[Histopathological study of retrolental membranes secondary to persistent hyperplastic primary vitreous].

OBJECTIVE: To study the pathological characteristics of retrolental membranes (RLMs) secondary to persistent hyperplastic primary vitreous (PHPV), and to discuss the possible pathogenesis of PHPV. METHODS: Experimental study. Six RLMs obtained from six patients with PHPV during vitrectomy were examined by light microscopy (HE & PAS staining). All of them were observed with proliferating cell nuclear antigen (PCNA) immunostaining, together with collagen I, factor VIII related antigen, smooth muscle actin (SMA), epithelial membrane antigen (EMA), neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP) staining. Apoptosis were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL). RESULTS: Light microscopy showed that the RLM was a dense connective tissue with numerous inflammatory cells including mast cells and lymphocytes. PAS staining showed that RLMs contained a larger amount of polysaccharides. Histopathology and immunohistochemistry showed that there were vascular channels, smooth muscle cells, nervous cells and epithelial cells scattered in RLMs. Collagen I was the main component of RLMs. PCNA-positive nuclei were widely found in RLMs. TUNEL-positive nuclei were also found in all RLMs, as well as in the posterior subcapsular epithelial cells of lens. CONCLUSIONS: The cell types of RLMs secondary to PHPV are similar to those of the primary vitreous. It is possible that the mechanism of the progression of RLMs is the over-development and incomplete regression of the retrolental vascular system. Inflammation may play an important role in the regression of RLMs.

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.

[Studies on multidrug resistance associated protein in retinoblastoma].

OBJECTIVE: To detect the expression of P-glycoprotein (P-gp), lung resistance associated protein (LRP) and multidrug resistance associated protein (MRP) in retinoblastoma (Rb), to analyze the relationship between the expression of multidrug resistant (MDR) markers with clinic-pathological factors, the correlations among these three markers, and to study the possible mechanism of multidrug resistance in Rb. METHODS: It was an experimental study. Seventy-five cases of Rb were studied with immunohistochemical methods using antibodies against P-gp, LRP and MRP. The relationship between their expression and the clinicopathological features of Rb, and the relationship between the expression of these three markers were investigated. RESULTS: The positive expression rates of P-gp, LRP and MRP were 64.0%, 25.3%, 36.0% in Rb, respectively. The co-expression rates of P-gp and LRP, P-gp and MRP, LRP and MRP were 18.7%, 32.0%, 20.0%, respectively. All tested proteins showed significant correlation to the differentiation of the tumor (P = 0.006, 0.000, 0.000, respectively), but no correlation was found between the expression of these markers and the age or sex of the patients. Significant positive correlations were observed between P-gp and MRP expression (P = 0.001), and between LRP and MRP expression (P = 0.000). CONCLUSIONS: The intrinsic multidrug resistance of Rb involves the combined effects of P-gp, LRP and MRP.

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.

[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.

[Photodynamic therapy of pigmented choroidal melanomas in rabbits using hematoporphyrin monomethyl ether].

OBJECTIVE: The purpose is to determine the effectiveness of photodynamic therapy of experimental choroidal melanoma in rabbits using hematoporphyrin monomethyl ether (HMME). METHODS: Pigmented choroidal melanomas were established in 46 New Zealand albino rabbit eyes. The animals were treated with daily injection of cyclosporine A. The tumors were followed up with funduscopic examination and ultrasonography until they were 1.5 to 4.6 mm in height. Then the rabbits were divided randomly into two groups. In the treatment group, 41 rabbits were injected intravenously with hematoporphyrin monomethyl ether (HMME, 10 mg/kg). 3 hours later, the tumors were irradiated at 630 nm through an He-Ne laser at estimated total light doses of 60 approximately 150 J/cm(2). Control animals (5 rabbit eyes) were treated with light only (2 rabbit eyes), photosensitizer only (2 rabbit eyes), or observation only (1 rabbit eyes). Each animal then was followed up for 4 to 5 weeks with indirect ophthalmoscopy, ultrasonography, and fundus photography (16 rabbit eyes among the treatment group were extirpated for pathologic examination 24 hours or 1 week after the treatment). In the end, all the rabbits were sacrificed and the pathologic examinations were performed. RESULTS: With the fluences of >or= 70 J/cm(2), all the tumors regressed evidently. With the fluence of 60 J/cm(2), not all the animals showed complete tumor arrest. In the control group, all the tumors showed continuous growth and filled most of the vitreous cavity in 2 to 3 weeks. CONCLUSION: The photodynamic therapy with homemade photosensitizer HMME may have a role in the treatment of pigmented choroidal melanomas.

[The effects of matrine on cell proliferation and telomerase activity in retinoblastoma cells in vitro].

OBJECTIVE: To evaluate the effects of matrine on cell proliferation and telomerase activity in retinoblastoma cells in vitro. METHODS: HXO-Rb44 cells were treated with 0.1 to 3.2 mmol/L matrine for 24 h, then cell viability was measured by MTT assay. Apoptosis rates were evaluated by flow cytometry and TUNEL assay after the cells were treated for various durations. The telomerase activity were measured by telomeric repeat amplification protocol. RESULTS: MA inhibited the growth of HXO-Rb44 cells. Ma induced the apoptosis and down-regulated the telomerase activity of HXO-Rb44 cells, which were time dependent. There was a positive correlation between the telomerase activity and the apoptosis (r = -0.961, P < 0.01). CONCLUSIONS: Ma can induce the apoptosis and down-regulate the telomerase activity of retinoblastoma cells, which may be one of important mechanisms to inhibit the cell proliferation. It suggests that Ma may be a potent drug for the treatment of retinoblastoma.

[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.

[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.

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.

[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.