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

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

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DNA extraction from paraffin embedded colorectal carcinoma samples: A comparison study of manual vs automated methods,using four commercially kits

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World Journal of Clinical Oncology 2019年第9期10卷 307-317页

作者： Zsolt Kovacs ioan jung Erzsebet Csernak Zoltan Szentirmay Laura Banias Genoveva Rigmanyi Simona Gurzu Department of Pathology University of MedicinePharmacySciences and TechnologyTargu-Mures 530149Romania Research Center(CCAMF) University of MedicinePharmacySciences and TechnologyTargu-Mures 540139Romania

BACKGROUND Nucleic acid isolation from formalin-fixed, paraffin-embedded tissue(FFPET)samples is a daily routine in molecular pathology laboratories, but extraction from FFPET is not always easily achieved. Choosing the right extraction technique is key for further *** To compare the performance of four commercially available kits used for DNA extraction in routine *** DNA isolation was performed on 46 randomly selected formalin-fixed, paraffinembedded(FFPE) colorectal adenocarcinoma(CRC) surgical specimens. Four commercially available extraction kits were used: two for manual DNA extraction(the Pure Link Genomic DNA Mini Kit from Invitrogen and the High Pure FFPE DNA Isolation Kit from Roche) and two for automated DNA extraction(the i Prep Genomic DNA Kit from Invitrogen and the Magna Pure LC DNA Isolation Kit from Roche). The DNA concentration and quality(odds ratio) among the four systems were compared. The results were correlated with the clinicopathological aspects of CRC cases: age, gender, localization, macro-and microscopic features,lymph node metastases, and the lymph node *** The highest DNA concentration was obtained using the manual kits: 157.24 ±62.99 ng/μL for the Pure Link Genomic DNA Mini Kit and 86.64 ng/μL± 43.84 for the High Pure FFPE DNA Isolation Kit(P < 0.0001). Lower concentrations were obtained with automated systems: 20.39 ± 21.19 ng/μL for the Magna Pure LC DNA Isolation Kit and 8.722 ± 6.408 ng/μL for the i Prep Genomic DNA Kit,with differences between the systems used(P < 0.0001). The comparison between age, gender, tumor localization, pT or pN stage and the lymph node ratio indicated no statistically significant difference in DNA concentration using any of the nucleic acid isolation kits. DNA concentration was influenced by the macroscopic features and grade of differentiation. A higher DNA concentration was obtained for well-differentiated polypoid colorectal adenocarcinomas(CRCs), compared with undif

关键词： DNA isolation Colorectal cancer Paraffin-embedded PureLink Genomic DNA Mini Kit High Pure FFPE DNA Isolation Kit iPrep Genomic DNA Kit MagnaPure LC DNA Isolation Kit

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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

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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

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Mixed adenoneuroendocrine carcinoma of gastrointestinal tract: Report of two cases

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World Journal of Gastroenterology 2015年第4期21卷 1329-1333页

作者： Simona Gurzu Zoltan Kadar Tivadar Bara Tivadar Jr. Bara Adrian Tamasi Leonard Azamfirei ioan jung Department of Pathology University of Medicine and Pharmacy540139 Tirgu MuresRomania Department of Surgery University of Medicine and Pharmacy 540139 Tirgu Mures Romania Intensive Care Unit University of Medicine and Pharmacy540139 Tirgu MuresRomania

Mixed adenoneuroendocrine carcinoma(MANEC) is a rare tumor of the gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendocrine differentiation, each component representing at least 30% of the tumor. To date, only seven cases have been reported in the cecum, and less than 40 in the stomach. Our first case was diagnosed in a 74-years-old female as a polypoid lesion of the cecum with direct invasion in the transverse colon, without lymph node metastases. The second case was diagnosed in the stomach of a 46-years-old male as a polypoid tumor of the antral region that invaded the pancreas and presented metastases in 22 regional lymph nodes. The metastatic tissue was represented by the glandular component. In both cases, the tumor consisted of a moderately-differentiated tubular adenocarcinoma(with mucinous component in Case 1) intermingled with neuroendocrine carcinoma. Ki67 index was lower than 20% in Case 1, respectively higher than 20% in Case 2. The neuroendocrine component was marked by synaptophysin and neuron specific enolase, being negative for Keratins 7/20. The neuroendocrine component represented 60% in Case 1, and 40% in Case 2, respectively. The glandular components were marked by carcinoembryonic antigen, maspin and keratin 20/7(Case 1/2). Both cases were proved to be microsatellite stable. Independently by the localization and tumor stage, MANECs appear to be highly malignant tumors, with high risk for distant metastases. The aggressiveness seems to depend on the endocrine component, independent of its proportion. The neuroendocrine component could be a dedifferentiated adenocarcinoma with a neuroendocrine phenotype.

关键词： Mixed adenoneuroendocrine carcinoma Composite tumo

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Subcellular expression of maspin – from normal tissue to tumor cells

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World Journal of Meta-Analysis 2019年第4期7卷 142-155页

作者： Laura Banias ioan jung Simona Gurzu Department of Pathology University of MedicinePharmacy Sciences and Technology of Tirgu-Mures Department of Pathology Clinical County Emergency Hospital

Maspin or SerpinB5, a member of the serine protease inhibitor family, was shown to function as a tumor suppressor, especially in carcinomas. It seems to inhibit invasion, tumor cells motility and angiogenesis, and promotes apoptosis. Maspin can also induce epigenetic changes such as cytosine methylation, de-acetylation,chromatin condensation, and histone modulation. In this review, a comprehensive synthesis of the literature was done to present maspin function from normal tissues to pathologic conditions. Data was sourced from MEDLINE and PubMed. Study eligibility criteria included: Published in English, between 1994 and 2019, specific to humans, and with full-text availability. Most of the 118 studies included in the present review focused on maspin immunostaining and m RNA levels. It was shown that maspin function is organ-related and depends on its subcellular localization. In malignant tumors, it might be downregulated or negative(e.g., carcinoma of prostate, stomach, and breast) or upregulated(e.g.,colorectal and pancreatic tumors). Its subcellular localization(nuclear vs cytoplasm), which can be proved using immunohistochemical methods, was shown to influence both tumor behavior and response to *** the number of maspin-related papers increased, the exact role of this protein remains unknown, and its interpretation should be done with extremely high caution.

关键词： Maspin SerpinB5 Prognosis Cancer Tumor suppressor

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