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O Straume

Publications and source records attributed to O Straume.

12 recordsLinked to original sources
PubMed2005

Strong expression of ID1 protein is associated with decreased survival, increased expression of ephrin-A1/EPHA2, and reduced thrombospondin-1 in malignant melanoma.

The ID1 protein, an inhibitor of basic helix-loop-helix transcription factors, has been involved in multiple cellular processes including cell cycle regulation, apoptosis, and angiogenesis. To evaluate the importance of ID1 in malignant melanoma, tumour cell expression was examined by immunohistochemistry in 119 cases of nodular melanoma using tissue microarray technique, and related to multiple tumour markers including proliferation, p16 expression, angiogenesis and patient survival. Strong ID1 expression was significantly associated with increased tumour thickness, and significantly reduced survival. Also, increased ID1 was associated with loss of thrombospondin-1 (TSP-1) expression, a known inhibitor of angiogenesis, and increased intensity of ephrin-A1 and its receptor EPHA2. Presence of BRAF mutations was related to strong ID1 expression, but there was no relationship with p16 protein expression. Further, no significant correlation was found between ID1 and microvessel density. In conclusion, our study supports a significant role of the ID1 protein in melanoma progression and patient prognosis. The absence of correlation with p16 protein expression and angiogenesis suggests that other regulatory pathways and mechanisms might be influenced by ID1 in melanomas. An inverse relation between ID1 and TSP-1 expression support an important role of ID1 in the regulation of this complex multitarget protein.

Biomarkers, Tumor↗
PubMed2003

Glomeruloid microvascular proliferation is associated with p53 expression, germline BRCA1 mutations and an adverse outcome following breast cancer.

Glomeruloid microvascular proliferation (GMP) in breast cancer independently adversely affected survival (relative risk 1.9, 95% CI: 1.2-3.0), particularly among women who received adjuvant chemotherapy (10-year survival 27 vs 69%, P=0.0003), and was significantly associated with p53 overexpression and BRCA1 germline mutations. The presence of GMP may influence treatment decisions.

Adult↗
PubMed2001

A single nucleotide polymorphism in the 3'untranslated region of the CDKN2A gene is common in sporadic primary melanomas but mutations in the CDKN2B, CDKN2C, CDK4 and p53 genes are rare.

In this report we present the results of mutational analysis of the CDKN2B, CDKN2C, CDK4, p53 genes and 5'UTR of the CDKN2A gene in a set of 44 sporadic primary melanomas, which had been earlier analysed for mutations in the CDKN2A (p16/p14(ARF)) gene. No tumour-associated mutations were detected except in 1 melanoma where we found a CC>T* deletion-mutation in the codon 151-152 (exon 5) of the p53 gene. On the basis of our preliminary results, we did extended genotyping of the 500 C>G and 540 C>T polymorphisms in the 3'UTR of the CDKN2A gene in 229 melanoma cases and 235 controls. The T-allele frequency (for 540 C>T polymorphism) in melanomas was significantly higher than in controls (0.14 vs. 0.08; chi(2) = 5.95, p = 0.01; OR = 1.71, 95%CI = 1.11-2.66). The heterozygote frequency for this polymorphism was 0.26 (59/229) in melanomas compared to 0.13 (30/235) in healthy controls (chi(2) = 11.4; p = 0.0007; OR = 2.34, 95% CI = 1.40-3.92). The frequency of the 500 C>G polymorphism in the 3'UTR in the CDKN2A gene was not significantly higher in melanomas compared to healthy controls. The 500 C>G polymorphism, however, was in linkage disequilibrium with approximately 50 kb apart the C>A intronic polymorphism in the CDKN2B gene (determined in 44 melanomas and 90 controls; Fisher exact test, p<0.0001). Finally, the sequence analysis of genomic DNA isolated from T cell lymphocytes of healthy individuals exhibited that the codon reported as last of exon 2 of the CDKN2C gene is rather the first codon of exon 3.

3' Untranslated Regions↗
PubMed2001

Expresson of vascular endothelial growth factor, its receptors (FLT-1, KDR) and TSP-1 related to microvessel density and patient outcome in vertical growth phase melanomas.

Microvessel density (MVD) was estimated in a series of 202 vertical growth phase (VPG) melanomas and 68 corresponding metastases, using a marker for angiogenic endothelial cells (CD105) and Factor-VIII. The expression pattern of vascular endothelial growth factor (VEGF), FLT-1, KDR and thrombospondin-1 (TSP-1) was studied by immunohistochemistry, in situ hybridization and reverse-transcriptase polymerase chain reaction. CD105 stained significantly less vessels, but gave only limited additional prognostic information compared with Factor-VIII, and MVD was an independent prognostic factor for both markers. Ninety-eight percent of all cases showed expression of VEGF, and higher expression was found significantly more frequent in thinner and less vascularized tumors. Possible autocrine loops were suggested by co-expression of VEGF and its two receptors in tumor cells, and by a significant correlation between KDR and tumor cell proliferation (Ki-67) in the subgroup of thicker tumors. Staining of VEGF receptors in endothelium was not correlated with MVD. Strong expression of TSP-1 in tumor stroma was found in 43% of the primary tumors, and was significantly correlated with increased thickness, proliferation and MVD, as well as decreased survival. These data suggest that MVD is associated with prognosis in cutaneous melanomas, and that the VEGF system and particularly TSP-1 seem to be involved in the regulation of angiogenesis and progression of these tumors.

Blood Vessels↗
PubMed2000

Loss of nuclear p16 protein expression correlates with increased tumor cell proliferation (Ki-67) and poor prognosis in patients with vertical growth phase melanoma.

The CDKN2A (p16INK4alpha) cell cycle-inhibitory gene has been associated with development of familial melanoma. Additionally, recent studies indicate that p16 alterations occur frequently in sporadic melanomas. To investigate whether differences in p16 expression are associated with tumor cell proliferation, tumor progression, and patient survival, we examined the immunohistochemical staining of p16 protein in a consecutive series of 202 vertical growth phase melanomas and 68 corresponding metastases and compared the results with Ki-67 expression, p53 expression, clinicopathological variables, and survival data. Forty-five percent of the primary tumors showed absent or minimal nuclear staining for p16 protein. These cases were significantly associated with high Ki-67 expression (P < 0.0001), ulceration (P = 0.001), and vascular invasion (P = 0.03). Further loss of p16 expression was observed in metastatic lesions (77% were negative; P < 0.0001). Absent/minimal nuclear p16 staining significantly predicted poor patient survival (log-rank test, P = 0.0003), with 37% and 67% estimated 10-year survival rates for cases with absent or present p16 expression, respectively. In multivariate analysis, p16 staining was an independent prognostic factor (hazard ratio, 2.5; 95% confidence interval, 1.5-4.2; P = 0.0008), along with p53 expression, Ki-67 expression, anatomical site, Clark's level of invasion, and vascular invasion. Our findings indicate that loss of nuclear p16 protein expression in vertical growth phase melanomas is associated with increased tumor cell proliferation (Ki-67) and independently predicts decreased patient survival. Cases without p53 expression had improved survival.

Aged↗
PubMed1999

Angiogenesis is prognostically important in vertical growth phase melanomas.

The association between microvessel density (MVD) and patient survival has recently been established for various types of human cancers. Immunohistochemical staining (factor-VIII related antigen) was performed on a series of 102 vertical growth phase melanomas and vessels were counted in areas. Increased MVD was associated with large histologic tumor diameter (p=0.006) and tumor ulceration (p=0.04). Further, high vascular density was significantly related to decreased patient survival (p=0.04), with borderline significance (p=0.10) in the final multivariate model. The results of this study suggest that microvessel density is of prognostic importance in aggressive vertical growth phase melanomas.

Cell Division↗
PubMed1998

Frequent mutations of the p53 gene in cutaneous melanoma of the nodular type.

The frequency and significance of p53 alterations in cutaneous melanoma have not been completely clarified. In the present study, 31 primary melanomas of the nodular type and 15 metastases occurring between 1981 and 1983 were studied with respect to mutations in exons 7 and 8, as well as to p53 protein immunostaining using different antibodies. Altogether 13% of the primary tumors showed strong p53 staining using the DO-7 antibody. Different results were obtained with other antibodies. Seven mutations were found in primary and metastatic tumors; all of these were single base changes, most of which occurred in the core domain of the p53 protein responsible for sequence-specific DNA binding (residues 102-293). The mutations were not significantly associated with p53 staining results, and p53 alterations (mutations or marked immunopositivity) had no prognostic value. Our results indicate that point mutations in exons 7 and 8 are more frequent than previously reported in primary melanomas, and such changes may be important for the development of certain melanoma subgroups.

Adult↗
PubMed1997

Alterations and prognostic significance of p16 and p53 protein expression in subgroups of cutaneous melanoma.

The role of p16 and p53 alterations in cutaneous melanoma has been recently discussed, but it remains to be clarified. In the present immunohistochemical study, the expression of p16 and p53 proteins and their possible prognostic relevance have been examined in 102 melanomas of the aggressive nodular type. Twelve percent showed a strong expression of p53 protein, and these cases were significantly more frequent in the head/neck area compared with other sites (32% vs. 6%). Expression of p16 protein was negative or weak in 9% of the cases, and this tended to be less frequent in head/neck tumors compared with the others (0% vs. 12%). Whereas p53 staining was not prognostically important, loss of p16 staining was significantly associated with markedly reduced recurrence free and patient survival in univariate analysis (product-limit method). In multivariate analysis, lack of p16 staining was significantly associated with recurrent disease (p = 0.013). Our findings indicate an important role of altered p16 protein expression in a subgroup of melanoma patients.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed1996

Independent prognostic importance of vascular invasion in nodular melanomas.

BACKGROUND: The role of vascular invasion as an independent predictor of outcome in cutaneous melanoma is controversial, mostly because of a close relationship with tumor thickness. Therefore, the prevalence of vascular involvement and its prognostic impact has been studied in a series of patients with aggressive cutaneous melanoma. METHODS: One hundred and two patients with nodular malignant melanoma diagnosed between 1981 and 1989 were studied retrospectively. The vessels were stained with factor VIII antibody, and vascular invasion as well as other features of the primary tumor and essential clinical variables were related to time to recurrence and death due to melanoma using univariate survival analysis (product-limit method) and the multivariate Cox regression method. RESULTS: Definite vascular invasion was present in 15 cases (15%), and it was significantly associated with tumor thickness, histologic diameter, ulceration, and presence of lymph node metastases and distant spread at the time of diagnosis. In univariate analysis, vascular invasion was a significant predictor of patient survival (P = 0.006), and this variable also showed an independent prognostic impact in multivariate analysis (P = 0.02). Furthermore, anatomic site (P = 0.03), histologic diameter (P = 0.004), and Clark's level of invasion (P = 0.006) were independently associated with decreased patient survival. In the multivariate analysis of time to recurrence, anatomic site (P = 0.003), tumor thickness (P = 0.002), and histologic diameter (P = 0.003) were independent risk factors. CONCLUSIONS: Although vascular invasion was significantly associated with tumor thickness and histologic diameter of the primary tumor, it provided an independent prognostic information by multivariate analysis of patient survival, in addition to anatomic site and indicators of tumor size (histologic diameter and level of invasion). Our findings further indicate that the prognostic importance of vascular invasion is associated with both lymphatic and hematogeneous spread, although the latter is probably more important.

Blood Vessels↗
PubMedDate not supplied

Frequent loss of p16 protein expression and high proliferative activity (Ki-67) in malignant melanoma from black Africans.

Malignant melanomas in black Africans are predominantly located on the lower extremities. Since their biological features have not been well focused, we studied 28 such cases with special reference to proliferative activity (Ki-67 expression), p16 and p53 staining, as well as microvessel density, all known to be involved in the progression of melanomas among whites. The findings were related to clinico-pathological characteristics. The tumours had a median thickness of 6.4 mm, ulceration was present in 71%, and vascular invasion in 36%, indicating the presence of advanced and aggressive melanomas. Further, loss of p16 protein expression was found in 50%, and high proliferative activity was present (median 41%). In contrast, strong p53 staining was rare (11%), although most tumours showed low-level positivity. Angiogenesis, as estimated by microvessel density, was significantly associated with vascular invasion (p = 0.022), supporting its role in the progression of these tumours. Thus, our findings indicate that melanomas located on the lower extremities in black Africans show several features of aggressiveness; in particular, the proliferative activity was high, and p16 alterations was frequent as evidenced by loss of protein staining. Our findings also indicated that the diagnosis is delayed among black Africans.

Adult↗