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Biomedical subjects

A Reinthaller

Publications and source records attributed to A Reinthaller.

At least 37 records · Page 2Linked to original sources

Tumor angiogenesis in stage IB cervical cancer: correlation of microvessel density with survival.

OBJECTIVE: Because angiogenesis is considered essential for tumor growth and the development of metastasis, we assessed the correlation of microvessel density with overall survival in patients with clinical stage IB carcinoma of the uterine cervix. STUDY DESIGN: Histologic slides were immunostained for factor VIII-related antigen. Microvessel density was determined within each tumor by enumeration under a light microscope at 200x magnification and an examination area of 0.25 mm2. The Cox proportional hazards model was used for multivariate analysis. RESULTS: In 166 patients with stage IB cervical cancer the 5-year survival was as follows: 89.7% in 102 patients whose tumors had a microvessel density < or =20/field, and 63.0% in 64 patients whose tumors had a microvessel density >20/field (log rank p < 0.0001). In the multivariate Cox model microvessel density, lymph node involvement, tumor size, and the application of radiation therapy remained independent prognostic factors for survival, whereas lymphatic vascular space involvement failed to retain a significant value. CONCLUSION: High microvessel density adversely influences patients' survival in clinical stage IB cervical cancer and identifies patients with negative nodes at risk for relapse.

Adult↗

The prognostic value of CD44 isoform expression in endometrial cancer.

Isoforms of the transmembrane glycoprotein CD44 have been implicated in tumour cell adhesion, tumour differentiation and metastatic spread in various human malignancies. We investigated the expression of CD44 isoforms containing variant exons v3, v5, v6 and v7-8 in 156 human endometrium cancer specimens by means of immunohistochemistry. CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 were detected in 26% (41 out of 156), 31% (48 out of 156), 22% (35 out of 156) and 15% (23 out of 156) of the tumour samples respectively. The expression of CD44 isoforms CD44v3, CD44v5 and CD44v7-8 showed no prognostic impact. In the univariate analysis, the expression of CD44v6 showed an association with shortened overall survival (log-rank test, P = 0.06). Multivariate analysis correcting for the confounding variable histological grading revealed CD44v6 not to be a prognostic factor in endometrial cancer (log-rank test, P = 0.06). Comparing the expression of CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 in 45 specimens of normal endometrial tissue, we found an up-regulation of all investigated CD44 isoforms in the secretory phase compared with the proliferative phase of the menstrual cycle. Our data indicate that the expression of CD44 isoforms, while obviously playing a role in the functional changes of normal endometrium, is not an adverse predictive factor in endometrial cancer.

Aged↗

CD44v3 and v6 variant isoform expression correlates with poor prognosis in early-stage vulvar cancer.

Expression of alternatively spliced CD44 isoforms has been reported to correlate with poor prognosis in human squamous cell cancers, i.e. squamous cell cancer of the lung and cervix. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in early-stage squamous cell cancer of the vulva. Seventy cases of squamous cell carcinoma of the vulva International Federation of Gynaecology and Obstetrics (FIGO) stage I were examined immunohistochemically for expression of CD44 isoforms. We used four different variant exon sequence-specific murine monoclonal antibodies to epitopes encoded by exons v3, v5, v6 and v7-8 of human variant CD44. The correlation of CD44 expression with histological grade and disease-free and overall survival was investigated. CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 were detected in 28% (20/70), 47% (33/70), 33% (23/70) and 17% (12/70) of the tumour samples respectively. Patients suffering from tumours expressing CD44v6 had a poorer relapse-free (log-rank test, P = 0.02) and overall survival (log-rank test, P = 0.03). Likewise, patients suffering from tumours expressing CD44v3 had a poorer relapse-free (log-rank test, P = 0.04) and overall survival (log-rank test, P = 0.01). Expression of CD44v5 and CD44v7-8 did not compromise the patients' outcome. Histological grade did not correlate with CD44 isoform expression. Immunohistochemically detected expression of CD44 isoforms containing variant exon v6 or v3 is correlated with a poor relapse-free and overall survival in FIGO stage I vulvar cancer patients.

Adult↗

CD44 is an independent prognostic factor in early-stage cervical cancer.

The expression of specific cell-adhesion molecule CD44 isoforms (splice variants) is associated with metastatic spread and poor prognosis in human malignancies. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in early-stage cervical cancer. We used 4 different variant exon sequence-specific murine monoclonal antibodies to the CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 to study the prognostic value of CD44 splice variants in 200 cases of International Federation of Gynecology and Obstetrics (FIGO) stage-IB cervical cancer by immunohistochemistry. In the univariate analysis, the expression of CD44v3 (log-rank test, p = 0.03) and CD44v6 (log-rank test, p = 0.03) was correlated with poor overall survival. In the subgroup of patients without metastatic disease in the pelvic lymph nodes, expression of CD44v6 was correlated with poor disease-free and overall survival (log-rank test, p = 0.04 and p = 0.01, respectively). Multivariate analysis, correcting for the confounding variables pelvic lymph-node involvement, depth of invasion and histologic grading, revealed CD44v6 to be an independent prognostic factor for overall survival of patients with early-stage cervical cancer. The results of this study indicate that CD44v6 is an additional prognostic marker in surgically treated cervical cancer. The assessment of CD44 isoform expression could be of clinical value in deciding upon adjuvant therapy, resulting in a more individualized management of therapy.

Adult↗

Taxol as second-line treatment in patients with advanced ovarian cancer after platinum-based first-line chemotherapy.

Salvage chemotherapy in platin-resistant patients typically results in low response rates and short survival, therefore new active cytotoxic agents must be found. One of these agents is paclitaxel (Taxol), isolated from the bark of the western yew which acts as an antimicrotubule agent. In our study 28 patients were treated with Taxol, 20 of whom had platinum-resistant tumors. Taxol was administered at a starting dose of 175 mg/m2, infused over 3 hr every 21 days. A total of 145 courses of Taxol was infused. Dexamethasone, diphenhydramine, and ranitidine were given as premedication. The response rate was 25% (3 complete and 4 partial remissions), the median survival duration was 15 months. In contrast to other studies we found a lower response rate in patients resistant to platinum-based therapy: 15% (no complete, 3 partial remissions). The most common severe toxicity was leukopenia, with grade 3 toxicity occurring in 10% of the courses; no grade 4 leukopenia or neutropenia was noted. Neurologic toxicity was a clinically significant adverse effect, with 1% of patients experiencing grade 3, 9% experiencing grade 2, and 3% experiencing grade 1 toxicity. Other adverse effects were less frequent and less severe. We conclude that paclitaxel, which in a prospective randomized trial has been shown to be the most active treatment of advanced ovarian cancer, yields low response rates in platinum-resistant patients. Only a few of them profited from second-line treatment with Taxol. This could be a new aspect in the treatment of platinum-resistant ovarian cancer with Taxol.

Adult↗

Serum M3/M21 in cervical cancer patients.

Cytokeratins are polypeptides which constitute a subclass of intermediate filaments in epithelial cells. The serum tumour marker M3/M21 is based on monoclonal antibodies against the epitopes M3 and M21 of cytokeratin 18. In the present study, we measured M3/M21 serum levels in 50 patients with FIGO stage IB-IIB cervical cancer and in 50 control subjects using a two-site radiometric immunoassay directed against soluble fragments of cytokeratin 18. Median serum levels of M3/M21 in patients with cervical cancer and in normal controls were 70.6 U/ml (range 0-397.7) and 6.5 U/ml (range 0-205.2), respectively (Mann-Whitney U-test, P = 0.0001). Median serum levels of M3/M21 prior to therapy and 4 weeks after therapy were 104.2 U/ml (range 24.6-397.7) and 39.3 U/ml (range 0-234.7), respectively (Mann-Whitney U-test, P = 0.004). We found a significant correlation between elevated M3/M21 serum levels and metastatic disease in pelvic lymph nodes (Mann-Whitney U-test, P = 0.002). 24 patients relapsed after complete remission. In these patients, elevated M3/M21 serum levels before the detection of relapse by computed tomography was observed in 13 cases. Considering these preliminary results, further studies with an increased number of patients are justified to clarify the prognostic value and the monitoring abilities of M3/M21 in cervical cancer patients.

Antibodies, Monoclonal↗

Serum M3/M21 in ovarian cancer patients.

Cytokeratins are polypeptides that constitute a subclass of intermediate filaments in epithelial cells. The aim of the present study was to evaluate the clinical usefulness of the serum evaluation of M3/M21 in patients with ovarian cancer. This retrospective study comprises 75 patients suffering from ovarian cancer FIGO stages Ia-III. M3/M21 reached a sensitivity of 78%, a specificity of 85%, a PPV of 89% and a NPV of 83% using a cut-off level of 45 U 1(-1). Forty-four women developed recurrent disease after complete remission during the observation period. M3/M21 showed lead time effects in 19 patients, ranging from 2 to 8 months (median 3.2 months). Elevated M3/M21 serum levels before therapy were associated with a poor overall survival (log-rank test, P = 0.02). Considering these preliminary results, the value of M3/M21 as a serum tumour marker, i.e. to evaluate the tumour burden, seems promising.

Adult↗

Prognostic value of immunohistochemically detected CD44 expression in patients with carcinoma of the vulva.

BACKGROUND: Overexpression of alternatively spliced CD44 isoforms has been reported to correlate with poor prognosis in several human malignancies. To the authors' knowledge, there are no studies concerning the prognostic value of CD44 isoform overexpression in patients with squamous cell carcinoma of the vulva. METHODS: Thirty cases of squamous cell carcinoma of the vulva with International Federation of Gynecology and Obstetrics Stage I to III were examined immunohistochemically for overexpression of CD44 isoforms. We used 3 different variant exon sequence-specific murine monoclonal antibodies to CD44 isoforms containing variant exons v5, v6, and v7 to -8, respectively. The correlation of CD44 overexpression with clinical stage, histologic grade, and disease free and overall survival was investigated. RESULTS: CD44 isoforms CD44v5, CD44v6, and CD44v7-8 were detected in 83% (25/30), 63% (19/30), and 27% (8/30) of the tumor samples, respectively. Patients with tumors overexpressing CD44v6 showed a significantly shorter relapse free (log rank test, P = 0.002) and overall survival (log rank test, P = 0.003) compared with patients with tumors lacking CD44v6 overexpression. Expression of CD44v5 and CD44v7 to 8 had no impact on patients' survival. Clinical stage and histologic grade did not correlate with CD44 overexpression. CONCLUSIONS: Immunohistochemically detected overexpression of CD44 isoforms containing variant exon v6 is correlated with a poor relapse free and overall survival in patients with carcinoma of the vulva.

Adult↗

p53 protein overexpression in early stage endometrial cancer.

Overexpression of p53 protein has been reported to correlate with a poor prognosis in endometrial cancer. Most endometrial adenocarcinomas are clinical stage I at the time of diagnosis and the majority of women to die of this neoplasm had stage I disease at initial presentation. The aim of our study was to evaluate the prognostic significance of p53 overexpression in early stage endometrial carcinoma. Ninety-two patients with surgically treated endometrial adenocarcinoma FIGO stage I were examined for overexpression of immunohistochemically detected mutant p53 protein. Follow-up time ranged from 0.4 to 137.8 months (mean, 34.8). Thirteen women died of their tumor. A nuclear staining reaction for p53 was observed in eight cases. Women with p53 protein overexpression showed a significant poorer overall survival in univariate analysis (relative risk, 4.78; 95% confidence interval, 1.56-14.61; P = 0.006, Wald test) and also in multiple analysis adjusted for grading (relative risk, 4.39; 95% confidence interval, 1.39-13.90; P = 0.01, Wald test). Histological grading and histologic stage did not correlate with p53 protein overexpression (P = 0.26, P = 1.0, respectively, exact chi 2 test). Immunohistochemically detected p53 protein overexpression in early stage endometrial adenocarcinoma could aid in predicting prognosis and subsequently have some impact on adjuvant therapy.

Adenocarcinoma↗

Influence of microvessel density and vascular permeability factor/vascular endothelial growth factor expression on prognosis in vulvar cancer.

Microvessel density (MVD) and expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), acting as a highly specific inducer of angiogenesis, were evaluated in tissue specimens of 25 patients with squamous cell cancer of the vulva. MVD was quantified by immunostaining for factor VIII-related antigen at one field of 0.25 mm2. VPF/VEGF expression was evaluated immunohistochemically using a monoclonal anti-VEGF antibody. FIGO stages I, II, and III were diagnosed in 12, 7, and 6 patients, respectively. MVD >20/field was found in 10 of 25 tumors and moderate or strong expression of VPF/VEGF in 10 of 25 tumors. High MVD was significantly more frequent in tumors with moderate or strong VPF/VEGF expression compared to tumors with no or weak VPF/VEGF expression (P = 0.01). Overall survival rates of patients with tumors of high MVD (P = 0.01) and strong VPF/VEGF expression (P < 0.01) were significantly poorer compared to those patients with low MVD or poor VPF/VEGF expression. Strong VPF/VEGF expression and high MVD are considered important parameters of tumor angiogenesis and therefore are related to poor survival probability in vulvar cancer patients.

Adult↗

Radiosurgery in the management of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the loop electrosurgical excision procedure (LEEP) and large loop excision of the transformation zone-conization (LLETZ-conization) in the management of cervical intraepithelial dysplasia using high-frequency, filtered waveform energy (radiosurgery). STUDY DESIGN: Two hundred thirteen women attending the outpatient cervical colposcopy clinic with smears consistent with an epithelial abnormality, but macroscopically or colposcopically not consistent with invasive carcinoma, were included in the study. LEEP and LLETZ-conization were performed in 72 and 141 women, respectively. A matched pair group of patients undergoing cold knife conization was used for the comparison with LLETZ-conization. Using LEEP, in 83% a clear resection margin of the biopsy specimen was achieved. In this subset, diagnosis and therapy were achieved in a single visit. No complications, such as hemorrhage, occurred during the operation or postoperative period. RESULTS: Comparison of LLETZ-conization with the matched-pair group undergoing cold knife conization showed a significantly shorter duration of surgery for LLETZ-conization (mean, 10.8 vs. 16.5 minutes, P < .001). We found no differences concerning posttreatment bleeding complications (2.8% vs. 3.3%) or clear resection margins (92% vs. 86%). Patients undergoing LLETZ-conization needed significantly less analgesic (P < .01). CONCLUSION: Radiosurgical loop excision is a safe and cost-effective method in the diagnosis and treatment of cervical intraepithelial neoplasia.

Biopsy↗

Prognostic value of immunohistochemically detected p53 expression in vulvar carcinoma.

BACKGROUND: Overexpression of the p53 protein has been reported to correlate with poor prognosis in several types of tumors. To the authors' knowledge, there are no studies concerning the prognostic value of p53 protein overexpression in squamous cell vulvar carcinoma. METHODS: Twenty-five cases of squamous cell carcinoma of the vulva with International Federation of Gynecology and Obstetrics (FIGO) Stage I-II were examined for p53 protein overexpression using immunohistochemistry. The correlation of p53 protein overexpression with clinical stage, histologic grade, and overall survival was investigated. Follow-up ranged from 36 to 120 months. RESULTS: Clinical stage and histologic grade did not correlate with p53 protein overexpression. p53 protein overexpression was associated with poorer overall survival (log rank: P < 0.05). CONCLUSION: Immunohistochemically detected p53 protein overexpression is significantly correlated with a reduced overall survival rate for patients with vulvar carcinoma.

Adult↗

Serum evaluation of basic fibroblast growth factor in cervical cancer patients.

We present the data of 105 serum samples from 20 patients suffering from cervical cancer. Mean serum levels of basic fibroblast growth factor (bFGF) in patients with or without tumor present were 31.3 +/- 32.1 (minimum 0, maximum 156.7) pg/ml and 4.8 +/- 6.8 (minimum 0, maximum 29.6) pg/ml, respectively (P = 0.0001). bFGF reached a sensitivity of 65.7% at a specificity of 91.5% when applying a cut-off level of 15 pg/ml. Four patients relapsed after complete remission. A continuous increase of bFGF serum levels before the clinical detection of relapse (lead time) was seen in two cases with a mean lead time of 4 months. Preoperative serum levels were not of prognostic value and showed no correlation with pelvic lymph node metastasis. These preliminary results indicate that in cervical cancer patients soluble bFGF may be useful in early detection of primary tumors, recurrences and monitoring of therapy.

Adenocarcinoma↗

Serum CD44 splice variants in cervical cancer patients.

Aberrant expression of the cell adhesion molecule CD44 has been detected in human tumours and has been shown to be associated with metastasis and poor prognosis in human malignancies. We evaluated serum levels of different soluble CD44 molecules (CD44 standard form and CD44 splice variants v5 and v6) in cervical cancer patients stage IB to IIIB. Two-hundred three serum samples were analysed. Serum levels of CD44st and CD44v5 showed no significant correlation with the presence or absence of cervical cancer. The splice variant CD44v6 showed a mean concentration of 227.3 +/- 90.9 (minimum 71.4, maximum 543.9) ng/ml when tumour was present and a mean concentration of 198.7 +/- 135.4 (minimum 67.2, maximum 696.3) ng/ml in cases of complete remission (P-value = 0.0001). However, in this preliminary study the sensitivity/specificity characteristic of CD44v6 was poor.

Adenocarcinoma↗

Cytokeratin subunit 19 measured by CYFRA 21-1 assay in follow-up of cervical cancer.

The purpose of this study was to evaluate the serum tumor markers CYFRA 21-1 and squamous-cell carcinoma antigen (SCC) in the follow-up of squamous-cell cervical cancer patients. One hundred-ninety-three serum samples, which were collected pretherapeutically and during follow-up of 30 patients suffering from squamous-cell cervical cancer FIGO stage III, were analyzed for SCC and CYFRA 21-1. Cutoff values for SCC and CYFRA 21-1 were 3 and 3.3 micrograms/liter, respectively. Fifteen cases were keratinizing and 15 nonkeratinizing squamous-cell carcinomas. Serum tumor marker results were correlated to the results of the clinical and radiologic examinations. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum SCC and serum CYFRA 21-1 for the whole study group and separately for the keratinizing and nonkeratinizing squamous-cell carcinoma group. Sensitivity, specificity, PPV, and NPV of serum SCC were 66, 91, 93, and 60%, respectively. Serum CYFRA 21-1 showed a sensitivity of 63%, specificity of 96%, PPV of 96%, and NPV of 59%. The combination of SCC and CYFRA 21-1 increased the sensitivity to 78%, with a specificity, PPV, and NPV of 87, 91, and 69%, respectively. In keratinizing squamous-cell carcinoma serum SCC, CYFRA 21-1 and the combination of both had a sensitivity of 76, 64, and 85%, respectively. In nonkeratinizing squamous-cell carcinoma sensitivity was 58, 61, and 72%, respectively. The detection of cervical cancer recurrences with SCC is improved by the combination with CYFRA 21-1. Especially in nonkeratinizing squamous-cell carcinoma CYFRA 21-1 showed promising results.

Antigens, Neoplasm↗

Mutant p53 in patients with invasive cervical cancer stages IB to IIB.

The present study evaluates the prognostic value of mutant p53 protein overexpression in 109 surgically treated cervical cancer stages IB to IIB. Squamous cell carcinoma stages IB, IIA, and IIB were present in 52, 13, and 44 cases, respectively. We performed immunohistochemistry using a monoclonal antibody against the p53 suppressor gene product (clone BP53-12). Data were analyzed for the end points of disease-free survival and overall survival. In 109 tissue specimens we detected 22 cases of p53 expression. Six of 22 patients with p53 expression and 21 of 87 patients without p53 expression showed tumor recurrences. p53 expression showed no significant correlation to age, tumor stage or lymph node involvement. In the univariate analysis p53 expression showed no prognostic value for disease-free (P = 0.5) and overall survival (P = 0.6). Multivariate analysis showed a significant prognostic value for established prognostic parameters while p53 expression had no prognostic value for recurrence-free (P = 0.6) and overall survival (P = 0.5). In contrast to other malignancies mutant p53 overexpression showed no relation to prognosis in surgically treated cervical cancer stage IB to IIB.

Adult↗