cyst was observed to be covered by Keratin 7/Keratin 20 positive intestinal type epithelium and the muscularis layer was shared by the cyst and adjacent jejunum, without a cleavage plane between the cyst wall and jejunal muscularis propria. In the deep muscularis propria, a Heinrich's type Ⅰ ectopic pancreas was also noted. In the pancreatic tail, a low grade intraepithelial lesion(panIN-1a) was diagnosed. This case highlights the necessity for a correct differential diagnosis of such rare lesions. Roughly 30 cases of jejunal duplication cysts have been reported to date in the PubM ed database.

关键词： Intestine Duplication Embryogenesis Ectopic pancreas

Angiogenesis of hepatocellular carcinoma: An immunohistochemistry study

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World Journal of Hepatology 2019年第3期11卷 294-304页

作者： Decebal Fodor ioan jung Sabin Turdean Catalin Satala Simona Gurzu Department of Pathology University of MedicinePharmacy Sciences and Technology Research Center (CCAMF) University of Medicine Pharmacy Sciences and Technology

BACKGROUND Although hepatocellular carcinoma(HCC) is one of the most vascular solid tumors, antiangiogenic therapy has not induced the expected *** To uncover immunohistochemical(IHC) aspects of angiogenesis in *** A retrospective cohort study was performed and 50 cases of HCC were randomly selected. The angiogenesis particularities were evaluated based on the IHC markers Cyclooxygenase-2(COX-2), vascular endothelial growth factor(VEGF) A and the endothelial area(EA) was counted using the antibodies CD31 and *** The angiogenic phenotype evaluated with VEGF-A was more expressed in small tumors without vascular invasion(pT1), whereas COX-2 was rather expressed in dedifferentiated tumors developed in non-cirrhotic liver. The CD31-related EA value decreased in parallel with increasing COX-2 intensity but was higher in HCC cases developed in patients with cirrhosis. The CD105-related EA was higher in tumors developed in patients without associated *** In patients with HCC developed in cirrhosis, the newly formed vessels are rather immature and their genesis is mediated via VEGF. In patients with non-cirrhotic liver, COX-2 intensity and number of mature neoformed vessels increases in parallel with HCC dedifferentiation.

关键词： Hepatocellular carcinoma Angiogenesis Endothelial area Antiangiogenic therapy