卵巢上皮癌的预后影响因素分析

目的:探讨卵巢上皮癌预后的影响因素.方法:回顾分析自2005年1月至2010年12月在陕西省肿瘤医院收治的292例卵巢上皮癌患者的临床资料.采用Kaplan-Meier法分析生存时间,应用Log-rank法进行组别间生存率差异检验,采用OR值对各因素间进行危险度分析.结果:年龄、手术分期、组织学类型、病理分化程度、肿瘤细胞减灭术后残余瘤的大小以及术后化疗疗程数是卵巢上皮癌的预后生存指标.以FIGOⅠ期患者的死亡风险为1,则Ⅱ期、Ⅲ期、Ⅴ期的死亡风险分别为Ⅰ期的3倍、14.7倍、21.8倍;以术后残余瘤直径≤2cm患者的死亡风险为l,则残余瘤直径＞2cm的患者的死亡风险为残余瘤直径≤2cm患者的死亡风险的80.7倍;化疗疗程数＜6疗程的死亡风险为≥6疗程的2.3倍.以高分化患者的死亡风险为l,则中、低分化的死亡风险分别为高分化的2.4倍、3.8倍.结论:FIGO分期,首次肿瘤细胞减灭术后残余瘤的大小、化疗疗程数、病理分化程度是卵巢上皮癌的独立预后因素.因此尽力做到早诊断、早治疗,术后辅以正规、足程的化疗是提高卵巢上皮癌生存率的关键.     

Prognostic value of centromere protein-A expression in patients with epithelial ovarian cancer

Altered expression of centromere protein-A (CENP-A) is observed in various types of human cancers. However, the clinical significance and pathological role of CENP-A in epithelial ovarian cancer (EOC) remains unclear. The main objective of this investigation was to clarify the relationships between CENP-A expression and the clinicopathological features of patients with EOC. Real-time quantitative PCR and Western blot were performed to examine CENP-A expression in 20 pairs of fresh-frozen EOC tissues and corresponding noncancerous tissues. Using immunohistochemistry, we performed a retrospective study of the CENP-A expression levels on 120 archival EOC paraffin-embedded samples. Prognostic outcomes correlated with CENP-A were examined using Kaplan–Meier analysis and Cox proportional hazards model. Our results showed that the expression levels of CENP-A mRNA and protein in EOC tissues were both significantly higher than those in noncancerous tissues. By immunohistochemistry, the data revealed that high CENP-A expression was significantly correlated with pathological grade (P?=?0.02) and International Federation of Gynecology and Obstetrics stage (P?=?0.006). Consistent with these results, we found that high expression of CENP-A was significantly correlated with poor survival in EOC patients (P?<?0.001). Furthermore, Cox regression analyses showed that CENP-A expression was an independent predictor of overall survival. Our data suggest that CENP-A could play an important role in EOC and might serve as a valuable prognostic marker and potential target for gene therapy in the treatment of EOC.     

Prognostic value of the flow cytometric DNA index in human ovarian carcinoma

Flow cytometric measurements were done on 51 ovarian carcinoma specimens collected from consecutive patients in a prospective study. The ploidy status was related to the course of the disease. The tumors from 26 (52%) of 50 evaluable patients had DNA aneuploidy. Patients with diploid tumors were more often considered disease-free after initial operation (P less than 0.01). Patients with aneuploid tumors had a more aggressive course of the disease in all respects of comparison. The median survival of patients with diploid tumors was 18 months as compared to 8 months for those with aneuploid tumors (P less than 0.0005). Flow cytometric DNA measurements give important prognostic information and such analyses should be included in future clinical trials. Through the development of high-speed instrumentation they also may become feasible in routine clinical work.     

Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma

The influence of vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) on prognosis and the relationship between VEGF expression and MVD in ovarian carcinoma are not well defined. We studied VEGF expression in parallel with MVD by immunohistochemistry in 94 ovarian tumours (64 malignant, 13 borderline, and 17 benign) and correlated the results with the clinicopathologic prognostic factors of the disease to clarify their significance in this disease. Assessment of VEGF mRNA isoforms by RT-PCR was also performed. Of the malignant, borderline, and benign ovarian tumours respectively, two (3%), four (31%) and 16 (94%) were negative, 31 (48%), seven (54%) and one (6%) had low expressions, and 31 (48%), two (15%) and none (0%) had high expressions of VEGF. There were significant associations between the VEGF expression and disease stage (P= 0.002), histologic grade (P= 0.0004), and patient outcome (P= 0.0002). MVD did not correlate significantly with the clinicopathologic parameters. Likewise, no correlation was found between MVD and VEGF expression. The survival of patients with high VEGF expression was significantly worse than that of patients with low and negative VEGF expression (P = 0.0004). Multivariate analysis revealed that disease stage and VEGF expression were significant and independent prognostic indicators of overall survival time (P = 0.008 and P = 0.006 respectively). These findings suggest that in conjunction with the established clinicopathologic prognostic parameters of ovarian carcinoma, VEGF expression may enhance the predictability of patients at high risk for tumour progression who are potential candidates for further aggressive therapy.     

Prognostic value of thymidine phosphorylase expression in breast carcinoma.

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is an enzyme that catalyzes the reversible dephosphorylation of thymidine, deoxyuridine and their analogs. TP has also angiogenic properties, although the precise mechanism by which it promotes angiogenesis is not known. We examined TP expression using immunohistochemistry (654-1 Mab) in 182 invasive breast carcinomas (67 N0 and 115 N1/2; median follow-up 78 months [range, 3-177]; 51 patients treated with adjuvant systemic cyclophosphamide, methotrexate and 5-fluorouracil [CMF] chemotherapy and 82 with tamoxifen). High TP expression was found in 142 cases (78%) and correlated with lower histologic grade and low p53 expression. No correlation was found between TP expression and vascular density. TP-positive tumors had a significant increase in both disease-free survival (DFS; p = 0.0025) and overall survival (OS; p = 0.0070) in the total cohort of patients and in the subgroups of node-positive patients and patients treated with CMF adjuvant therapy; no significant difference in either DFS or OS was observed in patients without CMF treatment. Our findings suggest that TP has little effect on tumor angiogenesis of breast carcinoma, whereas it could represent an interesting marker that could predict response to CMF chemotherapy.     

Prognostic value of E-cadherin expression in thyroid follicular carcinoma.

AIMS: To evaluate the expression of E-cadherin, its association with various clinicopathological features and its possible relation with distant metastasis-free survival (DMFS) in follicular carcinoma of the thyroid. METHODS: E-cadherin expression was assessed immunohistochemically in sections from paraffin embedded tissues in a group of 54 patients with follicular carcinoma and its variants who were followed for a median of 7.25 years. RESULTS: Reduced E-cadherin expression, defined as <90% of cells showing membrane positivity, was found in 15 tumours and was significantly associated with widely invasive growth, insular morphology and lesser degree of differentiation, but was not related to patient sex and age or tumour size. In univariate analysis, DMFS was significantly worse in male patients (P<0.03), widely invasive tumours (P=0.0002), moderately/poorly differentiated tumours (P<0.05) and tumours showing reduced E-cadherin expression (P=0.0001). In multivariate analysis, the degree of invasiveness and E-cadherin expression were the only independent prognostic factors. Among widely invasive cases, those with reduced E-cadherin expression had significantly worse DMFS than those with preserved expression. CONCLUSIONS: Our findings suggest that E-cadherin expression could be used as a prognostic marker in widely invasive follicular carcinomas of the thyroid. Larger studies are needed to assess its prognostic value in the group of minimally invasive carcinomas.     

Prognostic value of hormonal receptors, p53, ki67 and HER2/neu expression in epithelial ovarian carcinoma

OBJECTIVE: The role of molecular and biological factors in ovarian cancer is controversial. We investigated the levels of the estrogen (ER) and progesterone (PR) receptors, HER2/neu, p-53 and Ki 67 in patients with advanced ovarian cancer and correlated the results with the clinical course in order to define their predictive or prognostic significance. METHODS: Paraffin-embedded tumor tissues from 72 patients with ovarian cancer treated from 1999 to 2003 were analyzed. Overexpression of C-erb-B2 was defined as herceptest ++/+++ and positive fluorescence in situ hybridization (FISH) or herceptest +++/+++. Positivity for ER and PR was determined by > or =10% of the cellular membranes immunostained. Statistical analysis was performed to evaluate the prognostic impact of the molecular markers. RESULTS: 49 of the 72 patients were ER + (68%) and 36 PR + (50%). In 45 patients (62.5%) expression of p53 was > or =10%. Overexpression of C-erb-2 was found in 4 tumor samples (5%). A Ki67 labelled nuclear area >30% was found to be associated with a higher rate of complete response (chi(2); p=0.05). None of the biological markers were significantly associated with progression free survival (PFS). By multivariate analysis residual tumor after debulking surgery and ER status were associated with OS (p< or =0.05). CONCLUSIONS: Ki67 nuclear expression >30% is predictive of complete response in advanced ovarian cancer. HER2/neu overexpression is scarce in our study. Positive ER is an independent prognostic factor for OS. Further research with larger studies and hormonal treatment is guaranteed.     

Prognostic value of overexpression of p53 in human ovarian carcinoma patients receiving cisplatin

A major obstacle to the treatment of ovarian carcinoma is intrinsic/acquired resistance to cisplatin-based chemotherapy. The clinical significance of p53 overexpression in patients with ovarian carcinoma is still controversial. The aim of this study was to investigate the independent prognostic significance of p53 overexpression in patients with ovarian carcinoma who are treated with cisplatin. We retrospectively examined the overexpression of p53 in primary ovarian carcinoma, and its association with chemotherapeutic efficacy. One hundred and thirty four ovarian carcinomas were surgically removed from patients who received adjuvant cisplatin-based chemotherapy. Immunohistochemical analysis of p53 was performed using a DO7 antibody against the p53 protein in 134 ovarian carcinomas. The significance of p53 in the prognosis of patients with ovarian carcinomas was also examined by a survival analysis of mortality follow-up data covering the period from 1988 to 2001. Thirty-three tumors (25%) exhibited p53 overexpression. Overexpression of p53 in grade 2/grade 3 tumors was significantly higher than that seen in grade 1 tumors (P=0.0088, 0.0229). Patients with tumors who also showed overexpression of p53 had a significantly inferior response to chemotherapy compared with the patients with p53-negative tumors (P=0.04). Cox regression analysis revealed that p53 overexpression was prognostic for poor disease outcome after adjustment for FIGO stage, grade and residual tumor. These findings suggest that overexpression of p53 in ovarian carcinoma is associated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Therefore, detection of p53 overexpression using the DO7 antibody may be considered as a predictive marker of chemoresistance for cisplatin in patients with ovarian carcinoma.     

Prognostic factors for survival in stage I epithelial ovarian carcinoma

In a retrospective analysis prognostic factors were studied in 204 patients with primary Stage I epithelial ovarian carcinoma (borderline tumors were excluded) treated between 1975 and 1987. Only histologic grade (P = 0.01) and kind of surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy +/- omentectomy versus unilateral salpingo-oophorectomy, P = 0.02) were found to have a significant influence on survival prognosis (Cox model). All other factors (age, the International Federation of Gynecology and Obstetrics [FIGO] stage, integrity of the capsule, unilaterality versus bilaterality, and histology) were of no prognostic importance. Unilateral salpingo-oophorectomy without any additional staging reduces five-year survival probability (62% versus 84%). Therefore this kind of operation should be abandoned. Furthermore, histologic grade should be a stratification criterion in studies, which will be necessary for proving the value of adjuvant therapy in Stage I epithelial ovarian carcinoma.     

Second-look laparotomy in epithelial ovarian carcinoma. Prognostic factors associated with survival duration

This article that reports on 70 consecutive patients is one of only a few studies of advanced ovarian cancer that have attempted to define predictive factors associated with survival duration after second-look laparotomy. As in many other investigations, several factors have been analyzed for predicting second-look outcome. The prognostic variables analyzed in this study included age, stage, histologic grade, residual disease status after initial surgery, and type (cisplatin versus no cisplatin) and number of cycles of chemotherapy. Only stage (P = 0.002) and optimal disease (less than 2 cm residual tumor size) after initial surgery (P less than 0.001) were significantly associated with the absence of disease at second-look laparotomy, and both were significant predictors of second-look outcome in a multivariate logistic regression model. Their impact on actuarial survival after second-look laparotomy diminished, however. Actuarial survival after second-look laparotomy was associated with residual tumor size at second-look surgery (P = 0.02). According to second-look findings, the 3-year actuarial survival rates and standard errors were as follows: no pathologic evidence of disease, 80.7% +/- 13.4% 3-year survival; microscopic disease plus less than or equal to 2 cm residual disease, 49.1% +/- 13.1% survival; and gross residual disease (i.e., greater than 2 cm maximum tumor diameter), 29.5% +/- 11.4% survival. We also examined the effect of extensive tumor resection at second-look laparotomy on survival for patients with greater than 2 cm gross residual disease. Optimum resection (less than 2 cm residual tumor mass) resulted in significantly greater survival than suboptimum resection (P less than 0.001). This strongly suggests that there is a survival advantage associated with optimum resection at second-look laparotomy.     

肿瘤相关巨噬细胞在晚期上皮性卵巢癌组织中的浸润及其与预后的关系

背景与目的:肿瘤相关巨噬细胞(tumor-associated macrophage,TAM)浸润与肿瘤进展有关.本研究探讨TAM在卵巢癌组织中的浸润及对卵巢癌患者生存和预后的影响.方法:应用免疫组化方法检测卵巢癌及卵巢良性病变组织中TAM的特异性标志物CD68,了解TAM在卵巢癌组织中和卵巢良性病变中的浸润密度,并比较TAM高密度组与低密度组卵巢癌患者的生存差异,对影响预后的多个临床病理因素进行单因素及多因素分析.结果:67例卵巢癌组织标本中TAM平均密度为57.7/HP,22例卵巢良性病变组织标本中TAM平均密度为25.3/HP.在卵巢癌组织中TAM浸润密度较良性病变组织中明显为高(P<0.01).卵巢癌患者中TAM低密度组的中位生存时间为(129.2±12.3)个月,5年累积生存率为73.3%;TAM高密度组的中位生存时间为(69.1±11.6)个月,5年累积生存率为41.2%.TAM低密度浸润卵巢癌患者5年生存率较TAM高密度患者为高(P=0.01).在卵巢癌患者中,浆液性癌、中低分化癌及年龄大于40岁患者的癌组织中,TAM浸润较明显.多因素分析显示:组织学分级及TAM浸润的密度是影响晚期上皮性卵巢癌生存的独立的预后因子.结论:晚期上皮性卵巢癌组织中有明显的TAM浸润,TAM高密度浸润状态提示预后不良.     

Prognostic and therapeutic implications of increased ATP citrate lyase expression in human epithelial ovarian cancer

Altered metabolism is one of the most significant features of cancer cells. ATP citrate lyase (ACL), a key enzyme in de novo lipid synthesis, has been reported to be overexpressed or activated in several cancer types. To determine the role of ACL in ovarian cancer progression, we detected ACL expression in human epithelial ovarian cancer tissues. qRT-PCR and western blotting showed higher ACL expression in malignant tissues compared to normal ovarian tissues. Immunohistochemical analysis showed that phosphorylated ACL was increased in ovarian cancer tissues and that its expression correlated well with tumor grade, FIGO stage and poorer prognosis. To explore the therapeutic potential of ACL, we assessed the effect of ACL-siRNA on cellular proliferation and cell cycle distribution. ACL knockdown inhibited cellular proliferation and induced cell cycle arrest in A2780 cells. Taken together, our findings suggest that ACL may contribute to the pathogenesis of human epithelial ovarian cancer, and may serve as a novel therapeutic target.     

卵巢上皮癌组织微血管密度及血管形成相关分子的检测及预后价值

目的 探讨卵巢上皮癌组织微血管密度(MVD)、血管内皮生长因子(VEGF)、血小板反应素1(TSP1)和p53蛋白表达与患者预后的关系.方法 采用免疫组化法检测57例原发性卵巢上皮癌组织中VEGF、TSP1和p53蛋白的表达情况,用CD34免疫染色后计数MVD.对VEGF、TSP1、p53蛋白和MVD与患者复发及生存时间的关系进行回顾性分析.结果卵巢上皮癌组织中VEGF、TSP1和p53蛋白表达阳性率分别为70.2%(40/57)、47.4%(27/57)和61.4%(35/57),MVD为30.3±8.5,MVD、VEGF和TSP1与复发相关(P值分别为0.030、0.025和0.026).高MVD、VEGF和p53蛋白阳性患者的中位生存时间短于低MVD、VEGF和p53蛋白阴性者(P值分别为0.0187,0.010和0.005),MVD、VEGF和p53蛋白是影响预后的危险因素.TSP1是影响患者预后的保护因素,其阳性患者的中位生存时间长于阴性患者(P=0.042).多因素分析表明,MVD和p53蛋白是影响卵巢上皮癌预后的独立因素(P值分别为0.018和0.009).结论 VEGF、TSP1和p53蛋白可能参与了卵巢上皮癌的血管形成,MVD和p53是影响卵巢上皮癌预后的独立因素.     

KLK10和VEGF在卵巢癌组织中的表达及其临床意义

目的：分析激肽释放酶10（kallikrein 10,KLK10）和血管内皮生长因子（vascular endothelial growth factor,VEGF）在卵巢癌组织中的表达,探讨两者在卵巢癌临床诊断、治疗及预后中的意义。方法：收集2004年1月至2009年1月在南通大学附属医院妇科收治的45例卵巢癌、10例良性和12例交界性卵巢肿瘤组织石蜡切片标本,应用免疫组化法检测标本中KLK10蛋白和VEGF的表达,并分析两者表达的相关性及与卵巢癌各临床病理指标和预后的关系。结果：KLK10 \[86.7%(39/45) vs 10.0%(1/10)、58.3%(7/12), P <0.05\]和VEGF\[（82.2%(37/45) vs 20.0%(2/10)、41.4%(5/12), P <0.05\]在卵巢癌组织中的阳性表达率均明显高于卵巢良性、交界性肿瘤组织。KLK10和VEGF表达阳性率分别与分期、肿瘤分化、淋巴结转移、5年生存率有关（ P <0.05）,与患者年龄、病理分型、血清CA125水平、腹水及残余肿瘤直径无关（ P >0.05）;KLK10和VEGF蛋白在卵巢癌中的表达呈正相关性（ r =0.5279, P =0.043）。结论：KLK10和VEGF蛋白在卵巢癌中均为高表达,两者表达呈正相关,两者均似可作为卵巢癌诊断、治疗及预后的标志物。     

40岁以下妇女卵巢上皮癌的预后因素

目的探讨40岁以下妇女卵巢上皮癌的预后因素.方法1980年1月-1992年12月本院收治40岁以下妇女卵巢上皮癌86例,回顾性分析有关预后因素.结果40岁以下妇女卵巢上皮癌二年生存率79.07%,五年生存率54.65%.按FICO分期Ⅰ期49例,按细胞学分级G1期41例,4例保留卵巢功能者均无复发.逐步COX模型多因素分析显示其细胞学分级、残留灶大小、手术方式是影响预后的独立因素(P＜0.01);但与40岁以上卵巢癌病例,并无差异(P＞0.05).单因素分析显示其病理类型、FIGO分期、细胞学分级、残留灶大小、手术方式是影响预后的重要因素(P＜0.01).结论40岁以下妇女卵巢上皮癌临床分期早,细胞分化好,预后较好,部分Ⅰa、G1期患者可保留生育功能.     

Prognostic value of apoptosis-regulating protein expression in anal squamous cell carcinoma.

PURPOSE: This study evaluated the prognostic value of pro and antiapoptotic protein expression, as well as that of spontaneous apoptosis, in anal carcinoma patients treated by radiotherapy (RT) with or without chemotherapy. EXPERIMENTAL DESIGN: Ninety-eight patients with available pretreatment biopsy specimens were studied. Patients had been treated with split-course RT: 30-40 Gy fractionated external beam, followed by a 20-22-Gy boost using interstitial or external RT. Fifty-one patients also received concomitant mitomycin-C and 5-fluorouracil. Median follow-up for surviving patients was 124 months. Tissue sections were examined immunohistochemically for expression of proapoptotic proteins (Bax, p53), antiapoptotic proteins (Bcl-2, Mcl-1), and spontaneous apoptosis (M30). Except for M30, staining of less than 5% of tumor cells was considered negative. Protein expression was correlated with local tumor control (LC) and disease-free survival (DFS) outcomes. The Kaplan-Meier method was used for the monovariate analysis and the Cox proportional hazard models for the multivariate analysis. RESULTS: For LC, beside advanced T- and N-categories and longer overall treatment time (OTT), lack of Bcl-2 expression was associated with poorer 5-year outcome (62 versus 84%, P = 0.009). For DFS, advanced T- and N-categories, longer OTT, and the lack of Bcl-2 expression correlated significantly with lower rates. In the multivariate analysis, N-category (P = 0.0026), OTT (P = 0.04), Bcl-2 (P = 0.0015), and M30 (P = 0.035) expressions were significant factors for LC. For DFS, age (P = 0.049) an N-category (P < 0.0001), as well as expression of Bcl-2 (P = 0.001), p53 (P = 0.003), and M30 (P = 0.03), were found to be independent significant variables. Patients with Bcl-2(+)/p53(-) tumors had a significantly higher 5-year LC compared with patients whose tumors were Bcl-2(-)/p53(+) (93 versus 53%, P = 0.004). CONCLUSIONS: Bcl-2 and particularly the combination of p53 and Bcl-2 expression may prove to be useful predictors of tumor response to RT or radiochemotherapy in anal carcinomas. Patients having tumors that are Bcl-2(-) and p53(+) may require intensified radiochemotherapy or adoption of an alternative therapeutic approach.