The significance of immunohistochemical expression of Ki-67, p53, p21, and p16 in meningiomas tissue arrays

Although histologic grading of meningiomas has prognostic and clinical implications, it is difficult in some cases to predict the outcome of patients. There have been several efforts to evaluate the use of different immunohistochemical markers for predicting meningioma prognosis. We analyzed the immunohistochemical expression of Ki-67, p53, p21, p16, and PTEN proteins in 130 meningiomas (64 benign, 39 atypical, and 27 malignant meningiomas) using tissue microarray. The tumors were graded according to the World Health Organization classification. There was a statistically significant correlation between the expression of Ki-67, p53, p21, p16, and the grade of meningiomas (p0.001). By ordinal logistic regression, p53 and Ki-67 were significantly associated with grade, and an increase of 1% in the labeling index of these markers resulted in an increase in the risk of raising the grade by 2.17 and 1.49, respectively. Histological grade, p53, Ki-67 labeling indices, and overexpression of p16 were strongly associated with decreased event-free survival in univariate analysis. In contrast, multivariate analysis revealed that only tumor grade is an independent factor for predicting meningioma recurrence. We conclude that the Ki-67 and p53 labeling indices are useful additional tools in discriminating atypical from benign or anaplastic meningiomas, especially in histological borderline cases.     

Expression of E-cadherin and catenins in meningioma: ubiquitous expression and its irrelevance to malignancy

The expression of cell adhesion molecules in 107 meningiomas was analyzed with immunohistochemical methods using antibodies to epithelial (E)-cadherin and catenins (alpha, beta and gamma). According to the provided World Health Organization (WHO) grading, 84, 18 and five cases were classified as grade I, II and III, respectively. In addition, hemangioblastoma (15 cases) and hemangiopericytoma (four cases) were also evaluated. In most meningiomas, E-cadherin, alpha- and beta-catenins were expressed along the cell membrane or inside the cytoplasm. The tumor cells constituting whorls and glandular structures of secretory type showed a strong immunoreactivity. gamma-Catenin expression tended to be weak and infrequent in fibrous meningiomas, while other types exhibited diffuse stainings. Even in meningiomas of more than grade II, the expressions of cell adhesion molecules were detected in all cases. Hemangiopericytoma was positive for alpha- and beta-catenins, and hemangioblastomas were positive for beta-catenin alone, which was distinct from the expression pattern in meningiomas. Quantitatively, there were no correlations between the histological variants, Ki-67 indexes, or grades of meningiomas and the immunoreactive scores except for gamma-catenin scores of fibrous meningiomas. The present study demonstrates that cell adhesion molecules are ubiquitously expressed in all variants of meningioma and may be involved in the tumor morphogenesis. This result suggests that the expression of cell adhesion molecules is not a reliable indicator of malignancy in meningiomas. The present study also suggests that these markers may be useful for the differential diagnosis of meningioma.     

Correlation of p63 immunoreactivity with tumor grade in meningiomas

Predicting tumor behavior in meningiomas based on morphologic features alone remains difficult. The present study was undertaken to assess the correlation between p63 expression and histological grade of meningiomas. A total of 37 archival intracranial meningiomas were classified into 20 grade I, 13 grade II, and 4 grade III meningiomas. Using immunohistochemical methods, staining was scored based on nuclear and/or cytoplasmic distribution as follows: 0, no staining; 1, 50% or less of the cells; 2, more than 50% of the cells. Of grade I meningiomas, 95% (19/20) lacked nuclear p63 expression and none exhibited cytoplasmic staining. Overall, 92% of grade II tumors showed nuclear expression and 31% (4/13) showed cytoplasmic expression. Grade III tumors showed an overall nuclear expression of 75% (3/4) with all exhibiting cytoplasmic staining. Our results indicate a good correlation exists between histological grade and p63 protein expression, suggesting that p63 expression might be correlated with the clinical outcome.     

Impact of p53 and Ki-67 in predicting recurrence and progression of superficial (pTa and pT1) urothelial cell carcinomas of urinary bladder

In predicting the aggressive behavior of bladder tumors, the histopathological characteristics of grade and invasive stage are of principal importance. However, for predicting tumor recurrence and progression, these are sufficient only to a limited extent, particularly in the case of superficial (pTa and pT1) urothelial cell carcinomas. New prognostic factors are therefore needed to avoid either insufficient or excessive treatment. In this retrospective study, we investigated the prognostic value of the p53 and Ki-67 immunoreactivity indices. The present study included 118 superficial urinary bladder tumors consisting of 58 recurrent and 60 non-recurrent cases. Twenty of the recurrent tumors progressed into a higher grade and/or invasive stage. Paraffin immunohistochemical analysis was carried out using anti-p53 and anti-Ki-67 antibodies on the initial tumor tissues. We concluded that there is a highly significant relationship between the p53 and Ki-67 immunoreactivities and the histological grade and pathological stage of the tumors (P < 0.0001). We observed a significant relationship between the presence of recurrence and progression and the p53 immunoreactivity index (P < 0.01 and P = 0.017, respectively) and Ki-67 immunoreactivity index (P < 0.0001 and P = 0.046, respectively). Positivity for p53 and Ki-67 can demonstrate the risk of recurrence (p53: sensitivity = 76%, specificity = 58%; Ki-67: sensitivity = 86%, specificity = 48%) and progression (p53: sensitivity = 80%, specificity = 46%; Ki-67: sensitivity = 85%, specificity = 36%; ). We believe that both of these immunohistochemical markers can be considered valuable in addition to classical histopathological prognostic parameters for predicting recurrence and progression risks.     

Significance of COX‐2 and VEGF expression in histopathologic grading and invasiveness of meningiomas

Meningiomas are slow‐growing neoplasms that recur locally. Their morphologic grading does not always correlate with patient outcome. We evaluated the status of several immunohistochemical markers with histopathologic parameters in various grades of meningioma.Eighty‐eight meningioma specimens were examined immunohistochemically to determine the status of Ki‐67, cyclin D1, epidermal growth factor receptor (EGFR), cyclooxygenase‐2 (COX‐2), vascular endothelial growth factor (VEGF), and bcl‐2. Several clinical and pathological parameters were investigated.Forty‐nine Grade I, 33 Grade II, and 6 Grade III meningiomas were observed. VEGF and Ki‐67 expression was correlated with higher tumor grade. The association between grade and other immunohistochemical markers expression was not significant. A correlation was observed between COX‐2 expression and invasiveness to the brain or adjacent soft tissue. Tumor recurrence was correlated with brain or adjacent soft tissue invasion. We also observed a relationship between VEGF level and COX‐2 expression, and they were both correlated with necrosis.Immunohistochemical evaluation of VEGF, COX‐2, and Ki‐67 expression can provide information regarding the behavior of meningiomas, particularly for cases in which histological grading is not straightforward.     

Osteopontin predicts the behaviour of atypical meningioma

Lin C‐K, Tsai W‐C, Lin Y‐C & Hueng D‐Y
(2012) Histopathology  60, 320–325
Osteopontin predicts the behaviour of atypical meningioma Aim: Although the World Health Organization (WHO) histological criteria distinguishing benign from atypical and malignant meningioma are clear, discerning benign from atypical meningioma is still somewhat difficult, leading to interobserver diagnostic variability. Osteopontin (OPN) and cortactin play important roles in tumorigenesis, invasion and metastasis of several human cancers. The aim of this study was to evaluate the usefulness of OPN and cortactin immunohistochemistry for distinguishing between benign, atypical and malignant meningioma and predicting their recurrence. Methods and results: Seventy‐five specimens (48 benign, 17 atypical and 10 malignant meningiomas) were investigated immunohistochemically. The mean immunohistochemical scoreimmunohistochemical score ± SE of the mean of both OPN and cortactin were significantly higher in grade II or grade III meningiomas than in grade I meningioma. Discriminant analysis of immunohistochemical OPN expression showed correct classification of 97.7% of WHO grade I meningiomas and 88.2% of WHO grade II meningiomas (95.4% accuracy). However, the same analysis of cortactin expression showed correct classification of 95.8% of WHO grade I meningiomas and only 23.5% of WHO grade II meningiomas (76.9% accuracy). A cut‐off for predicting grades I and II meningioma recurrence was determined for OPN (3.0) but not for cortactin. Finally, logistic regression identified both this cut‐off (P < 0.05) and WHO grade (P < 0.05) as independent risk factors for recurrence. Conclusions: OPN expression is a valuable marker for diagnosis of atypical meningioma and prediction of grades I and II meningioma recurrence.     

An immunohistochemical study of HER2 expression in meningioma and its correlation with tumor grade

Meningiomas account for about 15-30% of all primary intracranial tumors. According to the 2007 WHO classification, meningiomas are divided into three grades (I, II and III). Recurrence is an issue following surgical treatment of meningioma, especially in grades II and III. HER2 (also known as erbB-2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity. HER2 is expressed in some human malignancies and can be a potential target for therapeutic intervention with selective inhibitors. There are only a few studies on the relationship between meningioma and HER2 expression, and the results are different as well. The aim of this study was to determine this relationship. Seventy-two paraffin blocks of meningioma were selected randomly, and immunohistochemical staining was then performed for each specimen. Thirty-one of the 72 meningiomas were HER2-positive. HER2 expression was observed in 11 (55%) of the 20 grade II/III, and 20 (38.5%) of the 52 grade I meningiomas. Consequently, HER2 expression was detected in 43% of meningiomas. No significant difference was seen between grade I and grade II/III meningiomas, primary and recurrent tumors, and males and females from the point of view of HER2 expression.     

Role of p53 gene mutation in tumor aggressiveness of intracranial meningiomas.

The mutations that occur in the p53 tumor suppressor gene have been studied in various human malignant tumors. However, little is known about this gene in meningiomas. To investigate the relationship and frequency of p53 gene mutations, the p53 polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) and immunohistochemical study were performed on the 41 intracranial meningiomas (21 benign, 11 atypical, and 9 malignant). The higher the p53 protein expression rate, the poorer the histologic grade (9.5%, 72.7%, and 88.9% in benign, atypical and malignant meningioma, respectively) (p=0.000). The p53 protein expression rate was higher in recurrent meningioma (71.4%) than in nonrecurrent meningioma (10.5%) (p=0.002). PCR-SSCP method was performed in positive p53 protein immunoreactivity cases. p53 gene mutation rate was higher in the atypical (62.5%) and malignant (25%) meningiomas than in the benign meningioma (0%) (p=0.232). Also, the rate was higher in recurrent menigioma (20%) than in nonrecurrent meningioma (0%) (o=0.495). Among five to eight exons of the p53 gene, the mutation was observed on exon 7 more frequently. In conclusion, p53 immunoreactivity and p53 gene mutation are closely correlated with histologic grade and histologic atypia of intracranial meningiomas. p53 gene mutation would be considered as a useful marker to detect the progression of intracranial meningiomas.     

Correlation between histological grade, MIB-1, p53, and recurrence in 69 completely resected primary intracranial meningiomas with a 6 year mean follow-up

Sixty-nine intracranial, totally excised meningiomas were immunostained for MIB-1 and p53 protein expression. According to the 1993 WHO criteria, revised by Perry et al., the 69 meningiomas were classified into: grade I = 54 benign meningiomas, grade II = 10 atypical meningiomas, grade III = 5 malignant meningiomas. The patients were followed until death or for an average of 6.7 years. The 69 meningiomas were divided into two groups, according to the absence (n = 42) or presence (n = 27) of recurrences. In the last group we included 3 patients who died of meningioma recurrence. According to the percentage of MIB-1 positively stained cells, meningiomas were divided into three groups: <1% (n = 36), 1-10% (n = 28), >10% (n = 5). We found the MIB-1 labeling index (LI) <1% in 33 grade I (61%) and in 3 grade II (30%) meningiomas. On the other hand, 7 grade II (70%) and all grade III (100%) meningiomas presented a MIB-1 LI >1%. Correlation between histological grade and MIB-1 LI was statistically significant (p = 0.0006). The correlation between MIB-1 LI and follow-up was also highly significant (p < 0.001): the majority of meningiomas which did not recur (32/42 equal to 76%) were characterized by a low (<1%) MIB-1 LI. In the recurrence group MIB-1 LI was significantly higher than in the disease-free patients' group. Moreover, MIB-1 appeared to be a prognostic parameter not strongly related to the histological grade. In fact, it was significantly higher in recurrent histologically benign meningiomas, as compared with benign meningiomas without recurrence (p = 0.0006). Positive p53 protein expression (>1%) was shown in 26/45 meningiomas (57%), with an LI of 1-10% in 18 (40%) and an LI of >10% in 8 (17%) meningiomas. Although the p53 LI tended to be higher in atypical and malignant meningiomas, no significant correlation was found between the p53 expression and the recurrence (p = 0.05). The authors conclude that quantitative MIB-1 labeling is a useful technique in the routine diagnostic assessment of meningiomas, and helpful in obtaining more information about prognosis and thereby in planning the most suitable treatment.     

Increased Co-Expression of Macrophage Migration Inhibitory Factor and Matrix Metalloproteinase 9 Is Associated with Tumor Recurrence of Meningioma

Background and Objective: We detected the expression of MIF and matrix metalloproteinase 9 (MMP9) in meningiomas to determine whether they are valuable recurrence predictor for meningioma.Methods: 67 cases of meningiomas, including 57 benign tumors (WHO grade I) and 10 non-benign tumors (WHO grade II and III), were collected, and expression of MIF and MMP9 in tissue microarray was evaluated immunohistochemically. The correlations between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, were analyzed statistically.Results: Increased expressions of both MIF (58.2%, 39/67) and MMP9 (55.2%, 37/67) were significantly associated with microvessel density (MVD) of tumor, but only dual high-expression of MIF and MMP9 was in relation to tumor invasion (P=0.016) and tumor recurrence (P=0.001). Based on univariate analysis, histological grade, tumor invasion and co-expression of MIF and MMP9 were significant predictors for recurrence. However, only histological grade and co-expression of MIF and MMP9 in tumor were independent recurrence factors with a hazard ratio of 49.033 (P=0.002) and 37.766 (P=0.002) in multivariate analysis.Conclusions: Together with histological grade, increased co-expression of MIF and MMP9 in tumor might be a valuable predictor for recurrence, especially for benign meningiomas.     

Ki-67、早期凋亡相关蛋白M30在子宫内膜癌的表达及其与预后的关系

目的　探讨子宫内膜癌增殖抗原Ki 6 7及早期凋亡相关蛋白M 30 (M30CytoDEATH ,细胞角蛋白 18)的表达与其生物学行为间的关系。方法　采用免疫组织化学链霉素抗生物素蛋白 过氧化物酶 (SP)法 ,分别检测了 79例子宫内膜癌Ki 6 7及M30蛋白的表达情况。结果　 79例子宫内膜癌中 ,不同病理学分级间Ki 6 7平均指数分别为 :G1:2 0 4 8± 14 86 ;G2 :2 4 12± 14 4 2 ;G3:38 84± 11 88。不同临床分期间Ki 6 7平均指数分别为 :Ⅰ期 :2 0 6 5± 13 5 6 ;Ⅱ期 :2 6 92± 14 71;Ⅲ期 :35 14± 14 70。不同病理学分级间M30蛋白平均指数分别为 :G1:1 0 3± 1 4 2 ;G2 :1 0 3± 1 6 4 ;G3:1 94± 1 2 0。不同临床分期间M30蛋白平均指数分别为 :Ⅰ期 :0 30± 0 5 8;Ⅱ期 :1 6 6± 1 74 ;Ⅲ期 :2 0 7± 1 6 2。研究结果还显示子宫内膜癌M30指数随Ki 6 7指数增高而增高 ,它们之间呈显著正相关。生存分析表明 ,Ki 6 7指数≥ 30、M30指数≥ 2的患者比Ki 6 7指数≤ 10、M 30指数≤ 1的患者生存率显著降低。结论　Ki 6 7指数、M 30指数越高 ,子宫内膜癌生物学行为越差 ,患者预后也越差。Ki 6 7指数、M 30指数较高的患者 ,生存率显著降低。高分化子宫内膜癌 (G1)中 ,Ki 6 7指数≥30、M30指数≥ 2者可能提示患者预     

The significance of Ki-67/MIB-1 labeling index in human meningiomas: a literature study

Histology alone does not always predict the clinical outcome of human meningiomas. Determination of proliferative activity has therefore become an important diagnostic and prognostic tool to identify more aggressive meningiomas, and the Ki-67/MIB-1 monoclonal antibody has become widely used. The aim of this study was to assess the prognostic value of the Ki-67/MIB-1 labeling index (LI) in human meningiomas by a search in the literature. In PubMed/Medline databases, 53 articles were found, and they all showed positive correlations between Ki-67/MIB-1 LI and histological malignancy grade. The average mean labeling indices were 3%, 8%, and 17% for grade I-III meningiomas, respectively. There was, however, considerable overlap of indices between the malignancy groups. Concerning recurrence, meningiomas with a labeling index beyond 4% may indicate an increased relapse rate. Consequently, Ki-67/MIB-1 LI represents a useful predictor of tumor grade and risk of recurrence, however, it must be interpreted cautiously in the individual tumor.     

DNA topoisomerase II-alpha and cyclin A immunoexpression in meningiomas and its prognostic significance: an analysis of 263 cases

CONTEXT: Routine pathologic examination cannot distinctively predict the clinical course of meningiomas because even histologically benign tumors may recur after gross total resection. Therefore, numerous efforts have been made to evaluate the meningioma growth fraction and its prognostic value. However, a universally applicable proliferative marker for meningioma outcome is not yet a reality. OBJECTIVE: To investigate the prognostic utility of 3 proliferative markers, namely, Ki-67, DNA topoisomerase II-alpha (topoII), and cyclin A in a representative series of intracranial meningiomas. DESIGN: Two hundred sixty-three adult patients with intracranial meningiomas (208 benign, 42 atypical, and 13 anaplastic) were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to Ki-67 (MM-1), topoII, and cyclin A. A computerized color image analyzer was used to count immunostained nuclei. RESULTS: The topoII and cyclin A scores exhibited a close correlation with Ki-67 immunostaining. Significant differences between the indices for all 3 markers were noted among the 3 grades of meningiomas. The scores for all 3 markers were significantly different between recurrent and nonrecurrent meningiomas, including benign tumors that were treated with gross total resection. Recurrence-free survival was significantly reduced for cases with a Ki-67 labeling index (LI) of 4.4% or greater, a topoII LI of 3.2% or greater, and a cyclin A LI of 3.1% or greater. Multivariate analysis revealed that the risk of recurrence for the entire meningioma cohort was significantly associated with tumor grade (hazard ratio = 2.7; P =.004), topoII LI of 3.2% or greater (hazard ratio = 5.5; P <.001), and a cyclin A LI of 3.1% or greater (hazard ratio = 2.4; P =.01). CONCLUSIONS: There is a close correlation in the expression of these 3 proliferative markers in meningiomas, and all of the markers showed a significant association with tumor grade, recurrence rate, and recurrence-free survival. Consequently, in addition to Ki-67, immunoexpression of topoII and cyclin A is available for predicting meningioma recurrence. Moreover, the topoII and cyclin A staining scores were found to be more sensitive predictors for meningioma progression than Ki-67 and, therefore, either of these 2 markers may prove to be clinically informative and useful.     

Immunohistochemical expression of SPARC is correlated with recurrence,survival and malignant potential in meningiomas

Meningioma is a common neoplasm that constitutes almost 30% of all primary central nervous system tumors and is associated with inconsistent clinical outcomes. The extracellular matrix proteins play a crucial role in meningioma cell biology and are important in tumor cell invasion and in progression to malignancy. SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) is a matricellular glycoprotein that regulates cell function by interacting with different extracellular matrix proteins. The aim of this study was to evaluate the expression of SPARC with proliferation index, p53 reactivity in WHO grade 1 (benign), grade 2 (atypical) and grade 3 (anaplastic) meningiomas and correlate with clinical features of the patients, including location of the tumor, recurrence of the tumor and survival of patients. We studied 111 meningiomas, 69 being benign, 34 being atypical and eight being anaplastic meningiomas of various histological types. Using immunohistochemical analysis, we evaluated the expression of SPARC, Ki‐67 (MIB‐1) and p53 in meningiomas. Immunohistochemical scores of SPARC were determined as the sum of frequency (0–3) and intensity (0–3) of immunolabeling of the tumor cells. A high immunohistochemical score (4–6) for SPARC was more frequent in atypical and in anaplastic meningiomas than in benign meningiomas (p < 0.01). MIB‐1 proliferation index showed significant association between tumor grades in meningiomas (p < 0.01). At the end of a follow‐up period of 47.53 ± 25.04 months, 30 tumors recurred. A high SPARC expression was significantly associated with tumor recurrence (p = 0.02). The immunoreactivity of p53 protein and MIB‐1 score were significantly higher in recurrent meningiomas than in non‐recurrent meningiomas. The cumulative survival of patients with high SPARC expression was significantly lower than patients with low SPARC expression. The high SPARC expression scores were predominantly identified in meningothelial, fibrous and chordoid meningiomas; low SPARC expression scores were mostly spotted in secretory and psammomatous meningiomas. Evaluating SPARC expression might help assessing recurrence risk and survival estimation in meningiomas.     

Expression of merlin,NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence

Meningiomas are common, usually benign tumors of the central nervous system that have a high rate of post-surgical recurrence or regrowth. We determined expression of the proteins merlin, NDRG2, ERBB2, and c-MYC in meningiomas using immunohistochemistry and assessed relationships between protein expression and gender, age, tumor grade, and recurrence or regrowth. The study sample comprised 60 patients, (44 women and 16 men) with a mean age of 53.2±12.7 years. Tumors were classified as grade I (n=48) or grades II and III (n=12). Expression of merlin, NDRG2, ERBB2, and c-MYC was not significantly different statistically with relation to gender, age, or meningioma recurrence or regrowth. Merlin was expressed in 100% of the cases. No statistically significant difference between tumor grade and recurrence or regrowth was identified. Statistically significant differences were identified between the mean age of patients with grade I (54.83±11.60) and grades II and III (46.58±15.08) meningiomas (P=0.043), between strong c-MYC expression and grades II and III (P<0.001), and between partial surgical resection and tumor recurrence or regrowth (P<0.001). These findings reveal the lower mean age among grades II and III meningioma patients than grade I patients, the influence of the protein merlin on tumorigenesis, the association of c-MYC with aggressive meningiomas, and that partial surgical resection is associated with tumor recurrence or regrowth.     

Histopathologic indicators of recurrence in meningiomas: correlation with clinical and genetic parameters

Meningiomas in general are circumscribed slow-growing tumors. However, despite gross total resection, tumor relapse and patients’ outcome are still an issue. Risk stratification based on histomorphology alone remains problematic. This study explored the independent prognostic value of potential risk factors among 206 patients who underwent meningioma resection and followed-up until death or a median of 44 months. The statistical analysis considered clinical data, histomorphologic parameters, cytogenetic findings, Ki-67 immunoreactivity, and activity of tissue non-specific alkaline phosphatase (ALPL). Recurrence-free survival estimates were computed and prognostic factors were identified using Cox proportional hazards model. Independent predictors of recurrence included (1) anaplasia; (2) mitotic index ≥20/10 high-power fields; (3) subtotal tumor resection; (4) loss of short arm of chromosome 1 (1p−); and (5) Ki-67 labeling index (LI) >12%. Among totally resected WHO grade I meningiomas, neither histopathologic nor clinical parameters were predictive, whereas 1p− was the only independent prognostic factor. ALPL did not reach significance in the multivariate modeling, however, the fast and low-cost histochemical detection of ALPL expression could be proved as a highly sensitive screening method for 1p−. In particular, biologically aggressive meningiomas of histologically benign or “borderline” phenotype could be therefore identified by ALPL detection followed by 1p in situ hybridization.     

胎儿性RNA结合蛋白p62在肝细胞癌中表达的意义

目的　探讨表达p6 2的肝癌组织的病理形态学特点 ,以及 p6 2与癌细胞增殖和转移等生物学特性的关系。方法　用免疫组织化学方法检测 4 0例原发性肝细胞肝癌 p6 2和Ki 6 7的表达。结果　p6 2阳性率是 6 7.5 % (2 7/ 4 0 ) ,其中 p6 2强阳性表达的 12例中 9例为肝癌病理学分级为Ⅲ级的病例。p6 2表达强阳性的癌组织往往间质有大量的纤维组织或有大片坏死癌细胞 ,其增殖活性也高 ,Ki 6 7标记指数为 2 8 3%± 15 1% ,与 p6 2表达阴性组 (7 5 %± 9 8% )比较 ,差异具有显著性意义 (t=3 0 87,P =0 0 0 5 ) ;5例有肺转移或腹腔淋巴结转移的病例 ,其中 3例p6 2表达强阳性。结论　p6 2的表达与癌细胞的增殖和转移有一定的关系 ,和间质纤维组织较多的微环境有关     

Association of loss of 1p and alterations of chromosome 14 in meningioma progression

Meningiomas are usually benign tumors; however, they can recur after surgical resection and occasionally show histologic progression to a higher grade II and III malignancy. The second most frequently reported genetic abnormality after 22q loss is deletion of 1p, although alterations in 9q, 10q, and 14q are also implicated in meningioma progression. Fourteen tumors comprising six benign, four atypical, and four malignant meningiomas were examined by means of cytogenetic and fluorescence in situ hybridization analysis. All tumors showed losses in different regions of 1p, with 1p11, 1p13, 1p21, 1p22, 1p32, and 1q21 breakpoints; eight tumors also presented alterations of chromosome 14. Five of the six cases with deletions on 1p and normal chromosome 14 were grade I, and two were recurrent. All but one of the eight cases with simultaneous 1p deletion and alterations of chromosome 14 were grade II (3 cases) and grade III (4 cases); all the grade III cases were recurrent. These results support the possible association between changes in 1p and chromosome 14 with the evolution of aggressive meningiomas through tumor progression.     

Ki-67 reactivity in primary fallopian tube cancers

Forty-four cases of primary cancer of the fallopian tube (PFTC) were analyzed as to Ki-67 expression, grade, stage and the cancer histological type. Among patients with an average age of 57.5 years (range 38-70 years), 27 patients were FIGO I, 7 were FIGO II and 10 were FIGO III. Histological classification of PFTC revealed 18 cases of endometrioid type, 9 serous, 7 undifferentiated, 6 urothelial, 2 clear-cell and 2 of other type. Histological grading revealed 11 cases of G1, 16 of G2 and 17 of G3 tumors. The quantity of Ki-67 positive cells was counted on 300 cancer cells in random high-power fields (10 x 40) and recorded as the labeling index (LI, %). Positive staining for Ki-67 was shown in the nuclei in all cases. Ki-67 LI values ranged from 14.2 to 97.2% (median 36.1). Ki-67 LI values were graded as > or = 36.1% as high and <36.1% as low. We did not find any significant differences in Ki-67 LI values among tumors of various clinical stages, histological grades and histological types. The p value was statistically significant only for stage as a prognostic factor.     

Methylation status of TP73 in meningiomas

Deletions at 1p are frequent in meningioma and represent a genetic marker associated with the genesis of atypical WHO grade II forms. Previous mutational analysis of TP73, a structurally and functionally TP53 homologous gene located at 1p36.33, failed to demonstrate a significant rate of sequence variations linked to gene inactivation in meningiomas with 1p loss. As an alternative, TP73 may be inactivated through aberrant 5' CpG island methylation, a primary mechanism participating in the inactivation of tumor suppressor genes during tumorigenesis. We determined the methylation status of the TP73 gene in a series of 60 meningiomas (33 grade I, 24 grade II, and 3 grade III samples), including tumors with deletion at 1p (n=30) and with intact 1p (n=30). Aberrant methylation was detected in 10 cases (33%) with 1p deletion and in 3 tumors (10%) with retention of alleles at this chromosome arm. The distribution of the 13 cases of methylation according to malignancy grade was 7 grade I, 5 grade II, and 1 grade III tumor. Accordingly, although TP73 aberrant methylation was more frequent in meningiomas with 1p deletion (P<0.05), no association with the grade of malignancy could be established. These findings, together with the previously reported increased TP73 expression in malignant meningiomas suggest that opposing functions of this gene may characterize distinct subsets of tumors: suppressed or reduced expression as a result of CpG methylation in some grade I-grade II tumors, and enhanced expression in some more malignant forms.