Gene expression profiling in human endometrial cancer tissue samples: utility and diagnostic value.

OBJECTIVE: Recently, gene expression profiling techniques have been used on several human cancers to classify tumor subgroups with a specific biological behavior, which were previously undetected by the conventional histopathologic staging systems. In the current study, the clinical usefulness and prognostic value of gene expression profiling in human endometrial carcinomas were studied. METHODS: A macro cDNA array, containing cDNAs of 588 genes selected from different areas of cancer research, was used to generate gene expression profiles of tumor tissue samples. The gene expression profiles of 12 endometrial cancers, 3 benign (e.g. noncancer) endometrial tissue samples and 3 myometrial tissue samples, taken from human surgical specimen, were compared. RESULTS: The efficacy to generate a gene expression profile of these tissue samples was 77%. The RNA samples could be randomly taken from the tissue samples and were highly reproducible. Cluster analysis of gene expression profiles of the different samples showed that the benign endometrial and the myometrial samples clustered separately from the tumor samples, indicating that the gene expression profiles were tissue specific and not patient specific. Cluster analysis of the tumor samples revealed two distinct tumor clusters. Ranking of the tumors in the two clusters showed high similarity with the histopathologic classification [International Federation of Gynecology and Obstetrics (FIGO) grading]. CONCLUSION: Classification of endometrial tumors on basis of their gene expression profiles showed similarity with the FIGO grading system.

Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method.

The recently developed cDNA expression array technique can be used to generate gene-expression fingerprints of tumour specimens. To gain insight into molecular mechanisms involved in the development and progression of cancer, this cDNA expression array technique could be a useful tool, however, no established methods for interpreting the results are yet available. We used the Atlas cancer cDNA expression array (Clontech, USA) for analysing total RNA isolated from four human endometrial carcinoma samples (two cell-lines and two tissue samples), one benign endometrial tissue sample and a human breast cancer cell-line, in order to develop a method for analysing the array data. The obtained gene-expression profiles were highly reproducible. XY-scatterplots and regression analysis of the logarithmic transformed data provided a practical method to analyse the data without the need of preceding normalization. Three genes (Decorin, TIMP3 and Cyclin D1) were identified to be differentially expressed between the benign endometrial tissue sample and the endometrial carcinoma samples (tissue and cell-lines). These three genes may potentially be involved in cancer progression. A higher degree of similarity in gene-expression profile was found between the endometrial samples (tissue and cell-lines) than between the endometrial samples and the breast cancer cell-line, which is indicative for an endometrial tissue-specific gene-expression profile.

Massive solitary metastasis of hepatocellular carcinoma in the ovary two years after liver transplantation.

Case report of a 47-year-old woman with a mass in the lower abdomen, was referred to us by the surgeon, two years after orthotopic liver transplantation for hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP), which was elevated at the time of initial diagnosis, was in the normal range. Frozen section examination during exploratory laparotomy showed appearances consistent with metastatic HCC in the ovary. This was confirmed at the final pathological examination. Definitive pathological conclusions were based on the findings of tumor cells arranged in trabecular and papillary aggregates, and the presence of bile-pigment, along with the patients history. This is the sixth case of metastatic HCC in the ovary being described in literature and the first case in which this metastasis was not accompanied by elevated AFP.

Magnetic resonance imaging (MRI) in endometrial carcinoma; preoperative estimation of depth of myometrial invasion.

BACKGROUND: The incidence of pelvic and aortic lymph node involvement in endometrial carcinoma depends on both tumor differentiation grade and myometrial invasion depth. It was evaluated whether magnetic resonance imaging (MRI) provides a preoperative technique to assess the depth of myometrial invasion. METHODS: The study includes 34 patients with an endometrial carcinoma. MRI (T5 Gyroscan, Philips) was made a few days before operation. Myometrial invasion was divided in four categories. Cervical invasion was classified as absent, superficial or deep. For comparison an in vitro MRI of the uterus was made directly after the operation. Histo-pathological examination of the uterus was used as a golden standard of the depth of myometrial invasion. RESULTS: The estimation by MRI of the myometrial invasion depth was correct in 25 out of 31 patients. In three patients estimation was not possible, because of bad image quality. In four patients the MRI underestimated the cervical invasion. CONCLUSIONS: Preoperative MRI in patients with an endometrial carcinoma can be used to estimate myometrial and cervical invasion. Therefore, in combination with the histological grading of the tumor, a preoperative MRI can be used to select patients at high risk of nodal involvement.

The incidence of cervical intraepithelial neoplasia among women with renal transplant in relation to cyclosporine.

OBJECTIVE: To evaluate the policy of an annual smear to screen renal transplant recipients for cervical intraepithelial neoplasia and invasive carcinoma and to determine the incidence of abnormal smears and CIN before and after the introduction of cyclosporine (1983). DESIGN: A retrospective study over the period 1971 to 1992. SUBJECTS: Postmenarchial women who received renal transplants and who were on immunosuppressive treatment for at least one month. MEAN OUTCOME MEASURES: Cytology and histology results. RESULTS: A total of 144 women who received renal transplantation were eligible for our study. Observation time varied from 1 to 227 months (median 59 months) with a mean for the group transplanted before 1983 (Group A) of 103 months, and for the group transplanted after 1983 (Group B) of 46 months. Of these women, 25 had an abnormal smear. Of these, 14 were confirmed by histology and repeated smears of the other 11 patients were negative. Within the 60 women in Group A with an abnormal smear, six had CIN I or CIN II, three had CIN III and one showed adenocarcinoma of the endometrium. Among the 84 women in Group B, four had CIN I or CIN II and none had CIN III. The overall incidence of abnormal cytology was 17.3%, with no invasive cervical carcinoma in this group. CONCLUSIONS: Our policy of screening is adequate. With the introduction of cyclosporine the incidence of abnormal cytology and histology has a tendency to decrease. However, the duration of risk is not comparable yet.

The occurrence of diversion colitis in patients with a sigmoid neovagina.

Diversion colitis is an inflammatory process occurring in segments of the colorectum surgically diverted from the fecal stream. Clinical symptoms of this condition are rectal discomfort, pain, discharge, and bleeding. We diverted isolated segments of sigmoid to create neovaginas in patients with aplasia vaginae and in male to female transsexuals. In contrast to what is reported in most studies of diversion colitis, the neovagina consists of an isolated segment not connected to the anus in patients without any pre-existing bowel disease. To investigate the occurrence of diversion colitis in these sigmoid-neovaginas we studied biopsy specimens from 13 patients. Most of the patients complained of discharge and slight blood loss from their sigmoid-neovagina. Microscopic examination of the biopsy specimens showed lymphocytic infiltration in all cases. Four cases showed an acute inflammatory infiltrate in the lamina propria. Our results indicate that the changes observed on clinical and histopathologic examinations represent the entity of mild diversion colitis. We conclude that diversion colitis also occurs in a sigmoid neovagina.

Tubal damage after intratubal methotrexate treatment.

We report on a case of seriously hampered tubal repair 6 months after local MTX treatment. Histopathological examination showed destruction of tubal mucosa and remnants of the EP.

Epithelial markers to detect occult microinvasion in serous ovarian tumors.

Ovarian serous lesions with severe cytological and architectural atypia without obvious destructive stromal invasion may be diagnosed as serous borderline malignant tumor or as serous cystadenocarcinoma, depending on the criteria that individual pathologists use. The recent introduction of the diagnosis "serous borderline tumors with stromal microinvasion" seems an important improvement for the accuracy of the diagnosis of serous ovarian tumors. The aim of this study was to determine if immunohistochemical epithelial markers could help to detect stromal microinvasion in serous ovarian tumors and to compare these findings with the occurrence of "eosinophilic metaplastic" cells. Therefore, we studied the presence of eosinophilic metaplastic cells. Three immunohistochemical epithelial markers were applied in a group of 42 borderline and invasive serous tumors. The histopathologic diagnosis of the tumors was established by a reference center for gynecologic pathology in the Netherlands. We found that "eosinophilic metaplastic" cells were a constant feature in the serous borderline tumor lesions both with and without microinvasion. The presence of these cells should therefore not be considered as pathognomonic for microinvasion. The three investigated antibodies against epithelial epitopes helped to detect microinvasion, with the monoclonal antikeratin (CAM5.2) the best of these antibodies. Serous tumors diagnosed as carcinoma with dubious invasion showed no evidence of microinvasion in 83% of cases. In 13% of serous borderline malignant tumors, microinvasion was detected by the antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Vulvar pseudolymphoma.

We report a 31-year-old patient with longstanding complaints of vulvar itching and painful intercourse treated with many antimycotic drugs. On examination a small tumor, clinically not differentiable from a malignant lymphoma, on and near the clitoris was found. After excision biopsy the lesion proved to be a pseudolymphoma. Six months after excision of this rare vulvar tumor the patient was completely free of complaints. Although pseudolymphomas are small benign tumors they may case diagnostic problems and major complaints. To our knowledge this very rare disorder has not been reported in the gynecological literature until now.

Extra-uterine endometrial stromal sarcoma with DNA flow cytometric analysis.

A case of a primarily extra-uterine low-grade endometrial stromal sarcoma is described. The patients clinical course, including various surgical, chemotherapeutical and hormonal therapies, is outlined and discussed. Transition from benign endometriosis to clinically malignant endometrial stromal sarcoma is illustrated by microscopy and DNA flow cytometry. A change in nuclear DNA content is demonstrated. This is possibly a useful aid in identifying the malignant potential of this tumor with such a misleading microscopic appearance.

Leiomyoma of the ovary.

Ovarian leiomyoma is a rarity. Usually it is not associated with any clinical symptoms. Macro- and microscopically it is indistinguishable from the uterine leiomyoma. Treatment consists of simple removal of the tumor. The possible histogenesis of this tumor is reviewed. It is concluded that the ovarian leiomyoma probably originates from the smooth muscle cells of the ovarian blood vessel or from the smooth muscle fibers near the attachment of the ovarian ligament.