Aberrant expression of hypoxia-inducible factor 1α, TWIST and E-cadherin is associated with aggressive tumor phenotypes in endometrioid endometrial carcinoma.

OBJECTIVE: Intratumoral hypoxia promotes angiogenesis, invasion and epithelial-mesenchymal transition, a pivotal event in tumor metastasis. TWIST is a master regulator of multiple developmental processes and has recently been shown to be the key factor responsible for cancer metastasis via the inhibition of E-cadherin expression, a hallmark of epithelial-mesenchymal transition. This study aimed to determine the expression of hypoxia-inducible factor 1α, TWIST and E-cadherin in patients with endometrioid endometrial carcinoma and to examine their clinical significance in endometrioid endometrial carcinoma progression. METHODS: Using immunohistochemical and tissue microarray approaches, we evaluated the expression of hypoxia-inducible factor 1α, TWIST and E-cadherin in normal endometrial (n = 35), atypical hyperplasia (n = 28) and endometrioid endometrial carcinoma samples (n = 124). Furthermore, we statistically analyzed the association between these markers, as well as their correlation with clinicopathologic variables. RESULTS: The expression of hypoxia-inducible factor 1α and TWIST were markedly increased, whereas E-cadherin was decreased, as lesions progressed from normal endometrium to atypical hyperplasia to carcinoma (P < 0.01). Among various clinical parameters, the expression of hypoxia-inducible factor 1α and TWIST was strikingly elevated with aggressive tumor characteristics, including higher pathologic grade, deep myometrial invasion and lymph node involvement (P < 0.05). More importantly, overexpression of hypoxia-inducible factor 1α positively correlated with enhanced TWIST expression in endometrioid endometrial carcinoma samples (r = 0.249, P < 0.01); however, statistical analysis showed a negative relationship between TWIST upregulation and E-cadherin downregulation (r = -0.183, P = 0.042). CONCLUSIONS: These results demonstrated for the first time that the hypoxia-inducible factor 1α/TWIST/E-cadherin pathway may play a critical role in invasion and metastasis of endometrioid endometrial carcinoma. The combined evaluation of these markers may be useful in predicting aggressive phenotypes and thus prognosis in patients with endometrioid endometrial carcinoma.

Extraskeletal myxoid chondrosarcoma in the lung: asymptomatic lung mass with severe anemia.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma, which primarily occurs deep in the extremities, especially in skeletal muscle, or tendon. EMC of the pleura has been described, however, no case of primary EMC arising from lung has been previously reported. We describe herein, a 51-year-old Asian female initially manifested with signs of severe anemia who presented with a lung mass unrelated to pleura that was morphologically typical EMC, with strong immunoreactivity for vimentin and NSE. Two weeks after resection, the anemia was cured. The patient continued with follow-up, without sign of abnormality 32 months after operation. Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2882199847396682.

Expression of PTTG1 and PTEN in endometrial carcinoma: correlation with tumorigenesis and progression.

Human pituitary tumor-transforming gene 1 (PTTG1) is a newly identified proto-oncogene, and its overexpression occurs in a wide variety of human cancers. The tumor suppressor gene phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is frequently mutated or deleted in numerous tumors, especially in endometrial carcinoma. The aim of this study was to investigate whether the aberrant expression of PTTG1 and PTEN is associated with tumorigenesis and progression of endometrial carcinoma. Tissue microarray and immunohistochemical staining were undertaken in 124 endometrial carcinoma, 28 atypical hyperplasia and 35 normal endometrium samples. Then, the correlation of PTTG1 and PTEN expression with the clinicopathological features and with the levels of estrogen and progesterone receptor was analyzed. The presence of PTTG1 and PTEN protein was significantly increased and decreased, respectively, as lesions progressed from normal endometrium to atypical hyperplasia to carcinoma. PTTG1 protein showed a significantly positive correlation with TNM stage, but not with other characteristics. In addition, PTEN protein did not correlate with any parameters except for histological grade, to which it was found to be inversely related. Statistical analysis confirmed a significant relationship between an increase in PTTG1 and a decrease in PTEN. These results indicate that high expression of PTTG1 and low expression of PTEN may be involved in pathogenesis and development of endometrial carcinoma. The findings also provide evidence that combined evaluation of the two markers may be useful in predicting tumor behavior and thus prognosis.

N-myc downstream-regulated gene 1 as a downregulated target gene of PTEN in the controlling of tumourigenesis in endometrioid carcinoma.

BACKGROUND & OBJECTIVE: Mutation/deletion of PTEN has been known to be involved in the development of many cancers including endometrial carcinoma. NDRG1 (N-myc downstream-regulated gene 1) is reported to be associated with tumourigenesis. PTEN expression has been shown to be correlated with NDRG1 in both prostate and breast cancer. In this study, we explored the possibility that PTEN alteration may cause carcinogenesis of endometrioid carcinoma by regulating the expression of the NDRG1 gene. METHODS: Tissue blocks of 103 patients with pathologically confirmed endometrioid carcinoma were included. All the carcinoma tissues were accompanied with varied degree of necrosis. Using two-step method and avidin-biotin peroxidase complex immunohistochemistry method, the correlation of the two genes expression in ischaemic area and the relationship of NDRG1 expression between ischaemic and non-ischaemic area in endometrioid carcinomas was evaluated. RESULTS: PTEN alteration and NDRG1 expressions were significantly increased in the ischaemic area of endometrioid carcinoma compared with their expressions in the normal endometrium respectively (P<0.001, P<0.001). A positive correlation was found between PTEN alteration and NDRG1 expression in the ischaemic area of endometrioid carcinoma. INTERPRETATION & CONCLUSION: We suggest that NDRG1 may be an important candidate gene in facilitating endometrium carcinogenesis in the adaptation of hypoxia for survival. Alteration of PTEN may upregulate NDRG1 expression, which plays an important role in the process leading to endometrial carcinogenesis.

Correlation between NDRG1 and PTEN expression in endometrial carcinoma.

N-myc Downstream-Regulated Gene 1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 has recently been shown to be associated with carcinogenesis and tumor progression in a wide variety of tumors. Phosphatase and tensin homolog deleted from chromosome (PTEN), a phosphatase and tensin homolog located on chromosome 10, is shown to be a tumor suppressor and is often mutated or deleted in various tumor cells, particularly in endometrial carcinoma. Using an immunohistochemical approach, we investigated the expression of NDRG1 and PTEN in normal endometrium, atypical hyperplasia, and endometrial carcinoma. All tumor tissues harvested in this study were derived from endometrioid carcinoma Type I, that were estrogen-related. Our results demonstrate that the expression of NDRG1 was up-regulated in 5/40 (12.5%), 18/34 (52.94%), and 86/103 (83.5%) normal endometrium, atypical hyperplasia, and endometrial carcinoma cases, respectively (P < 0.01), while in 6/40 (15%), 20/34 (58.82%), and 89/103 (86.41%) normal endometrium, atypical hyperplasia, and endometrial carcinoma cases, respectively. PTEN expression was significantly decreased (P < 0.01). Statistical analyzes demonstrated a positive correlation between NDRG1 up-regulation and PTEN down-regulation (P < 0.01). The expression of NDRG1 had no correlation with the differentiation degree of the tumor cells, lymph-node metastasis, and/or abdominal cavity implantation (P > 0.05). Our results indicated that development of endometrial carcinoma is associated with an overexpression of NDRG1 and the loss of PTEN expression. Identification of changes in the NDRG1 and PTEN expression may be a significant diagnostic tool for the early detection of endometrial carcinoma.

[Expression of S-100 positive dendritic cell, TIMP-1 and p63 and its significance in the primary laryngeal carcinoma].

OBJECTIVE: To evaluate the predictive role of S-100 positive dendritic cell, tissue inhibitor of metalloproteinases-1 (TIMP-1) and p63 gene in primary laryngeal carcinoma with epidemiology (smoking and drinking), histological grading, surgical treatment, TNM stage and prognosis by the tissuechip technology. METHODS: We studied the expression of dendritic cell (S-100), TIMP-1 and p63 gene on a series of 85 primary laryngeal carcinoma patients who had ever received in our hospital between 1992 and 2000 by the tissuechip technology and SP method. The correlation of each score according to the intensity and percentage of labeled cells or intercellular substance with relevant clinical dada was statistically analyzed. RESULT: Some cases were lost or boasted no tumor tissue in our tissuechip. In available 79 patients, the rate of expressing S-100 positive dendritic cell is 59.5% (47/79), and the average percentage of its labeled cells in them is 8.71%. S-100 positive dentritic cells showed significant difference among different pathological grade group, early and late stage( P < 0.05). The rate is 55.7% (44/79) of the specimens whose basal membrane and extracellular matrix was strongly stained by TIMP-1; There was statistical significant in TIMP-1 protein demonstration between early and late stages, lymph node metastasis and 3-year survival rate ( P < 0.05) by chi-square test, but no relation with smoking, drinking, gender, age and histological classes (P > 0.05). There was wo statistical significant in p63 protein demonstration between TNM stages, lymph node metastasis, 3-year survival rate, smoking, drinking, gender, age and histological classes (P > 0.05). CONCLUSION: The tissue microarray technique spent shorter time and less expense, and showed higher consistency in our essays. And the present study suggests TIMP-1 and S-100 could be the clinical discriminators in laryngeal carcinoma.

Asymptomatic process of hepatic artery thrombosis in a patient after orthotopic liver transplantation.

BACKGROUND: Hepatic artery thrombosis is one of the serious complications after liver transplantation. It will mostly cause a failure of the transplantation. This case of hepatic artery thrombosis showed a stable clinical course and minimal histological change, and now has been surviving for 4 years with normal liver function. We investigated the possible causes for asymptomatic hepatic artery thrombosis in one patient after orthotopic liver transplantation (OLT) and discussed the diagnosis of ischemia of OLT pathologically and clinically. METHODS: Liver function test, color Doppler ultrasonography, and hepatic arteriography were performed during the development of hepatic arteriothrombosis. Possible factors for the asymptomatic process of the thrombosis were analyzed. RESULTS: On the 4th postoperative day, thrombosis formed at the anastomotic stoma of the hepatic artery, and on the 11th postoperative day, the artery was completely occluded. Serial liver biopsies revealed intrahepatic cholestasis, hydropic degeneration of hepatocytes, atrophy of the biliary epithelium, and fibrosis in the portal area. Monitoring of liver function showed nothing abnormal except elevation of gamma-GT and ALP levels. On the 71st day after OLT, arteriography demonstrated that the hepatic artery remained completely occluded in addition to the establishment of collateral circulation and compensation of the portal vein. The patient didn't show any symptoms of arterial thrombosis. CONCLUSION: Collateral circulation and compensation of the portal vein are beneficial to allograft survival and avoidance of retransplantation after thrombosis of the hepatic artery. Color Doppler ultrasonography within 2 weeks after OLT is helpful to the early diagnosis of hepatic arteriothrombosis.

Application of tissue microarray: evaluation of the expression of S-100-positive dendritic cells, tumor suppressor gene p63 and tissue inhibitor of metalloproteinase-1 in laryngeal carcinoma.

OBJECTIVE: To evaluate the predictive role of S100-positive dendritic cells, tissue inhibitor of metalloproteinase-1 (TIMP1) and p63 gene in laryngeal carcinoma using a tissue chip. MATERIAL AND METHODS: The expression of dendritic cells, TIMP1 and p63 gene in a series of 85 primary laryngeal carcinoma patients who had undergone operations in our hospital between 1992 and 2000 was studied immunohistochemically using the streptavidin-biotin peroxidase-conjugated method. RESULTS: Some cases were lost or showed no tumor tissue in the tissue chip. The rate of expression of dendritic cells was 59.5% and there were significant differences in expression between the differential degrees of laryngeal squamous carcinoma and the different clinical stages (p <0.05). The basal membrane and extracellular matrix of the specimens were strongly stained by TIMP1 in 55.7% of cases. There were statistically significant correlations between TIMP1 protein expression and early- and advanced-stage tumors, lymph node metastasis and 3-year survival rate (p <0.05). No statistically significant correlations were found between p63 protein expression and any of the clinical parameters. CONCLUSIONS: The tissue microarray technique used in this study is quick, inexpensive and very consistent. It is suggested that TIMP1 and S100 should be used as clinical discriminators of laryngeal carcinoma.

[Research of fibronectin, p53 and Ezrin protein with occurrence, progress and prognosis in the primary laryngeal carcinoma by the tissuechip technology].

OBJECTIVE: To evaluate the predictive role of fibronectin, p81 (Ezrin protein) and p53 gene in primary laryngeal carcinoma, it's relationship with epidemiology(smoking), histological grading, surgical treatment, TNM stage and prognosis were studied by the tissuechip technology. METHODS: The expression of fibronectin, p53 gene and p81 (Ezrin protein) on a series of 85 primary laryngeal carcinoma patients treated in our hospital between 1992 and 2000 was studied with tissuechip technology. The correlation of each score according to the intensity and percentage of labeled cells or intercellular substance with relevant clinical dada was statistically analyzed. RESULTS: Some cases were lost or boosted no tumor tissue in our tissuechip. Among the 70 cases available, 45.71% (32/70) of the specimens' basal membrane and extracellular matrix were strongly stained with fibronectin; there is statistical significance (P < 0.05) between primary tumor grading groups. Ezrin protein expressing rate is 87.3%, and the average percentage of its labeled cells is 53.68% (ranging from 0% to 100%, median is 58. 69%). There were significant difference between tumor grading groups, clinical early and late stages and 3-year survival rates (P < 0.05) after chi-square test. But no relation with smoking, gender, age and histological classes (P > 0.05). The average percentage of p53 positive cells is 21.6% (ranging from 0% to 90.3%, median is 5.85%) and 46.8% showed positive stains in our research. There was no statistical prominence in p53 protein demonstration between TNM stages, lymph node metastasis, 3-year survival rate, smoking, gender, age and histological classes (P > 0.05). CONCLUSIONS: The tissue microarray technique spent shorter time and less expense, and showed higher consistency in our essays. And the present study suggests fibronectin and p81 (Ezrin protein) could be the clinical discriminators in laryngeal carcinoma.

[Study on the effects of various dosage of dexamethasone in accelerating fetal lung maturation and the accompanied side effects in rats].

OBJECTIVE: To compare the effect of various dosage of dexamethasone (Dex) in accelerating fetal lung maturation and the accompanied side effects. METHOD: Sixty time-bred Wistar rats were randomly assigned to one of the four groups (15 rats each group). They were given normal saline 0.8 ml (group A); Dex 0.2 mg (group B); Dex 0.4 mg (group C); Dex 0.8 mg (group D) IH, separated for 4 times on gestational day 15, 16. ten rats in each group were killed and hysterectomy were made immediately on day 17. The neonate breathing scale and their lung were observed and scored; the amniotic lamellar bodies (LB) were counted to assess the preterm fetal lung maturation. The remaining 5 rats in each group delivered naturally. The mother rats' condition in perinatal period, the birth weight of their neonates, and the structure of the livers and adrenal glands of the neonates were recorded to assess the side effects of the drug. RESULTS: The scores of neonatal breathing scale in group A to D were: 1.4 +/- 0.5, 3.6 +/- 0.7, 4.2 +/- 0.5, 4.5 +/- 0.5; their lung histologic maturation degree: 1.4 +/- 0.6, 3.9 +/- 0.9, 4.2 +/- 0.7, 4.4 +/- 0.6; and the account of their amniotic LB were: (8.6 +/- 3.0), (30.2 +/- 4.2), (33.0 +/- 3.4), (35.8 +/- 2.7) x 10(9)/ml respectively. All the indexes in the three Dex groups were higher than group A, and there were no statistical difference among in the three Dex groups except the neonatal breathing scale scores, which were higher in the high dose group D than the low dose group B. When high dose Dex was used, there was a reductive tendency in mother rats weight and its ability to resist infectious disease; meanwhile, the birth weight of their neonates reduced, the number of stillbirth and neonate liver necrosis increased. CONCLUSION: By the preterm gravid rat model, low dosage of antenatal dexamethasone administration accelerate fetal lung maturation to the extent equally to the middle even high doses of the drug. When high dosage of Dex was administered, the increasing side effects on the mother rats and their fetuses were accompanied.