Urothelial carcinoma with an inverted growth pattern can be distinguished from inverted papilloma by fluorescence in situ hybridization, immunohistochemistry, and morphologic analysis

Inverted papilloma of the urinary bladder and urothelial carcinoma with an inverted (endophytic) growth pattern may be difficult to distinguish histologically, especially in small biopsies. The distinction is important as these lesions have very different biologic behaviors and are treated differently. We examined histologic features and undertook immunohistochemical staining and UroVysion fluorescence in situ hybridization (FISH) to determine whether these methods could aid in making this distinction. We examined histologic sections from 15 inverted papillomas and 29 urothelial carcinomas with an inverted growth pattern. Each tumor was stained with antibodies to Ki-67, p53, and cytokeratin 20. In addition, each tumor was examined with UroVysion FISH for gains of chromosomes 3, 7, and 17 and for loss of chromosome 9p21 signals. None of the inverted papillomas stained positively for Ki-67 or for cytokeratin 20. Only 1 of 15 inverted papillomas stained positively for p53. By contrast, 66%, 59%, and 59% of urothelial carcinomas with an inverted growth pattern stained positively for Ki-67, p53, and cytokeratin 20, respectively. Only 3 of the urothelial carcinomas stained negatively for all 3 immunohistochemical markers. UroVysion FISH produced normal results for all cases of inverted papilloma. By contrast, 21 of 29 cases (72%) of urothelial carcinoma with an inverted growth pattern demonstrated chromosomal abnormalities typical of urothelial cancer and were considered positive by UroVysion FISH criteria. Morphologic features, as well as immunohistochemical stains (including stains for Ki-67, p53, and cytokeratin 20) and/or UroVysion FISH can help to distinguish inverted papilloma from urothelial carcinoma with an inverted growth pattern.     

Ki-67和P53的表达与原发性上尿路尿路上皮癌术后发生膀胱癌的关系

目的 研究肿瘤标记物Ki-67和P53在上尿路尿路上皮癌中的表达情况,结合传统临床病理参数分析原发性上尿路肿瘤根治术后发生膀胱癌的危险因素.方法 回顾性分析1 15例原发性上尿路肿瘤根治术后的临床病理资料.免疫组织化学检测肿瘤标记物Ki-67和P53蛋白在尿路上皮癌中的表达情况,联合传统临床病理参数多因素分析上尿路肿瘤术后发生膀胱癌的危险因素.结果 Ki-67在肿瘤标本中正常表达率44.87％ (48/107),过表达率55.13％(59/107).P53在肿瘤标本表达阴性率34.86％ (38/109),弱阳性率25.69％ (28/109),阳性率17.43％(19/109),强阳性率22.02％ (24/109).Ki-67和P53表达均与肿瘤分级有关(P =0.003).原发性上尿路尿路上皮癌术后膀胱癌的发生率为11.30％(13/115),平均随访时间为48.50个月(7～130个月).多因素生存分析发现患病年龄＞65岁(P=0.040),输尿管下段肿瘤(P =0.008)和Ki-67低表达(P=0.041)可作为膀胱癌出现的预测因素.结论 Ki-67正常表达可作为原发性上尿路尿路上皮癌术后发生膀胱癌的独立危险因素.     

奥曲肽对人胆囊癌裸鼠皮下种植瘤的抑制作用

目的：探讨奥曲肽对人胆囊癌裸鼠皮下种植瘤生长的影响及其机制。方法：建立人原发性胆囊癌皮下种植瘤裸鼠模型。将荷瘤裸鼠随机分成实验组和对照组各9只,分别自腹腔注射奥曲肽100 μg/(kg·d)和生理盐水,用药共6周。观察两组种植瘤生长情况。流式细胞术测定肿瘤细胞凋亡率,免疫组化法检测p53,bcl-2,Ki-67的表达。结果：实验组裸鼠皮下种植瘤的生长明显受到抑制,实验组肿瘤重量显著低于对照组［(0.99±0.54)g vs. (1.58±0.51)g,t=2.38,P<0.05］,抑瘤率达37.3%,肿瘤细胞的凋亡率显著高于对照组［(7.76±2.62)% vs. (4.27±1.50)%,P<0.01］;实验组的p53,bcl-2,Ki-67阳性细胞百分率均低于对照组［(79.48±5.22)%vs. (87.13±8.26)%,(46.72±6.40)%vs.(53.85±7.72)%,(37.56±6.67)%vs(45.45±8.73)%,P均<0.05］。结论：奥曲肽能抑制人胆囊癌裸鼠皮下种植瘤的生长,可能系通过抑制肿瘤细胞增殖、诱导凋亡的机制而实现的。     

靶向表皮生长因子受体和血管内皮生长因子受体-2治疗多形性胶质母细胞瘤

目的 观察靶向表皮生长因子受体(EGFR)的单克隆抗体C225和靶向血管内皮生长因子受体-2(VEGFR-2)的单克隆抗体DC101单独或联合应用后对人脑多形性胶质母细胞瘤(GBM)裸小鼠脑内移植瘤的疗效.方法 将40只荷瘤鼠随机分为磷酸盐缓冲液(PBS,0.1 ml/20 g·次)、C225(50 mg/kg·次)、DC101(40 mg/kg·次)及C225+DC1O1(50+40 ms/ks·次)等4组,10只/每组,2d1次腹腔用药或PBS,共4次.治疗后观察移植瘤微血管密度(MVD)、体积、形态、增殖和凋亡变化.结果 与对照组比较,DCl01组移植瘤MVD减少了64.O%.体积下降了59.7%,增殖指数下降了53.2%,凋亡指数增加了66.7%(P＜0.05),但肿瘤侵袭性增强;C225组肿瘤侵袭性降低,但对移植瘤MVD、体积、增殖和凋亡无影响(P＞0.05);C225+DC101组移植瘤MVD减少了68.0%,体积下降了62.9%,增殖指数下降了56.4%,凋亡指数增加了75.0%(P＜0.05),肿瘤侵袭性明显下降.结论 DC101抑制血管生成同时增加了肿瘤的侵袭性,而C225能降低肿瘤侵袭性.联合用药不仅抑制GBM移植瘤生长还降低肿瘤侵袭能力.     

Establishment of primary human meningiomas as subcutaneous xenografts in mice

Meningiomas are the most frequently occurring benign central nervous system tumours. We determined whether a subcutaneous animal model of meningioma was feasible by implanting fresh meningioma tissue from six patients into 60 athymic (nude) mice, either as tissue blocks (38 mice) or as cell suspensions (22 mice). The tumour take-rates were 74% (block) and 50% (suspension), and the xenografts retained the original tumour grade and subtype morphology by light microscopy. Comparison of cell proliferation markers in xenografts and original tumours gave similar immunohistochemical score rates for Ki-67, but not for PCNA. With the exception of one atypical tumour surgical specimen, all tumours lacked p53 immunopositivity. Transmission electron microscopy of sections of tumour xenografts revealed ultrastructural features, including desmosomes and desmosome-like structures, characteristic of well-differentiated meningiomas. The xenografts grew progressively with a volume increase of more than 10-fold over 6-11 months and an apparent doubling time of 16 weeks. This study demonstrates the utility of the subcutaneous meningioma xenograft as a model for further biological and therapeutic studies.     

膀胱尿路上皮癌中S-100、p53和Ki-67的表达及临床意义

目的：研究膀胱尿路上皮癌中S-100、p53和Ki-67的表达及临床意义。方法：采用免疫组织化学SP法检测60例膀胱尿路上皮癌及15例正常膀胱组织中S-i00蛋白、p53和Ki-67的表达情况。结果：S-100、p53和Ki-67在膀胱尿路上皮癌中的表达均高于其在正常膀胱黏膜中的表达。膀胱尿路上皮癌组织中S-100阳性表达随着肿瘤病理分级、临床分期的升高而降低;p53与Ki-67阳性表达率随肿瘤病理分级、临床分期的升高而升高;S-100低表达和p53与Ki-67高表达与术后复发密切相关。结论：联合检测S-100、p53及Ki-67的表达可以作为判断膀胱尿路上皮癌生物学行为及预后的重要指标。     

Proliferation index of nonfunctioning pituitary adenomas: correlations with clinical characteristics and long-term follow-up results

OBJECTIVE: The recurrence of nonfunctioning pituitary adenomas (NFPAs) after surgical removal is common. The aim of our study was to investigate and correlate the growth fraction of NFPAs with clinical characteristics and long-term follow-up results. METHODS: Tumor specimens were obtained from 101 consecutive patients with NFPAs (48 female patients and 53 male patients; mean age, 52.0 +/- 1.5 yr). Specimens were immediately fixed in 10% buffered formalin and then embedded in paraffin. The Ki-67 antigen was assessed by immunocytochemical analysis using the monoclonal antibody MIB-1. The Ki-67 antigen labeling index (LI) was determined by counting a total of at least 1,000 neoplastic nuclei. RESULTS: The mean Ki-67 LI for the 101 patients was 2.4 +/- 0.3% (range, 0-23.0%). Only age at surgery was inversely correlated with the Ki-67 LI; sex, maximal tumor diameter, and invasiveness into the cavernous sinuses did not significantly affect the Ki-67 LI. The mean follow-up period was 39.7 +/- 2.1 months. During follow-up monitoring, 23 patients experienced tumor recurrence, after a mean period of 28.6 +/- 4.8 months. Invasiveness of the tumor on preoperative magnetic resonance imaging scans was the strongest predictor of late tumor recurrence, followed by previous pituitary surgery, younger age, and lack of postoperative radiotherapy. The Ki-67 LI had no independent prognostic value. CONCLUSION: Our study suggests that the clinical characteristics of patients with NFPAs, except for age at surgery, are not correlated with the Ki-67 LI. Moreover, the Ki-67 LI does not seem to provide independent information to identify patients at high risk for tumor recurrence.     

Ki-67 expression and prognosis for smokers with resected stage I non-small cell lung cancer

BACKGROUND: The cigarette smoking status of patients before surgery is an important prognostic factor in evaluation of stage I non-small cell lung cancer, and the proliferative activity of lung tumors is also related to the patient's prognosis. This study evaluates relationships between various clinicopathologic factors, including tumor proliferative activity and smoking status, and the patient's prognosis in stage I non-small cell lung cancer. METHODS: One hundred eighty-seven stage I adenocarcinoma and squamous cell carcinoma cases were evaluated. The patients underwent complete resection between 1988 and 1993 at Chiba University Hospital. Expression levels of Ki-67 nuclear antigen, p53 protein, and retinoblastoma protein were determined immunohistochemically, and postoperative survival rates for patients in the categories of clinicopathologic factors were estimated. RESULTS: The mean Ki-67 labeling index (LI) for all cases was 19.3%. Labeling index values were significantly higher in squamous cell carcinoma than in adenocarcinoma (p < 0.0001). Postoperative survival of adenocarcinoma patients was significantly related to the LI values and to the patient's smoking status (p = 0.0164 and 0.0268, respectively). The LI values were also related to smoking status and the extent of histologic differentiation (p = 0.0112 and p < 0.0001, respectively). For non-smoking adenocarcinoma patients, higher LI values were associated with abnormalities in p53 expression (p = 0.0048). Retinoblastoma protein abnormalities were not related to LI values. CONCLUSIONS: In smokers with stage I pulmonary adenocarcinoma, tumor proliferative activity and smoking status before surgery were important prognostic determinants. The LI values were related to several clinicopathologic factors.     

人胆管癌CD24+ CD44+ EpCAMhigh细胞亚群的分选及其肿瘤干细胞样特性的鉴定

目的 检测及分选人胆管癌中的CD24+ CD44+ EpCAMhigh细胞亚群,探讨其是否具有肿瘤干细胞样生物学特性.方法 流式细胞术检测6例人胆管癌中CD24、CD44、EpCAM的表达率;取2例人胆管癌新鲜标本种植到NOD/SCID鼠皮下,建立荷人胆管癌小鼠模型.流式细胞术分选CD24+ CD44+ EpCAMhigh亚群细胞,NOD/SCID鼠移植瘤试验鉴定其成瘤和分化能力.结果 6例人胆管癌组织标本和2例移植瘤中,CD24+ CD44+ EpCAMhigh在人胆管癌中表达率为0.58%～2.43%(平均值0.94%).运用NOD/SCID鼠移植瘤模型,分选得到CD24+ CD44+ EpCAMhigh亚群细胞.NOD/SCID鼠移植瘤试验,1×103个CD24+ CD44+ EpCAMhigh细胞能成瘤(3/8),而CD24- CD44- EpCAMlow/-细胞在5×104才能成瘤(1/8).CD24+ CD44+ EpCAMhigh胆管癌细胞NOD/SCID鼠移植瘤的组织类型及标记物的表达率和原代肿瘤相似.结论 人胆管癌中含有CD24+ CD44+ EpCAMhigh细胞亚群,具有强成瘤能力、自我更新和分化的能力,可能是胆管癌干细胞.     

Cell proliferation of human bladder tumors determined by BrdUrd and Ki-67 immunostaining

The cell proliferation of bladder tumors was assessed in situ using BrdUrd (bromodeoxyuridine) and Ki-67 immunostaining. BrdUrd is incorporated into S-phase cells, and Ki-67 monoclonal antibody recognizes a nuclear antigen present in proliferating, but not resting cells. The percentage of labeled cells was expressed as the labeling index (LI). The average BrdUrd LI obtained applying this method to normal epithelium and to transitional cell carcinoma were 4.1% and 13.1%, respectively, while the Ki-67 LI had average values of 6.2% and 17.8%, respectively. Labeled cells were distributed throughout both the basal and surface layers of transitional cell carcinoma. In general, the value of the BrdUrd LI was correlated to that of the Ki-67 LI. A relatively large fraction of labeled cells was found in high grade or invasive tumors. Bladder tumors with lymph node involvement had higher LI than those without. In addition, a high frequency of S-phase cells within tumor tissue appeared to indicate a great potential for malignancy and thus a poor prognosis. These findings indicate that immunostaining with BrdUrd and Ki-67 may be useful tools for easy and quick evaluation of proliferating cells in bladder tumors.     

The progression potential of peritoneal dissemination nodules from gastrointestinal tumors

It is necessary to examine the characteristics of the dissemination nodules to establish a therapeutic strategy for peritoneal dissemination from digestive malignancy. Ki-67 expression as a proliferation marker in peritoneal dissemination nodules was investigated. The subjects were 15 patients with gastrointestinal cancers who underwent resection of the primary tumor and disseminated nodules. The expression of Ki-67 in both primary tumor and peritoneal dissemination nodule from each patient was evaluated by immunohistochemistry. Ki-67 labeling index in the original tumor was higher than that in the disseminated nodule in 13 of 15 patients (P < 0.0001). The mean value of Ki-67 labeling index was 42.2% in the 15 original tumors and 18.7% in the 15 disseminated nodules. Proliferative activity in the disseminated nodules was lower than that in the primary tumors. Further examination about characteristics of cancer dissemination is needed to treat patients with peritoneal metastasis.     

Immunohistochemical study of p53 and Ki-67 antigen expression in bladder carcinoma]

We examined the relationship between the expression of mutant p53 and Ki-67 antigens in urinary bladder transitional cell carcinoma and the pathological and clinical findings. Tissues were obtained from 28 patients with bladder carcinoma who underwent total or partial cystectomy. An ABC immunostaining method and two primary antibodies (DO-7 and MIB-1 antibodies) were used. The percentages of p53 and Ki-67 antigen-positive cells to the total number of cells were regarded as the p53 and Ki-67 labeling indices (LI) respectively. There were no statistically significant correlations between p53 LI and the histological grade or stage, although p53 LI increased slightly in the high grade and high stage group. There was a statistically significant correlation between Ki-67 LI and the histological grade and stage (p < 0.05). The correlation between p53 LI and Ki-67 LI was linear. Some cases had a p53 LI below the mean even though the Ki-67 LI was higher. The clinical course was characteristic of superficial bladder carcinoma initially, but progressed to invasive bladder carcinoma over the next several years. These results suggest that even cases initially diagnosed as superficial bladder carcinoma with a low p53 LI may progress to invasive bladder carcinoma in subsequent years. Therefore, it is important that the patient be followed-up.     

Roles of p53 and MDM2 in tumor proliferation and determination of the prognosis of transitional cell carcinoma of the renal pelvis and ureter

BACKGROUND: The significance of p53 overexpression for the prognosis of transitional cell carcinoma (TCC) of the renal pelvis and ureter remains controversial. Simultaneous evaluation of p53 and MDM2 may enable better prediction of tumor proliferation and patient prognosis than that obtained with evaluation of p53 alone. METHODS: Immunohistochemical detection of p53 protein, MDM2 protein and Ki-67 antigen as proliferation markers was performed for tissue samples obtained from 74 patients with TCC of the renal pelvis and ureter. The correlations of p53/MDM2 overexpression with conventional pathological features, Ki-67 labelling index (LI) and patient survival were studied. RESULTS: Overexpression of p53 was related to progression of each of the pathological features examined (grade, stage, type of infiltration, vascular invasion and lymphatic invasion) and Ki-67 LI was significantly higher with high p53 expression than with low p53 expression. However, overexpression of MDM2 was related to neither disease progression nor Ki-67 LI. Survival analyses were performed for 66 patients. Univariate analysis showed p53 to be a useful prognostic indicator, but in a multivariate analysis only type of infiltration and Ki-67 LI were independent survival markers, while p53 was not. Overexpression of MDM2 was unrelated to patient survival, and the combination of p53 and MDM2 for survival indication was found not to be useful. CONCLUSIONS: Overexpression of p53 is related to disease progression, increased tumor proliferation and patient survival for TCC of the renal pelvis and ureter, but the independent prognostic value of p53 did not reach statistical significance. Combined analysis of MDM2 with p53 cannot be recommended for examination of the malignant potential of TCC of the renal pelvis and ureter.     

p53 and Ki-67 expression as prognostic factors in cystosarcoma phyllodes

We have reviewed the histopathological, clinical outcome and immunohistochemical status in 21 women with cystosarcoma phyllodes (CSP) tumors of the breast. We assessed 12 tumors as histopathologically benign and 9 tumors as malignant. The median patient ages in benign and malignant CSP tumors were 39.6 and 45.4 years of age, respectively. The stromal cellularity, stromal cellular atypism, high mitotic activity, atypic mitoses, stromal overgrowth, infiltrative tumor contour, and heterologous stromal elements were significant features of the malignant CSP tumors. Benign CSP tumors were predominantly of fibroadenomatous architecture with cellular stroma (mild or moderate) and some distortion and elongation of glandular elements. Five malignant CSP tumors were stained positively with p53, and 6 malignant CSP tumors were stained immunohistochemically with Ki-67. All benign CSP tumors were negatively stained for p53 and Ki-67. The patients with benign CSP tumors were treated with local excision ( n = 11) and with subcutaneous mastectomy ( n = 1). Malignant CSP tumors were treated with wide local excision ( n = 1), partial mastectomy ( n = 1), simple mastectomy ( n = 2), and modified radical mastectomy ( n = 5). Two patients with a high mitotic rate and high values of p53 and Ki-67 received additional radiotherapy and chemotherapy. One case had liver metastasis. This tumor had high mitotic figures, stromal overgrowth, severe stromal cellularity, and 20% Ki-67 and mild p53 positivity. We suggest that p53 and Ki-67 can play an important role in predicting prognosis and yielding additional therapy besides conventional prognostic factors in the treatment of the CSP patients.     

Correlation and prognostic significance of p53, p21WAF1/CIP1 and Ki-67 expression in patients with superficial bladder tumors treated with bacillus Calmette-Guerin intravesical therapy

PURPOSE: We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. MATERIALS AND METHODS: The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. RESULTS: During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. CONCLUSIONS: Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.     

IMMUNOTHERAPY OF BLADDER CANCER TARGETING P53

PURPOSE: Superficial bladder cancer is often responsive to immunotherapy with bacillus Calmette-Guerin (BCG). However, some tumors progress despite BCG treatment, and most of these have mutations in the p53 tumor suppressor gene resulting in its over-expression. Overexpressed p53 is therefore a potential target for immunotherapy. The objective of this study was to demonstrate whether human bladder cancer xenografts in SCID mice could be eliminated by cytotoxic T cells (CTL) which recognize over-expressed p53. MATERIALS AND METHODS: Murine CTL which are specific for human p53 were previously generated in our laboratory by peptide immunization of HLA A2.1 transgenic mice. These CTL recognize and lyse human tumor cell lines which over-express p53 in the context of HLA A2.1. The p53 over-expressing HLA A2.1+ human bladder cancer cell line J82 was used to establish subcutaneous or intravesicular tumors in SCID mice. The mice were then administered tail vein injections of 5 x 10(7) p53-specific CTL, control CTL, or phosphate buffered saline (PBS). RESULTS: The subcutaneous tumor mean volume at 5 weeks for the p53-specific CTL treatment group was significantly lower than for both the control CTL or the PBS group (32 mm.3 versus 185 mm.3, p = 0.04 and 32 mm.3 versus 418 mm.3, p = 0.0001). In the mice with intravesicular tumors, a reduction to nonpalpable tumor size in vivo was seen with specific CTL therapy (14% palpable) versus control CTL treatment (86% palpable), the final tumor volume at necropsy was 127 mm.3 versus 246 mm.3 (N.S.). CONCLUSION: The overall response of the human bladder tumors in the SCID mouse model suggests the possibility of targeting p53 in patients with bladder cancer.     

Restriction of neuroblastoma angiogenesis and growth by interferon-alpha/beta

PURPOSE: We tested the hypothesis that the antiangiogenic activity of the type I interferons (IFNs), could affect tumor engraftment and growth in murine xenograft models of neuroblastoma. METHODS: Subcutaneous and retroperitoneal human neuroblastoma xenografts were established in SCID mice. Five days after tumor cell inoculation, daily subcutaneous injections of human IFN-alpha at several different doses were initiated and continued for 30 days. The effectiveness of continuous delivery of low-dose interferon was then tested using a gene therapy approach in which an adeno-associated virus vector encoding IFN-beta (rAAV-IFN-beta) was used to mediate expression prior to retroperitoneal tumor implantation. RESULTS: Subcutaneous and retroperitoneal tumors were significantly smaller in IFN-alpha-treated mice, as compared with control mice. Intratumoral basic fibroblast growth factor and vascular endothelial growth factor expression were also decreased, as was mean intratumoral endothelial cell density. Interestingly, the lower doses of IFN-alpha were more effective than the higher dose. No tumors developed in any of the mice given rAAV-IFN-beta, whereas each of the mice that received control vector developed large tumors. CONCLUSIONS: Treatment with IFN had a significant impact on neuroblastoma engraftment and growth in mice, particularly when delivered continuously using a gene therapy approach. This activity appears to be mediated in part by inhibition of tumor-induced angiogenesis through the downregulation of tumor-elaborated factors, including basic fibroblast growth factor and vascular endothelial growth factor.     

Prognostic significance of Ki-67 expression in advanced prostate cancers in relation to disease progression after androgen ablation

OBJECTIVE: This study was performed to examine the expressions of Ki-67 antigen, bcl-2 and p53 oncoprotein and to assess their capacity to predict the short-term response to the initial endocrine treatment and disease progression in prostate cancer. METHODS: Formalin-fixed and paraffin-embedded tumor tissues from a total of 73 patients with untreated prostate cancers were collected by transrectal ultrasound-guided biopsy. All patients with stage C or D prostate cancers had received continuous endocrine treatment. Ki-67 antigen, p53 and bcl-2 oncoprotein were detected by immunohistochemical methods. RESULTS: Short-term response to initial endocrine therapy judged at 3 months showed a significant correlation with Ki-67 labeling index (LI) and bcl-2 expression. Multivariate analysis showed that only a high Ki-67 LI was an independent potential predictor of prostate-specific antigen failure or the appearance of new metastasis. CONCLUSIONS: The findings suggested that the Ki-67 LI was the most useful parameter to predict disease progression after the initial endocrine treatment. Additional studies must be performed to evaluate the prognostic significance of both cell proliferation and apoptosis in detail.     

Proliferation potential of spinal meningiomas

Objectives: The goal of the present study was to quantitatively assess the proliferation index and progesterone receptor status of spinal versus intracranial meningiomas and to determine if these biological indicators can describe the clinical behavior of these tumors. This information could provide the spinal surgeon with important additional information concerning surgical management and follow-up recommendations for the individual patient. Methods: The study group consisted of 26 patients with spinal and 241 patients with intracranial meningiomas. Patients with atypical or anaplastic tumors as well as with neurofibromatosis type II were excluded from the study. Furthermore both groups were matched according to age, sex and resection grade (total resection according the Simpson classification). Proliferation index (Ki-67 Labelling index [LI]) and progesterone-receptor (PR) status of spinal and intracranial meningiomas were compared. Clinical charts including surgical and histological records and imaging studies were reviewed. Correlations with histological subtype, intratumoral calcifications, tumor vascularity and recurrence-free survival were analyzed. Results: Compared to the spinal group with a mean Ki-67 LI of 2.48% and a positive PR-status of 46%, proliferation rates of intracranial meningiomas were significant higher (Ki-67 LI 3.6%; P-value 0.041). No significant difference in PR status was seen (spinal PR-status 46%, P-value 0.261). Furthermore spinal meningiomas were less vascularized and showed less intratumoral calcifications. Time to recurrence was similar in spinal and intracranial tumors. Conclusion: Spinal and intracranial meningiomas differ in their proliferation activity but not in their PR status. However, despite lower proliferation rates, time to recurrence in spinal and cranial meningiomas is comparable in totally excised tumors. Further studies are needed to determine the role of other biological indicators in spinal meningioma growth and response to therapy.