584 research outputs found
Human Papillomavirus in Endometrial Adenocarcinomas: Infectious Agent or a Mere βPassengerβ?
Aims. To investigate the possible association
of human papillomavirus (HPV) with endometrial hyperplasias and
neoplasia. Does HPV play any role in the initiation or
prognosis of endometrial adenocarcinomas?
Methods. Twenty-five endometrial adenocarcinomas
of the endometrioid cell type, with and without squamous
differentiation, and twenty-four endometrial hyperplasias of various
forms (simple, complex, and atypical) were analyzed for the
presence of type 16 and 18 HPV by the polymerase chain
reaction (PCR). The results were related to histopathological
features of the tumour, and the patients' age, and
prognosis. Results. Six of 25 endometrial
adenocarcinomas were HPV 16-positive
(24%),
and 5 of 25
(20%)
were HPV 18-positive. Simple endometrial hyperplasias was
associated somewhat more commonly with HPV 16 and 18 (2/8 and
1/8 cases, resp.) than hyperplasias progressing to
endometrial adenocarcinomas, namely, atypical endometrial
hyperplasia (1/8 and 0/8 cases, resp.). None of the
positive cases in the series, whether hyperplastic or
neoplastic, demonstrated cytological evidence of HPV
infection. There was no relation between HPV-positive cases
and squamous differentiation, depth of myometrial invasion,
lymphatic involvement, lymphocytic response, patients' age,
or prognosis. Conclusion. It appears that the
presence of HPV in the endometrium, as detected by PCR, does
not play any role in the initiation or prognosis of
endometrial adenocarcinoma
Relation of hypoxia inducible factor 1Ξ± and 2Ξ± in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival
Hypoxia inducible factors HIF1Ξ± and HIF2Ξ± are important proteins involved in the regulation of the transcription of a variety of genes related to erythropoiesis, glycolysis and angiogenesis. Hypoxic stimulation results in rapid increase of the HIF1Ξ± and 2Ξ± protein levels, as a consequence of a redox-sensitive stabilization. The HIFΞ±s enter the nucleus, heterodimerize with the HIF1Ξ² protein, and bind to DNA at the hypoxia response elements (HREs) of target genes. In this study we evaluated the immunohistochemical expression of these proteins in 108 tissue samples from non-small-cell lung cancer (NSCLC) and in normal lung tissues. Both proteins showed a mixed cytoplasmic/nuclear pattern of expression in cancer cells, tumoural vessels and tumour-infiltrating macrophages, as well as in areas of metaplasia, while normal lung components showed negative or very weak cytoplasmic staining. Positive HIF1Ξ± and HIF2Ξ± expression was noted in 68/108 (62%) and in 54/108 (50%) of cases respectively. Correlation analysis of HIF2Ξ± expression with HIF1Ξ± expression showed a significant association (P < 0.0001, r = 0.44). A strong association of the expression of both proteins with the angiogenic factors VEGF (P < 0.004), PD-ECGF (P < 0.003) and bFGF (P < 0.04) was noted. HIF1Ξ± correlated with the expression of bek-bFGF receptor expression (P = 0.01), while HIF2Ξ± was associated with intense VEGF/KDR-activated vascularization (P = 0.002). HIF2Ξ± protein was less frequently expressed in cases with a medium microvessel density (MVD); a high rate of expression was noted in cases with both low and high MVD (P = 0.006). Analysis of overall survival showed that HIF2Ξ± expression was related to poor outcome (P = 0.008), even in the group of patients with low MVD (P = 0.009). HIF1Ξ± expression was marginally associated with poor prognosis (P = 0.08). In multivariate analysis HIF2Ξ± expression was an independent prognostic indicator (P = 0.006, t-ratio 2.7). We conclude that HIF1Ξ± and HIF2Ξ± overexpression is a common event in NSCLC, which is related to the up-regulation of various angiogenic factors and with poor prognosis. Targeting the HIF pathway may prove of importance in the treatment of NSCLC. Β© 2001 Cancer Research Campaignhttp://www.bjcancer.co
Relationship of vascular maturation in breast cancer blood vessels to vascular density and metastasis, assessed by expression of a novel basement membrane component, LH39
Angiogenesis, the formation of new vessels, has been demonstrated to be an indicator of prognosis in breast cancer patients. The extent of differentiation of the tumour vessels may affect access of peripheral white cells and egress or invasion of tumour cells. This has not been assessed in relation to tumour microvessel density or other variables and may be a marker of vascular remodelling. LH39 is a monoclonal antibody recognizing an epitope located at the lamina lucida of mature small veins and capillaries but not in newly formed vessels. To study vascular differentiation in breast tumours, we examined the vascular maturation index (VMI) in 12 normal and 50 breast carcinomas and this was correlated with different clinicopathological variables including angiogenesis. Mature vessels were defined by staining with antibodies to both LH39 and to CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31. VMI was defined as the % fraction of mature vessels (LH39-positive) / total number of vessels (CD31-positive). The VMI was significantly higher in normal (54β68.5%; median 66.5%) than in tumours (0β47%; median 8.8%) (P = 0.0005). There was a significant inverse correlation between the tumour VMI and nodal status (Fisher's exact test, P = 0.01) and between high VMI and low thymidine phosphorylase (TP) expression (MannβWhitney U -test, P = 0.01). No significant association between VMI and tumour size, oestrogen receptor, epidermal growth factor receptor, grade, angiogenesis, patient age, or E-selectin was seen. There was a significant reduction in relapse-free survival (P = 0.01) with high angiogenesis. These findings show that the VMI gives new information on the mechanism of tumour angiogenesis independently from microvessel quantitation, there is a wide variation in the differentiation of tumour vasculature but the degree of capillary differentiation is not associated with quantitative angiogenesis. The VMI identifies a subset of patients who have a high chance of regional node involvement. Β© 2000 Cancer Research Campaig
Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer
High microvessel density, an indirect measure of angiogenesis, has been shown to correlate with increased tumour size, lymph node involvement and poor prognosis in non-small-cell lung cancer (NSCLC). Tumour cell vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) expression correlate with angiogenesis and a poor outcome in this disease. In a retrospective study VEGF and PD-ECGF expression and microvessel density were evaluated immunohistochemically in surgically resected specimens (T1β3, N0β2) from 223 patients with operable NSCLC using the VG1, P-GF.44C and JC70 monoclonal antibodies respectively. High VEGF immunoreactivity was seen in 104 (46.6%) and PD-ECGF in 72 (32.3%) cases and both were associated with high vascular grade tumours (P = 0.009 and P = 0.05 respectively). Linear regression analysis revealed a weak positive correlation between VEGF and PD-ECGF expression in cancer cells (r = 0.21;P = 0.002). Co-expression of VEGF and PD-ECGF was not associated with a higher microvessel density than VEGF or PD-ECGF only expressing tumours. Furthermore a proportion of high vascular grade tumours expressed neither growth factor. Univariate analysis revealed tumour size, nodal status, microvessel density and VEGF and PD-ECGF expression as significant prognostic factors. Tumour size (P< 0.02) and microvessel density (P< 0.04) remained significant on multivariate analysis. In conclusion, VEGF and PD-ECGF are important angiogenic growth factors and have prognostic significance in NSCLC. Furthermore the study underlines the prognostic significance of microvessel density in operable NSCLC. Β© 2000 Cancer Research Campaig
Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis
Lactate dehydrogenase-5 (LDH-5) catalyses the reversible transformation of pyruvate to lactate, having a principal position in the anaerobic cellular metabolism. Induction of LDH-5 occurs during hypoxia and LDH-5 transcription is directly regulated by the hypoxia-inducible factor 1 (HIF1). Serum LDH levels have been correlated with poor prognosis and resistance to chemotherapy and radiotherapy in various neoplastic diseases. The expression, however, of LDH in tumours has never been investigated in the past. In the present study, we established an immunohistochemical method to evaluate the LDH-5 overexpression in tumours, using two novel antibodies raised against the rat muscle LDH-5 and the human LDH-5 (Abcam, UK). The subcellular patterns of expression in cancer cells were mixed nuclear and cytoplasmic. In direct contrast to cancer cells, stromal fibroblasts were reactive for LDH-5 only in a minority of cases. Serum LDH, although positively correlated with, does not reliably reflect the intratumoral LDH-5 status. Lactate dehydrogenase-5 overexpression was directly related to HIF1alpha and 2alpha, but not with the carbonic anhydrase 9 expression. Patients with tumours bearing high LDH-5 expression had a poor prognosis. Tumours with simultaneous LDH-5 and HIF1alpha (or HIF2alpha) overexpression, indicative of a functional HIF pathway, had a particularly aggressive behaviour. It is concluded that overexpression of LDH-5 is a common event in non-small-cell lung cancer, can be easily assessed in paraffin-embedded material and provides important prognostic information, particularly when combined with other endogenous markers of hypoxia and acidity
Does the act of surgery provoke activation of "latent" metastases in early breast cancer?
This paper is written in support of the challenging article by Retsky and colleagues in this issue of Breast Cancer Research, and develops on the idea that the act of surgery can provoke the outgrowth of dormant micrometastases, which often leads to the failure of screening to deliver its promise. The therapeutic consequence of this idea involves the use of antiangiogenic drugs before surgery
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