WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium.

The Wilms' tumor gene WT1 plays complex roles in the development of the organs of the genitourinary tract and mesothelium, as well as Wilms' tumors. Although its biologic role is still unclear, most serous carcinomas of the ovary and peritoneum, mesotheliomas, and Wilms' tumor have been shown to express WT1. A recent study, however, found no WT1 expression in serous carcinomas of the endometrium, suggesting that WT1 could be useful in identifying the primary site of serous carcinomas. We examined the expression of WT1 and p53 by immunohistochemistry in 69 cases of endometrial carcinoma (35 endometrioid, 18 clear cell, 16 serous), 68 cases of ovarian carcinoma (28 serous, 11 endometrioid, 18 clear cell, and 11 mucinous), 14 fallopian tube carcinomas (12 serous, 2 endometrioid), and 20 primary peritoneal serous carcinomas. WT1 nuclear reactivity of any extent and intensity was considered positive. Immunohistochemical stains were evaluated semiquantitatively using a four-tiered scale. Among endometrial carcinomas, WT1 immunoreactivity was seen in 10 of 16 serous, but in none of 35 endometrioid or 18 clear cell carcinomas. Among ovarian tumors, WT1 expression was seen in 24 of 28 serous and 4 of 18 clear cell carcinomas, but in none of 11 endometrioid and 11 mucinous tumors. All 12 serous carcinomas but none of 2 endometrioid carcinomas of the fallopian tube were positive for WT1. WT1 expression was seen in 19 of 20 serous primary peritoneal carcinomas. The difference in WT1 expression was highly significant between serous and other types of tumors in all sites (p<0.0001, chi-square test), although the level of WT1 expression was significantly different among serous carcinomas arising at different sites (p<0.0001, Kruskal-Wallis test). A significant positive correlation was found between the level of p53 and WT1 expression in all carcinomas combined (r = 0.3935, p<0.0001, Spearman test), but when only serous carcinomas were analyzed, the correlation between p53 and WT1 expression levels did not reach statistical significance. Our results suggest that WT1 expression in epithelial tumors of the female genital tract may be related to cell differentiation and histologic subtypes of carcinomas, rather than to primary site of origin.     

Genetic alterations of the WT1 gene in papillary serous carcinoma of the peritoneum

OBJECTIVE: The Wilms' tumor (WT1) gene product is consistently detectable in both normal ovarian germinal epithelium and human mesothelium. Ovarian carcinomas frequently exhibit alterations in WT1 function. Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining (mesothelium) of the pelvis and abdomen. The purpose of this study was to determine if genetic alterations of the WT1 gene are associated with the development of PSCP. METHODS: Normal and tumor tissue specimens were retrieved from patients with stage III and IV PSCP (n = 38) and serous epithelial ovarian carcinoma (n = 38). Immunohistochemistry was performed using the anti-WT1 (C-19) antibody. Loss of heterozygosity (LOH) was performed at the WT1 locus. Clinical data were obtained and correlated with molecular findings. RESULTS: Loss of normal WT1 expression was detected in 18 (51%) of 35 PSCP specimens and 18 (53%) of 34 ovarian carcinoma specimens. Six (27%) of 22 PSCP specimens and 3 (13%) of 24 ovarian carcinoma specimens had LOH at the WT1 locus (P = 0.27). Normal WT1 gene expression was maintained in 86% of tumors exhibiting LOH. Genetic alterations of the WT1 gene were not predictive of survival, nor were they associated with other clinical or molecular factors. CONCLUSIONS: Genetic alterations of the WT1 gene are associated with the development of PSCP. The loss of normal WT1 gene expression is a common event in both PSCP and advanced ovarian carcinoma, likely resulting from down-regulation by other regulatory factors-not from inactivating gene mutation and subsequent allelic loss.     

Overexpression of cyclin D1 and c-Myc gene products in human primary epithelial ovarian cancer

Cyclin D1 and c-Myc are key participants in the cell-cycle pathway, in which aberrancies have been associated with malignant transformation. To date, data on the relationship of expression of these proteins and histologic subtype of epithelial ovarian cancer are still scarce and discordant. Immunohistochemical analysis was performed on 12 normal ovaries and 47 cases of serous, mucinous, endometrioid, and clear cell ovarian carcinomas. No abnormal expression of cyclin D1 or c-Myc was demonstrated in any of the 12 normal ovarian specimens. However, compared to normal ovarian tissues, overexpression of cyclin D1 and c-Myc was observed in 42.6% (20/47) and 65.9% (31/47) of tumors examined, respectively. There was no significant difference of overexpression of cyclin D1 or c-Myc gene products between these four histologic subtypes of ovarian adenocarcinomas. This study shows that cyclin D1 and c-Myc are frequently overexpressed in epithelial ovarian carcinomas, but they are not correlated with a particular histologic subtype. Although our preliminary results need to be validated in a larger number of tumors, the abnormal expression of cyclin D1 and c-Myc in epithelial ovarian cancer reaffirms the notion that they are crucial components in the pathway of tumorigenesis and deserve further study.     

Genetic Alterations of the WT1 Gene in Papillary Serous Carcinoma of the Peritoneum

Objective. The Wilms' tumor (WT1) gene product is consistently detectable in both normal ovarian germinal epithelium and human mesothelium. Ovarian carcinomas frequently exhibit alterations in WT1 function. Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining (mesothelium) of the pelvis and abdomen. The purpose of this study was to determine if genetic alterations of the WT1 gene are associated with the development of PSCP.Methods. Normal and tumor tissue specimens were retrieved from patients with stage III and IV PSCP (n = 38) and serous epithelial ovarian carcinoma (n = 38). Immunohistochemistry was performed using the anti-WT1 (C-19) antibody. Loss of heterozygosity (LOH) was performed at the WT1 locus. Clinical data were obtained and correlated with molecular findings.Results. Loss of normal WT1 expression was detected in 18 (51%) of 35 PSCP specimens and 18 (53%) of 34 ovarian carcinoma specimens. Six (27%) of 22 PSCP specimens and 3 (13%) of 24 ovarian carcinoma specimens had LOH at the WT1 locus (P = 0.27). Normal WT1 gene expression was maintained in 86% of tumors exhibiting LOH. Genetic alterations of the WT1 gene were not predictive of survival, nor were they associated with other clinical or molecular factors.Conclusions. Genetic alterations of the WT1 gene are associated with the development of PSCP. The loss of normal WT1 gene expression is a common event in both PSCP and advanced ovarian carcinoma, likely resulting from down-regulation by other regulatory factors—not from inactivating gene mutation and subsequent allelic loss.     

In vitro chemoresistance and biomarker profiles are unique for histologic subtypes of epithelial ovarian cancer

OBJECTIVES: To determine whether there is a relationship between histologic subtype of epithelial ovarian cancer and chemoresistance, we evaluated ovarian carcinomas of six histologic subtypes and correlated histology with in vitro drug response. Biomarker profiles (p53, Her-2 neu, and EGFR) were also evaluated to determine if their expression patterns were associated with histology. METHODS: In vitro drug response profiles for different histologic subsets of epithelial ovarian carcinomas exposed to standard relevant chemotherapy agents were determined in the Extreme Drug Resistance assay (EDR). Immunohistochemistry techniques were employed to determine biomarker expression. RESULTS: Of 5195 referred serial cases of epithelial ovarian cancer, there were 2660 papillary serous, 303 endometrioid, 142 mucinous, 102 clear cell, 952 undifferentiated carcinomas, and 42 tumors of low malignant potential. For the samples as a whole, the incidences of extreme drug resistance to the tested chemotherapeutic agents were cisplatin 10%, carboplatin 16%, cyclophosphamide 16%, doxorubicin 40%, gemcitabine 21%, paclitaxel 22%, and topotecan 13%. When compared to papillary serous tumors, mucinous tumors were more frequently resistant to cisplatin (10% vs. 18%) but less frequently resistant to topotecan (13% vs. 5%) and doxorubicin (42% vs. 16%). Endometrioid tumors were less resistant to cisplatin (10% vs. 6%) and doxorubicin (42% vs. 20%). Clear cell and undifferentiated tumors had the lowest rates of EDR to paclitaxel (13% and 18%) and cyclophosphamide (7% and 11%), while borderline tumors showed high rates of EDR to these agents (52% and 63%, respectively). With respect to biomarker profiles, mP53 was detected in 46%, Her-2 neu in 16%, and EGFR in 30% of the cases evaluated. As compared to all other subtypes, clear cell carcinomas had significantly higher Her-2 neu expression (19%). Relative to papillary serous carcinomas, borderline tumors exhibited significantly lower rates of mP53 expression (60% vs.17%). CONCLUSIONS: We found significant differences in the frequencies of extreme drug resistance to chemotherapeutic agents and biomarker expression among histologic subtypes of epithelial ovarian cancer. The data collected in this investigation may provide a guide for stratification of patients entering clinical trials based on histology and biomarker expression.     

Histologic subtypes and laterality of primary epithelial ovarian tumors

OBJECTIVES: To determine if the likelihood of bilateral primary ovarian tumors differs by histologic subtype. METHODS: Using data collected by the Surveillance Epidemiology and End Results (SEER) program, the analysis included 22,328 women 25-84 years of age who were diagnosed with a borderline or malignant epithelial ovarian tumor during 1992-2000, categorized as to laterality and histologic subtype. RESULTS: Malignant serous tumors were bilateral in 57.5% of cases. Corresponding figures for mucinous, clear cell, endometrioid and other epithelial tumors were 21.3%, 13.3%, 26.8%, and 35.6%, respectively. Borderline serous tumors were bilateral in 29.8% of the cases compared to only 7.0% of mucinous tumors. The tendency for serous tumors to present as bilateral was consistent across all categories of race, age, and stage. CONCLUSIONS: Serous tumors of the ovary are more commonly bilateral than ovarian tumors of other histologic subtypes. The reasons for this tendency remain to be determined.     

Fallopian tube: Its role in infertility and gynecological oncology

Disorders of the fallopian tube play a very important role in both infertility and gynaecological oncology. Tubal factor infertility is considered among the leading causes of female factor infertility. Many tubal disorders are related to infertility including congenital anomalies, acute and chronic inflammatory diseases, endometriosis and other pathologies that result in partial or total fallopian tube obstruction. In the field of gynaecological oncology, ovarian surface epithelial tumors remain one of the most fatal malignancies in women worldwide carrying the worst prognosis among female genital malignancies. For decades, the cell of origin of epithelial tumors has remained controversial and was largely believed to be surface ovarian epithelium. Recently several studies suggested that there is a major role of the fallopian tube in the development of ovarian surface epithelial tumors, mainly high grade serous carcinoma and other tumour types. In this article we review the role of the fallopian tube in both infertility and gynaecological oncology.     

卵巢上皮性包涵体的起源与低级别卵巢浆液性癌的发病机制

目的 探讨卵巢上皮性包涵体的起源与低级别卵巢浆液性癌的发病机制.方法 收集山东大学齐鲁医院和美国亚利桑那大学附属医院病理科自2000年5月至2010年4月间收治的卵巢浆液性肿瘤患者及行预防性附件切除术患者的手术标本共198份.其中,卵巢肿瘤标本138份,包括卵巢浆液性囊腺瘤53份、卵巢交界性浆液性肿瘤44份、低级别卵巢浆液性癌41份;无明显病理学变化的同侧卵巢及输卵管标本116份(卵巢及输卵管分别为60、56份),取自60例行预防性附件切除术患者的一侧附件.HE染色后镜下观察所有标本的病理学形态特点;并采用免疫组化单染色法检测其免疫表型配对盒基因8抗原( PAX8)、钙结合蛋白(calretinin)、微管蛋白(tubulin)、核增殖相关抗原(Ki-67)的表达,免疫组化双染色法检测其免疫表型PAX8/calretinin的表达.结果 免疫组化PAX8、calretinin单染色法检测显示,90％( 54/60)的卵巢表面生发上皮细胞的免疫表型为PAX8阴性(-)、calretinin阳性(+),HE染色后镜下观察符合间皮组织的形态特点,为间皮型上皮;但有10％(6/60)的卵巢表面生发上皮细胞的免疫表型为PAX8(+)、calretinin(-),HE染色后镜下观察其与输卵管上皮组织的形态相似,为输卵管型上皮.60份正常卵巢中共有921个卵巢上皮性包涵体,表现出两种免疫表型,79％( 728/921)为PAX8(+)、calretinin(-),HE染色后镜下观察其与输卵管上皮组织的形态相似,为输卵管型包涵体;21％(193/921)为PAX8(-)、calretinin(+),HE染色后镜下观察其与间皮组织的形态相似,为间皮型包涵体.免疫组化PAX8/calretinin双染色法进一步验证了卵巢上皮性包涵体的这两种免疫表型.免疫组化PAX8、calretinin、tubulin单染色法检测显示,免疫表型为PAX8(+)、calretinin(-)、tubulin(+)的卵巢表面生发上皮和卵巢上皮性包涵体均包含纤毛型细胞和分泌型细胞2种柱状细胞,形态上接近输卵管黏膜上皮;而免疫表型为PAX8(-)、calretinin(+)、tubulin(+)的卵巢表面生发上皮和卵巢上皮性包涵体则为单层扁平或立方形细胞,与间皮组织的细胞形态类似.免疫组化tubulin、Ki-67单染色法检测显示,分泌型细胞与纤毛型细胞数的比值和细胞增殖指数在卵巢上皮性包涵体及卵巢浆液性囊腺瘤、卵巢交界性浆液性肿瘤、低级别卵巢浆液性癌中呈明显递增趋势(P＜0.05).结论 免疫表型为PAX8(+)、calretinin(-)的卵巢上皮性包涵体可能起源于输卵管,低级别卵巢浆液性癌的发生可能与分泌型细胞的克隆扩增有关.     

膜联蛋白A8在卵巢上皮性浆液性肿瘤中的表达及临床意义

目的:检测膜联蛋白A8(Annexin A8,ANXA8)在卵巢组织中的表达,探讨其表达与卵巢上皮性浆液性恶性肿瘤患者临床病理参数及预后的相关性。方法:采用免疫组织化学法检测75例卵巢组织(正常卵巢组织组11例、卵巢浆液性良性肿瘤组13例、卵巢浆液性交界性肿瘤组17例、卵巢浆液性恶性肿瘤组34例)中ANXA8的表达,分析其与卵巢癌患者临床病理参数及疾病预后的关系。结果:ANXA8主要定位于细胞膜及细胞质,ANXA8在卵巢浆液性恶性肿瘤组中的高表达率(23/34,67.65%)明显高于正常卵巢组织组(1/11,9.09%)、卵巢浆液性良性肿瘤组(3/13,23.08%)及卵巢浆液性交界性肿瘤组(5/17,29.41%),差异有统计学意义(P分别为0.001、0.006、0.010)。在34例卵巢浆液性恶性肿瘤患者中,FIGOⅢ~Ⅳ期患者的ANXA8的高表达率(21/24,87.5%)明显高于FIGOⅠ~Ⅱ期患者(2/10,20.0%),差异具有统计学意义(P<0.001);盆腹腔残余病灶直径>1 cm患者的ANXA8高表达率(15/17,88.2%)明显高于残余病灶≤1 cm患者(8/17,41.2%),差异有统计学意义(P=0.010)。Kaplan-Meier生存分析表明,FIGO分期、淋巴转移、残余病灶、ANXA8的表达都是影响总生存期(OS)的重要因素(均P<0.05)。Cox多元回归分析表明ANXA8的高表达是影响卵巢浆液性恶性肿瘤患者预后的独立危险因素(P=0.019,HR=11.465,95%CI:1.498~87.757)。结论:ANXA8在卵巢上皮性浆液性恶性肿瘤组织中表达升高,且与卵巢癌不良预后有关,可用于临床监测卵巢上皮性浆液性恶性肿瘤患者病情变化。     

Adenomatoid tumors of the female and male genital tracts express WT1.

Adenomatoid tumors are benign proliferations most often encountered in the female and male genital tracts. The mesothelial phenotype of these unusual tumors has been established by a variety of ultrastructural and immunohistochemical studies, although their etiology is by no means certain. The expression of the Wilms' tumor suppressor gene, WT1, in normal, hyperplastic, and malignant mesothelial cells prompted us to analyze the expression pattern of WT1 in a series of 24 adenomatoid tumors occurring in the uterus, fallopian tube, ovary, epididymis, scrotum, and testis. Twenty-three of the tumors expressed WT1 protein and the same number expressed calretinin, another marker of mesothelial differentiation. The one tumor that failed to stain with calretinin was positive for WT1. These results provide further support for mesothelial differentiation of adenomatoid tumors and suggest that the presence of WT1 expression may be useful in the differential diagnosis of these uncommon neoplasms, especially when they present in unusual settings or expression of other mesothelial markers is absent.     

Cytoplasmic CD24 expression in advanced ovarian serous borderline tumors

OBJECTIVES: CD24, originally described as a B-cell marker, has been revealed as one of the candidate molecular markers of epithelial ovarian cancer. We aimed to determine the pattern and extent of CD24 expression in ovarian serous tumors and to clarify its relationship with pathological parameters, especially those associated with the early events of tumor progression in serous tumors of borderline malignancy. METHODS: A total of 114 ovarian serous tumors, including 9 adenomas, 34 borderline, and 71 carcinomas, were analyzed immunohistochemically using a CD24 monoclonal antibody on paraffin blocks. RESULTS: In normal epithelium and serous cystadenomas, the CD24 expression was localized to the apical membranous portion. In some of borderline tumors (26.4%), additional cytoplasmic expression was observed. The cytoplasmic expression of CD24 in borderline tumors was associated with microinvasion (P = 0.001) and omental implants (P = 0.033) with statistical significance. Serous adenocarcinomas showed strong diffuse cytoplasmic expression of CD24, which was significantly associated with shortened survival rate both in univariate (P = 0.011) and multivariate (P = 0.009) analysis. CONCLUSION: The loss of apical localization with the acquisition of the cytoplasmic staining of CD24 protein is a surrogate marker of stromal invasion in ovarian serous tumors of borderline malignancy. Furthermore, the increase in the cytoplasmic expression of CD24 protein is a strong independent molecular marker for shortened survival rate of patients with ovarian serous adenocarcinomas.     

Differential expression of WT1 and p53 in serous and endometrioid carcinomas of the endometrium.

Wilms' tumor antibody (WT1) has recently been reported to be reactive in most ovarian and peritoneal serous carcinomas, but few studies have looked at WT1 reactivity in endometrial carcinomas. p53, like WT1, is a tumor suppressor gene and in its mutated form is frequently present in endometrial serous carcinoma. Routine immunohistochemical staining for p53 and WT1 was performed in 70 endometrial carcinomas (39 endometrioid and 31 serous) of varying differentiation using tissue microarrays. Only 2 (7.5%) serous carcinomas and none of the endometrioid carcinomas (0%) were reactive for WT1. p53 immunoreactivity was found in 26 (83.9%) serous carcinomas and in 2 (5.1%) endometrioid carcinomas. We conclude that WT1 and p53 expression are not related and that WT1 expression in endometrial serous carcinoma differs from that of its extrauterine counterparts.     

Cell proliferation activity unrelated to COX-2 expression in ovarian tumors

The objective of this study was to assess the expression of Cyclooxygenase-2 (COX-2) and cell proliferation activity (Ki67 expression) in benign, borderline, and malignant serous and mucinous ovarian tumors. Expression of COX-2 and Ki67 proteins were evaluated by immunohistochemistry, in paraffin-embedded sections of ovarian epithelial tumors. The study included 113 serous (67 benign, 15 borderline, and 31 malignant) and 85 mucinous (48 benign, 28 borderline, and 9 malignant) tumors, removed from women who underwent laparotomy between January 1997 and December 2003. From benign to malignant tumors, there was a progressive positive trend in COX-2 expression in both serous and mucinous tumors, more evident in mucinous ones (P < 0.001). Comparing histologic types, COX-2 expression was more prominent in serous than in mucinous benign tumors (P < 0.01), but this difference was not significant in the borderline (P= 0.11) or malignant categories (P= 0.71). There was a progressive Ki67 positivity in line with the tumor histologic gradient for both serous (P < 0.01) and mucinous lesions (P < 0.01), but this increasing expression did not correlate with COX-2 expression in the present series (P= 0.78). There was a higher COX-2 expression in serous ovarian adenomas than in mucinous ones. COX-2 positivity increases in line with the morphologic gradient, from benign to malignant in both histologic types, but it was more prominent in mucinous lesions, pointing to different oncogenic pathways related to different histologic types. A correlation between the expression of COX-2 and Ki67 was not found, suggesting that COX-2 may be required for carcinogenesis, but this pathway is not responsible for cell proliferation in ovarian tumors.     

Atypical mucinous metaplasia and intraepithelial neoplasia of the female genital tract—a case report and review of the literature

Müllerian metaplasia of the female genital tract is usually of limited extent and subtype. We describe the replacement of the lining of the entire genital tract and much of the overlying pelvic serosa by metaplastic müllerian epithelium, in a nulliparous 65-year-old woman with cervical agenesis. She did not have Peutz-Jeghers syndrome and had not had any form of prior hormonal treatment. The metaplastic epithelium extended from the vagina to the serosal surface of the pelvic organs. Mucinous epithelium predominated. In addition, there was multifocal dysplasia of the metaplastic epithelium; this was most prominent in the fallopian tubes where there was marked papillation with cytoarchitectural features reminiscent of a borderline mucinous ovarian tumor. Although müllerian metaplasia is well recognized at different sites within the female genital tract, this highly unusual finding of multiple metaplastic epithelial subtypes and dysplasia involving the mucinous metaplastic epithelium along the entire genital tract and pelvic serosal surface has not, to the best of our knowledge, been reported previously in the absence of Peutz-Jeghers syndrome.     

Human papillomavirus and epithelial ovarian neoplasia

In contrast to the strong association between human papillomavirus (HPV) and squamous cell carcinoma of the lower female genital tract, no viral DNA had been found in epithelial ovarian carcinoma. Recently, however, R. H. Kaufman, J. Bornstein, A. N. Gordon, E. Adam, A. L. Kaplan, and K. Adler-Storthy [Gynecol. Oncol. 27, 340-349 (1987)] reported the detection of HPV-6 DNA by in situ hybridization in 10 of 12 patients with advanced epithelial ovarian carcinoma. To further investigate the possible association between HPV and epithelial ovarian neoplasia, tumor from 12 patients with epithelial ovarian adenocarcinoma, 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian adenomas was examined for HPV DNA by the Southern hybridization technique. All the tissues were tested under low stringency for HPV-6 and under high stringency for HPV-6, HPV-16, HPV-18, HPV-31, and HPV-35. In addition, all tissues were tested by polymerase chain reaction for the presence of HPV-6 and HPV-11. Of the 12 patients with adenocarcinoma, 5 were poorly differentiated, 4 serous, 1 endometrioid, 1 mucinous, and 1 mixed. The neoplasms were of grades 2-4 with a predominance of stages III and IV (83%). Of the 3 patients with tumors of low malignant potential, all were serous and stage I. Of the 3 patients with adenomas, 1 was mucinous, 1 serous, and 1 Brenner. We were unable to detect HPV-related sequences in any of the specimens. On the basis of these findings, there appears to be no association between HPV and epithelial ovarian neoplasia.     

应用组织芯片技术研究卵巢癌组织中缺氧诱导因子1α与血管生成的关系

目的　探讨缺氧诱导因子 1α(hypoxiainduciblefactor 1α ,HIF 1α)在卵巢癌组织中的表达及其与血管生成的关系。方法　联合应用组织芯片和原位杂交、免疫组化技术 ,检测 2 95份卵巢上皮性肿瘤 (其中卵巢癌 2 38份、交界性卵巢肿瘤 19份、良性卵巢肿瘤 38份 )及 13份正常卵巢组织中HIF 1αmRNA和血管内皮生长因子 (VEGF)的表达情况 ,以CD3 4 单克隆抗体标记血管内皮细胞来检测微血管密度 (MVD)。结果　卵巢癌、交界性卵巢肿瘤和良性卵巢肿瘤、正常卵巢组织中HIF 1αmRNA的阳性表达率分别为 81 9%、4 2 1%、13 2 %和 0。交界性卵巢肿瘤和卵巢癌组织中HIF 1αmRNA的表达高于正常卵巢和良性卵巢肿瘤 ,卵巢癌高于交界性肿瘤 ,差异均有统计学意义 (P <0 0 1)。卵巢癌组织中HIF 1αmRNA的表达与手术病理分期和病理类型无关 (P >0 0 5 ) ,而与病理分级呈正相关 (r=0 2 4 6 ,P <0 0 1)。卵巢癌组织中HIF 1αmRNA表达与VEGF表达 (r =0 2 0 6 ,P =0 0 1)和MVD计数 (r =0 4 5 1,P <0 0 1)均呈显著正相关。结论　卵巢癌组织过度表达HIF 1αmRNA ,并通过诱导VEGF促进肿瘤的新生血管形成。     

Prostate-derived Ets factor is overexpressed in serous epithelial ovarian tumors.

The frequent overexpression of prostate-derived Ets factor (PDEF) mRNA in ovarian cancer has been previously reported. The aim of this study was to evaluate PDEF protein expression in ovarian cancer and how this expression might vary at different stages of epithelial ovarian tumors in comparison to normal ovary. A new rabbit polyclonal antibody to PDEF was prepared, and immunohistochemistry was performed on tissue sections from 12 normal ovaries, 10 cases of benign serous cystadenoma, 17 cases of low malignant potential tumor, 19 cases of stage 1, and 15 cases of advanced stage primary epithelial (serous) ovarian carcinomas and their peritoneal metastases. Expression levels were assessed based on the percentage of positively staining cells and the intensity of staining. All 12 normal ovary and 10 benign serous cystadenoma cases were negative for PDEF expression. In contrast, 6 of 17 (35%) low malignant potential tumors, 5 of 19 (27%) stage 1, and 5 of 15 (33%) advanced stage ovarian tumors stained positive for PDEF expression. Together, these results show frequent overexpression of PDEF protein in epithelial ovarian tumors and its lack of expression in normal ovary and cystadenomas, and this supports a role for PDEF in ovarian tumorigenesis. Furthermore, these results suggest that PDEF is a potential marker and target in ovarian cancer.     

Wilms Tumor Gene (WT1) and p53 expression in endometrial carcinomas: a study of 130 cases using a tissue microarray

OBJECTIVE: With the exception of ovarian serous carcinoma, Wilms tumor suppressor gene (WT1) expression in common gynecologic carcinomas has not been described in detail. We studied a large number of endometrial carcinomas to determine the range of tumors that express WT1; this could have prognostic and therapeutic significance. METHODS: We studied the immunohistochemical expression of WT1 and p53 in 130 primary human endometrial carcinomas of various histological subtypes, grades, and stages using a tissue microarray. The clinical data were retrieved from the medical records. RESULTS: WT1 was expressed in a wide variety of endometrial cancers and was most marked in malignant mixed Mullerian tumors (MMMTs) (70% positive). WT1 expression was significantly correlated with high histological grade, and there was a trend toward a worse clinical outcome for patients whose tumors expressed WT1. An association between expression of WT1 and p53 and between these and outcome was noted in a univariate analysis, but only stage and p53 status remained prognostically significant independent variables. CONCLUSION: WT1 is expressed in appreciable numbers of endometrial cancers, particularly MMMTs. These findings support further investigation of WT1 as a possible therapeutic target in gynecologic malignancies.     

Expression of epidermal growth factor receptor in normal ovary and in ovarian tumors.

Increased expression of epidermal growth factor (EGF) receptor has been recorded in many types of human tumors and has been associated with reduced survival in ovarian carcinoma. The purpose of this study was to examine the immunocytochemical distribution of the EGF receptor in normal ovaries (n = 30) and in ovarian tumors (n = 126). Staining was observed in two normal ovaries, in the granulosa cells of a developing follicle, and in surface epithelium. Forty-seven of 103 malignant common epithelial tumors were immunopositive. Staining was usually focal, always confined to the neoplastic epithelium, and showed a cytoplasmic distribution. There was a slight trend for increased EGF receptor expression in more advanced common epithelial malignancies, but this was not statistically significant. No correlation between immunoreactivity and histological subtype or grade of tumor was seen. A few other tumors were also examined: one each of Brenner tumor, mature teratoma, mature teratoma with squamous carcinoma, borderline serous tumor and fibroma; all were immunopositive.