Treatment of keloid scars with a 1210-nm diode laser in an animal model.

BACKGROUND AND OBJECTIVE: A temperature increase can improve wound healing by activation of heat shock protein 70 and stimulation of fibroblasts. Since keloids are a dysfunction of collagen fiber synthesis and organization, this study aimed to evaluate if a 1,210 nm diode laser could have effects in a new animal model of keloid scars. STUDY DESIGN/MATERIALS AND METHODS: A total of 39 nude mice were used for this study. Phototypes IV and V human keloids were grafted into their backs and after 1 month of healing, the mice were divided into four groups: Control, Laser, Resection, Resection/Laser. In the Laser group, the keloids were treated with a 1,210-nm diode-laser with the following parameters: 4 W; 10 seconds; fluence: 51 J/cm(2) ; spot: 18.9 × 3.7 mm(2) . In the Resection group, surgical intra-lesional excision was performed. In the Resection/Laser group, keloids were treated with the 1,210-nm laser-diode after surgical intra-lesional excision. Temperature measurements were made during the laser treatment. Clinical examination and histological study were performed on the day of treatment and 1 month, 2 months, and 3 months later. RESULTS: Mean temperature measurement was of 44.8°C (42-48°) in the Laser groups. No healing complications or keloid proliferation was observed in any group. Keloid histologic characters were confirmed in all grafts. No histologic particularity was observed in the laser groups in comparison with the Control and Resection groups. CONCLUSION: First, this keloid animal model appears to be adapted for laser study. Secondly, the 1,210-nm diode laser does not induce keloid thermal damage in vivo. Further studies with different 1,210-nm laser diode parameters should be performed in order to observe significant effects on keloids.

[Keloid scars: a case series study]. / Cicatrices chéloïdes : étude d'une série de cas.

Keloids scars are a pathological way of wound healing of the human skin. They are responsible for an unsightly and functional discomfort, and recurrence is common after surgery. There are specific treatments in order to lower this risk. They can be hard to distinguish from an hypertrophic scar on clinical and histological examination. Moreover, mixed forms exist, combining keloid and hypertrophic features. We retrospectively reviewed 52 patients who underwent surgery for keloid scars. On 54 scars, histological examination found 38 keloids, 8 hypertrophic, 7 mixed scars and 2 neither keloid nor hypertrophic. Mean age was 30 years. Sex ratio was 1.2 women per 1 man. Most frequent locations were ear (44.4%), thorax (33.3%), and shoulder (7.4%). In all cases, disease duration exceeded one year. Histology help to make the definitive diagnosis of keloid, hypertrophic and mixed scar, confirmed by trichrome or orcein staining and alpha smooth muscle actin immunostaining.

New fat-derived products for treating skin-induced lesions of scleroderma in nude mice.

INTRODUCTION: Scleroderma is characterized by cutaneous manifestations that mainly affect the hands, arms and face. As of today, there is no treatment for fibrotic skin lesions of scleroderma. Previously we generated and validated a model of scleroderma-like skin sclerosis in nude mice, appropriate to inject human derived products. We showed that the subcutaneous injection of micro-fat (MF), purified and injected using small caliber cannulas, have anti-fibrotic and pro-angiogenic effects and appears more suitable for the treatment of skin lesions of scleroderma compared to the gold standard (Coleman's technique or macro-fat). Here we compared the long-term efficacy of micro-fat "enriched" with other therapeutic products including the stromal vascular fraction (SVF) of fat and platelet-rich plasma (PRP) from blood in our murine model of scleroderma. METHODS: We used 72 nude mice in this study. We formed six experimental groups: Macro-fat, MF, SVF, PRP, MF + SVF, MF + PRP. This project has three phases: i) Induction of skin sclerosis by daily subcutaneous injections of bleomycin (BLM) for 4 weeks in nude mice; ii) Purification and injection of the different cell therapy products; iii) Histological analyses done 8 weeks post-injections. RESULTS: MF + SVF and MF + PRP significantly reversed dermal and epidermal sclerosis (P <0.01). Macro-fat, SVF, PRP only corrected the dermal sclerosis (P <0.05). Epidermal sclerosis was reduced in treatments containing MF (P <0.01). MF was more stable. Products containing the SVF were associated with a significant increase of the local vascularization (P <0.01). CONCLUSIONS: All tested substances were effective in treating skin-induced lesions of scleroderma with different levels of fibrosis and vascular improvement; MF derived products are more stable and SVF demonstrated better pro-angiogenic effects. The observed efficacy of this combination of products in the animal model provides a rationale for potential clinical applications to treat human disease.

Comparison of five dermal substitutes in full-thickness skin wound healing in a porcine model.

The wound healing attributes of five acellular dermal skin substitutes were compared, in a two-step procedure, in a porcine model. Ten pigs were included in this experimental and randomized study. During the first step, dermal substitutes (Integra(®), ProDerm(®), Renoskin(®), Matriderm(®) 2mm and Hyalomatrix(®) PA) were implanted into full-thickness skin wounds and the epidermis was reconstructed during a second step procedure at day 21 using autologous split-thickness skin graft or cultured epithelial autograft. Seven pigs were followed-up for 2 months and 3 pigs for 6 months. Dermal substitute incorporation, epidermal graft takes, wound contraction and Vancouver scale were assessed, and histological study of the wounds was performed. Results showed significant differences between groups in dermis incorporation and in early wound contraction, but there was no difference in wound contraction and in Vancouver scale after 2 and 6 months of healing. We conclude there was no long-term difference of scar qualities in our study between the different artificial dermis. More, there was no difference between artificial dermis and the control group. This study makes us ask questions about the benefit of artificial dermis used in a two-step procedure.

[High-throughput quantification of tissue microarrays: identification of candidate target proteins in inflammatory breast cancer]. / La lecture automatisée à haut débit des micro-biopsies en pathologie: mise en évidence de la surexpression de c-Met et PI3K dans les cancers du sein inflammatoire.

Inflammatory breast carcinoma (IBC) is a rare but very aggressive tumour phenotype. Increased c-Met protein expression correlates with reduced survival and a higher metastatic risk in many human malignancies, including breast cancer Several studies have shown that c-Met protein is targetable by specific drugs. Here we compared c-Met expression in IBC (n = 41) and non IBC (n = 480). Two microarrays of IBC and non IBC tissues were constructed and standardized. C-Met, P13K and E-cadherin were immunodetected (Ven-tana Benchmark Autostainer) on serial sections. The results were quantified with an automated image analysis device (SAMBA Technologies) by immunoprecipitate densitometry of each core section (0.6 microns thick). We found that (i) c-Met is significantly overexpressed in IBC compared to non IBC (p < 0. 001), (ii) P13K is also overexpressed (p < 0.001) in IBC, suggesting that overexpressed c-Met is functionally active, at least through the PI3K signal transduction pathway ; and (iii) E-cadherin is paradoxically overexpressed in IBC. We conclude that c-Met may constitute a target for specific therapy in patients with poor-prognosis malignancies like IBC Automated image analysis of TMA is a valuable tool for high-throughput quantification of the immunohistochemical expression of the tumor proteome.

Conditions of wound healing and cutaneous growth affect metabolic performance of skin following plastic surgery.

The mechanical and structural properties of skin subjected to expansion have been widely investigated in the context of plastic surgery. To determine the actual metabolic state of skin following skin expander placement, we determined the basic biochemical parameters for various conditions of postsurgical wound healing and cutaneous growth. Studying, for the first time, comprehensive metabolic profiles ("metabolomics") of the skin in a minipig model, we found that the lactate/alanine ratios were significantly increased (p<0.05) in skin attached to noninflated expanders vs. control skin, indicating increased anaerobic glycolysis. Furthermore, creatine/phosphocreatine ratios were decreased in skin from inflated vs. noninflated expanders, implying an improved energetic state for stretched skin. In contrast, no significant differences were detected for these parameters on comparing skin from four inflated expanders with different surface structures, even where the histologically determined capsule thickness was significantly different. Overall, the metabolic performance of skin recovering and growing under stretch was found to be superior to that of skin from noninflated expanders, and comparable to that of control skin. Our results are consistent with the assumptions of (i) major hypoxia/ischemia due to reduced perfusion in skin recovering from surgery without an appropriate supportive structure and (ii) minimal metabolic effects of expander surface structures.

Overexpression of c-Met and of the transducers PI3K, FAK and JAK in breast carcinomas correlates with shorter survival and neoangiogenesis.

c-Met is responsible for cell motility and tumour spreading. c-Met expression and signal transducers reflecting c-Met functionality were investigated in breast carcinomas, in correlation with patient outcome and tumour vasculature. Tissue microarrays of 930 breast carcinomas were constructed, categorised according to patients' follow-up (4- to 10-year follow-up; median, 6.5 years). Standardised immunocytochemical procedures were performed using anti-c-Met, -PI3K, -FAK, -JAK, and -CD146, -FYN and an automated autostainer (Ventana). High-throughput densitometry measuring the extent of immunoprecipitates was assessed by image analysis (SAMBA). c-Met overexpression correlated with poor survival along with PI3K and FAK reflecting c-Met functionality and CD146 and FYN expression in endothelial cells. Automated quantification of immunocytochemical precipitates using image analysis was shown to provide an objective means of measuring cellular proteins that are potentially relevant for current practice in pathological diagnosis and for specific therapy combining inhibitors of both c-Met and downstream transducer pathways, and of tumour angiogenesis.

[Organized cervical cancer screening for underpriviledged women]. / Le dépistage organisé des cancers du col utérin pour les femmes en situation médicosociale défavorisée.

Individual cervical screening with pap-smears is the major cause of the decrease in incidence and mortality of cervical cancer in France since more than 30 years. But, for the last ten years, the decrease in mortality is limited due to the persistence of poor prognostic cases and the insufficiency of treatment efficacy in such patients. These cases are mostly observed in women who did not participate to regular screening. They are generally from low socioeconomic levels or migrant populations, or both. Such an observation leads us to organize 3 successive pilot campaigns (2001, 2003, 2005) in the Northern part of Marseille city where the rate of such poor population is high (37 to 45%). The women without a pap-smear indexed in the National Insurance Register for the last 3-2 years were invited by individual mailing to perform, free of charge, a pap-smear. The evaluation of each campaign helps us to improve the next one. The major changes from the 1st one to the 3rd one were to increase the number of free screening services, to send a second invitation to the non responders, and to organize local meetings with social workers and nurses to explain to the women the importance of performing regular screening tests. The final results after the 3 campaigns showed : out of the eligible women the participation rates are dramatically low evolving from 1,56 % to 2,48% and 6,87% of pap-smears done along the 3 campaigns ; the selection of women "without pap-smear" from the national Insurance register was not good, a great number of missing data was identified, explaining partly the extremely low rate of participation ; the factors increasing a little the participation are the second mailing of invitation (39 % of pap-smears realised) ; the total gratuitous of the screening (both sampling and reading) ; the oral information delivered locally by social workers and the proximity of the places to perform the test ; the quality of the pap-smears collected by gynecologists was good but insufficient for other health professionals, requiring a specific training for cervical cell collection. The organization of such pilot projects need to be followed to find better solutions to increase the participation to cervical screening of such populations who are at high risk of poor prognosis cervical cancers.

Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype.

Genomic studies have led to new taxonomic classifications of breast carcinomas. Proteomic investigations using tissue microarrays have yielded complementary results and are useful in identifying potential molecular targets for specific therapies. Searching for new drug targets is particularly important for tumors of poor prognosis, such as breast tumors that lack estrogen receptors and HER2 amplification; in these tumors, certain molecules probably play a significant role in tumor spreading through the stromal microvasculature. We investigated 930 breast carcinomas categorized according to patients' survival (range of follow-up = 4-10 years; median follow-up = 6.5 years) using (1) automated immunohistochemical procedures (Ventana, Cedex, France) with tissue microarrays (Alphelys, Plaisir, France) and (2) quantification of immunoprecipitates assessed by automated image analysis densitometry (SAMBA, Meylan, France). Expression of c-Met and CD146 and that of signaling transducers PI3K, FAK, and FYN were compared in living and deceased patients. Expression of some proteins recently reported to be characteristic of basal cell carcinomas was also assessed, namely, CK5-6, caveolin-1, carbonic anhydrase IX, p63, and CD117; these also constitute potential targets for therapies for aggressive tumors. Overexpression of these proteins was observed in deceased or metastatic patients (P < .01 to P < .00001), particularly node-negative patients (except for FYN, p63, and CD146). c-Met and CD146 are involved in tumor spreading, and our results suggest that they probably play an important role in patients' death, along with other proteins involved in hypoxia (carbonic anhydrase IX) and other cell functions or structures (caveolin-1, CD117, CK5-6, and p63) that are expressed in an aggressive subtype of basal cell carcinoma for which no specific therapy is available.

[An unusual perianal abscess]. / Un abcès périanal inhabituel.

Aggressive angiomyxoma (AA) is a mesenchymal tumour occurring in connective tissue of the perineum or lower pelvis with a marked tendency to local recurrence but which usually does not metastasize. Only 130 cases had been reported to date. We report the case of a 58-year-old woman, presenting with a pelvi-perineal mass, which was considered to be an anal abscess. After surgical excision, an AA was diagnosed, with classical histological features (myxoid and vascular components) and which was positive for vimentin and CD34. This case report shows that clinical diagnosis of AA is difficult and that delayed diagnosis can prevent optimal treatment of these tumors.

[A tumor-like lymphocytis mastitis]. / Mastite lymphocytaire pseudo-tumorale.

A 44-year-old woman presenting with an inflammatory and palpable firm breast lump underwent surgical excision. Intraoperative frozen section analysis showed an extensive lesion consisting of ducts with intraluminal "necrosis". In addition, a very dense stromal inflammation was observed around these ducts, suggesting an invasive ductal carcinoma with predominant intraductal proliferation. However, on paraffin sections, epithelial cells close to the lymphocytic infiltrate were rare, subatrophic, without any neoplastic feature. The density and architecture of the lymphocytic infiltrate mimicked a breast lymphoma. However, immunochemistry and molecular biology investigation favored the diagnosis of a tumor-like lymphocytic mastitis. Although extremely rare, this particular form of lymphocytic mastitis, a diagnostic pitfall particularly during peroperative examination, should be recognized by pathologists.

[Plasmablastic lymphoma in a patient with HIV infection: an unusual case located in the skin]. / Lymphome plasmoblastique du sujet infecté par le VIH: a propos d'un cas très inhabituel de localisation cutanée.

We report the case of a plasmablastic lymphoma involving the skin in a 45 year-old HIV-positive patient. Plasmablastic lymphoma was first described in 1997 and is considered to be a diffuse large B-cell lymphoma with a unique immunophenotype and a predilection for the oral cavity. In this case, the tumor was revealed by multiple purple cutaneous nodules predominantly localized on the trunk and proximal parts of the limbs. A skin biopsy led to the diagnosis of plasmablastic lymphoma in view of the presence of a dense nodular infiltrate invading the dermis and subcutaneous fat composed of large cells that expressed neither the leucocyte common antigen nor the B- and T-cell antigens CD20 and CD3, but which showed a strong immunostaining with plasma cell marker VS38c. Most of the cells expressed Kappa light chain of immunoglobulins, they did not express Lambda light chain. In situ hybridization with EBER probe revealed detection of Epstein Barr virus in about 15 % of tumor cells. The clinical course was aggressive and rapidly fatal. Despite one cycle chemotherapy the patient died four months after presentation. HIV-associated plasmablastic lymphoma is a poor prognosis malignancy that may resist typing due to the lack of expression of commonly used lymphoid markers.

Overexpression of hypoxia-inducible factor HIF-1alpha predicts early relapse in breast cancer: retrospective study in a series of 745 patients.

Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that is involved in tumour growth and metastasis by regulating genes involved in response to hypoxia. HIF-1alpha protein overexpression has been shown in a variety of human cancers, but only 2 studies have documented the prognostic relevance of HIF-1alpha expression in breast cancer. The aim of our study was to determine accurately the impact of HIF-1alpha expression on prognosis in a large series (n = 745) of unselected patients with invasive breast cancer in terms of overall survival, local recurrence and distant metastasis risk. HIF-1alpha expression was investigated using immunohistochemical assays on frozen sections, and correlated with patients' outcome (median follow-up = 13.5 years). Univariate (Kaplan-Meier) analysis showed that high levels of HIF-1alpha expression (cutoff = 10%) significantly correlated with poor overall survival (p = 0.019). HIF-1alpha expression correlated with high metastasis risk among the whole group of patients (p = 0.008). Multivariate analysis (Cox model) showed that the HIF-1alpha predictive value was independent of other current prognostic indicators. Moreover among node negative ones, HIF-1alpha expression was also significantly predictive of metastasis risk (p = 0.03) and of relapse (p = 0.035). All the data suggest that HIF-1alpha is associated with a worse prognosis in patients with invasive breast carcinoma. Furthermore HIF-1alpha immunodetection may be considered as a potential indicator for selecting patients who could benefit from specific therapies interfering with HIF-1alpha pathway.

Comparison of the prognosis indication of VEGFR-1 and VEGFR-2 and Tie2 receptor expression in breast carcinoma.

The degree of angiogenesis in breast cancer has previously been shown to be an indicator of prognosis, and tumor microvasculature is a candidate target for new antiangiogenic therapies. The aim of this study was to investigate the prognostic value of vascular endothelial growth factor (VEGF) receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1), and Tie2/tek receptor tyrosine kinase in breast carcinoma. VEGF receptors and Tie2 expression was investigated using immunohistochemical assays with monoclonal antibodies on frozen sections in a series of 918 and 909 patients respectively. VEGFR-1 and VEGFR-2 and Tie2 were correlated with long-term (median, 11.3 years) patients' outcome. Univariate (Kaplan-Meier) analysis showed that VEGFR-1 positive tumor surface (cutoff = 5%) was significantly correlated with high metastasis risk (p=0.03) and relapse (p<0.01) in all patients, and in those with node negative tumors (p<0.001 and p<0.01 respectively), but not with overall survival. In contrast Tie2 positive tumor surface (cutoff = 7%) was significantly correlated with poor overall survival (p=0.025) and also with high metastasis risk particularly among node negative patients (p<0.01). Moreover, Tie2 immunoexpression was significantly predictive of relapse (p=0.003) in the node negative subgroup (p=0.02). In multivariate analysis (Cox model), VEGFR-1 and Tie2 immunoexpressions were identified as independent prognostic indicators. In contrast, univariate analysis showed that VEGFR-2 positive tumor surface (cutoff = 10%) was not correlated with survival or with metastasis and relapse risk. Our results suggest that VEGFR-1 and Tie2 immunohistochemical expression permits the identification of patients with poor outcome, and particularly node negative ones with a high risk for metastasis and relapse. VEGFR-1 and Tie2 immunodetection may also be considered as potential tools for selecting patients who could benefit in the future from specific antiangiogenic therapy interfering with VEGFR-1 and Tie2 activation pathways.

[Accuracy of intraoperative frozen section diagnosis in non palpable breast lesions: a series of 791 cases]. / Efficacité de l'examen peropératoire des lésions infracliniques mammaires: études sur une série de 791 cas.

The aim of this study is to estimate the accuracy and reliability of intraoperative frozen section of nonpalpable breast lesions. In fact, frozen section of palpable breast lesions has proven to be valid, but its use in breast infraclinic lesions has been discussed recently, with the publication of European recommendations. Diagnosis on frozen section was routinely performed in a serie of 791 patients with nonpalpable mammographically detected abnormalities breast lesions from January 1990 through July 2000. The initial frozen section diagnoses with known mammographic pattern were compared with the diagnoses obtained on permanent paraffin sections to estimate the accuracy of frozen sections. Frozen section diagnosis was delayed until final diagnosis assessed on permanent paraffin sections in only 8 cases (1%). Frozen section diagnoses were accurate in 744 of 783 cases (95%). The diagnosis was modified on the basis of permanent sections in 39 cases; consisting of 39 false negative. No false positive diagnosis was noted. Sensitivity and specificity of frozen section diagnoses were 87,69 and 100, respectively. When the comparison between frozen and permanent section was analyzed according to the mammographic pattern, the sensitivity among patients with microcalcifications was lower (75,23) than among patients with opacities (93,86). When frozen section and permanent section diagnoses were related according to the mammographic size ( 10 mm) the sensitivity among patients with opacities measuring less than 10 mm was lower (91,75) than among patients with opacities larger than 10 mm (95,65) and the sensitivity among patients with microcalcifications larger than 10 mm was greater (77,14) than among patients with microcalcifications size less than 10 mm (74,28). This results are similar to those obtained on palpable breast lesions, and show that frozen section is a feasible and reliable procedure in nonpalpable breast lesions, particularly more relevant in mammographic opacities than in microcalcifications, whatever the lesion size.

CD105 expression is a marker of high metastatic risk and poor outcome in breast carcinomas. Correlations between immunohistochemical analysis and long-term follow-up in a series of 929 patients.

CD105 (endoglin) is expressed significantly in activated endothelial cells in culture and in tumor microvessels. Quantification of CD105 immunocytochemical expression that may be clinically relevant has not been accurately evaluated. We studied CD105 expression on frozen tissue sections by using immunohistochemical assays in a series of 929 patients and correlated the findings with long-term follow-up (median, 11.3 years). Univariate (Kaplan-Meier) analysis showed that the number of CD105+ microvessels (cutoff, 15 vessels) correlated significantly with poor overall survival among all patients (P = .001). This correlation was less significant in node-negative patients (P = .035). Marked CD105 expression also correlated with a high risk for metastasis among all patients (P = .006) and among node-negative patients (P = .001). Multivariate analysis (Cox model) identified CD105 immunodetection as an independent prognostic indicator. Our results suggest that immunohistochemical expression of CD105 has practical clinical relevance for identifying node-negative patients with a poor prognosis. Moreover, immunodetection of CD105 also may be considered a potential tool for selecting patients who could benefit from specific antiangiogenic therapy, using anti-CD105 conjugates.

Tie2/Tek expression in breast carcinoma: correlations of immunohistochemical assays and long-term follow-up in a series of 909 patients.

The degree of angiogenesis in breast cancer has previously been shown to be an indicator of prognosis, and tumor microvasculature is at present a candidate target for new antiangiogenic therapies. Tie2/tek receptor tyrosine kinase is a novel marker of microvasculature of solid tumors that appears to play a key role in the angiogenesis process in breast cancer. However the prognostic significance of Tie2 has never been demonstrated in this neoplasm. In order to establish the prognostic value of Tie2 in breast carcinoma, we investigated Tie2 expression in a large series of patients and correlated it with long-term follow-up. Tie2 expression was investigated using immunohistochemical assays with a polyclonal antibody on frozen sections in a series of 909 patients, and was correlated with long-term (median, 11.3 years) follow-up. Univariate (Kaplan-Meier) analysis showed that a large Tie2 positive tumor surface (cut off = 7%) was significantly correlated with poor overall survival (p=0.025). Tie2 expression correlated with high metastasis risk among all patients (p=0.00067) and among node negative ones as well (p=0.01). Tie2 immuno-expression was also significantly predictive of relapse in all patients (p=0.003) and in the node negative subgroup (p=0.02). In multivariate analysis (Cox model) Tie2 immunodetection was identified as an independent prognostic indicator. Our results suggest that Tie2 immunohistochemical expression exhibits practical clinical relevance in terms of prognostic prediction. Tie2 expression permits identification of poor outcome patients, in particular node negative ones with high risk of metastasis and relapse. Tie2 immunodetection may further be considered as a potential tool for selecting patients who could benefit in the future from specific antiangiogenic therapy interfering with Tie2 pathway.

[The immunohistochemical expression of CD105 is a marker for high metastatic risk and worse prognosis in breast cancers]. / L'expression immunohistochimique du CD105 est un marqueur de risque métastatique élevé et de mauvais pronostic dans les cancers du sein.

The quantification of angiogenesis in human solid tumors has been shown to be an indicator of prognosis and tumor microvasculature is a candidate target for antiangiogenic therapy. CD105 (endoglin) is significantly expressed in activated endothelial cells in culture and in tumor microvessels. Quantification of CD105 immunocytochemical expression that may be of significant clinical relevance, has not been accurately evaluated as yet. In the present report, CD105 expression on frozen sections was investigated using immunohistochemical assays in a series of 929 patients and correlated with long-term (median = 11.3 years) follow-up. The CD105 immunostaining was observed on endothelial cells mostly in small cells. The number of vessels and the immunostained surface were evaluated in so called "hot spots" within tumor stroma. Both the number of vessels and immunostained surface were correlated to the patients' outcome (overall survival, disease free survival, metastases) in the whole group of patients and also specifically in node negative subgroup. Univariate (Kaplan Meier) analysis showed that the number of CD105 positive microvessels (cut-off n = 15) was significantly correlated with poor overall survival, among all patients (p = 0.001). This correlation was less significant in the group of node negative patients (p = 0.035). Marked CD105 expression was also correlated with high metastasis risk among all patients (p = 0.006) and among node negative patients as well (p = 0.001). In multivariate analysis (Cox model) CD105 immunodetection was identified as an independent prognostic indicator. Our results suggest that CD105 immunohistochemical expression has a practical clinical relevance for identifying node negative patients with poor prognosis. Moreover, the CD105 immunodetection may also be considered as a potential tool for selecting patients that could benefit from specific antiangiogenic therapy, using anti CD105 conjugates.