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.     

Comparison of early-stage primary serous fallopian tube carcinomas and equivalent stage serous epithelial ovarian carcinomas

ObjectiveTo investigate the outcome of patients with early-stage primary fallopian tube carcinomas (PFTC) and those of patients with equivalent-stage serous epithelial ovarian carcinomas (SEOC).Materials and methodsA balanced and matched, case–control comparison was conducted in a university-based tertiary hospital database between 1978 and 2007. All PFTC and SEOC patients were treated with complete staging surgery followed by multiagent chemotherapy. One SEOC control was matched for each PFTC patient in a very uniform manner (characteristics and treatment). Disease-free survival (DFS) and overall survival (OS) were then compared using Kaplan-Meier analysis.ResultsTwenty-six paired patients were analyzed. Patients with PFTC were significantly older than the SEOC patients (58 years vs. 51 years, p = 0.001). In terms of recurrence, PFTC patients frequently had an extra-abdominal metastasis (3/4, 75%), in contrast to the SEOC patients, who did not (1/5, 20%). The 5-year DFS rate was similar in both groups (85% vs. 81%, p = 0.05), contributing to a similar OS rate (89% vs. 85%, p = 0.50). The median DFS and OS of patients with PFTC and SEOC were also similar without a statistically significant difference (125 months vs. 109 months, and 125 months vs. 122 months, respectively).ConclusionOur study demonstrated that the survival outcome of International Federation of Gynecology and Obstetrics (FIGO) I/II PFTC patients was similar to that of FIGO I/II SEOC patients, and both groups had a >80% 5-year DFS rate after complete staging surgery, followed by multiagent chemotherapy. This finding is worthy of being investigated.     

Primary transitional cell carcinoma of the fallopian tube associated with primary carcinomas of the ovary and endometrium

A patient with primary transitional cell carcinoma of the fallopian tube, primary endometrial adenocarcinoma, and primary endometrioid carcinoma of the ovary is reported. The clinical picture was similar to that of adenocarcinoma of the fallopian tube, but the mode of spread was somewhat different and more aggressive. The patient was treated with surgery and a combination of internal and external radiotherapy.     

Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant low-grade serous carcinoma of the ovary, peritoneum, or fallopian tube

Objective

To evaluate the efficacy and tolerability of imatinib mesylate in patients with recurrent low-grade serous carcinoma (LGSC) of the ovary, peritoneum, or fallopian tube.

Methods

This open-label, single-institution phase II trial enrolled patients with platinum-resistant LGSC who had measurable disease, had received up to 4 platinum- and/or taxane-containing chemotherapy regimens, and had been previously screened for at least one imatinib targeted biomarker (c-kit, platelet-derived growth factor receptor [PDGFR]-β, or bcr-abl). Imatinib (600 mg) was administered daily for one 6-week course and continued in the absence of toxicity and disease progression.

Results

Thirteen patients were enrolled; 12 were evaluable for toxicity, and 11 were evaluable for response. A total of 17 courses were administered (median, 1 course; range, 1-5 courses). Complete or partial responses were not observed. One patient had stable disease for 7.3 months. c-Kit, bcr-abl, or PDGFR-β were present in 48%, 77%, and 100% of patients, respectively. No correlation between best response (stable disease) and the presence of imatinib-targeted biomarkers was observed. Adverse events included grade 3 skin rash in one patient leading to discontinuation of the drug, and grade 3 febrile neutropenia and grade 2 weight gain in two patients leading to dose reductions. The most common grade 1 or 2 toxicities were fatigue (66%), nausea/vomiting (66%), and diarrhea (41%); grade 3 toxicities included skin rash and granulocytopenia events. No grade 4 or 5 toxicities were observed. The median progression-free survival time was 1.3 months (95% CI, 1.27, 1.40 months), and the median overall survival time was 14.9 months (95% CI, 11.0, 18.9 months).

Conclusion

Imatinib is well-tolerated but has no activity in patients with platinum- and taxane-resistant LGSC or the ovary, peritoneum, or fallopian tube.     

Elevation of serum CA125 in carcinomas of the fallopian tube, endometrium, and endocervix

An immunoradiometric assay with the use of a monoclonal antibody can detect an antigenic determinant (CA125) in peripheral blood from more than 80% of patients with epithelial ovarian cancer. In this report elevated levels of CA125 were detected in serum from patients with adenocarcinomas of the fallopian tube, endometrium, and endocervix. Among patients with endometrial cancer, CA125 levels were elevated in recurrent or disseminated disease but not with tumors confined to the uterus.     

Four synchronous female genital malignancies: the ovary,cervix, endometrium and fallopian tube

Objective To present a unique case of a 63 year-old woman with coexistent adenocarcinoma of the ovary, endometrium, cervix and fallopian tube. Materials and methods A case report from a tertiary health center. Results A woman presenting with postmenopausal bleeding and abdominal distantion was assessed by endometrial biopsy and explorative surgery. The frozen section of the mass on the right adnex revealed malign mucinous carcinoma of the ovary. As usual, optimal debulking was performed as initial surgical staging procedure of ovarian cancer. The microscopic examination of the right ovary revealed a typical mucinous cystadenocarcinoma. Furthermore, the focal endometrial irregularity at the left uterine cornus turned out to be a well differentiated endometrial carcinoma of the endometrioid type with <1/3 myometrial invasion. The pale infiltrative lesion in the cervix also turned out to be an adenocarcinoma of the endocervical type with deep stromal invasion and areas of diffuse glandular dysplasia and in-situ glandular neoplasia at the periphery. Besides, several sections from the left fallopian tube uncovered diffuse dysplasia in the lining epithelium and a focus of adenocarcinoma with papillary and cribriform pattern. Discussion When compared with patients having metastatic lesions, most synchronous female malignancies are accompanied with early stage and low-grade with a more favorable prognosis. However, there is paucity of data for the exact criterion to distinguish primary tumors from metastatic lesions. In such cases, the validity of immunohistochemical and cloning studies are not clear.     

CA 125 in normal tissues and carcinomas of the uterine cervix,endometrium and fallopian tube

The distribution of cancer antigen 125 (CA 125) has been investigated in normal tissues and carcinomas of the Müllerian duct by immunohistochemical methods using the monoclonal antibody OC 125. Detection of CA 125 was most intense in cryostat sections and decreased in formalin fixed and paraffin embedded tissues according to the duration of fixation. Enzymatic digestion with neuraminidase or alkaline hydrolysis abolished specific staining suggesting the antigen is a sialylsaccharide bound to protein by alkali-labile linkage. Immunohistochemical staining demonstrated the presence of CA 125 in all normal glandular epithelia of the endocervix, endometrium and fallopian tube in different distribution patterns. In normal endometrium the cellular distribution pattern was related to the menstrual cycle. In endocervical, endometrial and tubal adenocarcinomas CA 125 was found in 73% of cases. In glandular structures the antigen was concentrated at the luminal surface of the tumour cells, in solid tumour areas it was spread throughout the cytoplasm or concentrated in large cytoplasmic vacuoles. The expression of CA 125 was considerably lower in solid tumour areas. These data show that CA 125 is not a true "tumour marker", but a product of female genital mucosae and of their cancerous derivates provided their synthesizing ability is not lost in the course of pathologic differentiation.     

CA 125 in normal tissues and carcinomas of the uterine cervix,endometrium and fallopian tube

Summary The study deals with the occurrence of cancer antigen 125 (CA 125) in the normal and neoplastic uterine cervix, endometrium and fallopian tube and its applicability as a tumour marker. CA 125 concentrations were measured in 52 secretion specimens, in cytosol fractions of 97 tissue biopsies and in serum from 47 women with nonmalignant disorders and from 334 patients with carcinomas. High quantities of CA 125 (780-454860 U/ml) were detected in cervical mucus, intra-uterine and tubal fluid, exceeding those in the corresponding serum samples by factors of up to 2000. CA 125 concentrations were 9–53 fold higher in cytosol fractions of normal and neoplastic glandular epithelia of the endocervix and endometrium than in those of cervical squamous epithelia and the cervical wall. Despite similarly high antigen concentrations in normal glandular epithelia and adenocarcinomas serum levels elevated to above 65 U/ml were only found in patients with malignant tumours. The positivity rates in serum increased with tumour extent and were 0–43% for primary and 63–79% for recurrent cervical, endometrial and tubal adenocarcinomas. During long-term follow-up, CA 125 serum concentrations were concordant with the clinical course in 10 out of 11 patients with progressive carcinomas. According to these results, the release of CA 125 into the peripheral blood is apparently dependent on the infiltrative growth and the mass of the tumour rather than on, the local tissue concentrations. The clinical use of CA 125 is limited to the detection of advanced adenocarcinomas of the Müllerian duct.Presented in part at the 46. Tagung der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe, Sept. 1986, Düsseldorf/FRGDedicated to Prof. Dr. A. Bolte, Köln, for his 60th birthday     

Mesodermal mixed tumor primary in the fallopian tube

Mullerian mixed tumors, as a group, are uncommon. Only 27 cases of this tumor of the fallopian tube have been reported to date. We report the 28th case of mixed mesodermal tumor, originating in the fallopian tube. A 79-year-old woman had mistaken a bloody vaginal discharge for hematuria. Various examinations showed no evidence of malignancy. However, computerized tomography revealed an intrapelvic tumor. Laparotomy was performed, with a suspicion of tubal malignancy. The final pathologic diagnosis was mixed mesodermal tumor, originating in the fallopian tube. Postoperatively, the patient was placed on oral adjuvant chemotherapy for 34 months. At present, she is doing well. Though no definite conclusions regarding the best method of therapy can be reached, an aggressive mode of therapy is recommended. The primary therapy is surgery; however, surgery followed by chemotherapy may have a potential benefit.     

Epithelial hyperplasia of the fallopian tube. Its association with serous borderline tumors of the ovary

We examined sections of fallopian tube from 99 patients with serous borderline tumors of the ovary (SBT) to determine the prevalence of epithelial hyperplasia. Fifty-eight patients with carcinoma of the cervix (CC) and 30 with grade 2 or 3 ovarian carcinoma (OC) served as controls. Patient ages were similar in each group. Epithelial hyperplasia was identified in 68 of 99 patients with SBT (68.7%), compared with 15 of 58 with CC (25.9%) and 4 of 30 with OC (13.3%). Epithelial thickness and nuclear crowding were greater in hyperplastic than in normal fallopian tubes. There was no correlation between hyperplasia and menstrual cycle. In patients with SBT, the presence of epithelial hyperplasia correlated with tumor stage. Hyperplasia was present in 38 of 60 (63%) patients with Stage I tumors. In Stage II and III tumors, hyperplasia was present in 18 of 25 (72%) patients with noninvasive peritoneal implants and 12 of 14 (86%) with invasive implants. Fallopian tube epithelial hyperplasia may represent an example of a field effect in müllerian carcinogenesis.     

20例原发性输卵管癌组织中ER、PR与p~(53)蛋白的表达

目的：分析原发性输卵管腺癌的ＥＲ、ＰＲ及ｐ５３蛋白的表达，研究其与该肿瘤的临床分期、病理分级及患者预后的关系。方法：材料选自２０份原发性输卵管腺癌及１０份正常输卵管组织的存档石蜡包埋标本，采用免疫组化法检测。结果：在２０份原发性输卵管癌标本中，ＥＲ、ＰＲ的阳性表达率分别为２５％和１５％，稍高于正常输卵管组的１０％，但差异无显著性（Ｐ＞０．０５）；ｐ５３蛋白在癌症组的阳性表达率为４０％，对照组则无１例阳性表达，差异有显著性（Ｐ＜０．０５）；ｐ５３蛋白在晚期、分化差及预后不良的输卵管癌病例中的表达呈上升趋势，但未达到统计学意义（Ｐ＞０．０５）；对侧输卵管炎症的存在与ｐ５３蛋白的阳性表达呈负相关（Ｐ＜０．０５）。结论：在原发性输卵管癌中，ＥＲ、ＰＲ有一定程度的表达，但均较低；ｐ５３基因的突变可能参与了该肿瘤的发生，并可作为综合判断其恶性程度及患者预后的指标之一。     

子宫内膜和卵巢原发性双癌的诊治和预后

目的探讨子宫内膜和卵巢原发性双癌的临床病理特点及预后。方法回顾性分析自1995年1月至2006年9月北京大学第一医院诊治的6例子宫内膜和卵巢原发性双癌病例资料。结果6例患者平均年龄为44.7岁,其中3例发生在绝经前。所有患者均接受手术治疗,术后3例病理报告子宫内膜和卵巢均为内膜样癌。5例患者术后接受化疗。全部患者随访3～112个月,1例术后60个月复发,再次接受化疗后病灶消失,所有患者均存活。结论子宫内膜和卵巢原发性双癌不同于单纯子宫内膜癌和卵巢癌,发病年龄早,以内膜和卵巢同为内膜样癌为主要病理类型,首选手术治疗,根据患者情况辅以化疗,预后良好。     

Congenital absence of fallopian tube and ovary.

Absence of one or both uterine tubes and ovaries is a finding that has rarely been described. Two such cases are presented. In one the anatomical abnormalities were discovered during investigations for primary infertility, in the other the absence was discovered at the time of laparoscopic sterilisation. There are two possible aetiologies. The first involves an asymptomatic torsion of one or both adnexes during adult life or childhood, or even before birth. Alternatively, the absence may be congenital, due either to a defect in the development of the entire Müllerian and Mesonephric systems on one side, or to a defect localised to the region of the genital ridge and the caudal part of the Müllerian duct.     

Distinctive gene expression profiles by cDNA microarrays in endometrioid and serous carcinomas of the endometrium.

Endometrial carcinomas are classified by their morphology into two major subtypes. Endometrioid carcinomas (type I) are generally estrogen dependent, well-differentiated, superficially invasive, and have a good outcome. Serous carcinomas (type II) are hormone independent, frequently deeply invasive and widely metastatic, and have a poor prognosis. Microarray technology and analysis allows us to determine if the global gene expression profiles of these two subtypes correlate with their morphologic phenotype. Fresh tissue from 18 endometrial carcinomas was studied: 7 well-, 2 moderately, and one poorly differentiated endometrioid, 4 serous carcinomas, and 4 high-grade mixed endometrioid-serous carcinomas. Labeled cDNA probes were synthesized (Cy5 for tumor, Cy3 for reference) and applied to microarrays containing 18,098 cDNA clones or ESTs. A pool of equal amounts of total RNA from each tumor served as the reference RNA. By unsupervised cluster analysis, the endometrioid carcinomas clustered together and were separate from the serous carcinomas. The high-grade mixed carcinomas clustered with the serous carcinomas. Using a statistical algorithm based on gene expression pattern and conducting a supervised analysis of the two defined groups, we have identified 315 genes that statistically differentiate type I from type II endometrial carcinomas. In addition to corroborating the predicted overexpression of known markers (e.g., ras and catenin in endometrioid carcinomas), the cDNA microarray technique has revealed novel alterations in gene expression relevant to cell cycle, cell adhesion, signal transduction, apoptosis, and tumor progression not previously implicated in endometrial carcinomas. For serous carcinomas, these include aldolase, desmoplakin, integrin-linked kinase, PKC, and metallopeptidase. In conclusion, the gene expression profiles of type I and type II endometrial carcinomas are different. Refinement of these profiles will permit more accurate diagnostic tumor classification and the development of prognosis assays.     

Synchronous carcinomas of endometrium and ovary

Five cases of synchronous carcinomas of uterine endometrium and ovary are reported. All uterine cancers were typical endometrial adenocarcinomas. Among the ovarian cancers, four were serous papillary cystadenocarcinomas and one was an endometrioid carcinoma. There is much controversy with respect to staging and management of such cases since these tumors may represent either two synchronously occurring primaries or a single primary with metastases. It is suggested that when each tumor is confined within the limits of its tissue of origin the tumors may be considered as two separate primaries and surgery may be less aggressive. When there is evidence that at least one tumor is spreading to adjacent tissues and organs the question of two separate primaries or one metastatic tumor becomes academic only and aggressive surgical treatment with adjuvant chemotherapy is indicated.     

Synchronous carcinomas of endometrium and ovary

Five cases of synchronous carcinomas of uterine endometrium and ovary are reported. All uterine cancers were typical endometrial adenocarcinomas. Among the ovarian cancers, four were serous papillary cystadenocarcinomas and one was an endometrioid carcinoma. There is much controversy with respect to staging and management of such cases since these tumors may represent either two synchronously occurring primaries or a single primary with metastases. It is suggested that when each tumor is confined within the limits of its tissue of origin the tumors may be considered as two separate primaries and surgery may be less aggressive. When there is evidence that at least one tumor is spreading to adjacent tissues and organs the question of two separate primaries or one metastatic tumor becomes academic only and aggressive surgical treatment with adjuvant chemotherapy is indicated.