PubMed Health⌕ Search

Biomedical subjects

A E Konstantinidou

Publications and source records attributed to A E Konstantinidou.

At least 19 recordsLinked to original sources
PubMed2006

Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas.

Caspase-3 is the ultimate executioner caspase that is essential for the nuclear changes associated with apoptosis. We investigated caspase-3 immunohistochemical expression in 58 primary intracranial meningiomas, using one monoclonal antibody detecting both precursor and cleaved caspase-3 (CPP32) and a second recognizing only the cleaved activated form (ASP175). Caspase-3 expression was analyzed in relation to baseline apoptosis-as illustrated by the expression of anti-single stranded DNA (ss-DNA), the antiapoptotic protein bcl-2, proliferation indices (Ki-67, PCNA, topoisomerase IIa, mitosin C), hormonal status (estrogen, progesterone, androgen receptors), standard clinicopathological parameters and patients' disease-free survival. Caspase-3 immunostaining was observed in 62% of cases for CPP32 and in 24% for ASP175. In both instances, the labeling index (LI) was significantly correlated with ss-DNA LI (p=0.038 and p=0.018). CPP32 but not ASP175 LI positively correlated with the mitotic index (p=0.001) and PCNA LI (p=0.004). Both CPP32 and ASP175 LIs were increased in nonbenign meningiomas (p<0.0001 and p=0.0035 respectively). In univariate and multivariate survival analyses, caspase-3 predicted meningioma recurrence, independently affecting disease-free survival (p=0.011 and p=0.047 respectively for CPP32; p<0.0001 and p=0.012 respectively for ASP175). Caspase-3 may prove to be a useful predictor of early recurrence in a group of neoplasms characterized by the frequent discordance between histology and clinical behavior.

Aged↗
PubMed2006

Association of hypospadias and cardiac defect in a Parvovirus B19-infected stillborn: a causality relation?

Parvovirus B19 intrauterine infection is a known cause of hydrops fetalis and fetal death. It is also associated with congenital malformations, although the teratogenic potential seems to be low. Postmortem examination of a male stillborn of 29 gestational weeks revealed mild subcutaneous edema, malformed micropenis, perineoscrotal hypospadias and atrial septal defect, along with fetal erythroblastosis and villitis. Polymerase chain reaction detected Parvovirus B19 DNA genome in tissues from the fetus and the placenta, confirming the hypothesis of an intrauterine infection.

Abnormalities, Multiple↗
PubMed2005

Apoptotic markers for primary brain tumor prognosis.

Molecular studies of brain tumors have provided insights into pathogenesis, yet it is unclear how important these markers are in predicting clinical outcome and response to treatment. Quantitation of apoptosis by various techniques and the expression of several apoptotic markers have been studied in brain tumors, seeking to refine the information gained from established prognostic variables, which traditionally dictate therapeutic approaches. In the present review we discuss the role of the most extensively examined molecules involved in the apoptotic procedure, such as bcl-2, bax, fas/fasL, survivin and p53, as well as the incidence of baseline apoptosis in various brain tumors, in relation to prognosis. Summarizing current evidence, increased apoptosis and p53 genetic alterations have been advanced as adverse prognosticators in various types of central nervous system neoplasms, while bcl-2 expression appears to be deprived of any predictive value in primary brain tumors. The prognostic significance of the remaining apoptosis-related molecules remains controversial or too limited to draw any firm conclusions. The lack of unanimity of results mostly based on single-center retrospective studies underscores the necessity for large prospective randomized clinical trials, to elucidate the role of these molecular markers as determinants of clinical decision-making and as potential correlates of a pathobiologically tailored and individualized treatment strategy.

Apoptosis↗
PubMed2004

Hypoxia-inducible factor 1alpha/vascular endothelial growth factor axis in astrocytomas. Associations with microvessel morphometry, proliferation and prognosis.

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that promotes ischaemia-driven angiogenesis. The aim of this study was to determine the relation of HIF-1alpha to vascular endothelial growth factor (VEGF; an important angiogenic molecule in brain tumours), p53 expression, angiogenesis, proliferative potential and clinical outcome in a large series of diffuse astrocytomas. Expression of HIF-1alpha, VEGF, Ki-67 (a proliferation-associated marker) and p53 was determined immunohistochemically in 83 adult patients with supratentorial diffuse astrocytomas. Microvessels, highlighted by means of anti-CD34 immunohistochemistry, were enumerated with computer-assisted image analysis. Although HIF-1alpha and VEGF were expressed in the majority of cases, their levels increased significantly with increasing grade and proliferative potential. HIF-1alpha positively correlated with microvessel counts and VEGF with total vascular area and the presence of rounder vessel sections. There was a positive correlation of VEGF with p53 expression in astrocytomas and anaplastic astrocytomas. In univariate analysis, both VEGF and HIF-1alpha were associated with shortened survival in the entire cohort, but lost significance when grades II/III and grade IV were analysed separately. Multivariate analysis revealed that the combination of HIF-1alpha with grade was a significant prognostic indicator. HIF-1alpha expression may be used to refine the prognostic information provided by grade in patients with diffuse astrocytomas. Its adverse prognostic effect is most likely mediated by hypoxia, the driving force for HIF-1alpha accumulation.

Adolescent↗
PubMed2003

Hormone receptors in non-malignant meningiomas correlate with apoptosis, cell proliferation and recurrence-free survival.

AIMS: A retrospective immunohistochemical and statistical analysis of patients with non-malignant meningiomas was undertaken to determine the correlation of steroid hormone receptor status with apoptosis, tumour cell proliferation, clinicopathological characteristics and prediction of recurrence. METHODS AND RESULTS: Paraffin sections from 51 primary intracranial totally resected benign and atypical meningiomas were immunohistochemically evaluated for the expression of progesterone (PR), oestrogen (ER) and androgen (AR) receptors, apoptotic rate, Bcl-2, p53 and Ki67 antigens. In addition to the above parameters, the mitotic index and the patients' clinicopathological data were statistically correlated and entered in a recurrence-free survival analysis. A high level of apoptotic cell death was associated with loss of PR expression by logistic regression analysis (P = 0.016). An inverse correlation existed between the mitotic index and PR counts (P = 0.009), while high Ki67 values correlated with increased ARs (P = 0.041). Atypical meningiomas had a lower ER staining score (P = 0.036). Multivariate analysis indicated that the absence of PR and large tumour size were significant factors for shorter disease-free intervals. CONCLUSIONS: The results suggest that ER expression is lost or reduced in atypical meningiomas, whereas loss of PR expression is an indicator of increased apoptosis and early recurrence. PRs and ARs may also influence tumour cell proliferation.

Apoptosis↗
PubMed2003

Mitosin, a novel marker of cell proliferation and early recurrence in intracranial meningiomas.

The expression of mitosin, a novel proliferation-associated molecule was evaluated immunohistochemically in a consecutive series of 47 patients with primary intracranial benign and atypical meningiomas. Mitosin expression was correlated with proliferation markers Ki-67 (MIB-1), proliferating cell nuclear antigen (PCNA), topoisomerase IIalpha (TopoIIalpha) and mitotic index, as well as with standard clinicopathological parameters and patient outcome. Seven tumors recurred (14.8%) following gross total resection, within a follow-up period ranging from 21 to 108 months (median 60 months). The higher proliferation indices were obtained with mitosin and PCNA and the lower ones with TopoIIalpha. Mitosin labeling index (LI) ranged from 0.1 to 57% (median 3%), with a significant overlapping of values between grades. A significant positive correlation was shown between mitosin LI on the one hand and Ki-67 LI (p < 0.001), or the mitotic index (p = 0.027) on the other. The incidence of recurrence was higher in cases with a mitosin LI higher than 3% (p = 0.048). Univariate analysis disclosed mitosin LI (p = 0.033) along with the mitotic index (p = 0.024) and tumor size (p = 0.028) as significant predictors of shortened recurrence-free survival. In multivariate analysis, the labeling indices of mitosin (p = 0.035) and Ki-67 (p = 0.032), along with tumor size, were shown to provide independent prognostic information, beyond that obtained by standard clinical and pathological parameters. However, as indicated by factor analysis, the prognostic information yielded by mitosin was superior to that provided by the remaining proliferation markers (p = 0.041). We conclude that mitosin immunohistochemical expression, although failing to discriminate between benign and atypical meningiomas, may be of use as a novel cell proliferation marker and as a predictor of tumor recurrence.

Antigens, Neoplasm↗
PubMed2003

Evaluation of the cyclin-dependent kinase inhibitor p21Cip1 in epithelial ovarian tumors of low malignant potential and adenocarcinomas.

OBJECTIVE: In view of the controversial information on the significance of the cyclin-dependent kinase inhibitor p21Cip1 in ovarian cancer, we conducted a retrospective investigation to clarify the relationships of this protein to proliferation rate, clinicopathological variables and prognosis of epithelial ovarian tumors. METHODS: Paraffin-embedded tissue from 43 ovarian tumors of low malignant potential (LMP) and 82 primary ovarian adenocarcinomas were stained immunohistochemically for p21Cip1, p53 protein and Ki-67 antigen (a marker of cell proliferation). RESULTS: p21Cip1 levels were significantly higher in LMP tumors (p<0.001) as well as in early stage adenocarcinomas (p=0.021) and those associated with minimal residual disease (p=0.008). However, no relationship existed between p21Cip1 expression and the proliferation rate of adenocarcinomas or LMP tumors. In the vast majority of LMP tumors p21Cip1 expression was not accompanied by p53 accumulation. This p21Cip1-positive/p53-negative phenotype prevailed in the early stage (p=0.026), lower grade (p=0.018) adenocarcinomas as well as in those left with minimal residual disease (p=0.059). In patients with lower grade adenocarcinomas, decreased p21Cip1 expression was adversely related to poor overall survival on its own (p=0.0500) and when combined with p53 protein overexpression (p=0.0323). In multivariate analysis, only the stage remained as the independent predictor of survival. CONCLUSIONS: Decreased p21Cip1 expression is related to several indicators of aggressiveness in ovarian adenocarcinomas and seems to be differentially regulated in LMP tumors and adenocarcinomas. On the contrary, deregulation of p21Cip1 expression does not seem to participate in the pathogenesis of LMP tumors. Furthermore, although p21Cip1 alone or combined with p53 is of prognostic significance in lower grade adenocarcinomas, it does not appear to add to the information gained from traditional prognosticators.

Adenocarcinoma↗
PubMed2002

Prognostic implications of microvessel morphometry in diffuse astrocytic neoplasms.

Astrocytic brain tumours, particularly malignant astrocytomas, are recognized to be highly vascular neoplasms with potent angiogenic activity. Recent research has shown that quantification of microvessel density (MVD), as a measure of the degree of angiogenesis, constitutes a strong prognostic indicator in patients with astrocytomas. However, the significance of other morphometric aspects of microvessel network has not been tested so far. In this report, histological sections from 70 astrocytomas (grades II to IV), immunostained for CD34, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to vessel size or shape. Minor axis length increased with grade (P = 0.045) but MVD and TVA presented a peak in grade III (P = 0.033 and P < 0.001, respectively). Size and shape related parameters affected survival in univariate analysis of grade IV and grades II/III, respectively. In multivariate analysis, only branching counts, along with age and grade, were the independent predictors of survival. Although MVD, TVA and branching counts were adversely related to disease-free survival in grades II and III (univariate analysis), only TVA remained statistically significant in multivariate analysis. It is concluded that TVA and branching counts are prognostically more informative than MVD for patients with diffuse astrocytic tumours.

Adolescent↗
PubMed2001

Detection of apoptotic cells in archival tissue from diffuse astrocytomas using a monoclonal antibody to single-stranded DNA.

Precise quantitation of apoptotic cells in gliomas is necessary to determine the role of apoptosis in tumour growth, prognosis, and treatment. This study investigated the incidence of baseline apoptosis in relation to proliferation status, p53 expression, standard clinicopathological parameters, and outcome, in a series of 61 patients with diffuse cerebral astrocytomas. Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing exposed single-stranded (ss) regions in the DNA of apoptotic cells during heating. Proliferative activity was expressed as the percentage of Ki-67-positive cells. Tissues consisted of primary formalin-fixed, paraffin-embedded astrocytoma specimens. The apoptotic index (AI) increased with grade, proliferative activity, and p53 expression. Increased AI tended to be accompanied by a shortened overall and disease-free survival in univariate analysis in glioblastoma multiforme and astrocytoma/anaplastic astrocytoma, respectively. Multivariate analysis demonstrated that increased AI was an independent predictor of adverse significance in overall and disease-free survival. These results implicate apoptotic rate in astrocytoma aggressiveness and show that the assessment of apoptotic potential by means of anti-ssDNA monoclonal antibody provides valuable prognostic information independently of standard parameters or tumour proliferation status.

Adolescent↗
PubMed2001

Tracheoesophageal malformation: pathogenetic evidence provided by two cases.

BACKGROUND: The aim of this observational study is to examine cases of upper respiratory atresia, in an effort to seek pathogenetic evidence suggestive of either a primary defect in embryogenesis or of a secondary etiology. METHODS: Archival material of 412 fetal and perinatal autopsies with congenital malformations was reviewed in an effort to identify infants with complete upper airway obstruction without tracheoesophageal (TE) communication. Histological sections of the upper and lower respiratory tract were examined, seeking evidence of previous amniotic fluid or meconium aspiration, indicated by the presence of amniotic squamous epithelial cells, lanugo hair, or bile-stained meconium in the airways. Immunohistochemical stain for epithelial membrane antigen (EMA) and high-molecular-weight cytokeratin (CK1) were used to identify amniotic fluid and keratinizing squamous epithelial cells. RESULTS: Eight infants with upper airway obstruction were identified, three of them without a TE communication. Two of the latter, one infant with multiple atresia born at 34 weeks gestation and another with tracheal atresia born at 32 weeks, presented evidence of amniotic fluid aspiration in their lungs. CONCLUSIONS: Evidence of amniotic fluid aspiration in the above two cases indicates that there had been a previous patency of the upper respiratory pathway, since the absence of a TE fistula excludes any communication with the oronasal cavity. This implicates a secondary pathogenesis for at least some cases of upper airway obstruction.

Amniotic Fluid↗
PubMed2001

Morphometric microvascular characteristics predict prognosis in superficial and invasive bladder cancer.

Recent research has shown that neovascularization, quantitated by microvessel density (MVD), constitutes a strong prognostic indicator in patients with invasive urothelial carcinomas. These studies, however, have focused only on MVD as the only factor reflecting angiogenesis in transitional-cell carcinomas (TCCs). The objective of this report was to evaluate multiple morphometric microvascular characteristics besides MVD in superficial and muscle-invasive TCCs separately, to provide a better approach to the relationship between angiogenesis, clinicopathological parameters, and prognosis. Histologic sections from 115 TCCs [35 superficial (T1) and 80 muscle-invasive] were immunostained for CD31 and evaluated using image analysis for the quantitation of MVD, area, total vascular area, major axis length, minor axis length, perimeter, compactness, shape factor, and Feret diameter. Patients were followed-up until death (n=31) or for an average of 42.2 months (median 38.5 months). MVD increased with progressing T category (P=0.049) but area (P=0.033), major axis length (P=0.022), perimeter (P=0.043), and Feret diameter (P=0.042) were highest in T2 tumors. Area was the single independent predictor of adverse significance in T1 TCCs, whereas for muscle-invasive tumors, survival was independently predicted by MVD. Regarding disease-free survival in superficial tumors, the single significant independent parameter was compactness, whereas area was an independent favorable indicator of disease-free survival for patients with invasive TCCs. It is concluded that the prognostic significance of neovascularization is better assessed by area and shape-related morphometric characteristics, whereas MVD becomes influential only with regard to overall survival of patients with invasive tumors.

Adult↗
PubMed2001

DNA topoisomerase IIalpha expression correlates with cell proliferation but not with recurrence in intracranial meningiomas.

AIMS: To assess the value of topoisomerase IIalpha (TopoIIalpha) as a novel proliferation-associated molecule, by correlating its immunohistochemical expression with Ki67 (MIB-1), cell proliferating cell nuclear antigen (PCNA) and mitotic index in meningiomas. Furthermore, to investigate its relation to standard clinicopathological parameters and patients' outcome. METHODS AND RESULTS: This retrospective study comprised a consecutive series of 57 patients with primary intracranial benign and atypical meningiomas. Six tumours recurred (10.5%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months (median 60 months). Archival formalin-fixed paraffin-embedded sections were stained with standard immunohistochemical methods. The lower proliferation indices were obtained with TopoIIalpha and the higher ones with PCNA. TopoIIalpha labelling index (LI) ranged from 0.1% to 10% (median 0.5%) and, along with Ki67 and PCNA LI, increased with malignancy grade (P=0.049, P=0.045 and P < 0.001, respectively), displaying though a significant overlapping between grades. A significant positive correlation was shown between TopoIIalpha and Ki67 (P < 0.001) or PCNA (P=0.032). In univariate and multivariate survival analysis, TopoIIalpha failed to predict meningioma recurrence and did not affect disease-free survival. Only tumour size and Ki67 LI provided significant prognostic information in this regard. CONCLUSIONS: TopoIIalpha expression may be useful as a novel proliferation marker in meningiomas, presenting several advantages over the markers currently in use, notably providing a better estimate of the number of cycling cells and a more uniform nuclear staining pattern. However, it fails to discriminate between benign and atypical neoplasms and does not provide prognostic information beyond that obtained by Ki67.

Antigens, Neoplasm↗
PubMed2001

Mitosin and DNA topoisomerase IIalpha: two novel proliferation markers in the prognostication of diffuse astrocytoma patient survival.

The expression of two novel proliferation-associated markers, mitosin and topoisomerase IIalpha (Topo IIalpha), was evaluated immunohistochemically in consecutive paraffin sections from 60 diffuse astrocytomas (grades 2 to 4) in relation to clinicopathologic parameters, proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1) expression and survival. The percentage of mitosin and Topo IIalpha-positive cells (LI) increased with grade and Ki-67 LI, but could not discriminate between grade 3 on the one hand and grades 2 or 4 on the other hand. In 51% of cases, Ki-67 LI exceeded Topo IIalpha LI, especially within grade 4. Topo IIalpha and mitosin expression was adversely related to overall and disease-free survival in the entire cohort and in grades 2/3. However, only Topo IIalpha LI affected disease-free survival in grade 4 tumors. Multivariate analysis selected only mitosin LI along with the age of the patient, as the independent parameters predicting overall survival, whereas Topo IIalpha emerged as the single independent predictor of disease-free survival. It is concluded that the proliferative potential of astrocytomas, as measured by mitosin and Topo IIalpha immunostaining, conveys useful prognostic information, in addition to that obtained by standard clinicopathologic parameters.

Antigens, Neoplasm↗
PubMed2000

Apoptosis in bladder carcinomas detected with monoclonal antibody to single-stranded DNA: relation to cell cycle regulators and survival.

OBJECTIVES: To investigate the incidence of baseline apoptosis in relation to p27(Kip1), p53, and p21(Cip1) expression, proliferation status, standard clinicopathologic parameters, and patient outcome. Cell cycle regulators and apoptotic cell death have been implicated in tumor aggressiveness in many human malignancies. Their interaction, however, in the prognosis of patients with transitional cell carcinoma (TCC) of the urinary bladder has not yet received intense scrutiny. METHODS: Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing single-stranded DNA regions in apoptotic nuclei in 103 paraffin-embedded primary TCC specimens. Proliferative activity was expressed as the percentage of Ki-67 positive cells (Ki-67 index). Tissue specimens were also stained for p27(Kip1), p53, and p21(Cip1) proteins. Patients were followed up until death (n = 30) or for an average of 40 months (median 36). RESULTS: The apoptotic index increased with grade, T stage, nonpapillary status, proliferative activity, and p53 expression and was inversely related to p27(Kip1) and independently to p21(Cip1) expression. A negative correlation was found between p27(Kip1) expression and proliferation. The increased apoptotic index had an adverse impact on overall and disease-free survival (univariate analysis) and, along with T stage, was an independent predictor in muscle-invasive TCC. CONCLUSIONS: An increased apoptotic rate, increased proliferative activity, and decreased p21(Cip1) expression are independently interrelated in TCC. More importantly, the assessment of apoptotic potential appears to be more informative than standard prognosticators in predicting overall survival in patients with muscle-invasive TCC.

Adult↗
PubMed2000

Cell cycle regulators in bladder cancer: a multivariate survival study with emphasis on p27Kip1.

Cyclin-dependent kinase inhibitors (CKIs) prevent cyclin-dependent kinases from phosphorylating critical substrates such as retinoblastoma gene protein (pRb), hence blocking the cascade of events leading to cell proliferation. Currently, the list of CKIs includes p21WAF1/Cip1, p27Kip1, p57Kip2 (the Cip/Kip family), p15/ INK4b, p16/INK4a, p18/INK4c, and p19/INK4d (the INK4 family). Among them, p27 plays a crucial role linking extracellular growth-regulatory signals to progression to or exit from the cell cycle. Unlike p53, p16, and Rb, mutations in Kip1 and WAF1 genes are distinctly rare in bladder cancer. We analyzed immunohistochemically the expression of p27 and other interacting G1 proteins (ie, p21, p16, pRb, p53) in 120 consecutive cases of transitional cell carcinomas (TCCs) and related it to proliferation rate, clinicopathologic parameters, and survival. p27 levels were significantly higher in low-grade (P = .001), superficial (Ta-T1) (P = .001), papillary (P < .001), and slowly proliferating TCCs (rs = -0.235, P = .05). p27 also positively correlated with p16 expression (rs = 0.212, P = .05). In univariate analysis, decreased p27 expression was associated with poor overall (P = .0109) and postrelapse (P = .0344) survival, especially if combined to increased Ki-67 expression (P = .0004 and P = .036, respectively). Furthermore, in multivariate analysis, Ki-67/p27 status had the strongest bearing on the overall survival of muscle-invasive TCCs (P = .0019). Our results indicate that low p27 expression is more common in poorly differentiated muscle-invasive TCCs and is a major player in cell cycle control in these neoplasms. More importantly, the combined Ki-67/p27 expression provides prognostic information beyond that provided by conventional parameters or other cell cycle-related proteins, concerning overall survival in muscle-invasive TCCs.

Adult↗
PubMed2000

WAF1/p21 protein expression is an independent prognostic indicator in superficial and invasive bladder cancer.

The inhibitor of cyclin-dependent kinases WAF1 gene product p21 is able to arrest mammalian cell cycle by mediating p53 and other factors. The prognostic value and interrelationships between p21 expression and various parameters in bladder cancer have not been fully elucidated. We retrospectively investigated the immunohistochemical expression of p21 protein in consecutive paraffin sections from 131 transitional cell carcinomas (TCCs) and related it to p53 protein expression, clinicopathologic parameters, proliferative fraction, and survival. Positivity was displayed in 45% of cases, among which one fourth was accompanied by p53 accumulation. p21 expression was statistically related to advanced T category. No association was shown between p21 and p53 or proliferation rate. Low grade invasive TCCs tended to be more often p21 positive than high grade invasive TCCs. Most superficial tumors displayed neither p21 nor p53 expression, whereas the combined phenotypes p53/p21+ and p53+/p21- predominated among invasive tumors. P21 labeling index emerged by multivariate analysis as the single independent indicator of shortened overall (P = 0.0294) and disease-free (P = 0.0414) survival in superficial TCCs. Conversely, in invasive tumors, loss of p21 expression was a predictor of shortened disease-free survival (P = 0.0234) and was associated with poor outcome when accompanied by p53 accumulation (P = 0.0033). In conclusion, our results indicate that p21 activation occurs early in tumorigenesis, appears associated with invasiveness, and is capable of cell cycle control in TCCs mostly through p53-dependent pathways. Finally, p21 expression, alone or in combination with p53 and irrespective of other clinicopathologic parameters, plays distinct roles in determining clinical outcome in superficial and invasive tumors, suggesting that urothelial bladder cancer represents two different diseases.

Adult↗
PubMed1998

A morphometric study of neovascularization in colorectal carcinoma.

BACKGROUND: Neovascularization reportedly is correlated with metastasis, recurrence, and prognosis in some types of tumors. Microvessel quantification in so-called "hot spots" has been studied extensively as the only factor reflecting angiogenesis in various malignant tumors. The objective of this report was to evaluate multiple morphometric microvascular characteristics in addition to microvessel density (MVD) in colorectal carcinomas to provide a better approach to examining the relation between angiogenesis and clinicopathologic factors and prognosis. METHODS: Histologic sections from 106 colorectal adenocarcinomas and 17 adenomas, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to the vessel size or shape. RESULTS: MVD gradually decreased with progressing Dukes stage. The vascular branching counts were significantly higher in carcinomas than in adenomas, and remained unaffected through progressing Dukes stages. Shape-related parameters showed significant differences between carcinomas and adenomas and between different grades of differentiation. Branching counts and TVA were the only factors found to be of prognostic significance. CONCLUSIONS: This study provides evidence that neovascularization is an early critical event in colorectal tumorigenesis, reaching a maximum level early in the malignant process. Its prognostic significance is better assessed by quantification of TVA and the branching pattern of microvessels, whereas MVD does not provide significant prognostic information for colorectal carcinoma patients.

Adenocarcinoma↗