Prognostic Value of Vascular Endothelial Growth Factor and its Receptors Flt-1 and Flk-1 in Astrocytic Tumours

Summary  Background. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) is an important regulator of angiogenesis and vascular permeability.  Method. We examined immunohistochemically expressions of VEGF and its corresponding receptors Flt-1 and Flk-1 in a series of 50 astrocytic tumours, and correlated their expressions with the degree of angiogenesis, brain edema and prognosis.  Findings. There were significant relationships between VEGF, Flk-1 expressions and glioma malignancy grading, intratumoural vascularity and peritumoural brain edema, respectively. Patients with VEGF positive low grade astrocytoma and glioblastoma multiforme had a significantly shorter mean overall survival time than those with negative tumours (P=0.0010 and 0.0180, respectively). Flk-1 is also a significant prognostic factor within each tumour grade, which has a negative impact on overall survival. Additionally, overexpression of VEGF and Flk-1 were significantly associated with earlier recurrence in patients with low grade astrocytomas (P=0.0018 and 0.0240, respectively).  Interpretation. It is possible to subcategorize each grade of astrocytic tumours based on their VEGF and Flk-1 staining pattern, which may be crucial in predicting the biological behavior of tumours and thus provide useful information with regard to adequate treatment.     

Expression of P27kip 1 and Ki-67 in Pituitary Adenomas: An Investigation of Marker of Adenoma Invasiveness

Summary  Mirroring the ambiguities noted with other endocrine tumours, histology is a poor predictor of the invasiveness of pituitary adenomas. Accordingly, the proteins p27^Kip 1 (p27) and Ki-67, which respectively block cell-cycle progression and reflect proliferative activity of cells, were studied immunohistochemically in 123 specimens of pituitary adenomas including 57 clinically verified invasive cases. Only Ki-67 had a significant association with invasiveness; only p27 differed significantly between functioning and nonfunctioning adenomas, with a higher frequency of cell labelling in the former. No relationship between Ki-67 and p27 was obtained. Ki-67 detected by MIB-1 is thus an important marker related to the invasive potential of adenomas, and thereby may be helpful in planning postoperative management of patients with pituitary adenomas.     

Endocrinological Outcome Following First Time Transsphenoidal Surgery for GH-, ACTH-, and PRL-Secreting Pituitary Adenomas

Summary. Summary.   Background: To study remission rates and pituitary functions following transsphenoidal surgery of newly diagnosed GH-, ACTH-, and PRL-secreting pituitary adenomas.   Methods: Out of a series of 329 newly diagnosed pituitary adenomas, 131 (39.8%) were hormone (67 GH-, 27 ACTH-, 37 PRL-) secreting. PRL-secreting adenomas were subjected to surgery because they failed to respond to previous medical treatment therapy. The data on secreting adenomas, regarding the results of standardised endocrinological testing, MRI findings and water metabolism disturbances, were extracted retrospectively from the pituitary data-base of the hospital. The mean follow-up was 3.7 years.   Results: The overall remission rate for PRL-secreting adenomas (27%) was significantly lower than for GH- (71.6%) and ACTH-secreting (81.5%) ones. Remission rates correlated negatively with the magnitude of preoperative hormone excess (not in Cushing's disease), tumour size (not in prolactinoma) and invasiveness. Generally, the improvement of the adenopituitary functions was statistically significant during the first three postoperative months, and thereafter remained unchanged. Diabetes insipidus persisting for more than three months occurred with similar frequency in the three patient groups (in 9.4% of GH-, in 6.7% of ACTH-, and in 10% of PRL-secreting adenomas). Tumour regrowths occurred more often in PRL-(20%) than in ACTH- (9.1%) and GH- (0%) secreting tumours.   Conclusions: In GH- and ACTH-secreting pituitary adenomas, remission rates were significantly higher and recurrence rates lower than in PRL-secreting adenomas, which had failed to respond to previous medical therapy. The overall postoperative adenopituitary function was improved in all patient groups. Diabetes insipidus occurred with similar frequency in all patient groups. When reporting on results of surgery for secreting pituitary adenomas, not only remission and recurrence rates, but also the results of the pituitary function should be included. Published online June 20, 2002     

MRI Prediction of Fibrous Pituitary Adenomas

Summary  The transsphenoidal approach is a less invasive and safer procedure for removing pituitary adenomas. However, this procedure becomes extremely difficult when the tumour consistency is fibrous as encountered in about 10% of pituitary adenomas. In this study, we investigated predicting factors of tumour consistency in magnetic resonance images (MRIs).  MRIs of two groups, twenty-one soft and five firm (fibrous) adenomas, were retrospectively evaluated and compared in respect of tumour consistency. To compare the two groups objectively, tumour densities on MRI films and percentage of collagen content on operative specimens were expressed as numerical data using NIH-image^TM. The relationships between collagen content and T1-weighted images, T2-weighted images, grade of enhancement effect, and heterogeneity of enhancement were investigated.  Signal intensities on T1-weighted images were not correlated with tumour consistency, whereas those on T2-weighted images were significantly correlated with the percentage of collagen content. Adenomas, showing lower signal intensities on T2-weighted images, contained more collagen. On enhanced images, homogeneously enhanced adenomas tended to include more collagen, even though the grade of enhancement effect showed only weak correlation with the tumour hardness.  MRIs give us useful information on tumour consistency. Adenomas may be firm and fibrous if they show low signal intensities on T2-weighted images and homogeneous enhancement. To remove such tumours, a long sized and small-calibred ultrasonic aspirators applicable to transsphenoidal approach must be prepared and multi-staged operations may be more than likely needed.     

Clinical Relevance of Vascular Endothelial Growth Factor for Thyroid Neoplasms

Angiogenesis is of vital importance during the development and progression of solid tumors. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and could be produced by some cancer cells. To investigate the clinical relevance of VEGF in the tumorigenesis of human thyroid, an immunohistochemical study was performed on archival materials of follicular adenomas (n= 13), Hürthle cell adenomas (n= 6), papillary carcinomas (n= 76), follicular carcinomas (n= 12), Hürthle cell carcinomas (n= 2), and anaplastic carcinomas (n= 8). Patterns of VEGF expression were analyzed in relation to histologic subtypes of thyroid tumors and were correlated to biologic indicators of papillary carcinoma. All papillary carcinomas and Hürthle cell neoplasms revealed a strong, diffuse staining reaction, whereas anaplastic carcinoma usually exhibited weak and infrequent immunoreactivity. VEGF levels were usually higher in follicular adenomas than in follicular carcinomas. With regard to prognostic value, VEGF expression did not correlate with tumor size, extent of invasion, or scores on the AGES system (i.e., patient age, tumor size, histologic grade, tumor extent, distant metastasis) or the MACIS system (i.e., metastasis, age, completeness of resection, invasion, tumor size) for papillary carcinomas (p > 0.05, respectively). The results of the current study indicate that VEGF may play a role in the development of human thyroid cancer. Determination of the angiogenic phenotype may have limited prognostic value for patients with papillary carcinoma.     

Angiogenesis and Brain Oedema in Intracranial Meningiomas: Influence of Vascular Endothelial Growth Factor

Summary The correlation between angiographic neovascularization, peritumoural brain oedema (PTBOe) and the expression of vascular endothelial growth factor (VEGF) , was analysed in 30 patients with intracranial meningiomas. Pre-operative angiograms were examined for the existence of either an exclusively dural tumour blush or an additionally pial tumour supply from cerebral arteries. Furthermore the presence of macroscopic tumour-neovascularization and dysplastic changes of tumour-draining cerebral veins was evaluated. VEGF expression was investigated on histological tissue samples, using immunohistochemical techniques. VEGF immunohistochemistry and neuroradiological evaluations were performed in double blind fashion. Tumour volume and the amount of oedema were calculated by computerized tomography (CT) or magnetic resonance imaging (MRI). The oedema-tumour volume ratio was defined as oedema index (OeI). Compared to VEGF-negative meningiomas, tumours with striking VEGF staining revealed a significant higher mean oedema index (OeI=4,2 vs. OeI=1,5; p<0.018), and a higher oedema incidence (91,7% vs. 44,4%; p<0.046). Equally, meningiomas with additionally tumour supply from cerebral arteries were associated with a significant higher mean OeI (OeI=4.1 vs. OeI=1.2; p<0.01) and oedema incidence (94,7% vs. 20,0%; p<0,0023) than meningiomas with exclusively tumour supply from dural arteries. All meningiomas with striking VEGF-expression were associated with vascular tumour supply from cerebral arteries, but VEGF-negative tumours only in 50% (p<0.029). These data suggest a link between VEGF-expression, arterial tumour supply and peritumoural brain oedema. The development of tumour supply from cerebral arteries may be important for formation of meningioma-related oedema. Therefore, VEGF may represent a potent mediator in the evolution of this type of vascularization in meningiomas.     

Recurrent intracranial germinoma outside the initial radiation field with progressive malignant transformation

Summary.  A 19-year-old man with a pure germinoma in the pineal region was successfully treated with chemotherapy followed by 24 Gy local irradiation. Eight months later, magnetic resonance (MR) imaging detected ventricular wall dissemination outside the radiation field. Near complete response was achieved again after 28.8 Gy whole brain and 24 Gy whole spine irradiation. Two months later, MR imaging demonstrated recurrence of a mass at the corpus callosum. Gamma knife radiosurgery did not control this mass, so tumour resection was performed. Histological examination revealed immature teratoma. Enlargement of the recurrent mass at the trigone of the left lateral ventricle was found in spite of additional chemotherapy. Tumour extirpation was performed and histological examination revealed embryonal carcinoma. The patient died of tumour progression 34 months after the initial treatment.  By a combination of chemotherapy regiments in use today, the initial radiation field to treat intracranial germinomas should not be confined to the tumour bed. Published online June 20, 2002     

Expression of Ki-67 antigen in nonfunctioning pituitary adenomas: correlation with growth velocity and invasiveness

OBJECT: The cell cycle-dependent nuclear antigen Ki-67 is related to growth potential in a variety of tumors. Elevated expression of Ki-67 was previously shown in recurrent pituitary adenomas; however, it has remained unclear whether this expression is related to the growth velocity or invasive behavior of these tumors. The aim of this study was to determine the correlation of Ki-67 antigen expression, growth velocity, and invasiveness in nonfunctioning pituitary adenomas. METHODS: Between April 1998 and April 2002, 23 patients with nonfunctioning pituitary adenomas who had participated in an observation period in which multiple computerized tomography and magnetic resonance imaging studies had been performed were surgically treated in our department. Tumor volumes were assessed using a stereological method based on the Cavalieri principle. The growth rate was calculated for each patient. Expression of Ki-67 antigen was examined using the monoclonal antibody MIB-1. The assessed growth velocity of the adenomas was best described by a linear growth model. The correlation between Ki-67 expression and growth rate was highly significant. Rapidly growing adenomas (> 0.07% daily increase in size) were found to have a Ki-67 labeling index (LI) exceeding 1.5%, whereas all five adenomas with a very slow growth rate (< 0.02% daily increase in size) had a Ki-67 LI lower than 1.5%. No correlation was found between the growth rate and the invasive character of the adenomas. CONCLUSIONS: Expression of Ki-67 antigen is significantly correlated to the growth velocity of pituitary adenomas. Invasive behavior is a feature independent of proliferative activity. The extent of Ki-67 expression is helpful for clinical decision making and routine assessment of Ki-67 is recommended during the histopathological workup of pituitary adenomas.     

Expression and Significance of Vascular Permeability Factor in Tumour Infiltrating Lymphocytes of Brain Metastases

Summary  Background. Recently, vasogenic edema has been related to the expression of vascular permeability factor (VPF) by tumour cells in brain metastases. On the other hand, expression of VPF has been reported in inflammatory cells. Keeping in mind the current presence of tumour-infiltrating lymphocytes (TIL) in brain metastases, our objective is to study the expression and significance of VPF in TIL-cells from specimens of brain metastases.  Method. Tumour samples from 16 brain metastases associated with peritumoural edema were immunohistochemically studied for demonstration of VPF. The degree of VPF-expression by tumour cells and TIL was determined, and correlated with the degree of peritumoural edema.  Findings. Our present results show that, independently of the VPF-positivity expressed by the tumour cells, VPF-expression is a constant finding in TIL-cells of brain metastases, and correlated with the amount of peritumoural edema.  Interpretation. Our present findings suggest a role for TIL-cells in the development of vasogenic edema associated with brain metastases.     

Clinical features and immunohistochemical expression levels of androgen, estrogen, progesterone and Ki-67 receptors in relationship with gross-total resected meningiomas relapse

Abstract Objective. To investigate the recurrent risk factors of intracranial meningiomas after gross-total resection (SimpsonGrade). Methods. We retrospectively analysed 162 meningiomas in the General Hospital of Shenyang Military Region and Changzheng Hospital in Shanghai China, which underwent nearly gross-total resection using microneurosurgery techniques from 2002 to 2007. Monofactorial and Cox regression statistics methods were carried out to analyse the relationship between the post-operation tumour relapse and some clinical features including the patient sex, age, tumour size, tumour shape, tumour pathological grade and the immunohistochemical expression levels of Ki-67, androgen receptor (AR), estrogen receptor (ER) and progesterone receptor (PR). Results. There are 53 recurrent meningiomas during the follow-up period. The recurrent rate is about 32.7%. Immunohistochemistry results indicate that AR, ER, PR, Ki-67 are positively expressed on some tumour cell nuclear. Cox regression analysis reveals that tumour size, tumour shape, pathological grade and Ki-67 expression levels are significantly correlated with the tumour relapse (p <0.05). Conclusions. Our results demonstrate high recurrent rate for gross-total resection meningiomas. Tumour diameter exceeding 5 cm, irregular shape tumour, pathological grade II and III and positive expression of Ki-67 were the risk factors for post-operation meningioma relapse. The recurrent rate increases coincidentally with the follow-up period.     

Prognostic value of the expression of Ki-67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma

OBJECTIVE: To determine if use of cell proliferation, cell adhesion, level of angiogenesis-related factors and presence of microscopic vascular invasion (MVI) could better predict the biological behaviour of renal cell carcinoma (RCC), which has a widely variable clinical outcome despite the use of conventional prognostic factors (staging and grading). MATERIALS AND METHODS: The expression of Ki-67, CD44H and vascular endothelial growth factor (VEGF) were assessed immunohistochemically in formalin-fixed, paraffin-embedded tissues from 48 RCCs, using a Ki-67 labelling index (LI), CD44 LI and level of VEGF expression, respectively. In addition all the pathological slides were reviewed retrospectively for the presence and absence of MVI. The prognostic value of all the variables assessed was then evaluated, and correlated with the usual prognostic variables and cancer-specific survival. RESULTS: Univariate analysis of cancer-specific survival showed that tumour stage (P < 0.001), tumour size (P = 0.005), metastasis, MVI, Ki-67 LI, CD44H LI and VEGF expression (all P < 0.001) were predictors of tumour-related death. There was a statistical correlation between CD44H LI and each of Ki-67 LI (r = 0.61), expression level of VEGF (r = 0.72) and presence of MVI (r = 0.71). Independent predictors of cancer-specific survival in a multivariate analysis were: in all patients with RCC, the MVI (P = 0.003) and VEGF expression (P = 0.01); in those with no metastases, MVI (P = 0.01); in patients with no MVI, VEGF (P = 0.04); and in patients with MVI, Ki-67 LI (P = 0.003). No independent predictor was identified in patient with metastases. CONCLUSION: This study suggests that cell proliferation, cell adhesion, the level of VEGF expression and the presence of MVI represent a complex tumour-host interaction that may favour the progression of RCC. Cell proliferation, CD44H and VEGF expression appear to be powerful markers for identifying patients with an adverse prognosis.     

P53 Overexpression and Proliferative Potential in Malignant Meningiomas

Summary  Meningiomas are generally benign, but some meningiomas show malignancy with invasion and high recurrence rates. We investigated whether alterations in p53 protein may contribute to malignant progression in meningiomas. Immunostaining for p53 protein was performed on paraffin and frozen sections from 61 patients with different grades of meningiomas using monoclonal antibodies (mAbs) DO-1 and pAb240. Immunoblot analysis was performed to quantitate the amount of p53 protein. Mutations in p53 genes were assessed by single-strand conformational polymorphism (SSCP) analysis. MIB-1 immunostaining was used to detect proliferative potentials of meningiomas. We found an overexpression of p53 protein in all of five cases of anaplastic meningiomas by immunohistochemistry using DO-1 mAb. No p53 positive cells were recognized in atypical meningiomas, and several cells were weakly stained in only two of 52 benign meningiomas.  p53 staining index and immunoblot analysis indicated increasing amounts of p53 protein associated with subsequent recurrences of anaplastic meningiomas. The MIB-1 staining index was positively correlated with tumour grade and p53 protein overexpression. Immunostaining of frozen sections using the mutant-specific mAb pAb240, as well as mutation gene analysis by SSCP, indicate that the overexpressed p53 protein is not a mutant- but wild-type p53 protein. Four atypical meningiomas did not recur after surgical removal and radiation, while 4 anaplastic meningiomas with overexpressed p53 protein recurred repeatedly at short intervals even after radiation. Our results suggest that accumulation of p53 protein associated with highly proliferative potentials is a common and characteristic feature that may indicate malignant biological behaviour in meningiomas.     

The expression of vascular endothelial growth factor and proliferative activity of cancer cells in gastric cancer

Background/aims: Vascular endothelial growth factor (VEGF) is one of the most important factors for angiogenesis in various malignant tumors. However, the clinicopathological and biological significance of the expression of VEGF in gastric cancer remains unclear. In this study, we investigated the relationship between the expression of VEGF and the clinicopathological and biological status of advanced gastric cancer, all of the same stage. Patients/methods: The expression of VEGF was immunohistochemically examined using the polyclonal antibody A-20 in tumors from 97 patients with invasion of the serosa but no lymph-node metastasis (t₃, n₀, stage II). The results were compared with clinicopathological and biological status (microvessel density and proliferative activity) of tumors. Results: Expression of VEGF was detected in 27 of 97 tumors (28%). The mean microvessel density (MVD) of 27 VEGF-positive tumors (458/mm²) was higher than that of 70 VEGF-negative tumors (331/mm², P=0.0001). However, the proliferative activity expressed as the Ki-67 labeling index (LI; percentage of immunostained cancer cells) of 27 VEGF-positive tumors (13.8%) was significantly lower than that of 70 VEGF-negative tumors (26.7%, P=0.0002). In 48 tumors with low proliferative activity of cancer cells (Ki-67 LI≤18%), 20 (42%) tumors expressed VEGF, and these tumors had a high MVD (4461/mm²). In the 93 surviving patients, the 5-year survival rate of the 25 patients with VEGF-positive tumors (64%) was not different from that of the 68 patients with VEGF-negative tumors (73%, P=0.4296). Conclusion: Advanced gastric carcinoma with low proliferative activity may produce VEGF and may have high angiogenic potential in order for the tumor itself to grow. However, the prognosis of patients with such tumors was not unfavorable. Received: 12 October 1998 Accepted: 28 January 1999     

血管内皮细胞生长因子与增殖细胞核抗原联合检测用于大肠癌临床预后判定

目的　探讨大肠癌血管内皮细胞生长因子 (VEGF)及增殖细胞核抗原 (PCNA)与大肠癌术后有无潜在性转移及复发的关系。方法　对 5 9例已获确诊的大肠癌石蜡标本作免疫组化SP法染色 ,检测其VEGF及PCNA的表达 ,并与 12例正常大肠组织和 16例大肠腺瘤进行比较。结果　大肠癌VEGF的表达明显高于大肠腺瘤 (P<0 .0 5 ) ;DukesA +B期大肠癌VEGF的表达与DukesC +D期比较 ,差异有显著性 (P<0 .0 5 ) ;术后复发组VEGF的表达明显高于无复发组 (P<0 .0 5 )。增殖活性表达提示 ,大肠癌分化程度越低 ,有淋巴结或肝转移时 ,其PCNA指数增高 ;术后有、无复发者之间 ,其PCNA指数差异有显著性 (P<0 .0 5 )。结论　大肠癌VEGF与PCNA的表达与肿瘤的浸润、转移密切相关。手术时虽然无明显转移灶 ,VEGF阳性及PCNA活性增强时仍可能有潜在的转移存在。     

Variations in the expression of platelet-derived endothelial cell growth factor in human colorectal polyps

Platelet-derived endothelial cell growth factor (PD-ECGF) has been identified to be an angiogenic factor, and a close relationship between the expression of PD-ECGF and tumor development has been postulated. This study was designed to assess both the role of PD-ECGF in human colorectal polyps as well as its relationship to the expression of other oncogenes during colorectal carcinogenesis. One hundred twenty patients with colon polyps who had undergone a polypectomy were studied. The polyps were classified based on the pathological findings as nonneoplastic or sporadic adenoma. The polyps were immunostained for PD-ECGF and vascular endothelial cell growth factor (VEGF), as well as for Ki-67 antigen and p53. The correlations between expression of PD-ECGF and clinicopathologic factors were examined. PD-ECGF was expressed at significant levels only in adenomas: in 4 of the 20 polyps with severe dysplasia (20%), and in 5 of the 20 cases of carcinoma in adenoma (25%). PD-ECGF was not detected in the nonneoplastic polyps and in adenomas with low-grade dysplasia. The intensity of immunostaining for PD-ECGF in adenomas correlated with the expression of Ki-67 antigen (P < 0.001) but not with that of p53. VEGF was not detected in any types of polyps. Angiogenic factors in colorectal adenomas might play an important role in carcinogenesis. The correlated expression of PD-ECGF and Ki-67 antigen suggests that PD-ECGF might not only act as an angiogenic factor, but also as a tumor growth factor. Received: October 6, 1999 / Accepted: March 24, 2000     

Tumour-associated angiogenesis in human colorectal cancer

Tumour angiogenesis is a critical step in the growth, metastatic spread and regrowth of colorectal cancer. Angiogenesis specific to tumour is a complicated process, the mechanisms of which remain unclear. Metastasis of colorectal cancer may result from passive entry into the circulation secondary to the effect of angiogenic factors. The survival and growth of colorectal tumour and thus their metastases are dependent on the balance of endogenous angiogenic and anti-angiogenic factors such that the outcome favours increased angiogenesis. Angiogenesis has become an attractive target for anticancer drug development, based on its important roles in tumour growth, invasion and metastasis. Several growth factors have been identified that regulate angiogenesis in colorectal cancer; the most important of these are vascular endothelial growth factors (VEGF), and of the several angiogenic factors, VEGF expression at the deepest invasive site of tumour is the most statistically significant prognostic indicator in advanced colorectal carcinoma. In this review article, we provide an overview on angiogenic factors and their receptors, and discuss the role of newly identified tumour endothelial markers (TEMs) that are involved in tumour-associated angiogenesis in colorectal cancer.     

The correlation of Ki-67 staining indices with tumour doubling times in regrowing non-functioning pituitary adenomas

Summary In order to improve our ability to predict the regrowth of nonfunctioning pituitary adenomas, we tried to assess the correlation between growth fractions with Ki-67 and PCNA (proliferating cell nuclear antigen) and tumour doubling times in regrowing tumours, and also to find out any difference of growth fractions between the regrowing and the cured cases.In 33 patients with non-functioning pituitary adenomas, 14 cases including 11 with cavernous sinus invasion showed residual tumour on MRI after the operation (regrowing group) and 19 cases had no tumour regrowth on MRI within 5 years after the operation (cured group). Immunocytochemical studies were done with monoclonal antibodies (anti-PCNA, anti-Ki-67: MIB-1). The growth fraction of each tumour was estimated by calculating the ratio of the positive nuclei to the total number of tumour cells with the aid of an image analyser (Mac SCOPE). The tumour doubling times were estimated from serial CT or MRI with the aid of the image analyser (NIH image).Ki-67 staining indices ranged from 0.2% to 1.5% (n = 14, 0.86±0.10%; mean±SEM) in the regrowing group, and from 0.1% to 0.5% (n = 19, 0.23±0.03%) in the cured group. PCNA staining indices of the regrowing group ranged from 0.6% to 24% (n = 14, 3.7±1.6%). In the regrowing group, the tumour doubling times ranged from 200 to 2550 days (930±180 days), and showed a significant inverse correlation with Ki-67 staining indices, but no correlation with PCNA staining indices. The regrowing group showed a significantly higher Ki-67 staining index (n = 14, 0.86±0.10%) than the cured group (n = 19, 0.23±0.03%) (p<0.01).These results indicate that immunocytochemical studies using MIB-1 may be better than those with PCNA for the prediction of regrowth in non-functioning pituitary adenomas. Immunocytochemical study with MIB-1 could lead to the accurate prediction of the rapid regrowing lesions in non-functioning adenomas.     

结直肠癌中F框蛋白2的表达与Ki-67、血管内皮生长因子及预后的关系

目的探讨结直肠癌中F-box蛋白家族成员F框蛋白2（FBXO2）的表达与肿瘤增殖指标（Ki-67）、血管内皮生长因子（VEGF）的表达及预后的关系。 方法采用免疫组织化学MaxVision两步法检测105例结直肠癌组织标本中FBXO2、Ki-67及VEGF的表达情况,统计分析其与临床病理特征及预后的相关性。 结果Ki-67、VEGF和FBXO2阳性表达率分别为53.3%（56/105）、51.4%（54/105）、44.7%（47/105）。Ki-67与结直肠癌的原发灶大小密切相关（P=0.017）,VEGF与结直肠癌临床病理特征无明显相关性,FBXO2与结直肠癌患者的远处转移、AJCC临床分期密切相关（P=0.045、0.027）。Pearson相关分析提示,FBXO2与Ki-67、VEGF的表达呈显著相关（r=0.305、0.223,P=0.002、0.022）,Ki-67与VEGF的表达无相关性（r=0.160,P=0.102）。多因素Cox比例危险模型分析提示,高表达的FBXO2是结直肠癌患者不良预后的独立影响因素（HR=2.183,95%CI=1.075~4.434,P=0.031）。生存分析显示,结直肠癌组织中Ki-67、VEGF及FBXO2高表达的患者生存时间明显低于低表达者,差异有统计学意义（P=0.019、0.036、<0.001）。 结论FBXO2在结直肠癌的发生、发展中起到促癌的作用,是结直肠癌不良预后的独立影响因素,可能机制是通过泛素蛋白酶体途径参与调节结直肠癌的肿瘤增殖活性及新生血管形成。     

Radiosurgery of Residual and Recurrent Vestibular Schwannomas

Summary.  Radiosurgery is either a primary or an adjunctive management approach used to treat patients with vestibular schwannomas. We sought to determine outcomes measuring the potential benefits against the neurological risks in patients who underwent radiosurgery after previous microsurgical subtotal resection or recurrence of the tumour after total resection. Gamma Knife radiosurgery was applied as an adjunctive treatment modality for 86 patients with vestibular schwannomas from April 1992 to August 2001. We evaluated the results of 50 patients who had a follow-up of at least 3.5 years (median 75 months, range 42–114 months). In 16 patients a recurrence of disease was observed after previous total resection. The median treatment volume was 3.4 ccm with a median dose to the tumour margin of 13 Gy. Tumour control rate was 96%. Two tumours progressed after adjunctive radiosurgery. Useful hearing (Gardner-Robertson II) (4 patients (8%)) and residual hearing (Gardner-Roberson III) (10 patients (20%)) remained unchanged in all patients, who presented with it before radiosurgery, respectively. Clinical neurological improvement was observed in 24 patients (46%). Adverse effects comprised transient neurological symptoms and signs (incomplete facial palsy, House-Brackman II/III) in five cases (recovered completely), mild trigeminal neuropathy in four cases, and morphological changes displaying rapid enlargement of a pre-existing macrocyst in one patient and tumour growth in another one. No permanent new cranial nerve deficit was observed.  Radiosurgery appears to be an effective adjunctive method for growth control of vestibular schwannomas and is associated with both a low mortality rate and a good quality of life. Accordingly, radiosurgery is a rewarding therapeutic approach for the preservation of cranial nerve function in the management of patients with vestibular schwannoma in whom prior microsurgical resection failed. Published online July 18, 2002     

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma

OBJECTIVE: To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. MATERIALS AND METHODS: Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27-89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTS: Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. CONCLUSION: Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression.