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Peter Birner

Publications and source records attributed to Peter Birner.

At least 37 records · Page 2Linked to original sources
PubMed2003

Expression of platelet-derived growth factor-AA is associated with tumor progression in osteosarcoma.

Platelet-derived growth factors are secreted by mesenchymal cells. The homodimer platelet-derived growth factor-AA especially stimulates bone cells through interaction with the platelet-derived growth factor-alpha receptor homodimer. In this study we wanted to determine the expression of the receptor and its ligand in human osteosarcomas and to correlate the expression of platelet-derived growth factor-AA and -alpha receptor with clinicopathological parameters. Fifty-seven osteosarcomas were immunohistochemically analyzed for expression of platelet-derived growth factor-AA and platelet-derived growth factor-alpha receptor. Spearman's correlation coefficient revealed a strong correlation between the expression of platelet-derived growth factor-AA and platelet-derived growth factor-alpha receptor (r = 0.867). No differences were observed relative to gender, age, tumor stage, tumor location, and response to neoadjuvant chemotherapy between high or low platelet-derived growth factor-AA and platelet-derived growth factor-alpha receptor expression. High platelet-derived growth factor-AA expression correlated with tumor progression in univariate analysis (P = .0415; log-rank test), whereas platelet-derived growth factor-alpha receptor expression showed a trend toward a shorter disease-free survival, which failed to reach significance (P = .0627, log-rank test). In multivariate analysis, platelet-derived growth factor-AA expression remained a significant independent predictor of tumor progression (P = .021, Cox regression). Immunohistochemical analysis of platelet-derived growth factor-AA expression in osteosarcoma may be a useful marker of prognosis and may be considered as a possible target for novel therapeutic strategies.

Adolescent↗
PubMed2003

Fluorescent in situ hybridization on isolated tumor cell nuclei: a sensitive method for 1p and 19q deletion analysis in paraffin-embedded oligodendroglial tumor specimens.

In oligodendroglial neoplasms, losses of chromosomal material at 1p and 19q associate with chemosensitivity and prolonged survival. Thus, 1p/19q testing is increasingly proposed for use in brain tumor diagnosis and prognostic assessment. Fluorescent in situ hybridization (FISH) is a classic technique for investigation of 1p/19q status in paraffin-embedded tissues. A major limitation of this method is truncation of tumor cell nuclei complicating assessment of hybridization results. In our study, we analyzed 1p and 19q status in a series of 79 oligodendroglial neoplasms (49 oligodendrogliomas, 30 oligoastrocytomas, WHO: 57 Grade II, 22 Grade III tumors) and controls (gliotic brain tissue: n = 4, diffuse low-grade astrocytoma: n = 4) using FISH on isolated whole tumor cell nuclei, prepared as cytospin preparations, thus bypassing the problem of nuclear truncation. For interpretation of FISH results, we used consensus criteria as defined by the SIOP-Europe Neuroblastoma Study Group for analysis of peripheral neuroblastic tumors. FISH yielded interpretable results in 98.7% for 1p and 92.1% for 19q. Chromosome 1p/19q alterations comprised deletions (1p: 79.5%, 19q: 80%) and imbalances (1p: 11.5%, 19q: 12.9%). 1p aberrations were more frequent in oligodendroglioma than in oligoastrocytoma (100% versus 75.9%, P =.001). The frequency of 1p/19q alterations was not significantly different in WHO Grade II or Grade III tumors or in primary and recurrent tumors. We conclude that FISH on isolated cell nuclei, with application of the SIOP Europe Neuroblastoma consensus criteria, is a sensitive method for detection and interpretation of 1p and 19q aberrations in paraffin-embedded tissue specimens of oligodendroglial neoplasms.

Brain Neoplasms↗
PubMed2003

Vascular patterns in glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins: evidence for distinct angiogenic subtypes.

No data exist on angiogenic patterns and their prognostic impact in human glioblastoma. Such data are relevant for translation of antiangiogenic therapies into clinical applications. Using immunohistochemistry for CD34, we assessed vascular patterns in 114 primary glioblastomas. Vascular patterns comprised unevenly distributed glomeruloid/garland-like/clustered bizarre vascular formations and evenly distributed delicate capillary-like microvessels ("classic" vascular pattern). The combination of low content of bizarre vascular formations and prominent classic vascular pattern (n=29) was an independent factor for longer survival (p=0.006, Cox regression), as well as postoperative high Karnofsky performance status (p=0.005). In patients with a prominent classic vascular pattern, there was no difference of MIB1 labeling index whereas microvessel density and apoptotic index (TUNEL) were significantly higher as compared to all other patients (p<0.05). In addition, diffuse expression of hypoxia-inducible factor (HIF)-1alpha and strong expression of vascular endothelial growth factor were more common (p<0.05, Chi-square test). FISH revealed loss of chromosomes 1p and 19q only in 1/7 long-time survivors with classic pattern. We conclude that vascular patterns in primary glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins. Our findings denote for the first time distinct angiogenic subtypes of human glioblastoma which may prove relevant for anti-angiogenic therapy approaches.

Adult↗
PubMed2003

Expression of platelet-derived growth factor-alpha alpha receptor is associated with tumor progression in clear cell renal cell carcinoma.

Platelet-derived growth factors (PDGFs) exert their biologic function by binding to 3 different tyrosine kinase receptor isoforms. Especially the PDGF-alpha alpha receptor binds PDGF proteins with high specificity, which results in growth stimulation. The expression of the receptor and its ligand was studied in human renal cell carcinomas (RCCs) by immunohistochemical analysis, and the expression of PDGF-alpha alpha receptor and PDGF-AA was correlated with clinicopathologic parameters of patients with clear cell RCC (CCRCC). In CCRCC, the mean expression of PDGF-alpha alpha receptor and PDGF-AA was 38.8% (range, 0.0%-96.0%) and 18.4% (range, 0.0%-90.0%), respectively. PDGF-alpha alpha receptor expression was significantly higher in grade 3 and grade 4 tumors compared with grade 1 and grade 2 tumors (P = .027; Mann-Whitney test), and high receptor expression correlated with tumor progression in univariate analysis (P = .0253; log-rank test), while PDGF-AA expression had no prognostic influence on the outcome of patients with CCRCC. Therefore, immunohistochemical detection of high PDGF-alpha alpha receptor expression in CCRCC is associated with adverse outcomes. Furthermore, the PDGF receptor-factor interaction loop may be considered as a possible target for novel therapeutic strategies.

Adult↗
PubMed2003

Level of Id-1 protein expression correlates with poor differentiation, enhanced malignant potential, and more aggressive clinical behavior of epithelial ovarian tumors.

PURPOSE: Id (inhibitor of differentiation/DNA binding) -1 is involved in neoangiogenesis, it antagonizes basic helix-loop-helix proteins, inhibits differentiation, and enhances cell proliferation. Aim of this study was to investigate Id-1 protein expression in epithelial ovarian tumors and its clinical relevance in ovarian cancer. EXPERIMENTAL DESIGN: We have investigated Id-1 expression by reverse transcription-PCR and Western blotting in ovarian cancer samples. On the basis of these results, Id-1 protein expression was determined by immunohistochemistry in 101 specimens of epithelial ovarian cancer, in 40 borderline tumors, and in 20 cystadenomas. In these cases, Id-1 expression was correlated with p21 expression, microvessel density, and survival. RESULTS: By immunohistochemistry, detectable expression of Id-1 was found significantly more often in ovarian cancers (74.3%) than in borderline tumors (32.5%) and cystadenomas (0%; P < 0.0001, chi(2) test). Cancer samples with poor or moderate histological differentiation (G3/G2) showed significantly stronger Id-1 expression than cancer samples with high differentiation (G1; P = 0.021, Mann-Whitney test), and no association of Id-1 with p21 expression or microvessel density was found. In cancer samples strong or moderate expression of Id-1 was a strong predictor for shorter overall survival in uni- and multivariate analysis (P = 0.001, Cox-regression). CONCLUSIONS: The level of Id-1 protein expression correlates with the malignant potential of ovarian tumors. In cancer samples, stronger Id-1 expression is associated with poor differentiation and more aggressive behavior of tumor cells, resulting in poor clinical outcome. Consequently, Id-1 inhibition in the future might be of benefit for patients with ovarian cancer.

Analysis of Variance↗
PubMed2003

Overexpression of hypoxia-inducible factor 1alpha indicates diminished response to radiotherapy and unfavorable prognosis in patients receiving radical radiotherapy for cervical cancer.

PURPOSE: The purpose is to investigate the impact of hypoxia-inducible factor (HIF)-1alpha expression on response to radiotherapy and prognosis of patients with primary irradiated cervical cancer. Because human papillomavirus (HPV) oncoprotein E6 might interact with HIF-1alpha in various pathways, we also investigated the relation of HIF-1alpha and HPV status. EXPERIMENTAL DESIGN: Expression of HIF-1alpha was investigated by immunohistochemistry in 67 specimens of patients who had received radical radiotherapy for cervical cancer stages IB-IIIB. HPV analysis was performed using type-specific PCR, cloning, and sequencing. Survival analysis was performed using univariate and multivariate analysis. RESULTS: Immunohistochemistry revealed expression of HIF-1alpha in 72.1% of the tumor samples. In 16 (23.9%) cases, there was a weak expression, in 25 (37.3%) a moderate expression, and in 7 cases (10.4%) a strong expression of HIF-1alpha. Nineteen samples (28.4%) were considered negative for HIF-1alpha expression. Strong/moderate expression of HIF-1alpha was associated with only partial response to radiotherapy (P = 0.037, chi(2) test). Strong/moderate expression of HIF-1alpha was also an independent prognostic factor for shorter progression-free survival (P = 0.036, Cox regression) and cervical cancer-specific survival (P = 0.04, Cox regression). No association between HIF-1alpha expression and infection with different HPV types could be found. CONCLUSIONS: Overexpression of HIF-1alpha has predictive and prognostic significance in cervical cancer patients receiving curative radiation therapy. Possibly, expression of HIF-1alpha could serve as intrinsic marker of hypoxia in cervical cancer.

Biomarkers↗
PubMed2002

Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer.

To obtain information on the incidence and the clinical significance of infection with various types of the human papillomavirus (HPV) in cancer of the uterine cervix, we retrospectively examined the HPV status of 106 patients who had received radical radiotherapy for cervical cancer stages IB to IIIB. DNA was extracted from formalin-fixed, paraffin-embedded biopsies and PCR was carried out to identify HPV types 16, 18, 31, 35, 33 and 45. To detect additional HPV types, consensus PCR products were cloned and sequenced. A catalyzed signal-amplified colorimetric in situ hybridization was carried out in 84 of 106 specimens as a positive control. Response to therapy, progression-free survival (PFS) and cervical cancer-specific survival (CCSS) were the statistical endpoints. Survival analysis was carried out using univariate and multivariate analysis (Cox regression). Ninety-six patients (90.6%) were HPV-positive and 42/96 (43.7%) were positive for multiple HPV types. Eight patients had persistent disease after radiotherapy. From these 8 patients, 7 were infected with multiple HPV types and only 1 patient had an infection with a single HPV type. After a median follow up period of 50 months, patients with multiple HPV infection had a significantly shorter PFS and CCSS compared to those with single HPV infection (24.8% and 34.9% vs. 64% and 60.8%, Log rank, p < 0.01 and 0.04). In multivariate analysis, the presence of multiple HPV types (RR 1.9), node status (RR 2.3), tumor size (RR 3.2) and histologic type (RR 4.8) were independent prognostic factors of CCSS. Our results demonstrate that the presence of multiple HPV types is associated with poor response and with reduced survival in cervical cancer patients who receive radiotherapy as the primary treatment.

Adenocarcinoma↗
PubMed2002

Expression of MUC1 splice variants in benign and malignant ovarian tumours.

MUC1 is expressed on the surface of ovarian cancer cells. Nine different splice variants of MUC1 have been described, but no study has reported on the expression of MUC1 isoforms in human ovarian cancer. Our study compares patterns of expression of MUC1 splice variants of malignant and benign ovarian tumours. Ovarian tissue samples were taken from patients with benign ovarian tumours (n = 34) and from patients who had surgery for primary (n = 47) or recurrent (n = 8) ovarian cancer. RT-PCR for MUC1 splice variants A, B, C, D, X, Y, Z, REP and SEC was performed and their expression compared to clinical and histopathologic parameters. Variants A, D, X, Y and Z were more frequently expressed in malignant than in benign tumours. All primary ovarian cancer cases were positive for variant REP but negative for variant SEC. No significant association of the expression of MUC1 splice variants with the response to chemotherapy or patient survival could be demonstrated. Expression of MUC1 splice variants A, D, X, Y, Z and REP is associated with the presence of malignancy, whereas expression of MUC1/SEC is associated with the absence of malignancy.

Alternative Splicing↗
PubMed2002

Expression of osteopontin and vascular endothelial growth factor in benign and malignant bone tumors.

Osteopontin (OPN), one of the major non-collagenous proteins of bone matrix, is together with vascular endothelial growth factor (VEGF) a potent angiogenic protein. In this study we determined the expression of OPN in benign and malignant bone tumors and investigated the prognostic influence of OPN expression on the outcome of osteosarcoma patients. Fifty-seven osteosarcomas and 11 osteoblastomas as well as 5 bone specimens with remodeling sites were immunohistochemically analyzed for expression of OPN and VEGF. OPN was not detected in osteoblasts of remodeling sites. Osteoblastoma osteoblasts as well as osteoclastlike giant cells and osteosarcoma mononuclear cells showed variable staining. In osteosarcomas OPN and VEGF expression correlated with each other (r=0.390, P=0.003, Spearman's test). Although osteosarcoma patients with high VEGF expression showed a trend towards shorter overall survival ( P=0.0841, log-rank test), OPN expression had no influence on patients overall or on disease-free survival. Our data indicate that expression of this protein might be upregulated in bone neoplasia. Although OPN expression correlates with VEGF expression in osteosarcomas, OPN expression does not provide predictive information about the outcome of osteosarcoma patients.

Adolescent↗
PubMed2002

DNA topoisomerase IIalpha predicts progression-free and overall survival in pediatric malignant non-brainstem gliomas.

Malignant non-brainstem glioma (MNBG) is a rare pediatric brain tumor. The prognosis for children harboring this lesion remains largely unpredictable. Assessment of histologic features alone only provides a marginal insight into the biologic behavior of these lesions. Hence, the identification of novel molecular markers capable of characterizing these lesions more accurately with respect to their biologic aggressiveness is definitely needed. Our current study examined the expression of nuclear DNA topoisomerase IIalpha (TIIalpha), a novel marker of cell cycle turnover and a determinant of tumor cell resistance to chemotherapy, in a series of 17 archival pediatric MNBGs. TIIalpha expression was found to extend over a wide range in the study cohort (3.9-69.1%). A cutoff labeling index of 12% was found to define 2 prognostic subgroups (TIIalpha <12 vs. >or=12) with profoundly different 5-year progression-free survival (60% vs. 8%; p = 0.0108, log-rank test) and overall survival (100% vs. 8%; p = 0.0038) rates. TIIalpha expression was significantly linked to MIB-1 antibody labeling of the Ki-67 nuclear antigen (R = 0.919, p < 0.001). A high TIIalpha labeling index remained associated with short progression-free survival (p = 0.022) and overall survival (p = 0.022) in multivariate analysis (Cox regression). In conclusion, considering that TIIalpha expression was not related to histopathologic grade, biological characteristics as assessed by TIIalpha labeling may complement the information obtained by tumor morphology as a means of improving the accuracy of patient prognosis prediction.

Adolescent↗
PubMed2002

DNA profiles and numeric histogram classifiers in nephrogenic adenoma.

BACKGROUND: The malignant potential of nephrogenic adenoma is still a matter of controversy and therapeutic regimens of this morphologic entity range from partial, even total cystectomy to watchful waiting. The objective of the current study was to evaluate several robust image cytometry-DNA histogram classifiers and to search among those for factors that separate a biologically nonaggressive metaplastic lesion from lesions with increased malignant potential. METHODS: The study included bladder irrigation specimens, 23 preceding transurethral resection of nephrogenic adenoma and 24 preceding resection of papillary bladder carcinoma. Feulgen-stained nuclei were imported to a static image analysis system, and densitometric data were interpreted by two different software programs. Histograms were described numerically by DNA index, 2c deviation index, and by 5c/9c-exceeding and euploid polyploidy rates. In addition, an interpretation algorithm based on a dual parameter analysis with an integrated automatic threshold was used. RESULTS: The numeric classification of DNA histograms of patients suffering from nephrogenic adenoma resulted in DNA indices between 0.91 and 1.15. The 2c deviation indices ranged from 0.03 to 0.43, and the 5c exceeding rates ranged from 0.0 to 1.58. None of the measurements showed nuclei exceeding 9c. The p25-75 ranges of 2c deviation indices in nephrogenic adenoma and papillary urothelial carcinoma did not overlap. These findings might be explained by minor proliferative activity in nephrogenic adenoma. Euploid polyploidy rates less than 5% confirm this explanation. Risk analysis documented high risk only for those patients with nephrogenic adenomas who had proven transitional cell carcinoma in their history. CONCLUSIONS: DNA estimation by image cytometry of urinary bladder irrigation specimens appears able to separate papillary bladder lesions. The method detects those lesions with higher malignant potential but is limited in separating entities with low malignant potential. Comparison of the discriminative power of robust numeric DNA classifiers reveals the 2c deviation index superior to the widely used DNA index and the 5c exceeding rate in this material.

Adenoma↗
PubMed2002

Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis.

Formation of lymphatic metastasis is the initial step of generalized spreading of tumor cells and predicts poor clinical prognosis. Lymphatic vessels generally arise within the peritumoral stroma, although the lymphangiopoietic vascular endothelial growth factors (VEGF)-C and -D are produced by tumor cells. In a carefully selected collection of human cervical cancers (stage pT1b1) we demonstrate by quantitative immunohistochemistry and in situ hybridization that density of lymphatic microvessels is significantly increased in peritumoral stroma, and that a subset of stromal cells express large amounts of VEGF-C and VEGF-D. The density of cells producing these vascular growth factors correlates with peritumoral inflammatory stroma reaction, lymphatic microvessel density, and indirectly with peritumoral carcinomatous lymphangiosis and frequency of lymph node metastasis. The VEGF-C- and VEGF-D-producing stroma cells were identified in situ as a subset of activated tumor-associated macrophages (TAMs) by expression of a panel of macrophage-specific markers, including CD68, CD23, and CD14. These TAMs also expressed the VEGF-C- and VEGF-D-specific tyrosine kinase receptor VEGFR-3. As TAMs are derived from monocytes in the circulation, a search in peripheral blood for candidate precursors of VEGFR-3-expressing TAMs revealed a subfraction of CD14-positive, VEGFR-3-expressing monocytes, that, however, failed to express VEGF-C and VEGF-D. Only after in vitro incubation with tumor necrosis factor-alpha, lipopolysaccharide, or VEGF-D did these monocytes start to synthesize VEGF-C de novo. In conclusion VEGF-C-expressing TAMs play a novel role in peritumoral lymphangiogenesis and subsequent dissemination in human cancer.

Antigens, CD↗
PubMed2002

High expression of DNA topoisomerase IIalpha and Ki-67 antigen is associated with prolonged survival in glioblastoma patients.

Assessment of tumour cell proliferation in glioblastoma (GB) has been a topic of considerable research interest over the past decade. However, the correlation of tumour proliferation and patient outcome has yielded controversial results. In this study, we examined immunohistochemically, using paraffin-embedded tissue, the expression of the proliferation-related markers DNA topoisomerase IIalpha (TIIalpha) and Ki-67 antigen in a cohort of 114 GB patients treated consecutively with surgery and radiochemotherapy, and correlated the expression with patient outcome. The TIIalpha labelling index (LI) ranged between 5.2 and 87.2% (median: 25.6%). Survival analysis disclosed an association between high TIIalpha expression levels and prolonged survival (P=0.040, log-rank test). TIIalpha expression correlates closely with Ki-67 labelling index (R=0.927, P<0.001), which itself is predictive of patient survival (P=0.044). However, in multivariate analysis, only the Karnofsky performance status remained predictive of patient survival. We conclude that high expression of TIIalpha and Ki-67 appears to be associated with a prolonged survival in our cohort of GB patients.

Adult↗
PubMed2002

Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer.

PURPOSE: Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that supports the adaptation of human cancer cells to hypoxia and is involved in various pathways supporting tumor growth and progression. The aim of this study was to determine the prognostic influence of HIF-1alpha expression in patients with advanced-stage breast cancer, evident by positive lymph nodes. EXPERIMENTAL DESIGN: Expression of HIF-1alpha was determined immunohistochemically in 206 patients with lymph node-positive breast cancer. Furthermore, the interrelationship of HIF-1alpha with p53 and HER-2 protein expression, estrogen receptor density, and survival was analyzed. Colocalization of p53 and HIF-1alpha proteins was analyzed by confocal laser scanning microscopy. RESULTS: Strong nuclear expression of HIF-1alpha by invasive cancer cells was found in 48 patients (23.3%), moderate expression was found in 74 patients (35.9%), and weak expression was found in 35 patients (17%); no expression was observed in 49 patients (23.8%). HIF-1alpha protein overexpression was associated with significantly shorter overall and disease-free survival time (P = 0.003 and P = 0.001, respectively; Cox regression analysis). No correlation of HIF-1alpha and HER-2 expression or estrogen receptor density was observed. CONCLUSIONS: This study shows that HIF-1alpha is an independent prognostic factor for an unfavorable prognosis in patients with lymph node-positive breast cancer. Our results indicate that patients with advanced-stage breast cancers might profit from future therapies targeting HIF-1alpha.

Breast Neoplasms↗
PubMed2001

Crohn's disease of the appendix.

Although appendectomy is often the first surgical procedure in patients with Crohn's disease (CD), only few data exist on appendiceal CD. The aim of this study was to analyze appendices of CD patients undergoing surgery. We analyzed 149 specimens from consecutive patients with CD who underwent primary right ileocolonic or (sub)total colonic resection. The appendix was present in 90 resection specimens. Histologic findings were compared with those of 180 age and sex matched controls. Thirty-six appendices showed histologic signs of CD (40%): A transmural inflammation was found in 24 cases (67%), and a mucosal inflammation in 12 cases (33%). Histologic hallmarks of mucosal involvement were focal or discontinuous inflammation with crypt distortion and a histiocytic and lymphocytic predominant inflammation. Furthermore, epitheloid granulomas and erosions or ulcers with abundant histiocytes at the lesions base were observed. In comparison to controls luminal obliteration was significantly overrepresented in CD whereas acute phlegmonous appendicitis was underrepresented ( P<0.01). Patients with CD of the appendix showed a more widespread colonic involvement than those without ( P<0.01). This study shows that CD of the appendix exhibits specific histologic features that allow a differentiation from non-CD-associated appendicitis. CD-associated appendicitis is a frequent event, probably signifying a more widespread colonic involvement.

Adolescent↗
PubMedDate not supplied

Lymphatic vessels and lymphangiogenesis in female cancer: mechanisms, clinical impact and possible implications for anti-lymphangiogenic therapies (Review).

Lymphatic vessels play a crucial role in a variety of human cancers, since invasion of lymphatic vessels by tumor cells and subsequent development of lymph node metastases significantly influences prognosis of cancer patients and therefore represent an integral part of tumor staging. Recent evidence on the important influence of lymphangiogenetic growth factors on intralymphatic cancer growth and metastasis raises hopes that lymphatic vessels and factors inducing their growth could serve as an additional target for tumor therapy. Nevertheless, in contrast to blood vessel angiogenesis, the mechanisms of new lymphatic vessel formation in human cancers, i.e. lymphangiogenesis, are still relatively unclear. In addition, only little data exist so far on the quantification and impact of this lymphangiogenesis, evident by lymphatic microvessel density (LMVD), on the prognosis of cancer patients. With expectation of possible anti-lymphangiogenic therapies, this review focuses on the mechanisms of lymphangiogenesis in general, and especially on the role of lymphatic vessels in gynecological and breast cancer, which are the so far most detailed investigated malignancies with regard to lymphangiogenesis.

Endothelial Growth Factors↗