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G Goovaerts

Publications and source records attributed to G Goovaerts.

At least 19 recordsLinked to original sources
PubMed2003

Inflammatory breast cancer shows angiogenesis with high endothelial proliferation rate and strong E-cadherin expression.

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Improved understanding of the mechanisms responsible for the differences between IBC and non-IBC might provide novel therapeutic targets. We studied 35 consecutive patients with IBC, biopsied prior to the initiation of chemotherapy. Angiogenesis was evaluated by Chalkley counting and by assessment of endothelial cell proliferation (ECP) and vessel maturity. The presence of fibrin, expression of the hypoxia marker carbonic anhydrase IX (CA IX) and epithelialcadherin (E-cadherin) expression were immunohistochemically detected. The same parameters were obtained in a group of 104 non-IBC patients. Vascular density, assessed by Chalkley counting (P<0.0001), and ECP (P=0.01) were significantly higher in IBC than in non-IBC. Abundant stromal fibrin deposition was observed in 26% of IBC and in only 8% of non-IBC (P=0.02). Expression of CA IX was significantly less frequent in IBC than in non-IBC with early metastasis (P=0.047). There was a significant positive correlation between the expression of CA IX and ECP in IBC (r=0.4, P=0.03), implying that the angiogenesis is partly hypoxia driven. However, the higher ECP in IBC and the less frequent expression of CA IX in IBC vs non-IBC points at a role for other factors than hypoxia in stimulating angiogenesis. Strong, homogeneous E-cadherin expression was found at cell-cell contacts in all but two IBC cases, both in lymphovascular tumour emboli and in infiltrating tumour cells, challenging our current understanding of the metastatic process. Both the intense angiogenesis and the strong E-cadherin expression may contribute to the highly metastatic phenotype of IBC.

Adult↗
PubMed2003

Cutaneous breast cancer deposits show distinct growth patterns with different degrees of angiogenesis, hypoxia and fibrin deposition.

AIMS: We postulated that skin metastases and cutaneous local recurrences from breast adenocarcinoma show different growth patterns with distinct angiogenic profiles. METHODS AND RESULTS: Fifty-one surgically resected dermal breast cancer deposits were evaluated for growth pattern, E-cadherin expression, presence of necrosis and a fibrotic focus, fibrin deposition, carbonic anhydrase IX expression (CA IX), microvessel density, endothelial cell proliferation and blood vessel immaturity. Growth patterns were infiltrative, with carcinoma cells infiltrating the dermis without significant disturbance of the pre-existing architecture, expansive, meaning that a nodule of carcinoma cells and desmoplastic tissue pushed aside the pre-existing dermal structures, or mixed. All lobular carcinomas showed an infiltrative growth and lacked membranous E-cadherin expression. Different growth patterns in the ductal carcinomas were not correlated with differences in E-cadherin expression. The presence of necrosis and/or a fibrotic focus and the expression of the hypoxia marker CA IX were significantly associated with an expansive growth. Fibrin was present in all expansive deposits and less frequently in the other growth patterns. There was a positive association between fibrin deposition, CA IX expression and microvessel density. The latter was significantly higher in the expansive and mixed growth patterns than in the infiltrative pattern. Endothelial cell proliferation was highest in the expansive growth pattern and was positively correlated with the presence of a fibrotic focus and with fibrin deposition. The maximum percentage of immature blood vessels was higher in the expansive and mixed growth patterns than in the infiltrative one. CONCLUSION: The recognition of different subgroups of cutaneous breast cancer deposits with different degrees of hypoxia-driven angiogenesis may have important implications for the usefulness of anti-angiogenic therapy.

Adenocarcinoma↗
PubMed2002

Comparative analysis of the biochemical and immunohistochemical determination of hormone receptors in invasive breast carcinoma influence of the tumor-stroma ratio.

Tumor samples obtained from 106 primary breast cancer patients were examined biochemically (DCCA) and immunohistochemically (IHC) for estrogen (ER) and progesterone receptors (PR) to assess a quantitative relationship between both assays and to study the influence of the tumor-stroma ratio on this quantitative relationship. We used a model of logit transformation of IHC values (% of positive cells) and logarithmic transformation of DCCA values (fmol receptor/mg cytosolic protein). Tumors were subdivided into three categories according to the tumor-stroma ratio (more (t > s), equal amounts (t = s) or less (t < s) tumor than stroma), and the influence of the tumor-stroma ratio was studied using multiple regression analysis. We report a mathematical relationship between the results of the biochemical and immunohistochemical assays for the determination of ER status and PR status in primary breast cancer patients (ER: log DCCA(fmol/mg) = 0.369 logit (IHC(%pos cells)) + 2.328 (r = 0.573; p < 0.0001); PR: log DCCA (fmol/mg) = 0.474 logit (IHC(%pos cells)) + 0, 00 (r = 0.634; p < 0.0001)). In tumors overexpressing ER immunohistochemically (>10% nuclear positivity), median ER-DCCA is significantly higher if the tumor-stroma ratio is greater than 1. As these patients respond to hormonal treatment, depending on the degree of expression of both receptors, this study suggests that the biochemical assay be avoided because this technique is hampered by false-negative or falsely low results due to the loss of morphological information on the tumor-stroma ratio.

Biochemistry↗
PubMed2001

Early distant relapse in "node-negative" breast cancer patients is not predicted by occult axillary lymph node metastases, but by the features of the primary tumour.

Early distant relapse occurs in a minority of node-negative breast cancer patients. Whether this poor prognosis can be predicted by the features of the primary tumour, or by the presence of occult metastases in the "negative" lymph nodes (LNs), remains a matter of debate. One hundred and four T(1-2)N(0)M(0) breast carcinoma patients were divided into two groups: group 1 (44%) showing early distant relapse with a median disease-free survival of 25 months, and group 2 (56%) showing no evidence of disease after a median follow-up of 91.5 months. All patients had received locoregional treatment only. All tumours were evaluated for medial/lateral location, histological type, size, grade, mitotic activity, fibrotic focus, necrosis, angiogenesis, growth pattern, and lymphatic vessel permeation. The haematoxylin and eosin-stained slides of all axillary LNs were revised and two additional levels were cut from each paraffin block for cytokeratin immunohistochemistry. In 24 patients (23%), occult metastases were found. These consisted of single cells or small clusters (SCs) in the marginal sinus in 17 patients (16%) and of larger colonies of cells in seven patients (7%). All detected metastases were smaller than 2 mm in diameter (micrometastases). There was no significant correlation between the presence of occult LN metastases (SCs or colonies) and the prognostically important features of the primary tumour. Early metastatic disease was significantly correlated with larger tumour size (p=0.02), higher histological grade (p=0.0008), mitotic activity (p<0.0001), presence of necrosis (p=0.0004), presence of fibrotic foci (p=0.0005), angiogenesis (p=0.0009), and lymphatic vessel permeation (p=0.018). Multiple logistic regression analysis showed that histological grade and the presence of a fibrotic focus were the only independent prognostic factors and that the presence of occult LN metastases was inversely correlated with early distant relapse. Prospective prognostic studies of occult LN metastases should consider the features of the primary tumour in a multivariate analysis.

Adult↗
PubMed2001

Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia.

The liver is a highly vascularized organ which frequently hosts metastases in patients with colorectal adenocarcinomas. The hypothesis of this study is that the hypoxic drive of angiogenesis might be minimal or absent in those growing liver metastases which are capable of preserving the stromal structure, including the numerous sinusoidal blood vessels. Representative paraffin sections of liver metastases from 26 patients with colorectal adenocarcinoma were investigated. Three different growth patterns were found. In the desmoplastic and in the pushing growth patterns (42% and 46% of all metastases, respectively), the architecture of the liver parenchyma was not preserved. In the replacement growth pattern (12% of all cases), the reticulin pattern of the liver parenchyma was conserved within the metastases at the tumour-liver parenchyma interface. The endothelial cells of the blood vessels near the interface in the metastases of the replacement type did not express CD34, nor were they surrounded by alpha-smooth muscle actin-positive mural cells. In the desmoplastic and in the pushing growth patterns, 23% and 52% of all blood vessels in this area were covered by pericytes. The fraction of proliferating endothelial cells was low in the metastases with a desmoplastic or a replacement growth pattern (about 3%), compared with metastases with a pushing growth pattern (11%). Tumour cell apoptosis was highest in the pushing-type metastases and was inversely correlated with microvessel density in liver metastases. The ratio of the proliferating tumour cell fraction and the proliferating endothelial cell fraction, roughly representing the degree of angiogenesis-dependent growth, was three- to four-fold higher in the replacement-type metastases compared with the other metastases. In summary, the present study has demonstrated that liver metastases are a heterogeneous group, with different growth patterns which predict the fraction of immature blood vessels, the fraction of proliferating endothelial cells, and the fraction of apoptotic tumour cells. The replacement growth pattern expands with minimal angiogenesis by co-opting the stroma with the sinusoidal blood vessels of the liver.

Actins↗
PubMed2001

Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node-negative breast cancer patients.

AIMS: To examine the importance of a fibrotic focus-a scar-like area in a carcinoma-as a marker of intratumoral hypoxia that correlates with angiogenesis and with clinical outcome in node-negative breast cancer. METHODS AND RESULTS: One hundred and four T1-2N0M0 breast carcinoma patients were divided into two groups: group 1 (n=46) showing early distant relapse (median disease-free survival 25 months) and group 2 (n=58) showing no evidence of disease (median follow-up 91.5 months). All tumours were evaluated for medial/lateral location, size, histological grade, mitotic activity, necrosis, fibrotic focus, angiogenesis, vascular permeation and growth pattern. Multiple regression analysis showed that only histological grade and the presence of a fibrotic focus were independent predictors of early distant relapse. A fibrotic focus was present in 53% of the tumours. The relative size (fibrotic focus/tumour ratio) was significantly correlated with an unfavourable outcome. The presence of necrosis inside the fibrotic focus and the absolute and relative size of the fibrotic focus were significantly correlated with angiogenesis. A fibrotic focus was significantly associated with large, expansively growing tumours with high histological grade and numerous mitoses. CONCLUSION: A fibrotic focus can be used as a surrogate for quantifying angiogenesis and is an independent predictor of early metastasis in lymph node-negative breast cancer.

Adult↗
PubMed2001

Prevalence of human papillomavirus in elderly women with cervical cancer.

To investigate the relation between the prevalence of human papillomavirus (HPV) and age in cervical cancer patients, material from 93 patients with Ia-IIb cervical carcinoma was analyzed for the presence of HPV by both type-specific and general primer polymerase chain reaction. Patients were divided into 2 groups: 64 years or younger, and 65 years and older. There was no statistically significant difference in either the prevalence of HPV DNA or distribution of genotypes amongst the 2 groups. Therefore, HPV detection can be equally well used in the management and follow-up of elderly cervical cancer patients.

Aged↗
PubMed2001

Human papillomavirus infection in the female population of Antwerp, Belgium: prevalence in healthy women, women with premalignant lesions and cervical cancer.

Worldwide there is a strong relation between the presence of human papillomavirus (HPV) and the development of cervical cancer. This study investigated the prevalence and genotype of HPV in women with normal smears, women with premalignant lesions and women with cervical cancer in Antwerp, Belgium. Type-specific polymerase chain reaction (PCR) for HPV types 16 and 18 and general primer PCR (GP5+/6+) was performed on DNA extracted from paraffin-embedded tissue from women with lesions or fresh material from controls. HPV was detected in 11% of controls, 61% of women with atypia, 77% of women with CIN lesions and 88% of women with cervical carcinoma (chi2 trend, 273, p<0.001). The odds ratio for high-risk HPV types was 9.3 for atypia (95%CI. 4.3-19.8), 33.6 for CIN lesions (95%CI, 19.3-58.6) and 78.8 for cervical cancer (95%CI, 39.2-158.3). In total, 19 different HPV genotypes were detected, including five low risk HPV types. Seven of the 14 high-risk HPV types were detected in cervical cancer patients. Based on our study it is suggested that a prophylactic vaccine based on a cocktail of a limited number of high-risk HPV types should be considered in order to protect most women from developing cervical cancer.

Adolescent↗
PubMed2000

Adenocarcinoid of the appendix presenting as a disseminated ovarian carcinoma: report of a case.

The occurrence of disseminated tumors of the appendix is a rare event. Usually appendix tumors are very small, located on the inside of the appendix, and can be pathologically diagnosed. Adenocarcinoid is an uncommon variant of carcinoid tumors that usually arises in the appendix. This report describes a case of a primary adenocarcinoid of the appendix in a patient who was preoperatively diagnosed to have uterus myomatosus but was intraoperatively found to instead have disseminated ovarian carcinoma. This case demonstrates that the clinical picture can be misleading, and that surgeons therefore always have to wait for the final pathological report before making a final diagnosis.

Adult↗
PubMed2000

The association between vascular endothelial growth factor, microvessel density and clinicopathological features in invasive cervical cancer.

OBJECTIVE: The aim of this study was to analyse the vascular endothelial growth factor (VEGF) expression in a series of cervical carcinomas and to compare the results with the microvessel density (MVD) and clinicopathological features. STUDY DESIGN: The immunoreactivity for VEGF was studied in 130 invasive cervical carcinomas and in 22 patients with a carcinoma in situ of the cervix. The results were compared with the MVD. RESULTS: Staining for VEGF of less then 50% per slide occurred in 80% of the invasive carcinomas and in 82% of the in situ carcinomas. The median MVD was 261 vv/mm(2) (range: 11-1000) in the invasive group and 146 vv/mm(2) (range: 25-536) in the in situ group. Unlike the microvessel density there was no association between VEGF expression and survival. The MVD was higher in VEGF poorer (<50%) tumours (P=0.055). Beside tumour histology (P=0.012) there were no other significant relationships between the remaining histopathological findings and VEGF expression. CONCLUSION: Tissue VEGF expression has no prognostic value in contrast with the MVD in patients with invasive cervical cancer.

Adenocarcinoma↗
PubMed1999

Prospective study of intratumoral microvessel density, p53 expression and survival in colorectal cancer.

Adjuvant treatment of patients with colorectal cancer is hampered by a lack of reliable prognostic factors in addition to the clinicopathological staging system. A poorly defined but considerable fraction of Astler-Coller stage B patients will experience tumour recurrence, and some of the stage C patients will probably survive for a prolonged time after surgery without adjuvant treatment. Assessing parameters related to tumour angiogenesis has provided valuable prognostic information in different tumour types. The formation of new microvessels is part of the malignant phenotype in the majority of tumours. Alterations in tumour-suppressor genes, such as the p53 gene, or oncogenes, such as the ras gene, have been found to be responsible for changing the local balance of pro- and antiangiogenic factors in favour of the former. In this prospective study, intratumoral microvessel density (IMD) was assessed by immunostaining tissue sections for CD31 and counting individual microvessels in selected and highly vascular regions in specimens of 145 colorectal cancer patients. p53 protein overexpression was semiquantitatively determined after immunohistochemistry. In both uni- and multivariate analysis, high IMD was significantly associated with shorter survival in the patients undergoing surgery with curative intent (Astler-Coller stages A-C). p53 added prognostic power to IMD, both in Astler-Coller stage B and stage C patients. An association between IMD and mode of metastasis was also noted. High IMD was strongly associated with the incidence of haematogenous metastasis during follow-up, but not with the presence of lymphogenic metastasis observed at surgery. This study confirms the results of previous retrospective analyses of IMD and survival in colorectal cancer and warrants a clinical validation by randomizing stage B tumour patients with high IMD and p53 overexpression between adjuvant treatment or not.

Adult↗
PubMed1998

Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer.

Tumour stromal neovascularization was investigated in 114 invasive and 20 in situ carcinomas of the uterine cervix by staining representative sections with the specific endothelial marker anti CD31 (clone JC/70A, isotope IgG1). A digital image analyser was used to measure the immunoreactivity. The following parameters were determined in the 'hot spots': vessel counts, vessel perimeter and endothelial stained area (expressed per mm2). The results were correlated with clinical and histopathological data. There was no significant relationship between the histopathological findings (tumour histology, tumour differentiation, FIGO stage, presence of lymph node metastasis or lymphovascular space involvement) and the median vessel count. In a univariate analysis all angiogenesis parameters had prognostic value: a higher vascularity was associated with worse prognosis (P < 0.05). Multiple regression analysis showed that vascular permeation (P < 0.001) and the median vessel count (P = 0.005) were the most important prognostic indicators. In the future these criteria may be used for selection of patients for anti-angiogenesis therapy.

Adult↗
PubMed1998

Growth factors in tympanic membrane perforations.

OBJECTIVE: Little is known about the arrested healing of chronic central tympanic membrane perforations and the mechanism involved in this process. Some authors have traced the failure to a growth factor deficiency at the perforation margin. In addition, recently, several growth factors have been tried out to improve tympanic membrane (TM) closure in animals. The authors sought to determine the expression of some well-known growth factor peptides in normal human TM and in TMs with a chronic central perforation. MATERIALS AND METHODS: Total TM specimens were obtained from patients with a normal TM (N = 10) soon after death and from patients with a chronic perforation (N = 20) undergoing myringoplasty with use of an allograft TM. Formaldehyde solution-fixed TMs were analyzed after immunohistochemical staining using highly purified monoclonal antibodies to determine whether epidermal growth factor receptor (EGF-r), transforming growth factor-alpha (TGF-alpha), basic fibroblast growth factor (b-FGF), or transforming growth factor-beta 1 (TGF-beta 1) was expressed in the TMs. RESULTS: The distribution pattern for EGF-r, TGF-alpha, and b-FGF was similar in perforated and nonperforated TMs. In contrast to this, TGF-beta 1 staining was markedly different in perforated and nonperforated TMs. No or minimal TGF-beta 1 was observed in normal TMs, whereas TGF-beta 1 staining was prominent in perforated membranes, mostly at the perforation border. CONCLUSIONS: The authors experimental findings imply that EGF-r, b-FGF, and TGF-alpha expression are not significantly different in TMs with and without a central chronic perforation. However, for TGF-beta 1, the authors found an increased staining pattern in perforated TMs when compared with that of normal TMs, and staining at the fibrotic and scarred perforation margin was pronounced. Based on these findings, the authors speculate on the possible role of TGF-beta 1 in the development of the fibrotic scar at the perforation margin explaining the deficient healing pattern of tympanic membranes in chronic otitis media. Possible clinical implications for the future, including growth factor therapy, are discussed.

Antibodies, Monoclonal↗
PubMed1997

Histology of the perforated tympanic membrane and its muco-epithelial junction.

A histological study was performed on total human tympanic membranes with a central perforation. The specimens originated from 30 consecutive and unselected operations in which a total myringectomy was performed prior to reconstruction by means of a tympanic allograft. Beside excessive thickening of the tympanic membrane in 73%, all membranes showed other histological abnormalities: inflammation (97%), excessive fibrosis (97%), tympanosclerosis (80%), hyperkeratosis (83%), rete riges (43%) and epithelial inclusions (6%). Histological localisation of the muco-epithelial junction showed a medial position in 30%, with extensive middle ear invasion by squamous epithelium in 7%. The surgeon performing myringoplasty should keep these findings in mind and he should closely examine the medial side of the perforated tympanic membrane in order to remove any ingrowing epithelium that otherwise would be trapped.

Adolescent↗
PubMed1997

Prognostic value of bcl-2 expression in patients with operable carcinoma of the uterine cervix.

AIM: To evaluate the patterns of bcl-2 expression in early stage cervical carcinoma; to compare bcl-2 expression with clinicopathological findings; and to assess its prognostic value. METHODS: Wertheim radical hysterectomy specimens from 76 patients (FIGO stages Ia-IIb) with untreated nonmetastatic invasive cervical carcinoma were studied. Expression of bcl-2 was detected immunohistochemically using a monoclonal antibody. A tumour was regarded as positive when more than 5% of the neoplastic cells exhibited bcl-2 immunoreactivity. RESULTS: Forty eight (63%) cervical carcinomas were scored as bcl-2 positive and 28 (37%) as bcl-2 negative. Most tumours showed heterogeneous cytoplasmic staining. Bc1-2 immunoreactivity did not correlate with tumour histology, tumour stage, presence of lymph node metastases, or involvement of the lymphovascular space. The five year survival rate for patients with bc1-2 negative tumours was 34% and was 71% for patients with bc1-2 positive tumours. On multiple regression analysis (Cox proportional hazards model), bc1-2 expression and vascular permeation were independent predictors of overall survival. CONCLUSIONS: Bcl-2 expression seems to be associated with less aggressive behaviour in early stage cervical carcinoma. The transition to bcl-2 independence may play an important role in tumour progression.

Adult↗
PubMed1995

Chondrosarcoma in a patient with relapsing polychondritis.

A case of a chondrosarcoma in a patient with relapsing polychondritis was presented. The association of these two unusual disorders of cartilaginous tissue has never been described before. The clinical presentation and radiologic and histologic features were discussed.

Bone Neoplasms↗
PubMed1995

Microvessel quantification in primary colorectal carcinoma: an immunohistochemical study.

The vascularisation of human primary colorectal carcinomas was studied immunohistochemically using the endothelial cell markers CD31 and factor VIII-related antigen. Tumour sections were systematically scanned at a magnification of x 100 to find areas of intense neovascularisation. Microvessel counts within these vascular 'hotspots' were performed at magnification x 250. Regions in which tumour cords were surrounded by a collagen IV-positive basement membrane were compared with those in which this was absent and with normal mucosa. CD31 appeared to be a more sensitive marker for endothelial cells than factor VIII-related antigen (mean 185 +/- 59 and 120 +/- 38 microvessels mm-2). Within individual tumour sections microvessel counts in vascular hotspots with highest vessel density correlated significantly with microvessel counts in vascular hotspots with second highest vessel density (P < 0.01). Microvessel counts in tumour areas where collagen IV-positive basement membrane were absent exceeded those in areas where it was present (factor of 1.7) and those in normal mucosa (factor of 1.6). The differences in vessel density between individual tumours and the low variability in vessel density within individual tumours using this quantification technique allow us to investigate the prognostic value of vessel density in areas of intense neovascularisation in human primary colorectal carcinomas.

Adult↗