Hypoxia-inducible factor-1alpha expression and angiogenesis in gastrointestinal stromal tumor of the stomach

Hypoxia inducible factor (HIF)-1 is reported to transactivate expression of vascular endothelial growth factor (VEGF), which is an important angiogenic factor. The aim of this study was to elucidate the clinical significance of HIF-1alpha expression in gastrointestinal stromal tumors (GIST). Specimens obtained from 53 patients who underwent surgical resection for GIST of the stomach were used in this study. Specimens were examined immunohistochemically for HIF-1alpha, VEGF, and Ki-67 expression. Tumor microvessel density (MVD) was determined immunohistochemically with anti-CD31 antibody and was estimated by averaging the counts from three high-power fields in the area showing the greatest neovascularization. HIF-1alpha expression was detected in 17 (32.1%) of 53 lesions and was correlated significantly with tumor size, liver metastasis, VEGF expression, and MVD. Prognosis was significantly poorer in patients with tumors expressing HIF-1alpha than in patients with tumors lacking HIF-1alpha expression. HIF-1alpha may play a role in angiogenesis and tumor progression of GIST through regulation of VEGF.     

Ki-67、VEGF在胃肠间质瘤中表达及与MVD的相关性

目的:探讨Ki-67和VEGF在胃肠间质瘤中的表达及与临床病理因素的关系,VEGF、微血管密度(MVD)和细胞增殖之间的相关性。方法:采用免疫组化S-P法检测44例胃肠间质瘤组织中Ki-67、VEGF表达及计数MVD值和Ki-67PI。结果:VEGF、Ki-67在GIST组织中阳性表达分别为77.3%、63.6%,VEGF、Ki-67表达在不同大小的肿块之间有统计学差异(P<0.01);MVD值和Ki-67PI在VEGF阳性和阴性组的比较有统计学差异(P<0.01);VEGF、MVD和Ki-67PI之间呈显著正相关(相关系数分别为0.26、0.44和0.84,P<0.01)。结论:VEGF促进GIST组织中的新生血管形成,为肿瘤组织提供了丰富的血液和营养,并使细胞增殖活性增强,促进肿瘤细胞的增殖、肿瘤的生长、发展和转移;Ki-67PI为GIST的预后判断提供了比较客观的依据。     

Carbonic anhydrase IX in early-stage non-small cell lung cancer.

PURPOSE: Tumor hypoxia is associated with poor prognosis and increased tumor aggressiveness. Carbonic anhydrase (CA) IX, an endogenous marker for tumor hypoxia, catalyzes the hydration of carbon dioxide into carbonic acid and contributes to the pH regulation of tumor cells. Therefore, CA IX might allow tumors to acclimate to a hypoxic microenvironment, promoting tumor cell proliferation. We hypothesized that CA IX expression is related to tumor cell proliferation and poor disease-free survival in patients with early-stage non-small-cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: CA IX expression was measured in 75 resected NSCLC tumors to assess prognostic implications for disease-free survival. The relationship of CA IX expression with microvessel density (MVD) and proliferation (Ki-67) index was assessed via colocalization analysis. RESULTS: All patients had operable NSCLC (stage I, 58; stage II, 17). CA IX expression was present in 54 (72%) of 75 patients and was associated with tumor necrosis (P < 0.05). CA IX-positive tumor areas showed greater cell proliferation as measured by Ki-67 index (P < 0.05) and less MVD (P < 0.05) than did CA IX-negative areas in colocalization analysis. The percentage of CA IX-positive tumor cells was significantly related to postoperative recurrence and poor disease-free survival (P < 0.05). Ki-67 index and pathologic stage were also independent prognostic factors for worse disease-free survival (P < 0.05). CONCLUSIONS: CA IX expression of tumor cells may be an indicator for poor disease-free survival in early-stage NSCLC.     

膀胱移行细胞癌的CT表现与Ki-67、VEGF和MVD表达的相关性

[目的]探讨膀胱移行细胞癌（BTCC）的CT表现与Ki-67、血管内皮生长因子（VEGF）和微血管密度（MVD）表达的关系。[方法]对41例经手术病理证实的BTCC，采用LDP免疫组化法，检测肿瘤标本中Ki-67、VEGF和MVD的表达，并分析其与术前CT征象的关系。[结果]Ki-67LI与VEGF、Ki-67LI与MVD、VEGF与MVD呈显著性正相关（r值分别为0．548、0．603、0．705，P均〈0．001）。Ki-67LI、VEGF和MVD表达与肿瘤呈分叶状、肿瘤多发、膀胱壁增厚、浆膜受侵、邻近器官受累等CT征象均有关（P〈0．05）。[结论]BTCC的CT征象与Ki-67LI、VEGF和MVD表达密切相关，当肿瘤有分叶征、肿瘤多发、相邻膀胱壁增厚、浆膜层受侵、邻近器官受累等CT征象时，提示肿瘤可能有较高的恶性程度、浸润能力及较差的预后。     

Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: a population-based endometrial carcinoma study.

PURPOSE: For endometrial carcinoma patients, there is a need for improved identification of high-risk groups that may benefit from postoperative adjuvant therapy. We therefore studied the prognostic impact of markers for cell proliferation, cell-cycle regulation, and angiogenesis among endometrial carcinoma patients in a population-based setting. PATIENTS AND METHODS: All patients diagnosed with endometrial carcinoma between 1981 and 1985 in Hordaland County, Norway, were studied. The median follow-up for the survivors was 11.5 years (range, 8 to 15 years), with no patient lost because of insufficient follow-up information. Paraffin-embedded tumor tissue, available in 96% of the cases (n = 142), was studied immunohistochemically for microvessel density (MVD) and expression of Ki-67, p53, and p21 proteins. We used the hot spot method for calculation of MVD, and expression of Ki-67 and p21 protein, because this approach may increase the probability of detecting small aggressive clones of possible prognostic relevance. The importance of these tumor markers was investigated in univariate survival analyses and Cox regression analysis. RESULTS: The majority of traditional clinicopathologic variables was significantly associated with the tumor biomarkers. Age, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, histologic grade, MVD, as well as Ki-67, p53, and p21 protein expression, all significantly influenced survival in univariate analyses (P < or = .05). In the Cox regression analysis, age, FIGO stage, MVD, Ki-67 expression, and p53 expression were the only variables with independent prognostic impact (P < or = .05), whereas histologic type, histologic grade, and p21 expression had no independent influence. A group of high-risk patients with more than one unfavorable marker was identified. CONCLUSION: In addition to age and FIGO stage, MVD, Ki-67, and p53 protein expression showed an independent prognostic impact. Thus, information derived from routine histologic specimens identified a subgroup of high-risk endometrial carcinoma patients in this population-based study.     

Expression of Ki-67, p53 and VEGF in Pediatric Neuroblastoma

Background: Neuroblastoma (NB), is a neuroectodermal tumor derived from neural crest cells, and it is thesecond most common pediatric malignant tumor. The biological and clinical behavior of NB is very heterogeneous.This study was conducted to evaluate the expression of Ki-67, p53 and VEGF markers in tissues obtained fromNB patients with different histologic types and stage. Materials and Methods: Tissue microarray (TMA) blockswere constructed from paraffin blocks of the NB tissues. Immunohistochemical staining was performed on TMAsections to detect the expression of Ki-67, p53 and VEGF markers. The association between the expression ofthese markers and clinicopathological parameters were then analyzed. Results: We had 18 patients with NB,one patient with ganglioneuroblastoma (GNB) and one with ganglioneuroma. Ki-67 was expressed in 13 (65%)tumors, and negatively correlated with age, prognosis, histologic type and stage of NB (all p<0.05). High andmoderate expression of VEGF was found in 5% (1/20) and 65% (13/20) of the tumors, respectively; and it waspositively correlated with age, prognosis and histologic types (all p<0.05) and negatively correlated with MKI(mitosis-karyorrhexis index). p53 expression was observed in 10% (2/20) of the tumors, which showed a relativecorrelation with MKI (p value=0.07). Conclusions: VEGF as a candidate for anti-angiogenic targeted therapywas correlated with the development and progression of NB; therefore, VEGF along with Ki-67 can serve as avaluable marker for the prognosis of this tumor type.     

The prognostic value of p53 and c-erbB-2 expression, proliferative activity and angiogenesis in node-negative breast carcinoma

AIMS AND BACKGROUND: p53, c-erbB-2 and Ki-67 protein expression and microvessel density (MVD) determined by CD34 antibody were evaluated by immunohistochemistry and their correlation with clinicopathological parameters including estrogen (ER) and progesterone (PR) receptor status and survival were investigated in patients with axillary lymph node-negative infiltrating ductal breast carcinoma. METHODS: The study population consisted of 47 patients with axillary lymph node-negative infiltrating ductal breast carcinoma. RESULTS: p53 and c-erbB-2 expression was detected in 36.2% and 31.9% of patients, respectively. Median Ki-67 expression was 10%. There were no statistically significant differences in the distribution of p53, Ki-67 and c-erbB-2 protein expression in relation to the age of the patients or to the size, histological grade or ER and PR status of the tumors. p53 protein expression correlated positively with c-erbB-2 and Ki-67 protein expression (P < 0.05). The mean MVD was 63.65 +/- 29.1 and it correlated positively with histological grade and Ki-67 expression (P < 0.05). Survival analysis revealed that age, tumor size, p53 and c-erbB-2 expression and PR status had no significant prognostic impact, whereas histological grade, proliferative activity and angiogenic activity were significant prognostic factors. Although ER-positive patients had a statistically significant overall survival advantage, the difference in disease-free survival was not significant. CONCLUSION: In axillary lymph node-negative breast carcinoma the histological grade and the proliferative and angiogenic activity of the tumor could be useful prognostic indicators.     

VEGF and bFGF expression and microvessel density of maxillary sinus squamous cell carcinoma in relation to p53 status, spontaneous apoptosis and prognosis

We have previously reported that p53 mutations, loss of bax expression or decreased spontaneous tumor apoptosis were associated with poorer prognoses in maxillary sinus squamous cell carcinoma (SCC)(Cancer 94: 1968-1980, 2002). In the present study, we analyzed tumor angiogenesis monitored by expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and tumor microvessel density, in correlation with p53 status, spontaneous apoptosis or disease prognosis in the same group of 70 maxillary sinus SCC patients. Tumor biopsy specimens obtained prior to initiation of treatment were examined for expression of VEGF and bFGF and tumor microvessel density using immunohistological methods. Average vessel density (AVD) (range: 3-75; median: 25) and maximum vessel density (MVD) (range: 4-125; median: 53) were assessed by the number of microvessels stained with anti-CD31 mAb in tumor lesions. VEGF was expressed in 35 (50%) of 70 patients and bFGF was in 43 (61%). Patients with VEGF expression showed significantly higher levels of MVD than those without VEGF expression (57 vs. 38; P=0.019). The VEGF expression was observed more frequently in patients with p53 overexpression and/or mutation than in those with normal p53 status (P=0.048). The MVD inversely correlated with the apoptotic index (AI) defined as the number of single stranded (ss)-DNA-positive cells per 1000 tumor cells (r= -0.23; P=0.022). Patients with neck lymph node and/or distant metastases after surgery showed significantly higher levels of MVD than patients without any metastasis (64 vs. 42; P=0.048). Low histological effectiveness of radiochemotherapy correlated with bFGF expression (P=0.0059). To clarify actual prognostic factors for maxillary sinus SCC, we selected 57 patients treated uniformly with preoperative radiochemotherapy followed by maxillectomy. Kaplan-Meier analysis showed that survival was significantly worse in patients with high MVD (> or =80) than in those with low MVD (<80) (P=0.042). These data suggest that the VEGF expression in association with the p53 overexpression and/or mutations may cause increased microvascularity, decreased spontaneous apoptosis or metastases, while the bFGF expression may be associated with resistance to radiochemotherapy, thereby resulting in poorer prognoses in maxillary sinus SCC. VEGF and bFGF expression and tumor microvessel density in tumor lesions were analyzed in 70 patients with maxillary sinus squamous cell carcinoma. The VEGF expression dependent of p53 overexpression and/or mutations was associated with angiogenesis, decreased spontaneous tumor apoptosis and metastases, while the bFGF expression was associated with resistance to radiochemotherapy, resulting in poor prognosis.     

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.     

Clinicopathologic Features of Breast Carcinomas Classified by Biomarkers and Correlation with Microvessel Density and VEGF Expression: A Study from Thailand

Background: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD),vascular endothelial growth factor (VEGF) expression and clinical features. Materials and Methods: Onehundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminalA [estrogen receptor (ER)+, HER2-, Ki-67≤14%], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%],HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factorreceptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGFand CD31 immunoperoxidase. Results: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56%with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas,3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14,20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degreeof tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression andsurvival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53and vimentin and decreased overall survival compared with nonTN. Conclusions: The distribution of breastcancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high gradecharacter of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. Nosignificant elevation of MVD or VEGF expression was apparent.     

Clinical significance of angiogenesis in rectal carcinoid tumors

This study was designed to examine angiogenesis in rectal carcinoid tumors in relation to the clinicopathologic features. Seventy-seven rectal carcinoid tumors were studied clinicopathologically and experimentally. Cellular proliferation and microvessel density (MVD) were examined immunohistochemically. We used the antibodies MIB-1 for Ki-67, DO7 for p53, and NU-4A1 for CD34 expression in this study. Ki-67 labeling index (LI) of all lesions was below 3%, and the median Ki-67 LI of all lesions was 0.68+/-0.70% (mean +/- SD). A correlation was recognized between tumor size, metastasis and Ki-67 LI (p<0.05). Median MVD of all lesions was 25.9+/-13.1 (mean +/- SD). MVD was correlated with the tumor size (p<0.01), presence of depression (p<0.01), lymphatic (p<0.01) or venous (p<0.05) invasion, and existence of metastasis (p<0.01). But there was no significant relationship between MVD and Ki-67 LI. p53 protein was detected sporadically in only 1 case (1.3%) demonstrating both liver and lymph node metastases. Rectal carcinoid tumors are slow-growing tumors with a lower proliferative activity. Angiogenesis plays an important role in progression of rectal carcinoid tumors independent of the cellular proliferative activity.     

Predictive value of Smac, VEGF and Ki-67 in rectal cancer treated with neoadjuvant therapy

The present study aimed to identify whether second mitochondria-derived activator of caspase (Smac), vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (Ki-67) expression in pre-treatment tumor biopsies are useful predictive markers of tumor response in patients with rectal cancer undergoing pre-operative chemoradiotherapy (CRT). Paraffin-embedded tissues obtained before and after therapy were evaluated by immunohistochemical staining for Smac, VEGF and Ki-67. The study evaluated the correlation of Smac, VEGF and Ki-67 immunoreactivity in tumor biopsies before treatment of tumor response to pre-operative CRT. Regarding Smac, patients with a favorable response to neoadjuvant CRT had higher pre-therapy levels (p=0.011). The level of Smac expression decreased after neoadjuvant therapy (p=0.044). However, VEGF expression was found to be negatively and significantly correlated with a favorable tumor response to neoadjuvant CRT (p=0.010). A transient increase in VEGF expression was detected in the resected specimens following neoadjuvant therapy (p=0.030). In addition, tumors with a low Ki-67 labeling index (Ki-67-LI) expression were found to be more sensitive to neoadjuvant therapy than those with a high expression of Ki-67-LI (p=0.034). In contrast to VEGF, the Ki-67 expression level decreased after neoadjuvant therapy. Smac, VEGF and Ki-67 expression levels, assessed immunohistochemically from pre-treatment tumor biopsies, may be useful predictive markers of rectal tumor response to pre-operative CRT.     

C-erbB-2、p53、Ki-67及VEGF在乳腺癌中的表达及相关性

目的探讨C-erbB-2、p53、Ki-67及VEGF在乳腺癌组织中的表达及其与乳腺癌临床病理特征之间的相关性。方法采用免疫组化SP法检测72例乳腺癌组织中C-erbB-2、p53、Ki-67及VEGF表达情况,并结合临床病理特征进行相关性分析。结果乳腺癌患者C-erbB-2、p53、Ki-67及VEGF阳性表达率分别为47.2%、48.6%、56.9%、65.3%。C-erbB-2、p53表达与淋巴结转移、雌激素受体、孕激素受体相关(P<0.05);Ki-67、VEGF与肿瘤直径、淋巴结转移相关(P<0.05);ER和PR呈正相关(P<0.05);C-erbB2与ER、PR呈负相关(P<0.05);p53与ER和PR呈负相关(P<0.05);p53、Ki-67、VEGF之间均呈正相关(P<0.05)。结论 C-erbB-2、p53、Ki-67及VEGF检测对判断乳腺癌预后有重要意义。     

Tissue factor expression correlates with tumor angiogenesis and invasiveness in human hepatocellular carcinoma.

PURPOSE: Recent studies have shown that tissue factor (TF) may be involved in tumor angiogenesis and metastasis. The role of TF in hepatocellular carcinoma (HCC) was unknown. This study evaluated whether TF expression correlates with microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, tumor invasiveness, and prognosis in human HCC. EXPERIMENTAL DESIGN: Tissue samples were obtained from 58 specimens of resected HCC. Immunohistochemical expression of TF was examined, and tumor MVD was evaluated using CD34 as the endothelial marker. TF and VEGF protein levels in the tumor cytosol were quantified by ELISA. Clinicopathologic and follow-up data of patients were prospectively collected. RESULTS: The immunohistochemical expression of TF in the tumors correlated significantly with tumor MVD (P = 0.002). The median cytosolic TF protein level in the tumors was 720 pg/mg total protein (range, 67-2406 pg/mg total protein). A significant positive correlation was found between TF and VEGF levels in the tumor cytosol (r = 0.475, P < 0.001). High tumor cytosolic TF level was associated with venous invasion (P = 0.004), microsatellite nodules (P = 0.024), unencapsulated tumor (P = 0.007), and advanced tumor stage (P = 0.010). A higher than median tumor cytosolic TF level was an independent predictor of poor survival (risk ratio, 1.836; 95% confidence interval 1.130-5.312, P = 0.023). CONCLUSIONS: This study shows that TF is related to tumor angiogenesis and invasiveness in HCC. Evaluation of tumor TF expression may be useful as a prognostic indicator in patients with HCC.     

Clinicopathological Significance of L-type Amino Acid Transporter 1 (LAT1) Expression in Patients with Adenoid Cystic Carcinoma

The expression of L-type amino acid transporter 1 (LAT1) is correlated with tumor cell growth and survival. However, the clinicopathological significance of LAT1 expression in adenoid cystic carcinoma (ACC) remains to be elucidated. The aim of this study is to investigate the clinicopathological significance of LAT1 expression in ACC. A total of 30 patients with ACC were retrospectively reviewed. Tumor sections were stained by immunohistochemistry for LAT1, p53, and CD98, and cell proliferation and microvessel density (MVD) were determined by Ki-67 and CD34, respectively. High LAT1 and CD98 expression were observed in 27 % (8/30) and 23 % (7/30) of samples, respectively (p?>?0.999). The high expression of LAT1 was significantly correlated with cell proliferation (Ki-67) and the cell cycle regulator p53. By univariate analysis, solid histological pattern, maxillary tumor site, LAT1, CD98, Ki-67 and p53 were significantly associated with poor prognosis. Multivariate analysis demonstrated that the high expression of LAT1 was an independent prognostic factor for predicting poor prognosis after surgical resection. LAT1 is a promising clinical marker to predict the outcome after surgery in patients with ACC.     

Ki-67在CD117阳性的中、高危险度胃肠道间质瘤中的表达及其意义

 目的　探讨Ki-67在CD117阳性的中、高危险度胃肠道间质瘤（GIST）中的表达及其临床意义。方法　检测Ki-67在CD117阳性的中危险度（GIST）18例、高危险度GIST 25例中的表达,与随访结果对照,并与极低危险度和低危险度组33例比较,分析Ki-67指数（LI）与危险度的关系。结果　中、高危险度组随访40例,其中26例健在,高危组7例、中危组5例死于GIST,另2例死于其他原因。Ki-67 LI> 5 %在危险度中、高组与极低和低组间表达差异有统计学意义（P＜0.01）,Ki-67 LI还与核分裂象计数（MI）（＞5／50 HPF）、肿瘤大小（＞5 cm）相关（P＜0.05）,与部位无关（P＞0.05）。结论　Ki-67 LI＞5 %与肿瘤大小＞5 cm、MI＞5／50 HPF一起可作为CD117阳性的GIST中、高危险度的有用评价指标。     

海锦窦侵袭性垂体腺瘤的MRI和生物学标志的临床实验研究(英文)

目的探索 MRI 和分子生物学标志在评价垂体腺瘤侵袭性行为中的作用。方法对45例垂体腺瘤患者术前的 MRI、术中所见结果和术后组织标本免疫组化分析结果进行前瞻性研究。结果 MRI 预测海绵窦侵袭的敏感性60%,特异性85%,阳性预测值83%,阴性预测值63%;免疫组化分析侵袭性垂体腺瘤的MVD、Ki-67标记指数、VEGF 和 MMP-9表达明显高于非侵袭性垂体腺瘤(统计学分析 P 值分别为:<0.001、=0.039、<0.001和<0.001);但侵袭性垂体腺瘤的 nm23表达却明显低于非侵袭性垂体腺瘤(P<0.001);另外,统计学分析 c-myc 标记指数和 Bcl-2表达与垂体腺瘤的侵袭性无关(P=0.061和 P=0.201)。结论增强扫描的 MRI 对海绵窦侵袭性垂体腺瘤的术前判断有一定参考价值;MVD、Ki-67标记指数、VEFG、MMP-9和 nm23表达与垂体腺瘤的侵袭性有关。     

海锦窦侵袭性垂体腺瘤的MRI和生物学标志的临床实验研究

目的探索MRI和分子生物学标志在评价垂体腺瘤侵袭性行为中的作用。方法对45例垂体腺瘤患者术前的MRI、术中所见结果和术后组织标本免疫组化分析结果进行前瞻性研究。结果MRI预测海绵窦侵袭的敏感性60％,特异性85％,阳性预测值83％,阴性预测值63％;免疫组化分析侵袭性垂体腺瘤的MvD、Ki-67标记指数、VEGF和MMP-9表达明显高于非侵袭性垂体腺瘤(统计学分析P值分别为：<0．001、=0．039、<0．001和<0．001);但侵袭性垂体腺瘤的nm23表达却明显低于非侵袭性垂体腺瘤(P<0．001);另外,统计学分析c-myc标记指数和Bcl-2表达与垂体腺瘤的侵袭性无关(P=0．061和P=0．201)。结论增强扫描的MRI对海绵窦侵袭性垂体腺瘤的术前判断有一定参考价值;MVD、Ki-67标记指数、VEFG、MMP-9和nm23表达与垂体腺瘤的侵袭性有关。     

Preoperative treatment with tegafur suppositories enhances apoptosis and reduces the intratumoral microvessel density of human colorectal carcinoma

BACKGROUND: This study examined the effect of tegafur, a depot of 5-fluorouracil, in human colorectal carcinomas in terms of apoptosis, cell proliferation, and expression of p53 gene and angiogenesis-related molecules. METHODS: A total of 32 patients with colorectal carcinoma were divided into 2 groups; 20 patients received tegafur suppositories (TS) at 1 g/day for 14 days before surgery, and 12 patients did not receive any chemotherapy. Surgically removed specimens were examined immunohistochemically for Ki-67, CD34, p53, p21, Bax, vascular endothelial growth factor (VEGF), and thymidine phosphorylase (dThdPase). Apoptotic tumor cells were visualized by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) procedure. RESULTS: The mean percentage of apoptotic index (AI) was 6.9 +/- 1.2 in the 20 TS-treated tumors and 4.4 +/- 1.0 in the 12 nontreated tumors (P < 0.001). In contrast, the mean percentage of Ki-67 labeling index (KI) became significantly lower in the former group (P < 0.05). The frequency of p21 expression was significantly higher in the TS-treated group than in the nontreated group (P < 0.05), whereas no difference was detected in p53 and Bax expression between the two groups. The mean intratumoral microvessel density was 47.8 +/- 19.8 in the TS-treated tumors and 66.8 +/- 16.5 in the nontreated tumors (P < 0.01). The frequency of dThdPase expression, but not of VEGF expression, became significantly lower with the TS treatment. p53 expression did not correlate with AI, KI, IMV density, or the expression of VEGF, p21, or Bax, except for dThdPase, which was significantly higher in the 18 p53 positive tumors (P < 0.05). CONCLUSIONS: Preoperative TS treatment enhances apoptosis and suppresses angiogenesis of colorectal carcinomas in a p53-independent manner.     

Association of Ki-67, p53, and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion

: The study was conducted to determine whether immunohistochemical analysis of Ki-67, p53, and bcl-2 in patients with non-small-cell lung cancer is associated with a higher rate of brain metastases and whether the intrapatient expression of these biomarkers (in the primary tumors vs. brain lesions) is similar.

: At the M. D. Anderson Cancer Center, tumors from 29 case patients with primary lung tumor and brain metastasis and 29 control patients with primary lung tumor but no brain metastasis were resected and examined for immunohistochemical expression. Ki-67, p53, and bcl-2 were analyzed in resected primary lung, lymph node, and metastatic brain tumors. Each control patient was matched by age, gender, and histology to a patient with brain metastasis.

: No significant differences in patient survival characteristics were detected between the case group and control group. Also, difference in patient outcome between the two groups was not generally predicted by biomarker analysis. However, when the groups were combined, the biomarker analysis was predictive for certain patient outcome end points. Using median values as cutoff points between low and high expression of biomarkers, it was observed that high expression of Ki-67 (>40%) in lung primaries was associated with poorer disease-free survival (p = 0.04), whereas low expression of p53 in lung primaries was associated with poorer overall survival (p = 0.04), and these patients had a higher rate of nonbrain distant metastases (p = 0.02). The patients with brain metastases were particularly prone to developing nonbrain distant metastases if the percentage of p53-positive cells in brain metastases was low (p = 0.01). There was a positive correlation in the expression of Ki-67 (p = 0.02)(r² = 0.1608), as well as p53 (p < 0.001) (r² = 0.7380), between lung primaries and brain metastases. Compared to Ki-67 and p53, bcl-2 was the least predictive.

: Differences in biomarker expression between the case and control groups did not serve as significant predictors of brain metastasis or patient survival. There was a strong correlation between lung primary biomarker expression and brain metastasis expression for Ki-67 and p53. Univariate analysis showed that low p53 and high Ki-67 expression predicted poor prognosis. This study shows that there may be a strong correlation between biomarker expression in non-small-cell lung cancer primary tumors and their brain metastases.