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1.
J Periodontal Implant Sci ; 50(3): 197-206, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32617184

RESUMEN

PURPOSE: The aim of this study was to determine the impact of different compressive forces on deproteinized bovine bone mineral (DBBM) particles covered by native bilayer collagen membrane (NBCM) during alveolar ridge preservation (ARP) in the molar area, and to identify any histomorphometric and clinical differences according to the compressive force applied. METHODS: Sockets were filled with DBBM after tooth extraction, and different compressive forces (30 N and 5 N, respectively) were applied to the graft material in the test (30 N) and control (5 N) groups. The DBBM in both groups was covered with NBCM in a double-layered fashion. A crossed horizontal mattress suture (hidden X) was then made. A core biopsy was performed using a trephine bur without flap elevation at the implant placement site for histomorphometric evaluations after 4 months. The change of the marginal bone level was measured using radiography. RESULTS: Twelve patients completed the study. The histomorphometric analysis demonstrated that the mean ratios of the areas of new bone, residual graft material, and soft tissue and the implant stability quotient did not differ significantly between the groups (P>0.05). However, the mean size of the residual graft material showed a significant intergroup difference (P<0.05). CONCLUSIONS: The application of 2 compressive forces (5 N, 30 N) on particulate DBBM grafts during open-healing ARP in the posterior area led to comparable new bone formation, implant feasibility and peri-implant bone level.

2.
J Pathol Transl Med ; 54(3): 228-236, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32460476

RESUMEN

BACKGROUND: Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis. METHODS: Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses ('not-NASH,' 'borderline,' and 'NASH') of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system. RESULTS: Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52-0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH. CONCLUSIONS: A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

3.
J Pathol Transl Med ; 50(3): 190-6, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27086596

RESUMEN

BACKGROUND: The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement. METHODS: Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson's trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics. RESULTS: Kappa values of the first review ranged from 0.0091-0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis. CONCLUSIONS: More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD.

5.
Pathol Int ; 65(6): 324-8, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25808197

RESUMEN

The clear cell/lipid-rich change has been described in neuroendocine tumors in several organs, but rarely observed in the appendix. In this study, we describe the morphologic, immunohistochemical features of incidentally discovered appendiceal carcinoids entirely represented by clear cells in a 22-year-old man and a 52-year-old woman. Ultrastructual examination demonstrated abundant lipid droplets and dense core granules. The mechanism leading to lipid accumulation in the cytoplasm has not been discovered, but degenerative processes following recurrent inflammatory change might be considered. This uncommon variant of appendiceal classic carcinoid tumors may bear a superficial resemblance to goblet carcinoid and/or appendiceal metastases from clear cell carcinoma. Awareness of clear cell carcinoid of the appendix will prevent incorrect diagnosis and unnecessary aggressive management.


Asunto(s)
Neoplasias del Apéndice/patología , Biomarcadores de Tumor/metabolismo , Tumor Carcinoide/patología , Neoplasias del Apéndice/metabolismo , Apéndice/metabolismo , Apéndice/patología , Tumor Carcinoide/metabolismo , Citoplasma/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
6.
Ann Coloproctol ; 30(3): 141-6, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24999466

RESUMEN

Distant metastasis of a colon carcinoma in situ has not yet been reported. We experienced a case of a sigmoid colon carcinoma in situ with common hepatic lymph node metastasis. After the first operation, we diagnosed dual intramucosal adenocarcinomas of the sigmoid colon without any regional lymph node metastasis. After the second operation, a metastatic adenocarcinoma was found in the common hepatic lymph nodes. We suggest that metastasis in cases of a colonic carcinoma in situ is rare, but possible. The parallel progression model of tumors can explain this early metastasis.

7.
Gut Liver ; 8(1): 79-87, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24516705

RESUMEN

BACKGROUND/AIMS: The current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival. METHODS: We analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs. RESULTS: p53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant. CONCLUSIONS: p53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Adulto , Anciano , Carcinoma Hepatocelular/cirugía , Supervivencia sin Enfermedad , Femenino , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-met/metabolismo , Receptor IGF Tipo 1/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Serina-Treonina Quinasas TOR/metabolismo , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/metabolismo
8.
J Korean Med Sci ; 28(12): 1835-8, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24339718

RESUMEN

Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and α-smooth muscle actin (α-SMA) were conducted with control group. The immunohistochemical stains for CD31 and α-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias del Colon/tratamiento farmacológico , Cirrosis Hepática/diagnóstico , Compuestos Organoplatinos/administración & dosificación , Esplenomegalia/diagnóstico , Actinas/metabolismo , Camptotecina/uso terapéutico , Quimioterapia Adyuvante , Fluorouracilo/uso terapéutico , Humanos , Hipertensión Portal/etiología , Inmunohistoquímica , Leucovorina/uso terapéutico , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Esplenomegalia/etiología , Trombocitopenia/etiología , Tomografía Computarizada por Rayos X
9.
Ann Coloproctol ; 29(5): 192-7, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24278857

RESUMEN

PURPOSE: The aim of this study is to evaluate the efficacy and the safety of additional 4-week chemotherapy with capecitabine during the resting periods after a 6-week neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer. METHODS: Radiotherapy was delivered to the whole pelvis at a total dose of 50.4 Gy for 6 weeks. Oral capecitabine was administered at a dose of 825 mg/m(2) twice daily for 10 weeks. Surgery was performed 2-4 weeks following the completion of chemotherapy. RESULTS: Between January 2010 and September 2011, 44 patients were enrolled. Forty-three patients underwent surgery, and 41 patients completed the scheduled treatment. Pathologic complete remission (pCR) was noted in 9 patients (20.9%). T down-staging and N down-staging were observed in 32 patients (74.4%) and 33 patients (76.7%), respectively. Grade 3 to 5 toxicity was noted in 5 patients (11.4%). The pCR rate was similar with the pCR rates obtained after conventional NCRT at our institute and at other institutes. CONCLUSION: This study showed that additional 4-week chemotherapy with capecitabine during the resting periods after 6-week NCRT was safe, but it was no more effective than conventional NCRT.

10.
Korean J Pathol ; 47(3): 227-37, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23837015

RESUMEN

BACKGROUND: There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients. METHODS: We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report. RESULTS: Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms. CONCLUSIONS: A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.

11.
Korean J Hepatobiliary Pancreat Surg ; 17(1): 38-41, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26155211

RESUMEN

Adenosquamous carcinoma (ASC) is a rare tumor of the liver, which carries a poor prognosis. It has been reported mostly in the form of case studies. Recently, we experienced a case of primary ASC of the liver that has been preoperatively considered as cholangiocelluar carcinoma of the liver. Microscopically, the tumor was composed of adenocarcinoma, squamous cell carcinoma, as well as transitional area, including the transformation of adenocarcinoma to squamous cell carcinoma. The patient remained well with no evidence of post-resection complication or recurrence for 15 month.

12.
Cancer Res Treat ; 44(3): 157-65, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23091441

RESUMEN

PURPOSE: As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea. MATERIALS AND METHODS: We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters. RESULTS: Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET. CONCLUSION: The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

13.
J Korean Soc Coloproctol ; 27(5): 270-4, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22102979

RESUMEN

A primary leiomyosarcoma of the kidney is a rare, but highly aggressive, neoplasm, accounting for only 0.1% of all invasive renal tumors. Local or systemic recurrence is common, but a leiomyosarcoma is difficult to diagnose preoperatively. We recently encountered an interesting case of an unusual recurrence of a renal leiomyosarcoma. A 57-year-old woman visited our hospital complaining of lower abdominal pain. Four years previously, she had undergone a left nephrectomy. She had a primary leiomyosarcoma of the kidney that had been misdiagnosed as a renal cell carcinoma. Colonoscopy revealed the presence of a lesion similar to a submucosal tumor in the descending colon. Postoperative pathologic examination confirmed that the mass was a recurrent leiomyosarcoma. We report this unusual case and present a review of the literature.

14.
Gut Liver ; 5(2): 171-80, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21814597

RESUMEN

BACKGROUND/AIMS: The diagnosis of gastrointestinal stromal tumors (GIST) relies on the demonstration of KIT expression, but KIT expression is absent or reduced in approximately 15% of GIST. METHODS: Eighty-one GISTs were diagnosed between January 1998 and December 2007 at the Department of Pathology at both Chungnam National University Hospital and Eulji University Hospital, Daejeon. Medical history, patient follow-up, and radiographic data were collected if available in the medical records. To determine diagnostic and prognostic markers for GISTs focused on PDGFRA mutation and clinicopathologic features, we analyzed 81 GIST cases for KIT, PDGFRA, DOG1, and p16 expression and for mutation of PDGFRA genes. RESULTS: Among 81 GIST cases, 20 high risk cases (24.7%) were recurred or metastasized. Immunohistochemically, KIT was positive in 76 (93.8%), PDGFRA in 75 (92.7%), and DOG1 in 77 (95.1%). With a cutoff value of 50%, p16 expression was positive in 26 cases were positive (32.1%). A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p<0.05). Four cases showed a missense mutation in exon 12 of PDGFRA gene, three of these were of epithelioid GISTs. Two cases showed a silent mutation in exon 18 of PDGFRA. CONCLUSIONS: These results indicate that the expression of DOG1 and PDGFRA is observed in a majority of GIST cases. Expression of p16 and negative DOG1 expression is predictive for development of recurrence and/or metastasis. Even though mutation of the PDGFRA gene is frequently seen in epithelioid GISTs, a clinicopathologic correlation was not demonstrated.

15.
World J Gastroenterol ; 17(21): 2602-10, 2011 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-21677827

RESUMEN

The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important, but the diagnostic criteria, terminology, and grading system are not the same in the East and West. A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists, but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion. Although the Vienna classification was introduced to reduce diagnostic discrepancies, it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions. Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine. Japan is geographically close to Korea, and academic exchanges are active. Additionally, Korean doctors are familiar with Western style medical terminology. As a result, the terminology, definitions, and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea. To solve this problem, the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis: (1) a diagnosis of carcinoma is based on invasion; (2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching, budding, or marked glandular crowding; (3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts, the lesion is considered high grade dysplasia; (4) if severe cytologic atypia is present, careful inspection for invasive foci is necessary, because the risk for invasion is very high; and (5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern, papillae, ridges, vesicular nuclei, high nuclear/cytoplasmic ratio, loss of nuclear polarity, thick and irregular nuclear membrane, and nucleoli.


Asunto(s)
Mucosa Gástrica/patología , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Conferencias de Consenso como Asunto , Humanos , Patología Clínica/métodos , República de Corea , Recursos Humanos
16.
Mod Pathol ; 24(6): 866-75, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21358619

RESUMEN

Pathological diagnosis of gastrointestinal stromal tumors (GISTs) is based on histological findings and immunohistochemical demonstration of the KIT protein. KIT-negative GISTs account for ∼5% of cases and cause diagnostic difficulties. In the era of imatinib therapy, a correct diagnosis of GISTs is important for therapeutic reasons regardless of KIT expression. Recently, DOG1 has been introduced as an important diagnostic marker with high sensitivity and specificity. In this study, immunohistochemical staining for DOG1 and protein kinase C-θ (PKC-θ) in whole tissue sections, and mutation analyses for KIT and PDGFRA were performed in 26 KIT-negative GISTs. Tissue microarrays of 112 KIT-positive GISTs were used as controls. Overall, 25 KIT-negative GISTs were located in the stomach, and 1 in the rectum. The histological subtype was spindle in 12, epithelioid in 11, and mixed in 3 cases. The expression of DOG1 and PKC-θ was positive in 24 (92%) and in 25 cases (96%), respectively. All 26 KIT-negative GISTs expressed either DOG1 or PKC-θ, and 23 cases (89%) were positive for both makers. PKC-θ was positive in two cases (8%), which lacked both KIT and DOG1 expressions. Mutation analysis showed PDGFRA exon 18 mutation in 15 cases (58%) and KIT exon 11 mutation in 1 case (4%), whereas the remaining 10 cases (39%) were wild type for both KIT and PDGFRA. The expression of DOG1 and PKC-θ showed no significant difference in KIT-negative and KIT-positive GISTs (P=1.000 and P=0.167, respectively). Our findings suggest that both DOG1 and PKC-θ can be used in the diagnosis of KIT-negative GISTs and they show positive staining even in KIT-negative tumors, which are wild type for KIT and PDGFRA on mutation analysis.


Asunto(s)
Tumores del Estroma Gastrointestinal/diagnóstico , Proteínas de la Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína Quinasa C/metabolismo , Neoplasias Gástricas/diagnóstico , Adulto , Anciano , Anoctamina-1 , Biomarcadores de Tumor/metabolismo , Canales de Cloruro , Análisis Mutacional de ADN , Femenino , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/metabolismo , Humanos , Inmunohistoquímica , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Proteína Quinasa C/genética , Proteína Quinasa C-theta , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Análisis de Matrices Tisulares , Adulto Joven
17.
Histopathology ; 56(6): 694-701, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20546334

RESUMEN

AIMS: Heat shock proteins (HSP) are up-regulated under conditions of increased stress, including cancer. Recently, HSP90 has been shown to be crucial to the expression and activation of the KIT oncoprotein. The aim was to explore the role of HSP90 expression as a prognostic marker and therapeutic target in gastrointestinal stromal tumours (GISTs) and other mesenchymal tumours. METHODS AND RESULTS: The expression of HSP90 was evaluated by immunohistochemistry in 92 GISTs, 47 mesenteric fibromatoses, six schwannomas, leiomyomas, melanomas, malignant peripheral nerve sheath tumours and leiomyosarcomas. Western blotting was performed in 22 selected cases. HSP90 overexpression was found in 33.7% of GISTs and was correlated with non-gastric location, mixed histological subtype, high mitotic index, high risk grades, and specific mutation genotypes. In mesenchymal tumours, HSP90 overexpression was found in 66.7% of malignant peripheral nerve sheath tumours, 83.3% of leiomyosarcomas, and 100% of melanomas. HSP90 expression by Western blotting correlated with the results of immunohistochemistry. The Cox proportional hazards model showed that HSP90 expression is an independent predictor of recurrence in GISTs (P = 0.003). CONCLUSIONS: Overexpression of HSP90 is predictive of adverse behaviour in GISTs and may provide a therapeutic solution to the challenge of imatinib-resistant GISTs and other mesenchymal sarcomas.


Asunto(s)
Tumores del Estroma Gastrointestinal/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Anciano , Femenino , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Humanos , Inmunohistoquímica , Masculino , Melanoma/genética , Melanoma/patología , Persona de Mediana Edad , Neoplasias de Tejido Muscular/genética , Neoplasias de Tejido Muscular/patología , Neoplasias de la Vaina del Nervio/genética , Neoplasias de la Vaina del Nervio/patología , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-kit/genética
18.
J Korean Med Sci ; 25(6): 853-62, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20514305

RESUMEN

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.


Asunto(s)
Tumores del Estroma Gastrointestinal/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antígenos CD34/metabolismo , Femenino , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Mitosis , Invasividad Neoplásica , Pronóstico , República de Corea/epidemiología , Factores de Riesgo , Proteínas S100/metabolismo , Factores Sexuales , Análisis de Supervivencia
19.
Pathology ; 42(1): 54-7, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20025481

RESUMEN

AIMS: Wilms' tumour-1 (WT-1) encodes a transcription factor originally identified as a tumour suppressor gene, whose mutations are responsible for tumorigenesis of Wilms' tumour. The overexpression of WT-1 has been demonstrated in variable tumours. In this study, WT-1 immunoreactivity was explored in 97 gastrointestinal stromal tumours (GISTs). METHODS: The expression of WT-1 was compared with other immunohistochemical markers of GIST and the association with clinicopathological features was also evaluated. For comparison, six melanomas and 71 soft tissue tumours were used. RESULTS: All 97 GISTs were positive for WT-1 and the staining intensity was strong in 59 (60.8%), moderate in 28 (28.9%) and weak in 10 cases (10.3%). Cytoplasmic staining with moderate to strong intensity was more frequent in GISTs positive for platelet-derived growth factor receptor-alpha (PDGFRA) (p = 0.04). However, WT-1 immunoreactivity was not related to the clinicopathological variables, including tumour location, histological subtype, risk of progression and recurrence status. Leiomyosarcomas, schwannomas, malignant peripheral nerve sheath tumours (MPNSTs) and melanomas showed cytoplasmic staining, whereas leiomyomas and mesenteric fibromatoses were totally negative for WT-1. CONCLUSIONS: Although the biological roles of WT-1 in GIST are still unknown, our findings might provide a rationale for immunotherapy targeting WT-1 and a therapeutic solution to the challenge of imatinib-resistant GISTs.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Tumores del Estroma Gastrointestinal/metabolismo , Neoplasias de los Tejidos Blandos/metabolismo , Proteínas WT1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Citoplasma/metabolismo , Citoplasma/patología , Femenino , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/cirugía
20.
Acta Cytol ; 53(5): 587-90, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19798890

RESUMEN

BACKGROUND: Low grade endometrial stromal sarcoma (LESS) with dissemination is rare, and its cytomorphology has not been well described. Recently, we experienced a case of LESS with peritoneal dissemination that was confirmed by peritoneal washing cytology and histology. CASE: A 51-year-old woman was admitted for evaluation of vaginal bleeding. Uterine ultrasonography revealed a diffisely thickened endomyometrium with a vaguely circumscribed nodular mass-like lesion measuring 7.4 cm in the largest dimension. Under the impression of adenomyosis, an exploratory laparotomy was performed. On examination of the abdominal cavity, multiple tiny, grayish nodular excrescences firmly attached to the peritoneal wall and the serosal surface of the small bowel and uterus were noted. A total hysterectomy with bilateral salpingo-oophorectomy and peritoneal fluid sampling were performed. The peritoneal fluid smear demonstrated several loosely packed clusters of monotonous cells showing round to oval nuclei, rare small nucleoli and scanty cytoplasm. CD10 immunostaining revealed cytoplasmic positivity in these cells, but reactive mesothelial cells showed a negative reaction. Histologic examination of the uterus revealed the typical histologic findings of LESS. CONCLUSION: Cytopathologic diagnosis of disseminated LESS is not always easy. Immunocytochemical staining for CD10 can be helpful.


Asunto(s)
Líquido Ascítico/patología , Neoplasias Endometriales/patología , Sarcoma Estromático Endometrial/patología , Líquido Ascítico/inmunología , Errores Diagnósticos/prevención & control , Neoplasias Endometriales/inmunología , Neoplasias Endometriales/cirugía , Endometriosis/patología , Femenino , Humanos , Histerectomía , Inmunohistoquímica , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neprilisina/análisis , Ovariectomía , Lavado Peritoneal , Valor Predictivo de las Pruebas , Sarcoma Estromático Endometrial/inmunología , Sarcoma Estromático Endometrial/cirugía
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