1.Association of EGFR expression with angiogenesis and chemoresistance in ovarian carcinoma.
Ai-ping CHEN ; Jing ZHANG ; Hui LIU ; Shu-ping ZHAO ; Shu-zhen DAI ; Xian-lu SUN
Chinese Journal of Oncology 2009;31(1):48-52
OBJECTIVETo clarify the association of EGFR expression with angiogenesis and chemoresistance in ovarian cancer.
METHODSImmunohistochemical PV-6000 staining was used to detect the expression of EGFR, LRP protein and MVD in 102 ovarian tumor specimens.
RESULTSEGFR, LRP positive rates and MVD in borderline and malignant ovarian specimens were significantly higher than those in the normal and benign ones (P < 0.01). EGFR positive expression rate in stage III-IV carcinoma tissues, poor differentiation and with ascites was higher than that in stage I-II carcinomas of well differentiation and without ascites (P < 0.05). MVD was related to histological grade, residual tumor and ascites, LRP positive expression had no correlation with the clinicopathologic parameters (P > 0.05). The effective rate of chemotherapy in patients with EGFR and LRP-positive expression were 57.1% and 53.7%, respectively, significantly lower than that in cases with EGFR and LRP-negative expression (85.0% and 90.9%, P < 0.05). In the 64 cases with complete data, the three-year survival rate was 53.0%. The survival time was shorter in the cases with EGFR and LRP-positive expression, poor differentiation, ascites and chemoresistance (P < 0.01), and only LRP-positive expression and chemotherapeutic effect were independently related to survival time (P < 0.05). There was a correlation between EGFR and MVD (r = 0.548, P < 0.01), EGFR and LRP positive expression (P = 0.020).
CONCLUSIONThe expression of EGFR in ovarian cancer is related to angiogenesis and chemoresistance. EGFR and LRP-positive expression are related to chemoresistance, and detection of the two proteins may be helpful in guiding chemotherapy choice for ovarian cancer. LRP-positive expression and chemotherapeutic effect may be independent prognostic factors.
Antigens, CD34 ; metabolism ; Ascites ; pathology ; Cystadenocarcinoma, Mucinous ; blood supply ; drug therapy ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; blood supply ; drug therapy ; metabolism ; pathology ; Cystadenoma, Mucinous ; blood supply ; drug therapy ; metabolism ; pathology ; Cystadenoma, Serous ; blood supply ; drug therapy ; metabolism ; pathology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; pathology ; Ovarian Neoplasms ; blood supply ; drug therapy ; metabolism ; pathology ; Receptor, Epidermal Growth Factor ; metabolism ; Survival Rate ; Vault Ribonucleoprotein Particles ; metabolism
2.Retroperitoneal lymph node metastasis in epithelial cancer of the ovary: a report of 58 cases.
Rong XIE ; Yu-Zhen LIN ; Gui-Lin CHEN
Chinese Journal of Oncology 2004;26(8):499-501
OBJECTIVETo analyze the retroperitoneal lymph node metastasis in epithelial cancer of the ovary and offer scientific indications for lymph node radical dissection.
METHODSFifty-eight patients with ovarian cancer treated from January 1990 to December 2000 were retrospectively reviewed. Single-factor and multifactor analysis with Logistic regression model were performed by SPSS 10.0 statistic software.
RESULTSThe metastasis rates of overall lymph nodes, pelvic nodes and para-aortic nodes were 48.3%, 37.9% and 25.9% respectively, among which no significant difference was noted (P > 0.05). Single-factor analysis showed that tumor location, ascitic condition, clinical stage and the size of residual tumor were associated with retroperitoneal lymph node metastasis. Multifactor analysis revealed that clinical stage and size of residual tumor were independent risk factors for metastasis of retroperitoneal lymph nodes.
CONCLUSIONFor early ovarian cancer patients, it is extremely important to perform radical dissection of the retroperitoneal lymph nodes. For advanced or residual lesions, radical dissection of pelvic nodes and para-aortic nodes could be considered in the second exploration.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Cisplatin ; administration & dosage ; Cyclophosphamide ; administration & dosage ; Cystadenocarcinoma, Mucinous ; drug therapy ; secondary ; surgery ; Cystadenocarcinoma, Serous ; drug therapy ; secondary ; surgery ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Middle Aged ; Ovarian Neoplasms ; drug therapy ; pathology ; surgery ; Retroperitoneal Space ; Retrospective Studies ; Second-Look Surgery
3.Clinical features and drug resistance characteristics of ovarian clear cell adenocarcinoma and analysis of its prognostic factors.
Chun-yu ZHANG ; Hong-yan GUO ; Hua LI ; Hong-wu WEN ; Xu-dong LIANG ; Jie QIAO
Chinese Journal of Oncology 2012;34(9):688-691
OBJECTIVETo investigate the clinical features and factors involved in the drug resistance and prognosis of ovarian clear cell adenocarcinoma (OCCA).
METHODSForty-seven OCCA patients and 53 ovarian serous cyst adenocarcinoma (OSCA) patients were included in this study. Their clinical characteristics, drug resistance, and prognostic factors were analyzed.
RESULTSThe onset age of OCCA was (49.09 + 11.80) years old, and that of OSCA was (55.51 + 1.38) year old. There were 53.3% (24/45) of OCCA and 98.0% (50/51) of OSCA patients who had elevated CA125 levels. There were 46.8% (22/47) of OCCA patients and 7.5% (4/53) of OSCA patients who suffered from endometriosis (EMS). The percentage of early stage (stage I and stage II) OCCA was 80.9% (38/47), and that of OSCA was 11.3% (6/53). A statistically significant difference was observed on all these aspects (P < 0.05). The percentage of drug resistant OCCA was 26.1% (12/46), and that of OSCA was 24.0% (12/50), with a non-significant difference (P = 0.814).Among the patients with advanced stage disease, the percentage of drug resistance was 87.5% (7/8) for OCCA, while that of OSCA was 25.0% (11/44), showing a statistically significant difference (P = 0.003). Multiple logistic regression analysis revealed that OCCA (OR = 21.774, 95%CI: 2.438 to 194.431) and advanced stage (OR = 58.329, 95%CI: 5.750 to 591.703) were independent risk factors of drug resistance in ovarian epithelial cancers. For the advanced stage patients, the median overall survival time of OCCA and OSCA were 11 and 29 months, respectively, with a statistically significant difference (P = 0.000). Cox survival analysis showed that OCCA, advanced stage, suboptimal surgery, fewer than 6 cycles of chemotherapy and drug resistance were all risk factors of OS in ovarian cancer patients (P < 0.05).
CONCLUSIONSThe age of onset in OCCA patients is younger than that of OSCA patients. The proportion of combination with endometriosis (EMS) is higher, and more early stage disease is observed in OCCA patients. The percentage of drug resistant in OCCA is higher, especially in advanced stage patients. The prognosis of advanced stage OCCA patients is poorer than that of OSCA patients in advanced stage.
Adenocarcinoma, Clear Cell ; complications ; drug therapy ; metabolism ; pathology ; surgery ; Adult ; CA-125 Antigen ; metabolism ; Cystadenocarcinoma, Serous ; complications ; drug therapy ; metabolism ; pathology ; surgery ; Drug Resistance, Neoplasm ; Endometriosis ; complications ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Ovarian Diseases ; complications ; Ovarian Neoplasms ; complications ; drug therapy ; metabolism ; pathology ; surgery ; Proportional Hazards Models ; Survival Rate
4.Clinicopathologic study on 61 cases of uterine papillary serous carcinoma with or without adjuvant therapy.
De-bin XUE ; Li-juan DING ; Ai-li XIA ; Dong CHEN ; Hua-ping XIA ; Xiao-dong TENG ; Shao-ting XU ; Suo-jiang ZHANG ; Xing-chang REN
Chinese Journal of Pathology 2010;39(10):671-674
OBJECTIVETo study the clinicopathologic features of uterine papillary serous carcinoma (UPSC) and the roles of adjuvant therapy.
METHODSSixty-one cases of UPSC with operation done and followed up for a period of 4 to 9 years were enrolled into the study. The histology of slides specimens were reviewed and immunohistochemical study was performed. The follow-up and survival data were analyzed.
RESULTSAll of the 61 patients were post-menopausal, with a median age of 68 years. The clinical presentations included abnormal vaginal bleeding, abdominal symptoms and abnormal Pap smears. The median size of the tumors was 7.5 cm (range=1.2 to 14.8 cm). There were 27.9% cases in FIGO stage I (8.2% in stage IA, 14.8% in stage IB and 4.9% in stage IC), 9.8% in stage II, 32.8% in stage III and 29.5% in FIGO stage IV. The histologic features were similar to those of the ovarian counterpart, with tumor cells containing the high-grade nuclei and arranged in complex papillae. Psammoma bodies were identified in 24.6% of the cases. Immunohistochemical study showed that the tumor cells demonstrated diffuse and strong nuclear staining for p53 and Ki-67. They were negative for estrogen receptor and progesterone receptor. Fifteen of the 61 cases (24.6%) showed no evidence of myometrial invasion. However, ten of the 15 cases had extrauterine disease, with peritoneal (6/15) and nodal (9/15) involvement. Tumors with deep myometrial invasion, lymphovascular permeation and nodal metastasis were associated with worse prognosis by univariate analysis. Fifty-six patients received adjuvant therapy. The number of patients receiving adjuvant chemotherapy alone, adjuvant radiotherapy alone and combined adjuvant chemotherapy/radiotherapy were 42, 24 and 10, respectively. The median survivals of the chemotherapy group and non-chemotherapy group (with or without radiotherapy) were 66.4 months and 32.8 months, respectively.
CONCLUSIONSUPSC has distinctive clinical and pathologic features. The tumor stage, lymph node status, lymphovascular permeation and depth of myometrial invasion were important prognostic factors. Adjuvant chemotherapy for stage III/IV tumors or recurrent UPSC may have survival benefit.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Papillary ; drug therapy ; pathology ; radiotherapy ; surgery ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Cystadenocarcinoma, Serous ; drug therapy ; pathology ; radiotherapy ; surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Radiotherapy, Adjuvant ; Survival Rate ; Uterine Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery
5.Evaluation of two-tier grading system and significance of p53 protein over-expression in ovarian serous carcinoma.
Jie LIN ; Juan DU ; Chun-yu ZHANG ; Qiao-ting XIE ; Bo ZHANG ; Cong-rong LIU
Chinese Journal of Pathology 2010;39(10):655-660
OBJECTIVETo evaluate the two-tier MDACC grading system for ovarian serous carcinoma by comparing with the WHO grading system, and to investigate the role of p53 immunostaining in ovarian serous carcinoma grading.
METHODS72 cases ovarian serous carcinoma of ovary were graded basing on the MDACC and WHO grading systems, respectively. Statistic analyses were made for the relationship between the data obtained from two grading systems and their clinical significance. All the cases were examined immunohistochemically by using antibody against p53 protein and the immunohistochemistry findings were analyzed with the two grading systems and clinical parameters.
RESULTSThere was a good correlation between the MDACC and WHO grading system (r=0.543, P=0.000). Neither system has a definite relationship with the disease-free survival time (P=0.170 vs. P=0.075), cytoreduction (P=0.478 vs. P=0.120), and the curative effect of platinum-based chemotherapy (P=0.418 vs. P=0.403). However, compared with the WHO grading system, MDACC grading system has a better correlation with tumor stage (P=0.041 vs. P=0.002), 3-year disease-free survival rate (P=0.077 vs. P=0.004), overall survival time (P=0.080 vs. P=0.046), and p53 immunohistochemistry results (P=0.334 vs. P=0.035). No significant difference was found between p53 immunohistochemistry results with other clinical characteristics and prognostic factors.
CONCLUSIONSCompared with the WHO system, the MDACC system showed a better prognostic value and was more likely correlated with the novel dualistic model for ovarian serous carcinogenesis. Although p53 immunostaining was valuable in assisting MDACC grading, it should be cautious to use it alone as an independent indicator in predicting the prognosis of ovarian serous carcinoma.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CA-125 Antigen ; metabolism ; Cystadenocarcinoma, Serous ; drug therapy ; metabolism ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Membrane Proteins ; metabolism ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Platinum Compounds ; administration & dosage ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism ; World Health Organization
6.Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin.
Hongxi ZHAO ; Zhifu YANG ; Xiaohong WANG ; Xianzhi ZHANG ; Meng WANG ; Yukun WANG ; Qibing MEI ; Zhipeng WANG
Experimental & Molecular Medicine 2012;44(11):633-641
Triptolide, a compound extracted from the traditional Chinese medicine preparation of Tripterygium wilfordii Hook F., has been reported to have anti-inflammatory and anti-cancer activities. However, its effect on ovarian cancer invasion is unknown. We observed that MMP7 and MMP19 expression increased in ovarian cancer tissue. Triptolide treatment inhibited the migration and invasion of ovarian cancer cells SKOV3 and A2780 at the concentration of 15 nM. We also observed that triptolide suppressed MMP7 and MMP19 promoter activity in a dose-dependent manner, down-regulating the expressions of these promoters on mRNA and protein level. Moreover, triptolide enhanced E-cadherin expression in ovarian cancer cells. In vivo, triptolide inhibited tumor formation and metastasis in nude mice, and suppressed MMP7 and MMP19 expression; it also enhanced E-cadherin expression in tumor in a dose-dependent manner. Over expression of MMP7 and MMP19, or suppression of E-cadherin expression partially abolished the inhibitory effect of triptolide on invasion of ovarian cancer cells. To summarize, triptolide significantly inhibited the migration and invasion of ovarian cancer cells by suppression of MMP7 and MMP19 and up-regulation of E-cadherin expression. This study shows that triptolide is a good candidate for the treatment of ovarian cancer and reduction of metastasis.
Animals
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Antineoplastic Agents, Alkylating/*pharmacology
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Cadherins/*genetics/metabolism
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Cell Line, Tumor
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Cell Movement/drug effects
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Cell Proliferation/drug effects
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Cystadenocarcinoma, Serous/*drug therapy/pathology
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Diterpenes/*pharmacology
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Epoxy Compounds/pharmacology
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Female
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Gene Expression Regulation, Enzymologic/drug effects
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Humans
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Matrix Metalloproteinase 7/genetics/*metabolism
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Matrix Metalloproteinases, Secreted/genetics/*metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Invasiveness
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Ovarian Neoplasms/*drug therapy
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Paclitaxel/pharmacology
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Phenanthrenes/*pharmacology
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Promoter Regions, Genetic
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Up-Regulation/drug effects
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Xenograft Model Antitumor Assays