Low Expression Levels of CXCL12, CXCR4, and CXCR 7 in Peripheral Blood and Decidual Tissues are Associated with Miscarriage in Women.

Miscarriage can cause significant physical and psychological harm to women. The stromal cell-derived factor 1 (SDF-1, also known as CXCL12)/C-X-C motif chemokine receptor 4 (CXCR4) and C-X-C motif chemokine receptor 7 (CXCR7) axis can promote the proliferation and invasion of trophoblast cells in early pregnancy, and maintain immune tolerance at the maternal-fetal interface to aid with pregnancy success. From our findings, the serum CXCL12 level of women who have miscarried (n = 25) was significantly lower than that of healthy early pregnancy women (n = 20) by ELISA (P < .001). Additionally, CXCL12 levels in normal non-pregnant women (n = 20) were significantly lower than those in early pregnancy women (P < .001) and women who have miscarried (P < .001). Quantitative real-time PCR detected no significant difference in the mRNA transcription levels of CXCR4 and CXCR7 in the decidua tissues of women with early pregnancy (n = 20) and miscarriage (n = 20) (P = .724, P = .281, respectively). However, Western blot and immunohistochemistry of CXCR4 and CXCR7 in decidual tissue of women who have miscarried (n = 20) were significantly lower than those in early pregnancy women (n = 20) (P < .05 for both). Therefore, we believe that the increased serum CXCL12 levels in pregnant offspring may benefit normal pregnancy maintenance. The low level of CXCL12 in peripheral blood and the low expression of CXCR4 and CXCR7 proteins in decidua may be associated with the occurrence of early spontaneous abortion, and the clinical application value of serum CXCL12 in predicting adverse pregnancy outcomes is worth further exploring.

STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia.

OBJECTIVES: Abnormal trophoblast behaviors during pregnancy contribute to the development of preeclampsia (PE). Syntaxin2 (STX2) has been shown to be a crucial epithelial mediator in numerous diseases. However, the functions of STX2 and the mechanisms underlying its role in PE remain largely unknown. The aim of this study was to explore the role of STX2 on trophoblast biology and unravel the molecular mechanisms that contribute to the development and progression of PE. MATERIALS AND METHODS: We first compared the expression of STX2 in placental tissues from women with PE and women with normal pregnancies. Then, we investigated the role of STX2 on trophoblast proliferation, migration and invasion in HTR-8/SVneo and primary human trophoblast cells by loss or gain of function experiments. In addition, co-immunoprecipitation, pulldown and immunofluorescence assays were performed to investigate the co-localization of STX2 with other proteins, and to help clarify the mechanisms underlying STX2-mediated functions on trophoblasts. RESULTS: We demonstrated that STX2 expression was downregulated in placental tissues of women with PE compared with those from normal pregnancies. Loss and gain of function experiments further confirmed a role for STX2 in cell proliferation, migration and invasion in trophoblasts. By co-immunoprecipitation, pulldown and immunofluorescence co-localization assays, we revealed that STX2 selectively interacted with p85, a subunit of PI3K, and directly recruited p85 to the cytomembrane, thereby activating the AKT signaling pathway. We further demonstrated that the AKT activation was abolished by the use of a PI3K inhibitor (LY294002), which negatively affected STX2-mediated functions on trophoblasts. CONCLUSION: All together, our findings point to a crucial role for STX2 in PE progression. Our new insights also suggest that STX2 may be a potential diagnostic tool and a novel therapeutic target for treating PE.

Epithelial tumors of the lacrimal gland in the Chinese: a clinicopathologic study of 298 patients.

OBJECTIVE: To examine the clinicopathologic characteristics and clinical features of epithelial tumors of lacrimal gland in China. METHODS: The retrospective case series study included all 298 patients of epithelial lacrimal gland tumors which had been collected in the ophthalmic pathologic laboratory of the Tongren Hospital Beijing in the study period from 1961 to 2005. RESULTS: Pleomorphic adenomas were the most common tumors (n = 213 (72%)), followed by adenoid cystic carcinoma (n = 58 (20%)), pleomorphic adenocarcinoma (n = 13 (4%)), primary adenocarcinoma (n = 8 (3%)) and other tumors (n = 6 (2%)). The most frequent symptoms and clinical signs were restrictions of the lid or eye motility (121 patients; 41%), any other kind of lid involvement (71 patients; 24%), swelling (57 patients; 19%), pain (57 patients; 8%), and decrease in vision (15 patients; 5%). A restriction of the eye motility was noted for 61 patients (21%), due to an involvement of the extraocular muscles with the tumor and due to a tumor-induced displacement of the globe. Apart from the duration of symptoms, the tumor types did not vary significantly in age, gender, and laterality. CONCLUSIONS: Based on the archives of the Beijing Tongren ophthalmo-pathological laboratory, the most common epithelial tumors of the lacrimal gland in mainland China were pleomorphic adenomas, followed by adenoid cystic carcinoma. The spectrum and clinical signs of epithelial lacrimal gland tumors did not differ markedly between Chinese patients and Caucasian patients.

Eyelid neoplasms in the Beijing Tongren Eye Centre between 1997 and 2006.

BACKGROUND AND OBJECTIVE: To examine the spectrum of eyelid neoplastic specimens obtained at the Beijing Tongren Eye Centre between 1997 and 2006. PATIENTS AND METHODS: A total of 2,639 eyelid neoplasms were included in the study. RESULTS: Of the 2,639 eyelid specimens, 2,276 (86.2%) were benign and 363 (13.8%) were malignant. The most common benign lesions were inflammatory lesions, melanocytic nevi, papillomas, dermoid and epidermoid cysts, and epithelial cysts. The most common malignant or semi-malignant tumors were basal cell carcinomas, sebaceous gland carcinomas, lymphomas, squamous cell carcinomas, and malignant melanomas. The mean age at diagnosis was 41 years for benign lesions and 60 years for malignant tumors. There was no significant gender predilection among the five major non-benign eyelid tumors. CONCLUSION: At the BeijingTongren Eye Centre between 1997 and 2006, the predominant non-benign eyelid tumors were basal cell carcinoma and sebaceous gland carcinoma, followed by lymphoma. The non-benign lesions occurred predominantly in elderly patients who were 60 years of age and older.

[Clinical and pathological analysis of 2639 cases of eyelid tumors].

OBJECTIVE: To describe the histopathologic spectrum and patient characteristics of eyelid tumors in Beijing Tongren Hospital. METHODS: It was a claims database analysis. A total of 2639 eyelid tumors verified histopathologically from January 1997 to December 2006 were included in the study. RESULTS: Of the 2639 eyelid tumors, the 5 most common eyelid benign lesions were inflammatory lesion, melanocytic nevus, papilloma, dermoid cyst and epidermoid cyst, and epithelial cyst. The 5 leading eyelid malignant tumors were basal cell carcinoma, sebaceous gland carcinoma, lymphoma, squamous cell carcinoma and melanoma. The mean age at diagnosis was 61 years for basal cell carcinoma and sebaceous gland carcinoma, 57 years and 52 years for squamous cell carcinoma and melanoma, respectively, and 48 years for lymphoma. There was no significant sex predilection in basal cell carcinoma and sebaceous gland carcinoma. Melanoma and lymphoma occurred more commonly in women, whereas squamous cell carcinoma occurred more commonly in men. CONCLUSIONS: Basal cell carcinoma and sebaceous gland carcinoma were the most common malignant eyelid tumors, and lymphoma ranked third and had an increasing trend. The malignant tumors occurred predominantly in the elderly of 60 years and above.

[Recognize the value of the individually combined therapy for children with retinoblastoma].

Retinoblastoma is the most common intraocular malignant tumor in children. With the introduction of the new therapeutic methods, the aim and the procedures of traditional therapy on retinoblastoma have been changed to the new combined therapeutic procedures, which are based on the preservation of the eyeball and visual function. Compared with the developed countries, there still exist some gaps in the acceptance of new therapeutic conceptions in China. At present, enucleation is still used commonly in China, whereas external beam radiation therapy is a main supplementary treatment. The therapeutic procedures of RB in China are relatively limited and simplistic. Therefore, the authors suggest that we should learn the experience from the developed countries, considering the status in our country, to change the traditional therapeutic idea and to establish a suitable system of individually combined therapy for patients with retinoblastoma in China.

[Study on the risk factors for optic nerve invasion in 381 cases of retinoblastoma].

OBJECTIVE: To investigate the clinical and pathologic outcomes of a large group of retinoblastoma (RB) cases to ascertain the risk factors of RB optic nerve invasion. METHODS: In this paper, we summarized the clinical and pathologic data of 381 retinoblastoma cases in Beijing Tongren Hospital observed from 1990 to 2002. Statistical analyses were performed on the sex, age, unilateral or bilateral cases, length of symptoms, clinical situation, stage, histological type and the degree of optic nerve invasion. RESULTS: The degree of RB optic nerve invasion was closely correlated to clinical stage and tumor differentiation. CONCLUSION: Avoiding the risk factors of RB optic nerve invasion is very important for the prognosis of RB.

[Clinical use of quantitative DNA pathologic examination in eye neoplasms].

Quantitative DNA pathologic examination is an important content of quantitative pathology, which is to use cytochemistry quantitative analytical technique for quantitative analysis of patho-histological structure and intra-cellular DNA level. Quantitative determination of DNA in tumor cells as an objective quantitative index reflecting biological behavior of tumor cells and has an important significance for distinguishing precancerous lesions, borderline tumors, benign and malignant tumors; and for estimating the malignant degree and prognosis. This review introduces the study about DNA quantitative analysis used in clinical pathology of eye neoplasms.

[A five-year overview of basic and clinical research of ophthalmic pathology in China].

This paper briefly reviews the growth and development over the past five years in relation to the work of Pathology Division of Chinese Society of Ophthalmology. In connection with major constitute member organizations of the Division, it depicts their key research areas, major projects undertaken and outcome of achievement, the progress in their research team building and talent nurture programs, as well as their publication status. It also summarily reports the important basic and clinical research carried out on ophthalmic pathology, ophthalmic tumors, ophthalmic orbital diseases, and in other various relevant fields. Finally, the paper contains recommendations as regards the mission and direction to be steered by the Division for future development of the work of ophthalmic pathology in China.

[Clinical and pathological features of 112 cases with ocular adnexal lymphoproliferative lesions].

OBJECTIVE: To investigate the histopathological classification and clinical features of ocular adnexal lymphoproliferative lesions. METHODS: The clinical, histomorphological and immuno-histochemical features of 112 cases of ocular adnexal lymphoproliferative lesions (116 paraffin specimens) were studied retrospectively. The lesions were classified according to the World Health Organization classification of tumors of haematopoietic and lymphoid tissues (2001). RESULTS: This group of patients' ages averaged at 49. The mean duration between the onset of the symptoms and the time of presentation was 22 months. Sixteen patients (14.3%) had bilateral lesions. Proptosis or local orbital mass was presented in 69 cases (61.6%). Reactive lymphoid hyperplasia was diagnosed in 11 cases (9.8%) and atypical lymphoid hyperplasia in 10 cases (8.9%). The rest 91 cases (81.3%) were diagnosed as lymphoma, among which 74 cases (81.3%) were extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-EMZL). CONCLUSIONS: MALT-EMZL is the most frequent type of ocular lymphoproliferative lesions in ocular adnexa. The ocular adnexal lymphoproliferative lesions show an indolent course clinically, tending to affect the old. Bilateral case is not uncommon.

Telomerase expression in sebaceous carcinoma of the eyelid.

BACKGROUND: In humans telomerase is expressed in most cancers and immortal cell lines, and activation of telomerase may play important roles in tumorigenesis and immortalization. This study was to investigate the roles of telomerase activity (TA) and human telomerase RNA (hTR) in sebaceous carcinoma of the eyelid. METHODS: The telomerase repeated amplification protocol (TRAP) was used to demonstrate telomerase activity in 12 cases of sebaceous carcinoma of the eyelid. In situ hybridization (ISH) was used to demonstrate the expression of hTR in 55 cases of paraffin-embedded sebaceous carcinoma of the eyelid, and the results were compared with the proliferative index determined by Mib-1 immuno-labeling, histological patterns and recurrence of the tumor. RESULTS: Different telomerase activity was shown in the 12 cases of sebaceous carcinoma of the eyelid. The positive expression of hTR was 85.5% (47/55) in tumor cells, but not in the adjacent tissues. The positive expression of hTR was correlated with the proliferative activity (as assessed by Mib-1 immunolabelling, r = 0.942, P < 0.001) and the differentiation of sebaceous carcinoma of the eyelid (chi(2) = 17.621, P < 0.001), but not significantly related to tumor recurrence. The level of hTR expression increased with the decrease of differentiation of sebaceous carcinoma of the eyelid. CONCLUSIONS: The results suggest that the up-regulation of telomerase expression plays some roles in tarsal gland carcinogenesis, and the expression of hTR is a useful marker for malignant degree of sebaceous carcinoma of the eyelid.

[Clinical significance of mdm2 and p53 expression in orbital rhabdomyosarcoma].

OBJECTIVE: To evaluate the role of oncogene mdm2 and p53 in the development of orbital rhabdomyosarcoma (ORMS) and demonstrate the feasibility of mdm2 and p53 as biological characteristic markers and prognostic indicators. METHODS: Immunostainings of mdm2, p53 and Ki-67 antigen were performed on archival paraffin-embedded tissues taken from 31 ORMS patients. In situ hybridization was used to demonstrate the expression of mdm2 and p53 on the mRNA level. The correlations between the two genes and the clinical histopathologic parameters including age, gender, cells subtype, differentiation grade and proliferation index were analyzed. RESULTS: The positive expressions of mdm2 and p53 were 77.4% (24/31) and 71.0% (22/31) respectively; and the co-expression of mdm2 and p53 was 61.3%. The expressions of mdm2 and p53 on the protein level were in coincidence with that on the mRNA level. (1)The poorly and moderately differentiated group showed significantly higher expression of mdm2 and co-expression of mdm2-p53 than the well-differentiated group (P = 0.007; P = 0.009, respectively). (2) The samples were divided into actively-proliferating group and inactively-proliferating group in accordance with the expression of Ki-67 protein. The positive expression of p53 was significantly higher in actively-proliferating group than inactively-proliferating group. No statistic correlation of the positive expression of mdm2 and p53 with the other histopathologic parameters was observed. CONCLUSIONS: mdm2 and p53 were significantly correlated with the differentiation and proliferation of ORMS. The co-expression of mdm2 and p53 expression suggested that mdm2 might play a role in deactivation of p53. The overexpression of mdm2 and p53 leaded to the loss of cell cycle control and may contribute to the tumorigenesis and tumor progression of ORMS. Mdm2 and p53 may be prognostic indicators of the tumor.

[Clinical and pathologic analysis of orbital pseudotumor].

OBJECTIVE: To investigate the relationship between the histopathology and the imaging analysis of orbital pseudotumor to judge the histopathological types of these tumors before treatment according to imaging analysis, in order to search for different therapeutic approaches for different pathologic types and to predicate prognosis. METHODS: Fifty-six cases (58 eyes) of orbital pseudotumor that had been operated in Tongren hospital were studied. The clinical manifestations of these patients were reviewed. Changes in the imaging analysis and histopathologic examination were observed and their relationship was studied. Methods of treatment and their prognosis were also analyzed. RESULTS: Historically, the lymphocytic infiltrated type of orbital pseudotumor composed of large amounts of chronic inflammatory cells, only a small amount of collagen was found, so the imaging features of the lymphocytic infiltrated type presented as low or none reflecting areas with a clear posterior demarcation on B scan, and the signals were low or equal on T(1)WI and high on T(2)WI, which could be enhanced by contrast. Oppositely, the fibrotic type was composed of large amounts of fibrotic tissue, and few chronic inflammatory cells were found, so that only the anterior border of the lesion could be identified and the posterior demarcation was blur on the B scan, and the signals were low or equal on T(1)WI and low on T(2)WI, which could not be enhanced or could be enhanced only slightly by changing the contrast. The mixed type presented as an admixture of chronic inflammatory cells and fibric hyperplasia, and the imaging of the mixed type was midway between the lymphocytic infiltrated type and the fibrotic type. Forty-two patients of lymphocytic and mixed types which were identified by histopathology and imaging analysis received a local and systemic corticosteroid therapy. The effect was unstable, and recurrence occurred easily. Therefore, operations were performed on these patients, thirteen of them were treated with low-dose radiotherapy (2 000 - 3 000 cGy) two weeks after operation. Fifteen cases recurred after the operation and 4 cases recurred after the radiotherapy. The fibrotic type of orbital pseudotumor was identified in 12 cases in which no effect could be observed after conservative therapy and operations were performed subsequently. Two cases recurred and were operated again. Exenteration was performed in 2 cases of 56 cases. The cure rate of the composite treatment in the present series was 68.5%. CONCLUSIONS: Different types of orbital pseudotumor present different imaging exhibition, and imaging features are closely related with histopathological changes. Lesions can be localized by CT scan, and also can be localized by B scan and MRI. While it is difficult to obtain a cure result in the orbital pseudotumor, the cure rate can be improved by composite treatment.

[Correlation of tumor angiogenesis with clinicopathologic prognostic parameters in choroidal melanoma].

OBJECTIVE: Tumor angiogenesis is an essential step for tumor growth, progression and metastasis. Vascular endothelial growth factor (VEGF) is a mitogen specific for vascular endothelial cells, and plays a key role in tumor angiogenesis. The purpose of the present study was to investigate the expression of VEGF mRNA and VEGF protein in choroidal melanoma and to correlate these factors and the microvessel density (MVD) with the clinicopathologic prognostic features. METHODS: In a total of 65 cases of choroidal melanoma from the Pathology Laboratory of Tongren Hospital, the expression of VEGF mRNA was assessed by in situ hybridization (ISH); the expression of VEGF protein and factor VIII-related antigen (FVIII-RAg) was assessed using immunohistochemical methods. MVD was evaluated by immunohistochemical staining of FVIII-RAg for vascular endothelial cells. RESULTS: VEGF mRNA expression was present in 56/65 cases (86%), while VEGF immunoreactivity was present in 55/65 cases (85%). Positive expression of VEGF and VEGF mRNA was correlated with the tumor size (P = 0.025) and local invasion of tumor to scleral emissaria (P = 0.034), but it's relation to the histologic type, the tumor location and the largest tumor diameter (LTD) was not statistically significant. MVD was significantly higher in the VEGF-positive melanoma than in the VEGF-negative melanoma (one way analysis of variance, P = 0.000). There was no significant correlation between MVD and tumor location, as well as the tumor height and the patient's age; however, significant correlation was found between MVD and LTD, as well as with the tumor size, cell type and the invasion of tumor to the scleral emissaria (t test, P = 0.012, 0.008, 0.001 and 0.000, respectively). CONCLUSIONS: Most choroidal melanomas express VEGF mRNA and VEGF protein, and this expression is correlated with MVD. This suggests that angiogenesis is significantly correlated with clinicopathologic prognostic factors of choroidal melanoma, such as LTD, tumor size, cell type and tumor invasion. MVD and the expression of VEGF may be useful prognostic indicators for the biological behavior and the outcome of choroidal melanoma.

[Clinical and pathological features of 273 cases of lacrimal epithelial tumors].

OBJECTIVE: A retrospective study of histopathological and clinical aspects of 261 cases of lacrimal tumors (273 paraffin specimens) from Ophthalmic Pathology Laboratory, Beijing Tongren Hospital (Dec. 1961 to Jun. 2002) was performed to investigate the pathological classification and clinical features of these tumors. METHODS: Clinical features were analyzed from 261 patients of lacrimal tumors, including patient's history, age, gender, laterality, visual acuity, ultrasound B scan, X-ray, CT, MRI, pre- and post-operation condition, follow-up data and others. These data were compared with the pathological features. RESULTS: Pleomorphic adenoma was the most common tumor in epithelial tumors of lacrimal gland, followed by adenoid cystic carcinoma, pleomorphic adenocarcinoma and adenocarcinoma. Recurrence was observed in 12 cases. The recurrence rate is 4.6%. Four cases was dead, the mortality was 1.5%. CONCLUSION: Pleomorphic adenoma shows a low mortality and a relatively high recurrence rate. The main treatment for pleomorphic adenoma is surgical treatment. It is important to have a correct clinical diagnosis, to select the proper surgical method, drug treatment and postoperative management based on the pathological diagnosis, which can result in a decrease of recurrence rate.

[The study on the correlation between telomerase and histopathologic features of retinoblastoma].

OBJECTIVE: To investigate the correlation between the expression of human telomerase RNA (hTR), human telomerase reverse transcriptase (hTRT) and the proliferation and differentiation of retinoblastoma (RB). METHODS: In 37 RB specimens, the expression of hTR and hTRT was investigated with the methods of in situ hybridization (ISH). Immunohistochemical method was performed to detect the expression of proliferating cell nuclear antigen (PCNA) in RB. All data were analyzed statistically with SPSS. RESULTS: Of 37 RB specimens, positive expression of hTR and hTRT was 83.8% and 89.2%, respectively, while negative results were observed in 2 normal retina tissues. The expressions of hTR and hTRT showed a close correlation to the proliferation and differentiation of RB. Furthermore, there was a close correlation among the expression of hTR and hTRT. CONCLUSIONS: These results suggest that higher expression of hTRT and hTR may be used as new parameters for evaluating the degree of malignancy of RB. The close correlation between the expression of hTR and hTRT and proliferation and differentiation degrees of RB indicats that the expression of telomerase can influence the proliferation and differentiation of RB. Because the telomerase is presented in the Rb, therefore, modulating the telomerase activity may be used as a novel treatment for the RB.