Retrospective clinicopathological study of 129 cancerous and 18 precancerous lesions of the eyelids in North-Western Greece.

This study aimed to present precancerous and cancerous epithelial eyelid lesions, their histopathological features, and possible correlations with clinical parameters. The retrospective study included 147 formalin-fixed, paraffin-embedded samples. We studied precancerous and cancerous epithelial eyelid lesions. Preneoplastic tumors were represented by 12 actinic keratoses and 6 in situ squamous cell carcinomas (Bowen disease) and skin epithelial tumors by 119 basal and 10 squamous cell carcinomas. We recorded the clinicomorphological and histopathological features of the specimens and investigated possible correlations. In our study, the vast majority of pre-malignant and malignant tumors occurred in advanced age (mean age of occurrence: 70.18 years). The data analysis showed that inflammation in patients with basal cell carcinoma (BCC) positively correlated with advanced age (p < 0.01), tumor diameter (p < 0.05), and the appearance of ulceration (p < 0.001). A prevalence of female sex was noted in the BCC group. We also found that inflammation with or without the presence of ulceration was more commonly seen in carcinomatous lesions than in preneoplastic lesions (p < 0.05). Inflammation occurrence is present in high proportions in the tumors studied and correlates with some clinicopathological parameters such as the age of patients, the mean tumor diameter, and the presence of ulceration. The comparison between premalignant and malignant conditions showed that inflammation probability increases as we move toward the more aggressive tumor phenotypes.

Clinicopathologic study of E-cadherin/beta-catenin complex, and topoisomerase-II in a series of 71 liposarcoma cases.

BACKGROUND: To investigate the expression of E-cadherin, beta-catenin and topoisomerase-II alpha and examine their clinical relevance in liposarcomas. MATERIALS AND METHODS: The expression of E-cadherin, beta-catenin and topoisomerase II alpha was examined immunohistochemically on formalin-fixed paraffin-embedded tissue specimens from 71 patients who underwent surgical treatment for liposarcomas of the extremities or the retroperitoneum in two major cancer reference centres between 1990 and 2000. Detailed medical notes were available for all patients who were followed for median 82 months (range 5 to 215 months). Obtained expression data were weighted against clinical and pathology parameters of clinical relevance. RESULTS: Patients were mostly male (59%), median age was 56 years for the liposarcomas of the extremities and 60 years for the retroperitoneal liposarcomas. The tumours were of diverse histology, grade and size (median diameters 7 and 17 cm for tumours of the extremities and retroperitoneum respectively). Expression of ß-catenin protein was weakly detected in 15 cases (21.1%). Similarly weak expression of topoisomerase II-alpha was detected in 14 (19.7%) cases of which only two had more than 20% of tumor cells stained positive. E-cadherin was not detected in the studied cohort of liposarcomas. We did not detect associations between the expression of the above proteins by liposarcoma cells and clinical outcome. CONCLUSIONS: Liposarcomas do not express E-cadherin, which matches the absence of epithelioid differentiation in this sarcoma subtype, and have low topoisomerase II-alpha expression, which justifies to some extend their resistance to anthracycline-based chemotherapy.

Prognostic impact of lymphangiogenesis and lymphatic invasion (CD105 expression) in small cell lung carcinoma.

BACKGROUND: Lymphangiogenesis, an essential process in the metastasis of malignant tumors, has not been thoroughly studied. The possibility of using it to define subsets of patients with different prognosis in cancer could be of vital clinical importance. MATERIALS AND METHODS: Fifty patients (5 women, 45 men; mean age, 64.47 years) with SCLC were retrospectively studied. Tumor specimens were stained for CD105, and intratumoral lymphatic microvessel density (ILMVD) and lymphatic invasion were determined. RESULTS: Twenty-five patients were diagnosed with limited and 25 with extensive SCLC. All patients received chemotherapy and 32.7% radiation therapy. A direct association between ILMVD (CD105 expression) and lymphatic invasion was observed (p<0.046). CD105 expression was significantly associated with the stage of the disease (p=0.004) and the presence of metastasis (p=0.05). CONCLUSION: CD105 expression and lymphatic invasion correlated significantly with the clinical parameters and patient outcome, therefore, constituting an important prognostic role in SCLC.

Immunohistochemical expression of cell-cycle proteins in gastric precancerous lesions.

BACKGROUND: The early indicator for the subject predisposed to gastric cancer is abnormal proliferation of gastric epithelial cells, such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia, which have been considered as precancerous lesions of gastric cancer. To determine whether p53 protein, cyclins D1, and D3, and p27(kip1) play a role in the carcinogenesis pathway of gastric cancer, we performed an immunohistochemical study of their expression in gastric precancerous lesions. METHODS: A total of 1 45 endoscopic gastric biopsy specimens of AG, IM, and gastric dysplasia were studied. These molecular markers were localized by immunohistochemistry. RESULTS: P53 was expressed in 15% of cases with gastric dysplasia and not in the pre-dysplastic stages of the gastric mucosa. All cases were concerning high-grade dysplasia. Cyclin D1 protein was almost undetectable in the precancerous lesions of gastric cancer. Cyclin D3 protein overexpression was seen in 10% of biopsies with IM, and 50% of biopsies with gastric dysplasia. High expression of p27(kip1) protein was demonstrated in all cases of chronic gastritis. As atrophy, IM, and dysplasia develop, expression of p27(kip1) protein is suppressed. In total, 15% of dysplastic cases showed no expression of p27(kip1) protein. CONCLUSIONS: (i) P53 mutation must be a late event during the development of gastric cancer. (ii) Cyclin D1 protein overexpression may not play a role in the progression from normal to neoplastic gastric mucosa, while overexpression of cyclin D3 is an earlier event during gastric carcinogenesis, and its role must be further evaluated. (iii) Reduced expression of p27(kip1) is a rather early event in gastric tumorigenesis, before dysplastic changes occur.

Necrotizing sarcoid granulomatosis: A distinctive form of pulmonary granulomatous disease.

OBJECTIVES: To define the characteristics of necrotizing sarcoid granulomatosis (NGS) a very rare pulmonary disease hardly recognised by pulmonologists and pathologists. DATA SOURCE: PubMed was searched for the term necrotising or necrotizing sarcoid granulomatosis. STUDY SELECTION: All cases reported in the English literature were included. RESULTS: NGS is presented at all ages (range 8-68 years) with a median age of 42 years old. It shows female (62%) and Caucasian (80%) predominance. The most frequent symptoms are cough, fever, dyspnoea and chest pain. Extra-pulmonary involvement is found in one third of the cases, with ocular being the most common (12.5%). At imaging, multiple nodules (64.75%) or a solitary mass (20.49%) are found accompanied by mediastinal lymphadenopathy at one third of the cases. It can be clinically mistaken for malignancy as it is tumour-like, increases rapidly in size and it is hyperfixating in PET-SCAN. Histologically, NGS is defined by large areas of necrosis, well-formed granulomas and vascularitis. CONCLUSION: NGS is a disease often confounded clinically with malignancy or with sarcoidosis even histologically when all criteria are not strictly applied. This review provides NGS' characteristics and discusses its differential diagnosis form sarcoidosis, Wegener granulomatosis and tuberculosis.

Alterations of p53 and Rb Pathways Are Associated with High Proliferation in Bladder Urothelial Carcinomas.

BACKGROUND/AIM: Since most cancers are associated with alterations of the p53 and Rb pathways, the expression of p53, p21, Rb, p16, p27, cyclin D1, cyclin A, cyclin B1 and Ki67 proteins were analyzed in bladder urothelial carcinomas (BUC). MATERIALS AND METHODS: One hundred twenty-two cases of BUC were studied by immunohistochemistry. RESULTS: The pathways p53/p21 and Rb/p16/cyclin D1 exhibited alterations in 81/115 and 63/84 cases, respectively. Alterations of the p53/p21 and Rb/p16/cyclin D1 pathways were positively correlated with high cyclin A expression. High expression of p53, Ki67, cyclin A and cyclin B1 was inversely correlated with the papillary morphology of the tumor and positively with tumor grade and T-stage. CONCLUSION: The results showed that a) alterations of the p53 and Rb pathways are associated with high proliferation of tumor cells in BUC and b) high expression of cell-cycle proteins is associated with adverse histopathological parameters of these tumors.

MRI in the histologic characterization of testicular neoplasms.

OBJECTIVE: The purpose of our study was to investigate the potential role of MRI in the preoperative characterization of the histologic type of testicular tumors and, more specifically, to differentiate seminomatous from nonseminomatous testicular neoplasms. MATERIALS AND METHODS: Twenty-one patients with histologically proven germ cell testicular tumors underwent MRI of the scrotum on a 1.5-T unit. T2- and T1-weighted sequences before and after i.v. administration of gadolinium chelate were performed. MRI studies were retrospectively reviewed by two radiologists and findings were correlated with the histopathologic diagnosis. An attempt was made to differentiate seminomatous from nonseminomatous testicular tumors on the basis of signal intensity and homogeneity of the lesions, presence of fibrovascular septa, tumor encapsulation, and patterns of contrast enhancement. Interobserver agreement was assessed using weighted kappa statistics. RESULTS: MRI findings correctly characterized 19 (91%) of 21 testicular neoplasms (nine seminomatous and 10 nonseminomatous testicular tumors), with excellent interobserver agreement. The presence of an intratesticular lesion of predominantly low signal intensity on T2-weighted images, with septa enhancing more than tumor tissue after contrast material administration, was more suggestive for the diagnosis of a seminoma. Tumors that were markedly heterogeneous both on unenhanced and contrast-enhanced images were indicative of a nonseminomatous neoplasm. CONCLUSION: Our study shows that MRI provides a credible preoperative differentiation of seminomatous from nonseminomatous testicular tumors, with excellent interobserver agreement.

Association of liver cirrhosis related IgA nephropathy with portal hypertension.

A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed.

Cytoplasmic expression of c-erb-B2 in endometrial carcinomas.

BACKGROUND: The aim of this study was to investigate the expression of c-erb-B2 in endometrial cancer with attention to both membranous and cytoplasmic staining, and to elucidate the significance of cytoplasmic signaling. MATERIALS AND METHODS: c-erb-B2 reactivity was assessed by immunohistochemistry in 110 patients using a polyclonal antibody, and evaluated semiquantitatively according to the percentage of cells demonstrating membranous or diffuse cytoplasmic staining. Correlation was made with tumor stage, grade, myometrial invasion, histologic type, and disease outcome. RESULTS: c-erb-B2 overexpression, indicated by membranous and cytoplasmic staining of at least 10% of the tumor cells, was found in 47 (42.7%) cases. Cytoplasmic expression of c-erb-B2 was observed more frequently than membranous (69.1 vs. 5.5%). Synchronous cytoplasmic and membranous signaling was noticed in 7.9% of cases. Interestingly, patients with cytoplasmic c-erb-B2-positive tumors had a significantly shorter survival (p = 0.047). CONCLUSIONS: These results indicate that c-erb-B2 is a specific marker of endometrial cancer. It is also an independent prognostic indicator of poor outcome. Cytoplasmic staining is as important as membranous staining, and is also a specific finding.

Neurological manifestations of connective tissue diseases mimicking multiple sclerosis.

The objective of the study was to analyze retrospectively the clinical, laboratory and imaging findings of multiple sclerosis (MS), such as the manifestations in a cohort of 132 patients referred to the neurology in and outpatient clinic. The proposed clinical and laboratory diagnostic criteria for MS and connective tissue disorders were systematically assessed in 132 consecutive patients. Cerebrospinal fluid serology and brain or spinal cord MRI were studied in all cases. In patients suspected for connective tissue disorder, schirmer test, rose bengal staining and biopsy of minor salivary glands were performed. A total of 115 (87%) patients were diagnosed to have definite MS, while 17 (13%) were diagnosed to have connective tissue disorder. Positive neurological and MRI findings were observed in both groups. The majority of patients with connective tissue disorder demonstrated extra-neurological manifestations like Raynaud's phenomenon, arthritis, livedo reticularis, purpura and presence of multiple autoantibodies in their sera. All patients with MS should be screened systematically for connective tissue disorder. In the absence of pathognomonic clinical and laboratory findings, the diagnosis of MS is a diagnosis of exclusion.

Primary Pulmonary Malignant Melanoma: Report of an Important Entity and Literature Review.

Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are extremely rare. Published data on primary pulmonary malignant melanomas are limited. Up to now 40 relevant cases have been reported in the English literature. Herein, we report a case of a 56-year-old female patient who presented with intracranial metastases due to primary pulmonary melanoma. She underwent bronchoscopy and died 5 months after the initial diagnosis despite the administered biochemotherapy and subsequent immunotherapy. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin was excluded by detailed examination and radiographic imaging. Moreover, an extensive review of the literature regarding this rare entity has been performed.

Dysadherin expression in head and neck squamous cell carcinoma: association with lymphangiogenesis and prognostic significance.

Dysadherin is a recently characterized cancer-associated cell membrane glycoprotein that has a crucial role to cell-cell adhesiveness. The aim of this study was to examine dysadherin expression in head and neck squamous cell carcinoma (HNSCC). A total of 108 tissue specimens of patients with HNSCC were examined using immunostaining for dysadherin, E-cadherin, and the specific lymphatic endothelium marker D2-40. We quantified dysadherin and E-cadherin expression, assessed intratumoral (ILD) and peritumoral lymphatic density (PLD), and examined the possible associations of all the above parameters with clinicopathologic features and outcome. Finally, we used double staining with dysadherin and D2-40 to examine the expression pattern of dysadherin simultaneously with the lymphovasculature environment of HNSCC. High dysadherin expression was correlated with higher clinical stage (chi2, P = 0.01), with the presence of lymph node metastasis at the time of diagnosis (chi2, P = 0.02), and with increased ILD (chi2, P = 0.001). We observed an impressive reverse association between increased dysadherin expression and decreased E-cadherin expression (chi2, P < 0.001). Surprisingly, dysadherin-positive cancer cells usually gathered around areas of high intratumoral lymphatic vessel concentration, surrounding and invading small intratumoral lymphatics. Higher clinical stage and increased dysadherin expression were found to be the only significant independent prognostic factors for overall survival (hazard ratio, 3.94; 95% confidence interval, 1.09-14.27 for clinical stage; hazard ratio, 3.92; 95% confidence interval, 1.46-10.51 for dysadherin). The loss of intercellular adhesiveness and increased dysadherin expression seems to be related to lymphangiogenesis in HNSCC, but this should be confirmed by additional studies. Dysadherin expression might be a promising prognostic marker for separation of patients at higher risk.

Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma.

Endoglin (CD105) is a proliferation-associated protein abundantly expressed in angiogenic endothelial cells. Recent studies revealed that CD105 is intensively expressed in tumor vasculature, whereas intratumoral microvessel density (MVD) determined with the use of antibodies to CD105 has been found to be an important prognostic indicator for the outcome in a number of malignancies. In the current study, we investigated endoglin expression and evaluated MVD in 108 patients with head and neck squamous cell carcinoma. Endoglin was intensively expressed in intratumoral blood vessels, whilst lymphatics were rarely positive for CD105. High microvessel density was associated with a more aggressive tumor phenotype, including advanced clinical stage (p = 0.008) and the presence of lymph node metastasis at the time of diagnosis (p = 0.02). When microvessel counts were assessed for their prognostic values (high vs low MVD), there was a statistically significant difference in the overall survival among patients with tumors of the oral cavity and larynx (p < 0.001) and in the disease-free survival among patients with tumors of the lower lip (p = 0.01). The prognostic impact of microvessel density was not dependent on clinical stage or lymph node status. The results of the current study suggest that CD105 is a promising target for tumor imaging and prognosis.

Microvascular density and immunohistochemical expression of VEGF, VEGFR-1 and VEGFR-2 in benign prostatic hyperplasia, high-grade prostate intraepithelial neoplasia and prostate cancer.

INTRODUCTION: The aim of our study was to determine and compare angiogenesis in benign prostatic hyperplasia (BPH), high-grade prostate intraepithelial neoplasia (HGPIN) and prostate cancer (Pca). Moreover, we evaluated its role as a prognostic factor for Pca. MATERIAL AND METHODS: We examined 39, 12 and 51 samples of BPH, HGPIN and Pca, respectively. Immunohistochemical methods were applied in order to evaluate the expression of VEGF and its receptors (VEGFR-1, VEGFR-2), while microvascular density (MVD) was determined using CD105. In Pca samples, we recorded stage, differentiation, perineural invasion, adjuvant radiotherapy and their correlation with angiogenesis. RESULTS: 225 The expression of VEGF, VEGFR-1 and VEGFR-2 was significantly higher in Pca than compared to BPH (p <0.001, p <0.001 and p <0.001, respectively) and HGPIN (p <0.001, p <0.001 and p = 0.04, respectively), while there was no difference between BPH and HGPIN. MVD was higher in Pca compared to BPH (p <0.001) and HGPIN (p <0.01), while there was no difference between BPH and HGPIN. VEGF expression and MVD were significantly greater in Pca samples with poor differentiation (p = 0.044 and p = 0.038, respectively) and perineural invasion (p <0.001 and p = 0.019, respectively), while overexpression of VEGF was associated with advanced pathological stage (p = 0.047). CONCLUSIONS: Angiogenesis is more prominent in Pca than in BPH and HGPIN, while there is no difference between BPH and HGPIN. Pharmaceutical inhibition of angiogenesis could be a valuable therapeutic option for Pca in the near future.

The expression levels of JunB, JunD and p-c-Jun are positively correlated with tumor cell proliferation in diffuse large B-cell lymphomas.

We analyzed the expression of Jun family in relation to CD30 expression, cell proliferation and B-cell differentiation immunophenotypes [Germinal Center and non-Germinal Center] in diffuse large B-cell lymphomas (DLBCL). Expression and high expression of phosphorylated-c-Jun (p-c-Jun), JunB, JunD and CD30 (cut-off scores 20% and 50%, respectively) was found in 18/103, 49/103, 72/101 and 26/102 cases, respectively, and in 6/103, 27/103, 60/101 and 21/102 cases, respectively. The following significant positive correlations were observed: (a) JunB with cyclin A (p = 0.046), cyclin B1 (p = 0.033), cyclin E (p = 0.003), MUM-1 (p = 0.002) and CD30 (p < 0.001), (b) JunD with Ki67 (p = 0.002) and cyclin E (p = 0.014), (c) p-c-Jun with CD30 (p = 0.015), and (d) high p-c-Jun with cyclin A (p = 0.034). The positive correlation between expression of JunB, JunD and p-c-Jun and tumor cell proliferation in DLBCL, suggests that increased JunB, JunD and p-c-Jun expression may be involved in the pathogenesis of DLBCL by increasing tumor cell proliferation.

Hypoxia-induced tumor angiogenic pathway in head and neck cancer: an in vivo study.

Numerous studies indicate the importance of hypoxia-induced pathway in tumor angiogenesis, but in vivo studies examining the importance of this mechanism in prognosis of patients with head and neck squamous cell carcinoma present conflicting results. We performed a retrospective analysis of 81 patients with head and neck squamous cell carcinoma in order to investigate whether hypoxia-inducible factor 1a (HIF-1a) immunohistochemical expression correlates with vascular endothelial growth factor (VEGF) expression and clinicopathologic parameters or prognosis. Our results showed a statistically significant association between HIF-1a and VEGF expression in tumors located in the lower lip and in larynx, but not in those located in the oral cavity. HIF-1a expression had no impact on prognosis, while VEGF expression correlated significantly with adverse prognosis. These findings support the hypothesis that tumor angiogenesis is close related, but not strictly dependent, on the hypoxic conditions of tumor's microenvironment.

Prognostic significance of VEGF immunohistochemical expression and tumor angiogenesis in head and neck squamous cell carcinoma.

PURPOSE: Tumor angiogenesis is crucial for both the growth of the primary tumor and the development of metastases. Among the factors causing tumor angiogenesis, vascular endothelial growth factor (VEGF) is considered as a leading candidate. We aimed to assess the prognostic significance of VEGF and tumor angiogenesis in head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a retrospective study of 69 patients with HNSCC, in order to investigate whether VEGF immunohistochemical expression and tumor angiogenesis correlate with clinicopathological parameters and outcome. Tumor angiogenesis was estimated by determining microvessel density (MVD), and VEGF expression was assessed quantitatively. RESULTS: Vascular endothelial growth factor and MVD correlated statistically significant with the clinical stage, but not with the presence of lymph node metastasis at the time of diagnosis. Tumors located in the oral cavity and larynx more often expressed high VEGF immunostaining compared with tumors located in the lower lip. High VEGF expression was associated with higher clinical stage and worse overall survival in this cohort of patients. CONCLUSIONS: Vascular endothelial growth factor expression may have prognostic significance for patients with HNSCC.

Expression of vascular endothelial growth factor and its receptor, KDR/Flk-1, in soft tissue sarcomas.

The aim of the present study was to evaluate the association of vascular endothelial growth factor (VEGF) and its receptor, KDR/Flk-1, with tumor grade, microvessel density (MVD) and clinical outcome in patients with soft tissue sarcomas (STSs). Tissue specimens of 28 patients with STSs were analyzed immunohistochemically using specific monoclonal antibodies. Tissue samples were obtained prior to any treatment. Half of the STSs exhibited strong expression of VEGF that was associated statistically significantly with high tumor grade. Strong expression of KDR/Flk-1 was detected in only 2 sarcomas. No association was demonstrated between VEGF and KDR/Flk-1 expression. MVD was significantly associated with tumor grade and was higher in sarcomas with strong VEGF expression. Limited data on clinical outcome precluded solid analyses for an association with disease progression. This study provides further evidence on the role of VEGF and MVD in tumor aggressiveness in STSs.

Pleural neoplastic pathology.

BACKGROUND/PURPOSE: Malignant pleural effusion is a frequent situation in pulmonary medicine. However, it is sometimes difficult to recognize the underlying etiology. The aim of this review is to provide the key characteristics of primary and metastatic pleural neoplasms. METHODS: A review of the recent literature regarding pleural neoplasia is provided. RESULTS: Malignant pleural mesothelioma (MPM) is the commonest primary pleural epithelial tumor showing remarkable histological heterogeneity often with prognostic significance. Various genetic alterations like changes in INK4 locus, NF2, BAP1 but also epigenetic changes are present in MPM. It should be distinguished from atypical mesothelial hyperplasia, mainly through morphological and clinical criteria, and from other rare primary and metastatic tumors, for which immunohistochemistry is rather important. Solitary fibrous tumor, the commonest primary pleural mesenchymal tumor is characterized by STAT6 overexpression. Other primary tumors, like adenomatoid tumor, well-differentiated papillary mesothelioma, synovial sarcoma, vascular tumors, various other sarcomas, thymic tumors and tumors of uncertain histogenesis are rarely encountered in the pleura. In contrast, metastatic disease is the commonest neoplasia of the pleura, and especially lung, breast and lymphoid malignancies. CONCLUSION: The basic pathological, immunohistochemical and molecular characteristics of these entities are provided in the current review, along with their differential diagnosis.

Estrogen receptor beta (ERbeta) is expressed in brain astrocytic tumors and declines with dedifferentiation of the neoplasm.

PURPOSE: Estrogen receptor beta (ERbeta) is the second identified receptor mediating the effects of estrogen on target tissues. The role of ERbeta in cancer pathobiology is largely unknown, because specific antibodies have not been available until recently. Initial studies have shown that ERbeta expression declines in breast, ovarian, prostatic, and colon carcinomas. Tamoxifen, a synthetic anti-estrogen compound that is a mixed agonist/antagonist of estrogen receptor alpha (ERalpha) and a pure antagonist of ERbeta, has moderate beneficial effects in human astrocytic neoplasms. However, most published studies agree that glial tumors do not express ERalpha. The purpose of this study was to explore the expression of ERbeta in astrocytic neoplasms. METHODS: ERbeta expression was monitored immunohistochemically in 56 cases of astrocytomas of all grades (grade I-IV) and in adjacent non-neoplastic brain tissue. RESULTS: Moderate or strong nuclear immunopositivity was obtained in non-neoplastic astrocytes and in low-grade astrocytomas, whereas the majority of high-grade tumors were immunonegative or displayed weak immunoreactivity. The progressive decline in ERbeta expression paralleled the increase in tumor grade. CONCLUSIONS: In as much as ERbeta is possibly the only ER expressed in astrocytes, its decreased expression may play an important role in astrocytic tumor initiation and in the potential response of glial neoplasms to tamoxifen.