The effect of interleukin-17F on vasculogenic mimicry in oral tongue squamous cell carcinoma.

Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers worldwide and is characterized by early metastasis and poor prognosis. Recently, we reported that extracellular interleukin-17F (IL-17F) correlates with better disease-specific survival in OTSCC patients and has promising anticancer effects in vitro. Vasculogenic mimicry (VM) is the formation of an alternative vasculogenic system by aggressive tumor cells, which is implicated in treatment failure and poor survival of cancer patients. We sought to confirm the formation of VM in OTSCC and to investigate the effect of IL-17F on VM formation. Here, we showed that highly invasive OTSCC cells (HSC-3 and SAS) form tube-like VM on Matrigel similar to those formed by human umbilical vein endothelial cells. Interestingly, the less invasive cells (SCC-25) did not form any VM structures. Droplet-digital PCR, FACS, and immunofluorescence staining revealed the presence of CD31 mRNA and protein in OTSCC cells. Additionally, in a mouse orthotopic model, HSC-3 cells expressed VE-cadherin (CD144) but lacked Von Willebrand Factor. We identified different patterns of VM structures in patient samples and in an orthotopic OTSCC mouse model. Similar to the effect produced by the antiangiogenic drug sorafenib, IL-17F inhibited the formation of VM structures in vitro by HSC-3 and reduced almost all VM-related parameters. In conclusion, our findings indicate the presence of VM in OTSCC and the antitumorigenic effect of IL-17F through its effect on the VM. Therefore, targeting IL-17F or its regulatory pathways may lead to promising therapeutic strategies in patients with OTSCC.

Endostatin induces proliferation of oral carcinoma cells but its effect on invasion is modified by the tumor microenvironment.

The turnover of extracellular matrix liberates various cryptic molecules with novel biological activities. Endostatin is an endogenous angiogenesis inhibitor that is derived from the non-collagenous domain of collagen XVIII. Although there are a large number of studies on its anti-tumor effects, the molecular mechanisms are not yet completely understood, and the reasons why endostatin has not been successful in clinical trials are unclear. Research has mostly focused on its anti-angiogenic effect in tumors. Here, we aimed to elucidate how endostatin affects the behavior of aggressive tongue HSC-3 carcinoma cells that were transfected to overproduce endostatin. Endostatin inhibited the invasion of HSC-3 cells in a 3D collagen-fibroblast model. However, it had no effect on invasion in a human myoma organotypic model, which lacks vital fibroblasts. Recombinant endostatin was able to reduce the Transwell migration of normal fibroblasts, but had no effect on carcinoma associated fibroblasts. Surprisingly, endostatin increased the proliferation and decreased the apoptosis of cancer cells in organotypic models. Also subcutaneous tumors overproducing endostatin grew bigger, but showed less local invasion in nude mice xenografts. We conclude that endostatin affects directly to HSC-3 cells increasing their proliferation, but its net effect on cancer invasion seem to depend on the cellular composition and interactions of tumor microenvironment.

High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.

Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer.

BACKGROUND: Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer. METHODS: Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53. RESULTS: L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis. CONCLUSIONS: L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.

Overexpression of chemerin was associated with tumor angiogenesis and poor clinical outcome in squamous cell carcinoma of the oral tongue.

OBJECTIVE: The present study aimed to explore expression and clinical significance of chemerin, a newly discovered adipokine, in squamous cell carcinoma of the oral tongue (SCCOT). METHODS: mRNA expression of chemerin in 19 pairs of fresh SCCOT samples matched with peritumoral mucosa tissues was quantified by real-time quantitative transcription polymerase chain reaction (qRT-PCR). Chemerin protein expression and microvessel density (MVD) were measured by immunohistochemistry on 147 cases of primary SCCOT specimen and their corresponding peritumoral noncancerous tissues. The relationship of chemerin expression with angiogenesis, clinicopathologic parameters, and cancer-related survival of patients was evaluated. RESULTS: Both qRT-PCR and immunohistochemistry results revealed that chemerin was overexpressed in SCCOT compared with peritumoral noncancerous tissues (P < 0.01). Overexpression of chemerin in SCCOT was significantly associated with poor differentiation, lymph node metastasis, and high clinical stage (P = 0.000, 0.012, and 0.015, respectively). In addition, overexpression of chemerin was positively related to MVD in SCCOT (r = 0.671, P = 0.002). SCCOT patients with overexpressed chemerin had a shorter cancer-related survival (P = 0.027). Moreover, multivariate survival analysis indicated that chemerin was an independent prognostic factor for SCCOT patients (P = 0.016). CONCLUSION: These results demonstrated that overexpression of chemerin in SCCOT was correlated with tumor angiogenesis and poor clinical outcomes of SCCOT patients. CLINICAL RELEVANCE: Our research implied that chemerin was a novel prognostic factor for SCCOT patients, and chemerin could be a new therapeutic target for regulating tumor angiogenesis and blocking tumor progression.

The role of angiogenin in pT1-T2 tongue carcinoma neo-angiogenesis and cell proliferation: an exploratory study.

BACKGROUND: Angiogenin (ANG) is a member of the ribonuclease superfamily and of medical interest largely because it supports the growth of primary and metastatic malignancies. This study is the first to investigate the potential role of ANG in tongue carcinoma neo-angiogenesis and cancer cell proliferation. METHODS: Angiogenin expression (in carcinoma cells and endothelial intratumor vessel cells), CD105-assessed micro-vessel density (MVD), and MIB-1 expression were correlated with prognostic parameters in 28 primarily consecutively operated pT1-T2 tongue carcinomas (squamous cell carcinoma [SCC]). Whenever feasible, a computer-based image analysis system was used for the immunohistochemical reaction analysis. RESULTS: No significant correlations emerged between ANG expression in the tongue carcinoma cells or endothelial intratumor vessel cells and tongue SCC recurrence rate or disease-free survival (DFS). ANG expression was also unrelated to CD105-assessed MVD or MIB-1 expression. Conversely, CD105-assessed MVD correlated directly with recurrence rate (P = 0.02) and DFS was significantly shorter in cases with CD105-assessed MVD >167 micro-vessels/mm(2) than in those with CD105-assessed MVD ≤167 micro-vessels/mm(2) (P = 0.042). CONCLUSIONS: Our results support the hypothesis that CD105-assessed MVD would be a valuable parameter for predicting which patients with tongue SCC are at greatest risk of disease recurrence. Despite our study results, the role of ANG in tongue carcinoma warrants further investigation in larger series.

[Medial sural artery perforator fasciocutaneous flap for the reconstruction of tongue and mouth base]. / Arteria suralis medialis perforator fasciocutan lebeny alkalmazása a nyelv és a szájfenék rekonstrukciójában.

BACKGROUND: Despite the well-known high donor site morbidity of the radial forarm flap, it has still remained the first option for the reconstruction of the tongue and the floor of mouth. However, a desire for an alternative, thin fasciocutaneous flap has led to the use of the median sural artery perforator flap. METHODS: Three patients had reconstructive surgery used MSAP flaps, after radical tumor excision. RESULTS: The flap was based in all cases on a dominant perforator vessel. The size of the skin paddles ranged between 20-32 cm2, and the length of the vascular pedicle between 8.2-11 cm. The mean thickness of the flap was 6.5 mm. CONCLUSION: MSAP flap is an ideal solution for surgical reconstruction in the oral cavity.

Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma.

AIMS: We evaluated the association of ligand cyclophilin A (CypA) and receptor CD147 with hypoxia, angiogenesis, lymph node metastasis and prognosis of patients with tongue squamous cell carcinoma (TSCC). METHODS AND RESULTS: We studied the expression of CypA, CD147, hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor A and C (VEGF-A and VEGF-C) protein by immunohistochemistry in 80 specimens of TSCC. CypA, CD147, HIF-1α, VEGF-A and VEGF-C were overexpressed in TSCCs, and were significantly higher than those in normal oral mucosa tissues (P<0.01). Increased ligand CypA and receptor CD147 correlated significantly with expression of HIF-1α, VEGF-A and VEGF-C. A significant relationship between VEGF-A and VEGF-C was also detected (P<0.01). Patients with overexpression of CypA, CD147, HIF-1α and VEGF-C had significantly worse overall survival (P<0.05) using Kaplan-Meier analysis. Multivariate Cox regression analysis showed that HIF-1α, recurrence and distant metastasis were independent prognostic factors on overall survival in TSCC patients. CONCLUSIONS: The association of expression of ligand CypA and receptor CD147 with carcinogenesis, hypoxia, angiogenesis, metastasis and prognosis of TSCC suggests that ligand CypA and receptor CD147 may have prognostic value and could be regarded as potential therapeutic targets in TSCC.

Intra-tumoral ligation and the injection of sclerosant in the treatment of lingual cavernous haemangioma.

INTRODUCTION: Haemangiomas are developmental vascular abnormalities and more than 50% of these lesions occur in the head and neck region, with the tongue, buccal mucosa, lips and palate most commonly involve. They are considered as harmatomas rather than true neoplasms Factors such as patient's age, size and site of lesion and the proximity of lesion to vital structure are paramount in the determination of the therapeutic approach 7 surgical excision, cryotherapy, injection of feeder vessels with sclerosants and embolization of the blood vessels. CASE REPORT: We report the management of cavernous haemangioma of the tongue in a 38 year old man using intra-tumoral ligation (The Popescu Procedure) and injection of sclerosant under general anaesthesia. RESULT: The efficacy of this method lies in the fact that it obstructs the vascular channels to and from the entire tumour mass leading to progressive atrophy of the vascular endothelia, fibrous hyperplasia and the substitution of the angiomatous tissues by a fibroconnective tissue mass which initially appears excessive but remodels and produces an acceptable appearance which can be further improved by plastic surgery. CONCLUSION: The procedure was well tolerated and the patient made excellent recovery. It is recommended in our centre where facilities for technologically demanding methods are not available.

Relationships of cervical lymph node metastasis to histopathological malignancy grade, tumor angiogenesis, and lymphatic invasion in tongue cancer.

Cervical lymph node (CLN) metastasis from oral cancer correlates with poor prognosis. Therefore, accurate assessment of CLN status is crucial in treatment planning. However, there are few reports focusing on CLN metastasis from tongue cancer. Further, the growth and progress of the tumor are known to be profoundly related to histological malignancy, tumor angiogenesis, and lymphangiogenesis. Thus, this study aimed to identify predictive factors for CLN metastasis in tongue squamous cell carcinoma (SCC). Initial biopsy specimens obtained from 30 patients with tongue SCC were examined to evaluate histological malignancy according to Anneroth's classification. In addition, blood vessel density, lymph vessel density, and lymphatic invasion in the tumor were evaluated immunohistochemically using CD31, CD34, D2-40, and AE1/AE3, and then the relationships of CLN metastasis to these parameters were investigated. Histological malignancy grade, blood vessel density, and lymphatic invasion were significantly related to CLN metastasis (P < 0.05), but there was no relationship between lymph vessel density and CLN metastasis. However, double immunostaining showed that lymphatic invasion by tumor cells was significantly related to CLN metastasis. The results indicate that Anneroth's histological malignancy grade of 16 or more, tumor blood vessel density of more than 37, and the presence of lymphatic invasion by tumor cells can be predictive factors for CLN metastases in tongue SCC.

Experimental study of antiangiogenic gene therapy targeting VEGF in oral cancer.

It is well known that tumor angiogenesis plays an important role in local growth and metastasis of oral cancer; therefore, inhibiting angiogenesis is considered to be effective for treating oral cancer. This study aimed to investigate the effectiveness of systemically available antiangiogenic gene therapy targeting vascular endothelial growth factor (VEGF), which is one of the most important angiogenesis accelerators. We administered a soluble form of VEGF receptor-expressing gene incorporated into adenovirus (AdVEGF-ExR) intraperitoneally to nude mice to which oral cancer cell lines (SAS, HSC-3, and Ca9-22) had been transplanted subcutaneously in vivo to inhibit angiogenesis and tumor proliferation. Then, we measured tumor volumes over time, and tumors were enucleated and examined histopathologically and immunohistologically at 28 days after AdVEGF-ExR administration. Compared to the controls to which we administered AdLacZ or saline, significant antiproliferative effects were observed (P < 0.05) in the AdVEGF-ExR administration group, and extensive tumor necrosis was found histopathologically. Immunohistochemical analysis with CD34 (NU-4A1) revealed tumor angiogenesis was suppressed significantly (P < 0.05), and that with ssDNA revealed apoptosis induction was significantly high (P < 0.05) in the AdVEGF-ExR group. However, analysis with Ki-67 (MIB-1) revealed tumor proliferative capacity was not significantly different between the groups. Consequently, we consider that AdVEGF-ExR administration achieved tumor growth suppression by inhibiting angiogenesis and inducing apoptosis, but not by inhibiting the proliferative capacity of tumor cells. Neither topical administration of a soluble form of VEGF receptor (sVEGFR) to the tumor nor a megadose was needed to achieve this inhibition effect. These results suggest gene therapy via sVEGFR would be an effective oral cancer therapy and benefit future clinical applications.

Photodynamic therapy with aluminum-chloro-phthalocyanine induces necrosis and vascular damage in mice tongue tumors.

In this paper we describe the efficacy of the liposomal-AlClPc (aluminum-chloro-phthalocyanine) formulation in PDT study against Ehrlich tumor cells proliferation in immunocompetent swiss mice tongue. Experiments were conduced in sixteen tumor induced mice that were divided in three control groups: (1) tumor without treatment; (2) tumor with 100J/cm(2) laser (670nm) irradiation; and (3) tumor with AlClPc peritumoral injection; and a PDT experimental group when tumors received AlClPc injection followed by tumor irradiation. Control groups present similar macroscopically and histological patterns after treatments, while PDT treatment induced 90% of Ehrlich tumor necrosis after 24h of one single application, showing the efficacy of liposome-AlClPc (aluminum-chloro-phthalocyanine) mediated PDT on the treatment of oral cancer.

Oral cancer overexpressed 1 (ORAOV1): a regulator for the cell growth and tumor angiogenesis in oral squamous cell carcinoma.

Oral Cancer Overexpressed 1 (ORAOV1) is a novel gene locating at chromosome band 11q13. Recent studies have suggested its role as a candidate oncogene in oral squamous cell carcinoma (OSCC) and its prognostic value for patients with OSCC. Till now, the detailed function of ORAOV1 in OSCC has remained undefined. In this study, we have investigated the role of ORAOV1 in OSCC tumorigenesis by down-regulating its expression. Small interfering RNA (siRNA) has been applied to inhibit the expression of ORAOV1 in OSCC cells. We found that the OSCC cells with reduced ORAOV1 showed retarded cell growth in vitro and displayed inhibition in both tumor growth and tumor angiogenesis in vivo. Further analyses reveal that the retarded cell growth is associated with an increase in apoptosis involving the activation of caspase 3-dependent pathway and a cell cycle arrest at the S-phase with a downregulation of cyclin A, cyclin B1 and cdc2. The suppressed tumor growth in vivo may be attributed to synergistic effect between inhibition in cell growth and suppression of tumor angiogenesis. The latter is most likely because of a suppression of VEGF. Taken together, we demonstrate that ORAOV1 plays pivotal roles in the growth and angiogenesis of OSCC. Thus, ORAOV1 may be a novel target that could be explored to develop therapeutic strategy in OSCC management.

Brachytherapy for oral tongue cancer: an analysis of treatment results with various biological markers.

OBJECTIVE: Low-dose-rate (LDR) brachytherapy is an effective treatment for tongue cancer. However, little is known about the biological mechanism underlying this therapy, characterized by delivery of continuous exposures of LDR irradiation. It is reported that lower microvessel density (MVD), lower Ki-67 index or higher expression of endogenous hypoxic markers such as carbonic CA IX and Glut-1 are related to the poor control of tumors treated with external irradiation. To elucidate the biological characteristics of LDR brachytherapy, we analyzed our results in cases of tongue cancer treated with LDR brachytherapy by using immunohistochemical stainings with antibodies against Ki-67 and MVD, Glut-1 and CA IX. METHODS: The prognostic value of Ki-67 index, MVD and the expression of CA IX and Glut-1 was assessed in 68 tongue cancers treated with LDR brachytherapy. The specimens were taken from tongue cancers before radiation therapy and immunohistochemical staining was performed. RESULTS: The local recurrence-free survival rates were significantly different between T1+T2 and T3 (P = 0.00067), but not between low and high Ki-67 indexes (P = 0.54), between low and high MVD (P = 0.071), low and high CA IX indexes (P = 0.062) or low and high Glut-1 indexes (P = 0.107). T stage, the size of the tumor was the only significant factor for local control in multivariate analyses (P = 0.0377). CONCLUSION: LDR could overcome the radioresistence of non-cycling and hypoxic cells; however, we cannot draw firm conclusions due to the limited number of patients.

[Clinical significance of angiopoietin-2 expression in oral squamous cell carcinoma].

OBJECTIVE: To investigate the expression of angiopoietin-2 (Ang-2) and its clinical significance in oral squamous cell carcinoma. METHODS: The expression of Ang-2 mRNA was measured by real-time RT-PCR, and the expression of Ang-2 protein in tissue samples was detected by immunohistochemical staining. RESULTS: The mean dCt value of Ang-2 mRNA expression in the cancer tissue was 6.86 +/- 1.37, significantly lower than that in the paired adjacent non-cancerous tissue (7.95 +/- 2.08, P < 0.05), indicating a significantly higher expression of Ang-2 mRNA in the cancerous tissue than that in the adjacent non-cancerous tissue. The distribution of Ang-2 protein was found not only in the vascular endothelial cells but also in tumor cells. Semi-quantitative analysis revealed that the expression of Ang-2 protein in tumor specimens (53.6%) was significantly higher than that (24.0%) in the paired adjacent non-cancerous tissue (P < 0.05), the result was well consistent with that measured by RT-PCR. The dCt value of Ang-2 mRNA expression was 6.48 +/- 1.16 in the patients with metastasis in lymph nodes versus 7.16 +/- 1.49 in those without, with a non-significant difference between the two groups (P > 0.05). As regards the clinical stages, no significant difference was found between the expressions of Ang-2 mRNA in stage I + II (7.11 +/- 1.63) and stage III + IV cases (6.49 +/- 1.10, P > 0.05). CONCLUSION: Angiopoietin-2 protein is expressed not only in vascular endothelial cells, but also in tumor cells, suggesting that angiopoietin-2 may take part in angiogenesis in oral squamous cell carcinoma. However, our results that high expression of angiopoietin-2 mRNA is not correlated with lymph node metastasis and clinical stages, needs to be further verified in a large scale study.

[Application of superselective lingual artery embolization in treatment of severe hemorrhange in patients with carcinoma of tongue].

To explore the clinical value of superselective lingual artery embolization in treating the severe hemorrhage in patients with advanced carcinoma of tongue. Four patients with advanced tongue cancer hemorrhage from March 2014 to February 2016 were enrolled in this study. T3N2M0 (2 cases) and T4N1M0 (2 cases) were diagnosed preoperatively. Two cases of advanced tongue carcinoma tumors had severe bleeding and the other 2 cases of hemorrhage were after radiotherapy. All cases including 3 squamous cell carcinoma and 1 adenocarcinoma were firstly demonstrated by arterigraphy under seldinger technique with digtial subtraction angiogarphy to ensure the rupture site and then all cases were followed by superselective artery embolization. The efficacy and complications of interventional embolizationg were observed. There was no serious complication of central nervous system injury such as hemorrhage and hemiplegia during follow-up. Superselective lingual artery embolization can accurately locate the responsibility of blood vessels, and the injury is small, significant effect, fewer complications.

Signal transducers and activators of transcription 3 up-regulates vascular endothelial growth factor production and tumor angiogenesis in head and neck squamous cell carcinoma.

Overexpression of vascular endothelial growth factor (VEGF) is associated with angiogenic phenotypes and poor prognosis of numerous tumors, including head and neck squamous cell carcinoma (HNSCC). However, the precise mechanism that causes VEGF overexpression in HNSCC remains unknown. Since there is evidence that a transcriptional factor, signal transducers and activators of transcription 3 (Stat3), is constitutively activated in HNSCC and this activation is significantly associated with aggressive phenotypes of this disease, we investigated the roles of Stat3 activation on VEGF production and tumor angiogenesis in HNSCC both in vitro and in clinical samples. VEGF promoter assays with YCU-H891 cells demonstrated that dominant negative Stat3 significantly inhibited VEGF promoter activity in the full length (-2279 to +54) and two truncated forms of VEGF promoter luciferase-reporter construct (-1179 to 54) or (-1014 to +54), which retain the putative Stat3 responsive elements (-849 to -842). However, this was not seen in the shorter construct (-794 to +54), which lacks the putative Stat3 responsive elements. In the derivative of YCU-891 cells that stably express dominant negative Stat3 protein, cellular levels of VEGF mRNA and VEGF protein were significantly inhibited. In the 51 clinical samples obtained from the patients with tongue carcinoma, the expression levels of phosphorylated (activated) form of Stat3 protein were significantly correlated with VEGF (P<0.05) production and intratumoral microvessel density IMVD (P<0.01). These results strongly indicate that Stat3 directly up-regulates VEGF transcription and thereby promotes angiogenesis in HNSCC. Inhibition of Stat3 activity may provide a new anti-angiogenic therapy in HNSCC.

[Is microvascular density an independent prognostic factor in squamous cell carcinoma of the tongue?]. / El la densidad microvascular un factor pronóstico independiente en el carcinoma epidermoide de lengua?

BACKGROUND: The relationship between tumour angiogenesis and prognosis in head and neck squamous cell carcinomas remains controversial in the literature. This study was designed to determine the role of tumour vascularization in tongue squamous cell carcinoma behaviour. MATERIAL AND METHOD: Tumour vascularization was evaluated in 43 patients with primary squamous cell carcinomas of the tongue. Anti-endothelial cell antigen (CD31) was used to stain the specimens. The correlation between tumour vascularization and both survival rate and tumour recurrence was established to determine the prognostic value of microvessel density (Cox proportional-hazards survival regression). RESULTS: Adequate staining was achieved in all specimens with anti-CD31. Mean microvessel density was 30.6 (x400 field), and the median was 27. After a 5-year follow-up, a local, regional, or distant recurrence of the tumour occurred in 29 patients (67.4 %). Twenty patients (46.5 %) were alive with or without tumour, while 23 patients (53.5 %) had died due to tumour recurrence. Statistical analysis failed to demonstrate any correlation between microvessel density and 5-year survival (P = .59) and recurrence rate (P = .31). CONCLUSIONS: Despite the controversy, these results suggest that microvascular density is not a valid independent prognostic indicator in patients with squamous cell carcinoma of the tongue.

Orthogonal polarization spectral (OPS) imaging and topographical characteristics of oral squamous cell carcinoma.

Tumor microcirculatory characteristics until now have only been assessed by histological examination of biopsies or invasive imaging technique. The recent introduction of orthogonal polarization spectral (OPS) imaging as a new tool for in vivo visualization of human microcirculation makes it possible to acquire high resolution images of the oral mucosa. In this study we report the microcirculatory changes in ten patients with oral squamous cell carcinoma of the tongue and compared the images to the normal contralateral side as the control. All carcinomas were T2 tumors without evidence for lymph node metastasis. The carcinomas were characterized by chaotic and dilated vessels accompanied by numerous areas of haemorrhage. The OPS technique seems very promising in the assessment of oral squamous cell carcinoma microcirculatory characteristics and may possibly play a future role in both the detection of early oral mucosal vascular aberrations and the effect of anti-tumor agents on the tumor microvasculature.