Biomedical subjects

G Sotiropoulou-Bonikou

Publications and source records attributed to G Sotiropoulou-Bonikou.

9 recordsLinked to original sources

PubMed2004

Androgen receptor (AR) expression is an independent unfavorable prognostic factor in gastric cancer.

PURPOSE: To investigate the expression of sex steroid receptors in gastric cancer and to correlate their tumor expression profile with the clinicopathological parameters and overall survival of the patients. METHODS: Immunohistochemical methodology was employed in formalin-fixed paraffin-embedded sections from 86 patients with gastric carcinoma. Monoclonal antibodies against androgen (AR), estrogen (ER), and progesterone (PR) receptors were used. Survival rates were estimated by the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed by the Cox proportional hazards model. RESULTS: Fifteen (17.4%) cases of gastric adenocarcinomas were positive for AR, two (2.3%) were positive for PR and three (3.5%) were positive for ER. Significantly higher AR expression was found in tumors with metastases to lymph nodes (P = 0.03). Patients with AR-positive tumors (AR+) had worse prognosis than (AR-) patients (median survival 9 months vs 24 months, P = 0.03). Patients with AR- and heat shock protein 27 (HSP27)-positive tumors (AR+/HSP27+) had a median survival of 6 months, whereas (AR-/HSP27-) patients had a median survival of 42 months (P = 0.017). Multivariate analysis revealed that AR expression and UICC stage were independent factors of unfavorable prognosis (P = 0.037 and P = 0.0055, respectively). CONCLUSIONS: Identification of AR-positive gastric carcinomas in gastric biopsies may warrant a more aggressive therapeutic approach and anti-androgen or AR-targeted agents may represent a novel strategy in tackling this devastating malignancy.

Adult↗

PubMed2004

Differential expression of retinoic acid receptor beta (RARbeta) and the AP-1 transcription factor in normal, premalignant and malignant human laryngeal tissues.

The anticancer effects of retinoids are mainly mediated by their nuclear receptors. Recent studies have demonstrated that retinoic acid receptor beta (RARbeta) plays a pivotal role from the early stages of laryngeal carcinogenesis; however, the exact mechanism of this detrimental effect has not yet been elucidated. One of the best-documented actions of retinoid receptors is the transrepression of activator protein-1 (AP-1) transcription factor activity, although this complex interplay has not been clarified. The present report is the first systematic morphological evaluation of the cross-talk of RARbeta and AP-1 transcription factor in a large series of human laryngeal tissues containing normal epithelium, premalignant lesions (hyperplasia and/or dysplasia) and squamous cell carcinoma. Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections by using a panel of monoclonal and polyclonal antibodies against RARbeta and the AP-1 components c-Jun, p-c-Jun (phosphorylated, active c-Jun) and c-Fos proteins. Their expression was screened and compared in 154 patients with various laryngeal histological entities. Nuclear expression of RARbeta, c-Jun, p-c-Jun and c-Fos was detected in 81 (89.2%), 48 (52.8%), 66 (72.6%) and 73 (80.3%), respectively, out of 91 specimens with normal-appearing laryngeal epithelium; in 86 (87.8%), 94 (95.9%), 94 (95.9%) and 94 (95.9%), respectively, out of 98 specimens with hyperplastic laryngeal epithelium; in 58 (56.8%), 92 (90.2%), 96 (94.1%) and 96 (94.1%), respectively, out of 102 specimens with dysplastic laryngeal epithelium; in 10 (22.3%), 41 (91.2%), 44 (97.8%) and 41 (91.2%), respectively, out of 45 specimens with well-differentiated squamous cell carcinoma; in 13 (30.3%), 37 (86%), 39 (90.7%) and 41 (95.3%), respectively, out of 43 specimens with moderately-differentiated squamous cell carcinoma; and in 8 (66.7%), 10 (83.3%), 12 (100%) and 12 (100%), respectively, out of 12 specimens with poorly-differentiated squamous cell laryngeal carcinoma. Statistical analysis and correlation of the intensity of nuclear immunostaining of the studied proteins among the various histological entities revealed statistically significant results. The progressive upregulation of the AP-1 transcription factor constituents and downregulation of the RARbeta protein detected from the onset of laryngeal tumorigenesis suggests an important role for the immediate-early AP-1/RARbeta on/off "switch" in the process of laryngeal carcinogenesis.

Adult↗

PubMed2003

Oestrogen receptor beta (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation.

Oestrogen Receptor beta (ERbeta) may protect against prostate and mammary cell proliferation and malignant transformation. Epidemiological studies indicate that oestrogens may reduce colon cancer risk. Since ERalpha is minimally expressed in normal and malignant colon, the aim of this study was to investigate the expression of ERbeta in both normal colonic wall and colon cancer. ERbeta expression was evaluated by immunohistochemistry in 90 cases of colon adenocarcinoma and nearby (>30-cm away) normal colonic wall, using a monoclonal antibody. Moderate or strong nuclear immunostaining was detected in superficial and crypt epithelium, endothelial cells, vascular smooth muscle cells, lymphocytes, enteric neurons and smooth muscular cells of the normal colonic wall. Superficial epithelial cells in normal colon demonstrated a significantly higher ERbeta expression than colon adenocarcinoma cells in both genders. The decline in ERbeta expression paralleled the loss of differentiation of malignant colon cells, regardless of the tumour's localisation. These findings suggest a protective role for ERbeta against colon carcinogenesis.

Adenocarcinoma↗

PubMed2002

Expression of the 27-kDa heat shock protein (HSP27) in gastric carcinomas and adjacent normal, metaplastic, and dysplastic gastric mucosa, and its prognostic significance.

PURPOSE: The investigation of heat shock protein 27 (HSP27) expression in gastric cancer and adjacent normal, metaplastic, and dysplastic gastric mucosa and its correlation with clinicopathological parameters and survival of patients. METHODS: Immunohistochemical methodology was performed on formalin-fixed paraffin-embedded sections by using a monoclonal anti-HSP27 antibody. HSP27 expression was screened and compared in 86 cases of gastric carcinoma and adjacent normal, metaplastic, and dysplastic gastric mucosa. RESULTS: In the normal mucosa, HSP27 was detected in 68 out of 86 cases (79%) and was more intense in the surface and upper two-thirds of gastric foveolae. In dysplastic gastric mucosa, HSP27 immunoreactivity was usually higher than that of the adjacent normal epithelium and was parallel to the severity of dysplasia. HSP27 expression was found in 54 out of 86 (62.7%) gastric carcinomas and was significantly related to more than six metastatic lymph nodes ( P =0.03). HSP27 expression was also higher in tumors of advanced stage and in those of female patients. HSP27 expression was associated with shorter overall survival in univariate analysis ( P =0.04), but this relationship was not retained in multivariate analysis. CONCLUSIONS: Our findings indicate that: i) HSP27 is commonly expressed in normal gastric epithelium where it seems to exert a protective role; and ii) HSP27 is involved in gastric carcinogenesis and its expression appears to be associated with parameters of unfavorable prognosis and shorter overall survival.

Adult↗

PubMed2002

Induction of the CBP transcriptional co-activator early during laryngeal carcinogenesis.

PURPOSE: CREB-binding protein (CBP) is a transcriptional "integrator" that is suspected of contributing to tumorigenesis. This is the first systematic morphologic study evaluating CBP expression in a large series of human laryngeal tissues containing normal epithelium, premalignant lesions (hyperplasia and/or dysplasia), and squamous cell carcinoma. METHODS: Immunohistochemical methodology was performed on formalin-fixed paraffin-embedded sections by using a monoclonal anti-CBP antibody. CBP expression was screened and compared in 156 patients with various laryngeal histologic entities. RESULTS: Nuclear expression of CBP was found in 44 out of 91 (48.4%) specimens with normal-appearing epithelium (46.2% weak and only 2.2% moderate positivity), 92 out of 100 (92%) with hyperplastic lesions (56% weak, 36% moderate/strong, and only 8% no positivity), 80 out of 103 (77.7%) with dysplastic lesions (45.6% weak, 32.1% moderate/strong, and 22.3% no positivity), 37 out of 45 (82.2%) with well-differentiated carcinoma (42.2% weak, 40% moderate/strong, and 17.8% no positivity), 31 out of 43 (72.1%) with moderately differentiated carcinoma (32.6% weak, 39.5% moderate/strong, and 27.9% no positivity) and eight out of 12 (66.7%) with poorly differentiated carcinoma (41.7% weak, 25% moderate/strong, and 33.3% no positivity). Statistical analysis and correlation of the intensity of nuclear immunostaining among the various histologic entities revealed statistically significant results. CONCLUSIONS: Overexpression of CBP is detected from the very early stages of laryngeal carcinogenesis, suggesting that CBP may play a role in malignant transformation of precancerous laryngeal lesions. It is possible that overexpression of this protein is a prerequisite for the observed p53 upregulation in premalignant lesions, implying an indirect role of CBP in p53-mediated tumorigenic potential.

Adult↗

PubMed2000

Immunohistochemical detection of retinoic acid receptor-alpha in prostate carcinoma: correlation with proliferative activity and tumor grade.

BACKGROUND: The use of retinoids as differentiation therapy is a novel approach to prostate cancer. Retinoids act via their own nuclear receptors, RARs and RXRs, modulating gene activity, cell growth and differentiation. This study provides new data on the content and cellular distribution of RARalpha protein in prostate cancer specimens, in correlation to tumor grade and proliferative activity. MATERIAL AND METHODS: A total of 84 cases of primary prostate carcinoma, divided into 3 subgroups according to tumor grade, were immunohistochemically evaluated for retinoic acid receptor-alpha (RARalpha) and Ki67 using the streptavidin/peroxidase method on formalin fixed, paraffin embedded tissues. RESULTS: RARalpha positivity was detected in all cases of prostatic carcinoma, with a more profound expression in well differentiated cancers. A statistically significant correlation between RARalpha staining and tumor grade was found (ANOVA, p < 0.031). Ki67 immunoreactivity was present in 35.7% of cases, but no correlation with tumor grade was found. When RARalpha staining was correlated with Ki67 positivity, a statistically significant correlation was present (unpaired t-test, p < 0.003). CONCLUSIONS: These findings indicate that RARalpha expression is correlated to some extent with tumor grade and its presence is more profound in highly proliferative tumors. Further studies are needed to establish the possible clinical value of the immunohistochemical evaluation of RARalpha content in tumor specimens.

Aged↗

PubMedDate not supplied

Prognostic significance of Hsp-27 in astrocytic brain tumors: an immunohistochemical study.

Formalin-fixed paraffin-embedded tumor specimens from 95 patients with supratentorial astrocytic brain tumors were immunostained by a monoclonal antibody against the heat shock protein-27 (Hsp-27) using the streptavidin/peroxidase method. The immunohistochemical analysis was scored in a semiquantitative fashion incorporating both the intensity and distribution of specific staining (score): the immunohistochemical results were correlated with the histological grade of the tumors and patients' sex and age. Furthermore, Hsp-27 expression was studied in two groups into which the patients were further divided: group (a) previously untreated patients (n = 76) whose biopsy or surgical resection was related to their initial presentation and diagnosis and group (b) patients (n = 19) with reccurent disease who underwent radiotherapy and/or chemotherapy. Strong Hsp-27 cytoplasmic immunopositivity was observed in 42 out of 51 (82%) glioblastomas, in 8 out of 20 (40%) anaplastic astrocytomas and in 2 out of 24 (8%) astrocytomas. The mean Hsp-27 score was 45.2 in glioblastomas, 6.5 in anaplastic astrocytomas and 0.4 in astrocytomas. The expression of Hsp-27 immunoreactivity appeared to be independent of the age and sex of the patients. A non significant difference was defined between untreated patients and previously treated patients. Hsp-27 immunoreactivity was observed in the microvascular endothelial proliferations and in tumor blood vessels. Normal astrocytes were Hsp-27 negative. These findings indicate that, in contrast with the low Hsp-27 expression found in benign astrocytomas, the expression of Hsp-27 in a number of poorly differentiated tumors, including glioblastomas and anaplastic astrocytomas, is consistent and independent of previous treatment of the patients. We support the involvement of Hsp-27 in the growth of astrocytic brain tumors.

Adult↗

PubMedDate not supplied

Microvessel density in brain tumors.

Sections from formalin fixed paraffin embedded tumor tissue from 165 patients with brain tumors including 62 meningiomas, 80 supratentorial astrocytomas (19 astrocytomas-grade I/II, 20 anaplastic astrocytomas-grade III, 41 glioblastomas-grade IV), 7 cerebellar astrocytomas-grade I/II, one gliosarcoma, 7 oligodendrogliomas, 3 ependymomas and 5 medulloblastomas were immunostained for factor VIII-related antigen in order to highlight microvessel endothelial cells. Microvessel count (MVC; the highest number of microvessels in three areas of highest vascular density at X200 magnification) was determined and correlated with histological grade of tumors and patients' sex and age. The mean MVC was 27.9 in meningiomas. Astrocytic tumors, particularly malignant astrocytomas (grade III, IV), were highly vascular. The mean MVC as regards the supratentorial astrocytic neoplasms was 14.5 in astrocytomas (grade I/II), 42.3 in anaplastic astrocytomas (grade III) and 50.2 in glioblastomas (grade IV). All cerebellar astrocytomas studied, even though well differentiated (grade I/II), were highly vascularised tumors (MVC: 41.1. A comparison of the mean MVC vlaues showed that there was a statistically significant difference between supratentorial astrocytomas (Grade I-II) and cerebellar astrocytomas (Grade I-II) (p = 0.0004), anaplastic astrocytomas (Grade I-II) (p = 0.00004) and glioblastomas (p = 0.00001). There was no significant difference between cerebellar astrocytomas and anaplastic astrocytomas (p = 0.8) and glioblastomas (p = 0.4). Astrocytic neoplasms showed statistically significant higher mean MVC from meningiomas (p = 0.002). The mean MVC was 14.1 in oligodendrogliomas, 22.7 in ependymomas and 19.6 in medulloblastomas. In one gliosarcoma that was studied the MVC was 40. The MVC appeared to be independent of the age and sex of patients. This study supports the importance of microvessel density as a measure of angiogenesis, as well as a further morphologic feature in the classification of brain tumors. The determination of microvessel density may become useful in the planning and monitoring of anti-angiogenesis therapies of these tumors.

Adult↗

PubMedDate not supplied

Does sex steroid receptor status have any prognostic or predictive significance in brain astrocytic tumors?

Formalin-fixed paraffin-embedded tumor specimens from 90 patients with supratentorial astrocytic brain tumors were immunostained following microwave pretreatment using monoclonal antibodies against estrogen receptor (ER), progesterone receptor (PgR), and PS2 protein (PS2) and the streptavidin/peroxidase method. The immunohistochemical analysis was scored in a semiquantitative fashion incorporating both the intensity and distribution of specific staining (SCORE) and the immunohistochemical results were correlated with histologic grade of tumors and patient's sex and age. Strong PgR nuclear immunopositivity was observed in 27 of 46 (59%) glioblastomas, in 9 of 20 (45%) anaplastic astrocytomas, and in 2 of 24 (8%) astrocytomas. The mean PgR score was 18.5 in glioblastomas, 11.3 in anaplastic astrocytomas, and 0.9 in astrocytomas. The expression of PgR immunoreactivity appeared to be dependent on the age and independent of the sex of patients. All tumors were negative for ER and PS2 protein. Normal astrocytes remained consistently negative for both sex steroid receptors and PS2. Our findings indicate a consistent expression of PgR in a number of poorly differentiated tumors including glioblastomas and anaplastic astrocytomas contrasting with the low PgR score values found in benign astrocytomas. The absence of ER and PS2 immunoreactivities supports the hypothesis that estrogen receptor in astrocytic tumors is probably truncated. However, regional tumor heterogeneity may be a limiting factor for the use of ER, PgR, PS2 immunohistochemistry in the evaluation of routine pathology specimens examination.

Adolescent↗