Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for pretreatment prediction of neoadjuvant chemotherapy response in locally advanced hypopharyngeal cancer.

Objective:The aim of this study was to predict response to neoadjuvant chemotherapy (NAC) in patients with locally advanced hypopharyngeal cancer by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Methods:A retrospective study enrolled 46 diagnosed locally advanced hypopharyngeal cancer. DCE-MRI were performed prior to and after two cycles of NAC. The volume transfer constant (Ktrans), extracellular extravascular volume fraction (Ve), and plasma volume fraction (Kep) were computed from primary tumors. DCE-MRI parameters were used to measure tumor response according to the Response Evaluation Criteria in Solid Tumors criteria (RECIST).Results：After 2 NAC cycles, 30 out of 46 patients were categorized into the responder group, whereas the other 16 were categorized into non-responder group. Compared with the pretreatment value, the post-treatment Ktrans and Kep was significantly lower (P < 0.05), but no significant change in Ve (P > 0.05). Compared with non-responders, a notably higher pretreatment Ktrans, Kep, lower post-treatment Ktrans, higher ΔKtrans and ΔKep were observed in responders (all P < 0.05). While the pretreatment Ve, post-treatment Ve, and ΔVe did not differ significantly (P>0.05) between the two groups. The receiver operating characteristic curve analysis revealed that pretreatment Ktrans of 0.202/min is the most optimal cut-off in predicting response to chemotherapy, resulting in an AUC of 0.837 and corresponding sensitivity and specificity of 76.7%, and 81.1%, respectively.Conclusion:DCE-MRI especially pretreatment Ktrans can potentially predict the treatment response to neoadjuvant chemotherapy for hypopharyngeal cancer.Advances in knowledge:Few studies of DCE-MRI on hypopharyngeal cancer treated with chemoradiation reported. The results demonstrate that DCE-MRI especially pretreatment Ktrans may be more potential value in predicting the treatment response to neoadjuvant chemotherapy for hypopharyngeal cancer.

Down syndrome critical region 1 positively correlates with angiogenesis in hypopharyngeal cancer.

Hypopharyngeal carcinoma has one of the highest mortality rates of head and neck cancer, therefore, the identification of markers associated with the pathogenesis and development of hypopharyngeal cancer is critical. Down syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. Activation of the vascular endothelial growth factor (VEGF) signaling pathway upregulates DSCR1. The aims of the present study were to determine the expression levels of DSCR1 and VEGF­C in hypopharyngeal cancer, and investigate the association between DSCR1 and angiogenesis in the disease. Tissue samples from 94 cases of pathologically confirmed hypopharyngeal squamous cell carcinoma were collected. The mRNA levels of DSCR1 and VEGF­C in cancerous and paracancerous tissues were examined using semi­quantitative reverse transcription­polymerase chain reaction. Microvessel density (MVD) was counted, according to the number of cluster of differentiation 34­positive cells. Spearman's correlation analysis was utilized to analyze the association between DSCR1 and angiogenesis. The relative mRNA expression levels of DSCR1 and VEGF­C, and the MVD were significantly increased in the cancerous tissue samples from the patients with hypopharyngeal cancer, compared with the paracancerous tissue samples from these patients. Higher levels of DSCR1 and increased MVD were associated with poorly differentiated tumors and lymph node metastasis. The mRNA expression levels of DSCR1 were positively correlated with the mRNA levels of VEGF­C in the cancerous tissues. The protein expression levels of DSCR1 were also positively correlated with MVD in the cancerous tissues. The results indicated that DSCR1 is involved in tumor angiogenesis in patients with hypopharyngeal cancer, and is closely associated with the progression of the disease.

Prognostic significance of GRP78/BiP expression in patients with Stage III/IV hypopharyngeal squamous cell carcinoma.

The immunoglobulin heavy chain binding protein (BiP)/glucose-regulated protein 78 (GRP78) plays an essential role in the endoplasmic reticulum (ER) stress, and GRP78/BiP is known to be highly expressed in various human neoplasms. The clinicopathological features of GRP78/BiP expression in patients with advanced hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. The aim of this study is to elucidate the prognostic significance of GRP78/BiP for HSCC.A total of 68 patients with advanced HSCC (stage III/IV) were analyzed, and tumor specimens were stained with immunohistochemistry for GRP78/BiP, Ki-67, and microvessel density (MVD), as determined through CD34 and p53 levels. GRP78/BiP was highly expressed in 80.8% (55/68) of all patients. The expression level of GRP78/BiP disclosed no significant relationship with any variables. Multivariate analysis confirmed that low expression of GRP78/BiP was an independent prognostic factor for predicting poor overall survival and progression-free survival in patients with advanced HSCC. The decreasing expression of GRP78/BiP was identified as a significant predictor related to shorter survival duration after surgery for advanced HSCC. Our study suggests that the reduced expression of GRP78/BiP contributes to worse survival for patients with advanced head and neck cancer.

Enhanced contact endoscopy for the detection of neoangiogenesis in tumors of the larynx and hypopharynx.

OBJECTIVES/HYPOTHESIS: Image-enhanced endoscopy, such as narrow band imaging and the Storz Professional Image Enhancement System, have been increasingly used in patients with suspect lesions of the larynx and hypopharynx during preoperative and intraoperative assessment. STUDY DESIGN: In the present study, a contact endoscope was coupled with the systems of image-enhanced endoscopy, as to precisely distinguish the peculiar neoangiogenetic changes in inflammation, and precancerous and cancerous lesions of the larynx and hypopharynx. METHODS: We performed a single-blind study with this original approach of a series of 44 patients with different lesions of the larynx and hypopharynx. RESULTS: We observed five obvious vascular patterns matching the diagnosis in 41 patients out of 44, with accuracy in the differential diagnosis between normal tissue and hyperplasia versus mild dysplasia and carcinoma of 97.6%. CONCLUSIONS: Enhanced contact endoscopy allows for predicting histologic changes of laryngeal and hypopharyngeal lesions from inflammation to cancer on based on fine evaluation of the neoangiogenetic changes of the chorion. This innovative procedure can be considered an important tool during diagnosis, treatment, and follow-up of patients with precancer and cancer of the larynx and hypopharynx.

Comparison of consecutive bolus tracking and flash replenishment measurements for the assessment of tissue hemodynamics using contrast-enhanced ultrasound (CEUS) in an experimental human squamous cell carcinoma model.

PURPOSE: To evaluate "bolus-tracking" (BT) and "flash-replenishment" (FR) for the assessment of tissue hemodynamics by contrast-enhanced ultrasound (CEUS) in an experimental small-animal-squamous-cell-carcinoma-model. Since the underlying tissue is the same, strong correlations between parameter outcomes of both techniques are expected. METHODS AND MATERIALS: Human hypopharynx-carcinoma-cells were subcutaneously injected into the left flank of 18 female athymic-nude-rats. After 10 days of subcutaneous tumour growth, bolus tracking and flash-replenishment measurements were performed consecutively in the same imaging plane in each rat after bolus-injection of SonoVue via the lateral tail vein using a high-end ultrasound system with a 15 MHz probe. Video-sequences were analysed with dedicated software (VueBox®, Bracco-Suisse®). From BT measurements, the parameters peak enhancement (PEBT), wash-in area-under-the-curve (Wi-AUCBT), mean transit time (MTTBT), wash-in-rate (WiRBT) and perfusion-index (Wi-PIBT) were derived; FR yielded estimates of relative-blood-volume (rBVFR), mean transit time MTTFR, relative blood flow rBFFR and wash-in rate Wi-RFR. RESULTS: In all rats, BT and FR measurements could be completed successfully. Highly significant correlations were observed between rBVFR and PEBT, rBVFR and Wi-AUCBT, rBVFR and MTTBT, rBVFR and WiPIBT, MTTFR and MTTBT, rBFFR and PEBT, rBFFR and Wi-AUCBT, rBFFR and WiRBT, rBFFR and WiPIBT, WiRFR and PEBT, WiRFR and Wi-AUCBT, WiRFR and WiRBT and WiRFR and WiPIBT. CONCLUSION: Whereas bolus tracking can be used in a wide range of modalities including CEUS, CT and MR, FR as a technique for the assessment of tissue hemodynamics is unique to CEUS. Although BT and FR yield different parameters, the underlying tissue hemodynamics are equal. In this work, we were able to demonstrate strong correlations between different parameters of both modalities in a small-animal-tumor-model, indicating that flash-replenishment is a valid alternative to the more established bolus-tracking technique. Although the lack of absolute, quantitative parameters hinders a direct comparison of both modalities, FR and BT should both be suitable for a relative comparison, e.g. between baseline and follow-up examinations.

Residual DNA double strand breaks in perfused but not in unperfused areas determine different radiosensitivity of tumours.

PURPOSE: Micromilieu-dependent quantification of γH2AX after irradiation in vivo and correlation with local tumour control. MATERIALS AND METHODS: Local tumour control was evaluated after irradiation of FaDu and SKX xenografts with ambient single doses. γH2AX foci were quantified in perfused and unperfused regions after different irradiation doses and at different time points. RESULTS: The TCD(50) of FaDu was 2-times higher compared to SKX (28.0Gy [95% C.I. 24.6; 31.3Gy] for FaDu; 14.9Gy [10.9; 18.9] for SKX, p<0.001). The induction of foci did not differ between the tumour models. Residual foci were twice higher in perfused SKX regions compared to FaDu, no difference was observed in the non-perfused region between both tumour models. The number of residual foci increased with a 2-times higher slope in perfused SKX-regions compared to FaDu, while no difference was detected in unperfused regions. Already within the perfused regions, this slope decreased with distance from perfused vessels. CONCLUSION: The dose-response of residual γH2AX foci is highly dependent on tumour cell oxygenation in well perfused areas. This dependence decreases further away from tumour vessels. Only γH2AX evaluation in perfused tumour areas can distinguish between the different radiocurability of the two tumour models.

Diagnosis of the extent of advanced oropharyngeal and hypopharyngeal cancers by narrow band imaging with magnifying endoscopy.

OBJECTIVES/HYPOTHESIS: Narrow band imaging combined with magnifying endoscopy (NBI-ME) is useful for the detection of superficial cancer in the oropharynx, hypopharynx, and esophagus. We used NBI-ME to evaluate the frequency of superficial cancer spread (SCS) contiguous with advanced oropharyngeal and hypopharyngeal cancers and esophageal cancers. STUDY DESIGN: Retrospective. METHODS: We retrospectively studied 45 patients with oropharyngeal and hypopharyngeal cancer and 44 with esophageal cancer who underwent NBI-ME from October 2006 through April 2009. The following variables were evaluated: 1) the frequency of SCS contiguous with advanced oropharyngeal and hypopharyngeal cancer and esophageal cancer, and 2) the influence of SCS contiguous with advanced oropharyngeal and hypopharyngeal cancer on clinical T category and clinical stage. RESULTS: SCS contiguous with the primary tumor was found in 49% (22/45) of the patients with advanced oropharyngeal and hypopharyngeal cancer and in 52% (23/44) of those with advanced esophageal cancer. When SCS contiguous with the primary tumor was included in the evaluation of tumor size in advanced oropharyngeal and hypopharyngeal cancer, the clinical T category and clinical stage were revised in 20% (9/45) and 4% (2/45) of patients, respectively; SCS was ≤ 2 cm in 64% of cases (14/22) and between >2 cm and ≤ 4 cm in 36% (8/22). CONCLUSIONS: NBI-ME should be included in the pretreatment diagnostic work-up to evaluate lesion extent and decide optimal surgical margins and radiation fields in patients with advanced oropharyngeal and hypopharyngeal cancer.

[The expression and relationship of vascular cell adhesion molecule-1 and P-selectin and microvessel density in hypopharyngeal carcinoma].

OBJECTIVE: To investigate the expression and significance of vascular cell adhesion molecule-1 (VCAM-1) and P-selectin in hypopharyngeal carcinoma, and explore the relationship of VCAM-1, P-selectin and microvessel density (MVD). METHOD: Expression of VCAM-1 and P-selectin were detected by immunohistochemistry staining in 40 specimens of hypopharyngeal carcinoma and 10 specimens of normal mucosa of oral pharynx. MVD was assessed based on the expression of CD34. RESULT: VCAM-1 and P-selectin were detected in 26 out of 40 (65%) and 29 out of 40 (72.5%) respectively in hypopharyngeal carcinoma, but none that in normal mucosa (P<0.01). MVD in hypopharyngeal carcinoma was higher than that in normal mucosa and it was related to lymph node metastasis. MVD level was significantly higher in VCAM-1 and P-selectin-positive specimens than in negative ones (P<0.01), which also positively correlated with the expression of VCAM-1 and P-selectin (P<0.01). The expression of P-selectin positively correlated with VCAM-1 in hypopharyngeal carcinoma specimens with lymph node metastasis. CONCLUSION: The higher expression of VCAM-1 and P-selectin play key roles in the invasion and metastasis of hypopharyngeal carcinoma and were correlated with vascularization.

Outcome prediction after surgery and chemoradiation of squamous cell carcinoma in the oral cavity, oropharynx, and hypopharynx: use of baseline perfusion CT microcirculatory parameters vs. tumor volume.

PURPOSE: To assess whether pretreatment perfusion computed tomography (PCT) may predict outcome in chemoradiated patients with oral cavity, oropharynx, and hypopharynx squamous cell carcinoma (SCCA) after surgical excision. MATERIALS AND METHODS: Twenty-one patients with SCCA were examined before treatment. The primary site was oral cavity in 6, oropharynx in 7, and hypopharynx in 8 patients; there were 11 T2, 6 T3, and 4 T4 tumors. PCT was performed at the level of largest tumor diameter based on standard neck CT. The data were processed to obtain blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS). Regions of interest were free-hand positioned on the lesions to obtain PCT measurements. Tumor volume was also calculated. Follow-up was performed with positron emission tomography (PET)/CT and endoscopy. Pearson correlation coefficient was used for comparison between the subgroups. A regression model was constructed to predict recurrence based on the following predictors: age, gender, tumor (T) and nodal (N) stage, tumor volume, and PCT parameters. RESULTS: BF(mean), BF(max), BV(mean), BV(max), MTT(mean), PS(mean), and PS(max) were significantly different between patients with and without tumor recurrence (0.0001, p < 0.04). T stage, tumor volume, N stage, BF(max), BV(max), MTT(mean), and radiation dose (p < 0.001) were independent predictors for recurrence. Cox proportional hazards model for tumor recurrence revealed significantly increased risk with high tumor volume (p = 0.00001, relative risk [RR] 7.4), low PS(mean) (p = 0.0001, RR 14.3), and low BF(max) (p = 0.002, RR 5.9). CONCLUSIONS: Our data suggest that PCT parameters have a prognostic role in patients with SCCA.

[Expression of alpha-v integrin subunit in the laryngeal and hypopharyngeal squamous cell carcinomas and its relationship with tumor angiogenesis].

OBJECTIVE: To investigate the expression of integrin alpha-v subunit in laryngeal and hypopharyngeal squamous cell carcinomas (LHSCC) and to correlate the expression ratio with clinic and pathologic features of LHSCC, meanwhile, to investigate the relationship between the expression of integrin alpha-v subunit and tumor angiogenesis. METHODS: A tissue microarray of LHSCC was designed and made. Using this microarray, the expression of integrin alpha-v subunit in LHSCC was studied by immunohistochemistry, and the expression disparity in different clinic and pathologic staging of LHSCC was analyzed. The immunohistochemical staining of CD105 was done in the same microarray, the intratumor microvessel density (IMVD) was calculated by CD105 staining. The relationship between integrin alpha-v subunit expression and the IMVD was analyzed. RESULTS: In primary cancer tissue, the expression ratio of integrin alpha-v subunit was 68.0% (51/75), significantly higher than normal tissue beside cancer (10.3%, 3/29, chi2 = 28.68, P < 0.001); the expression ratio of integrin alpha-v subunit in lymph node metastatic carcinoma was 100.00% (20/20), significantly higher than normal tissue (chi2 = 38.77, P < 0.001) and primary cancer tissue (chi2 = 12.69, P < 0.05); in group with lymph node metastasis, the expression ratio of integrin alpha-v subunit was significantly higher than group without lymph node metastasis (chi2 = 10.87, P < 0.001); the IMVD of the group with integrin alpha-v subunit positive expression was significantly higher than the group with integrin alpha-v subunit negative expression (P < 0.001). CONCLUSIONS: There was significant relationship between integrin alpha-v subunit expression and lymphatic metastasis of LHSCC. Overexpression of the integrin alpha-v subunit may have contributed to the tumor angiogenesis and lead to lymphatic metastasis. Integrin alpha-v subunit may become a novel lymphatic metastasis marker of LHSCC.

Application of ligating loops to control bleeding during endoscopic surgery for a highly vascular hypopharyngeal tumour.

Endoscopic treatment of hypervascular lesions of the hypopharynx is challenging because of difficulty in controlling bleeding during surgery. We report a highly vascular hypopharyngeal solitary fibrous tumour treated by endoscopic laser surgery combined with ligating loops. Application of dual ligating loops provided easy and secure haemostasis of the feeding artery before resection. Since the endoscopic approach is less invasive than the external approach, we confirm that it is worthwhile to attempt an endoscopic approach using ligating loops before resorting to the external approach in the treatment of hypervascular hypopharyngeal lesions.

Feeding artery of laryngeal and hypopharyngeal cancers: role of the superior thyroid artery in superselective intraarterial chemotherapy.

The purpose of this study was to elucidate the role of the superior thyroid artery in intra-arterial infusion chemotherapy for laryngeal and hypopharyngeal cancers. Thirty-nine patients with laryngeal cancer and 29 patients with hypopharyngeal cancer underwent intra-arterial infusion chemotherapy. We performed a retrospective analysis of the feeding arteries confirmed by computed tomography during selective arteriography and compared the results with the extent of the tumors. In 14 of 39 laryngeal and 15 of 29 hypopharyngeal cancers, the tumor did not cross the midline (group 1). In the remaining 25 and 14 cancers, respectively, the tumor crossed the midline or located in the center (group 2). For 13 of 14 laryngeal and 7 of 15 hypopharyngeal cancers in group 1 and for 6 of 25 laryngeal cancers in group 2, the entire tumor was contrast enhanced by the ipsilateral superior thyroid and/or superior laryngeal artery. For 12 of 25 laryngeal and 1 of 14 hypopharyngeal cancers in group 2, the entire tumor was contrast enhanced by the bilateral superior thyroid artery. For the other patients, infusion via the other arterial branches such as the inferior thyroid and the lingual arteries were needed to achieve contrast enhancement of the entire tumor. Superselective intra-arterial chemotherapy for laryngeal cancer from the superior thyroid artery is appropriate, whereas that for hypopharyngeal cancer is less sufficient. To accomplish contrast enhancement of the entire tumor, additional intra-arterial infusion from other arteries such as the inferior thyroid artery is often necessary.

Clinicopathologic significance of CD105 expression in squamous cell carcinoma of the hypopharynx.

BACKGROUND: Induction of angiogenesis is a key process in tumor growth and metastasis. We studied the CD105 (endoglin) and vascular endothelial growth factor (VEGF) in hypopharyngeal cancer to evaluate their clinicopathologic significance. METHODS: Seventy-three patients who underwent complete excision of hypopharyngeal cancer were included in this study. Clinicopathologic data were collected retrospectively. Immunohistochemical analysis was performed with antibodies of CD105 and VEGF. Positive-stained microvessels for CD105 were counted on hot spots of tumors. The staining intensity for VEGF was also evaluated. RESULTS: High expression of CD105 correlated significantly with positive nodal metastasis (p < .001) and TNM stage (p < .01). High expression of VEGF correlated significantly with advanced tumor (T) classification (p < .01). The overall 5-year survival rate was worse in patients with higher CD105 expression (p < .001), advanced TNM stage (p < .01), advanced T classification (p < .01), and positive nodal metastasis (p < .001). Furthermore, Cox regression analysis revealed that CD105 expression in microvessels of tumor tissue, advanced T classification, and nodal status were independent factors for survival. CONCLUSION: Our results suggest that expression of CD105 is a useful predictive prognostic factor in hypopharyngeal cancer.

Narrow band imaging: a new diagnostic approach to visualize angiogenesis in superficial neoplasia.

Although numerous gastrointestinal endoscopes pass through the oropharynx and the hypopharynx, it is extremely difficult to detect an early cancer in these sites during routine endoscopic examination. Most patients with cancer in these sites are usually diagnosed in advanced stages. If effective screening methods can detect an earlier stage, such as carcinoma in situ, it would obviously be of great benefit. Narrow band imaging is an innovative optical technology that can clearly visualize the microvascular structure of the organ surface. Herein, we demonstrate that narrow band imaging combined with magnifying endoscopy can identify a carcinoma in situ in oropharyngeal and hypopharyngeal mucosal lesions. Scattered irregular foci of microvascular proliferation projecting to the dysplastic squamous epithelium are the typical features. These results indicate that an approach to visualize angiogenesis or morphologic changes of microvessels in the superficial neoplasm can be a new diagnostic method not only for the head and neck region but also for other sites in the gastrointestinal tract.

Enhanced susceptibility of irradiated tumor vessels to vascular endothelial growth factor receptor tyrosine kinase inhibition.

Previous experiments with PTK787/ZK222584, a specific inhibitor of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, using irradiated human FaDu squamous cell carcinoma in nude mice, suggested that radiation-damaged tumor vessels are more sensitive to VEGFR inhibition. To test this hypothesis, the tumor transplantation site (i.e., the right hind leg of nude mice) was irradiated 10 days before transplantation of FaDu to induce radiation damage in the host tissue. FaDu tumors vascularized by radiation-damaged blood vessels appeared later, grew at a slower rate, and showed more necrosis and a smaller vessel area per central tumor section than controls. PTK787/ZK222584 at a daily dose of 50 mg/kg body weight had no impact on growth of control tumors. In contrast, tumors vascularized by radiation-damaged vessels responded to PTK787/ZK222584 with longer latency and slower growth rate than controls, and a trend toward further increase in necrosis, indicating that irradiated tumor vessels are more susceptible to VEGFR inhibition than unirradiated vessels. Although not proving causality, expression analysis of VEGF and VEGFR2 shows that enhanced sensitivity of irradiated vessels to a specific inhibitor of VEGFR tyrosine kinases correlates with increased expression of the molecular target.

Evaluation of tumor oxygenation by color duplex sonography: a new approach.

OBJECTIVE: Description of a new noninvasive method for the evaluation of tissue oxygenation in head and neck cancer. STUDY DESIGN AND SETTING: Prospective nonrandomized controlled study in an academic medical center on 20 patients with neck metastases of head and neck cancer. Metastases were investigated using color duplex sonography and pO2 histography. The vascularization in sonography was quantitatively evaluated by color pixel density and compared to the pO2 values of the same nodes. RESULTS: The correlation between vascularization and flow velocity was 0.71. For the mean/median pO2 -values and for the pO2 readings <10.0 mmHg correlations were r = 0.65 / 0.76 and 0.71. CONCLUSION: This sonographic method allows a safe and reliable evaluation of oxygenation in metastases of head and neck cancer. SIGNIFICANCE: The new approach is an alternative to pO2 histography and may play a future role in the planning of radiotherapy in the neck.

Intratumor microvessel density in biopsy specimens predicts local response of hypopharyngeal cancer to radiotherapy.

BACKGROUND: The aim of this retrospective study was to identify reliable predictive factors for local control of hypopharyngeal cancer (HPC) treated by radiotherapy. METHODS: A cohort of 38 patients with HPC treated by radical radiotherapy at the National Cancer Center Hospital East between 1992 and 1999 were selected as subjects for the present study. Paraffin-embedded pre-therapy biopsy specimens from these patients were used for immunostaining to evaluate the relationships between local tumor control and expression of the following previously reported predictive factors for local recurrence of head and neck cancer treated by radiotherapy: Ki-67, Cyclin D1, CDC25B, VEGF, p53, Bax and Bcl-2. The predictive power of microvessel density (MVD) in biopsy specimens and of clinicopathologic factors (age, gender and clinical tumor-node-metastasis stage) was also statistically analyzed. RESULTS: Twenty-five patients developed tumor recurrence at the primary site. Univariate analysis indicated better local control of tumors with high microvessel density [MVD >or= median (39 vessels/field)] than with low MVD (< median, P = 0.042). There were no significant associations between local control and expression of Ki-67 (P = 0.467), Bcl-2 (P = 0.127), Bax (P = 0.242 ), p53 (P = 0.262), Cyclin D1 (P = 0.245), CDC25B (P = 0.511) or VEGF (P = 0.496). Clinicopathologic factors were also demonstrated to have no significant influence on local control (age, P = 0.974; gender, P = 0.372; T factor, P = 0.602; N factor, P = 0.530; Stage, P = 0.499). CONCLUSION: Microvessel density in biopsy specimens was closely correlated with local control of HPC treated by radiotherapy.

[The expression difference of VEGF, PDGF/dThdPase and MVD on primary hypopharyngeal carcinoma and metastasis lymph nodes].

OBJECTIVE: To evaluate the difference of angiogenic factors PDGF/dThdPase,VEGF expression and microvessel density (MVD) in primary hypopharyngeal tumor and metastasis lymph nodes. METHOD: The author studied immunohistochemically a series of 48 primary hypopharyngeal carcinoma patients and metastasis lymph nodes were calculated. RESULT: The percentage of VEGF was 25.38% in primary tumor and 21.52% in lymph nodes. No significant difference was found. The percentage of PDGF/dThdPase was 29.59% in primary tumor and and 21.2% in lymph nodes. This showed significent difference. VEGF showed significent difference between live and death group(P < 0.05) and among differentiation group (P < 0.05). MVD showed significant difference between live and death group, early and late stage group, and T1-2 and T3-4 group (P < 0.05). There were statistically significant correlations between the score of PDGF/ dThdPase, or VEGF and the score of MVD respectively. CONCLUSION: The present study suggests that there was a correlation between VEGF or PDGF and MVD. VEGF and MVD were possible to be prognostic discriminators in hypopharyngeal carcinoma. PDGF expression in lymph nodes was significant higher than in primary tumors, and MVD expression in primary tumor was significant higher than in lymph nodes.

Vascular architecture and hypoxic profiles in human head and neck squamous cell carcinomas.

Tumour oxygenation and vasculature are determinants for radiation treatment outcome and prognosis in patients with squamous cell carcinomas of the head and neck. In this study we visualized and quantified these factors which may provide a predictive tool for new treatments. Twenty-one patients with stage III-IV squamous cell carcinomas of the head and neck were intravenously injected with pimonidazole, a bioreductive hypoxic marker. Tumour biopsies were taken 2 h later. Frozen tissue sections were stained for vessels and hypoxia by fluorescent immunohistochemistry. Twenty-two sections of biopsies of different head and neck sites were scanned and analysed with a computerized image analysis system. The hypoxic fractions varied from 0.02 to 0.29 and were independent from T- and N-classification, localization and differentiation grade. No significant correlation between hypoxic fraction and vascular density was observed. As a first attempt to categorize tumours based on their hypoxic profile, three different hypoxia patterns are described. The first category comprised tumours with large hypoxic, but viable, areas at distances even greater than 200 micrometer from the vessels. The second category showed a typical band-like distribution of hypoxia at an intermediate distance (50-200 micrometer) from the vessels with necrosis at greater distances. The third category demonstrated hypoxia already within 50 micrometer from the vessels, suggestive for acute hypoxia. This method of multiparameter analysis proved to be clinically feasible. The information on architectural patterns and the differences that exist between tumours can improve our understanding of the tumour micro-environment and may in the future be of assistance with the selection of (oxygenation modifying) treatment strategies.

[Study on the relationship between intratumor microvessel density and neck metastasis of laryngeal and hypopharyngeal squamous cell carcinomas].

Sixty-one laryngeal and hypopharyngeal squamous cell, carcinoma (LC, HPC) tissue slides were immunochemically stained using LSAB method to study epithelium cells. The results demonstrated that (1) intratumor microvessel density (ITMD) in LC and HPC group was higher than that of the benign group (P < 0.05). ITMD was higher in the subgroup of LC and HPC with positive lymph node positive than that with negative lymph nodes. This result suggest that ITMD is relevant not only to the nature of the tumor, but also to lymph node metastasis. The level of ITMD is an important predictive sign of metastasis. (2) The relationship between ITMD and the clinical staging had no statistic significance (P > 0.05). (3) The analysis on the relationship between ITMD and pathologic differentiation indicated that the level of ITMD raised gradually with the lowering of the pathologic differentiation.