Molecular classification of borderline ovarian tumors using hierarchical cluster analysis of protein expression profiles.

Ovarian tumors range from benign to aggressive malignant tumors, including an intermediate class referred to as borderline carcinoma. The prognosis of the disease is strongly dependent on tumor classification, where patients with borderline tumors have much better prognosis than patients with carcinomas. We here describe the use of hierarchical clustering analysis of quantitative protein expression data for classification of this type of tumor.

Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma.

The purpose of this study was to evaluate the prognostic impact of image cytometry DNA ploidy, MIB-1, and p53 in relation to clinicopathologic variables in 376 consecutive patients with endometrial carcinoma stages I-IV. Following primary treatment 358 patients were considered tumor-free. Relapses and tumor-specific deaths of these patients were noted.

Human papillomavirus infection, centrosome aberration, and genetic stability in cervical lesions.

DNA replication and centrosome duplication have to be strictly synchronized to guarantee genomic stability. p53, pRb, cyclin E, and cyclin A are reported to be involved in the synchronizing process. We investigated the relationship between papillomavirus infection, centrosome aberration and aneuploidy during genesis of cervical carcinoma.

A population-based five-year follow-up study of cervical human papillomavirus infection.

Objective: The purpose of this study was to determine the long-term tendency for cervical human papillomavirus infections to persist in the general population.

Study Design: From 500 women who participated in a 1991 population-based survey, 90 healthy women with normal results of cytologic examination (women with human papillomavirus deoxyribonucleic acid detected and age-matched control women without human papillomavirus deoxyribonucleic acid detected) were interviewed and examined 5 years later colposcopically, cytologically, and with human papillomavirus serologic testing and human papillomavirus deoxyribonucleic acid testing by polymerase chain reaction with 2 different consensus primer pairs (MY09 and MY11 and GP5(+) and GP6(+)), type-specific polymerase chain reaction, and deoxyribonucleic acid sequencing.

Results: The 5-year human papillomavirus clearance rate was 92%.

Classification of human ovarian tumors using multivariate data analysis of polypeptide expression patterns.

Large amounts of data on quantitative gene expression are generated by procedures such as 2-DE analysis of proteins or cDNA microarrays. Quantitative molecular variation may potentially be used for the development of methods for the classification of tumors. We used here the statistical concepts of principal components analysis (PCA) and partial least square analysis (PLS) in an attempt to type ovarian tumors.

Laminin-5 as a marker of invasiveness in cervical lesions.

Background: Treatment decisions for cervical cancer, a common disease worldwide, depend on demonstrating whether or not tumor invasion of the surrounding tissue has occurred. Invasion can be difficult to assess by standard histopathologic methods, especially when limited amounts of tissue are available. Several studies of a variety of cancers have reported increased expression of laminin-5-an important attachment protein for epithelial cells-in invasive carcinomas.

Two-dimensional gel analysis of protein expression in ovarian tumors shows a low degree of intratumoral heterogeneity.

The process of tumor progression leads to the emergence of multiple clones, and to the development of tumor heterogeneity. One approach to the study of the extent of such heterogeneity is to examine the expression of marker proteins in different tumor areas. Two-dimensional gel electrophoresis (2-DE) is a powerful tool for such studies, since the expression of a large number of polypeptide markers can be evaluated.

A multicenter study comparing two endometrial sampling devices--Medscand Endorette and Pipelle de Cornier.

Background: To compare two endometrial sampling devices Medscand Endorette and Pipelle de Cornier with respect to tissue collecting ability, diagnostic accuracy and side effects.

Methods: A prospective, multi-center, cross-over study in 152 women with a medical indication for endometrial biopsy. Samples were collected from each patient on the same occasion with both devices, the order of which was randomized.

Phenotypic analysis of ovarian carcinoma: polypeptide expression in benign, borderline and malignant tumors.

Studies of multiple markers in tumors are required for adequate biological characterization. We have characterized the expression of multiple proteins in human ovarian tumors using the technique of 2-dimensional gel electrophoresis (2-DE/PDQUEST). Tumor cells were prepared from the tissue of 22 ovarian tumors.

Aggressive endometrial cancer in a young patient.

An unusually aggressive case of endometrial cancer in a 30 year old woman is presented. The patient experienced abnormal uterine bleeding, at times requiring blood transfusions, for almost half a year before the diagnosis was revealed. For obvious reasons there is a reluctancy to perform invasive examinations in young women.

Tamoxifen-induced DNA adducts in endometrial samples from breast cancer patients.

Tamoxifen-induced DNA adducts were analyzed with the (32)P-postlabeling method using high-performance liquid chromatography (HPLC)-radioactivity detection from endometrial tissue of breast cancer patients and controls. Liver DNA from tamoxifen-treated rats was used as a positive standard. In blind analysis, five of the seven samples from tamoxifen-treated patients showed DNA adducts; none of the five controls were positive.

Premature rupture of the membranes (PROM) at term in nulliparous women with a ripe cervix. A randomized trial of 12 or 24 hours of expectant management.

Objective: To compare maternal and neonatal outcomes after 12 or 24 hours of expectant management in healthy nulliparous women with a ripe cervix and PROM at term.

Design: A prospective, randomized study.

Location: Karolinska Hospital, Stockholm, Sweden.

Human papillomavirus in cell samples from Stockholm Gynecologic Health Screening.

We compared the results of cytologic screening of 500 women in the Stockholm Gynecologic Health Control with human papillomavirus (HPV) detection by polymerase chain reaction (PCR) and in situ hybridization (ISH). There were two main age groups, one 30 years and younger and the other 40 years and older. There were relatively more women with HPV infection in the younger group than in the older one (15.

HPV detection in cytological cases with condylomatous or dysplastic changes: a study with PCR and in situ hybridization on cytological material.

Cytobrush samples of 80 patients, who previously had a cytological or histopathological diagnosis of condyloma and/or dysplasia were investigated for human papillomavirus infection (HPV) by polymerase chain reaction (PCR) and in situ DNA hybridization technique (ISH). The results were compared with concomitantly obtained cytological Pap-stained smears or, in some cases, histological sections. The time between the diagnosis of the original and the concomitant cytology/histopathology was less than 1 yr.

Value of uterine artery Doppler in endometrial cancer.

Twenty-seven women with endometrial cancer were studied with Doppler ultrasound coupled with a vaginal probe. Pulsatility index of the flow velocity of the uterine artery was recorded and compared to that of a control group. The subjects and the controls did not differ in blood flow measurements.

DNA-content in endometrial carcinoma of tamoxifen-treated breast cancer patients.

DNA measurements and histopathologic evaluation were performed in 17 patients treated with adjuvant tamoxifen for early breast cancer and who developed endometrial carcinoma during or after the tamoxifen therapy. The tumors were exclusively characterized by euploid DNA content except for two cases, one mixed mesodermal sarcoma, a highly malignant and rare tumor, and one adenocarcinoma. Although the use of adjuvant tamoxifen therapy most likely enhances the risk of developing endometrial carcinoma, the beneficial effects of adjuvant breast cancer treatment is of well-known clinical importance.

Descriptive clinicopathologic study of 17 patients with endometrial cancer during or after adjuvant tamoxifen in early breast cancer.

Background: Studies have shown that patients with early-stage endometrial cancer who have previously used endogenous estrogen (oral contraceptives or estrogen replacement therapy) have a favorable prognosis. This has not yet been demonstrated for patients with early-stage endometrial cancer who have received tamoxifen. In addition, studies have raised the question of whether women receiving tamoxifen are at increased risk of endometrial cancer.

The prognostic significance of growth pattern and its relation to tumor cell nuclear DNA content in endometrial carcinoma.

Hysterectomy specimens from 21 endometrial carcinoma patients, who died from their disease, and 23 patients selected at random from 307 survivors, were analysed for tumor growth pattern and tumor cell nuclear DNA content. The results indicate that tumor growth pattern, reflected by the mode of infiltration, is significantly correlated to the clinical course of the disease. Patients with carcinomas exhibiting contiguous growth pattern had a better outcome than patients with discontiguously growing carcinomas.

Methodological aspects on cytochemical DNA assessment of adenocarcinoma of the endometrium by means of image and flow cytometry using conventionally formalin-fixed and paraffin-embedded specimens.

Sometimes widely diverging results have been reported as regards the nuclear DNA ploidy pattern of adenocarcinomas of the endometrium. Since such discrepancies might be due to differences in the techniques applied, it seemed worthwhile to investigate this possibility in conventional uterine curetted specimens. In order to obtain a high incidence of tumours with cancer cell nuclei showing "aneuploid" DNA distribution pattern, a selection was made, so that only those adenocarcinomas that had led to a fetal outcome of the neoplastic disease were examined.

DNA and nuclear protein characteristics in non-neoplastic and neoplastic endometrial tissue.

Feulgen-DNA and nuclear protein (NP) measurements were performed on non-neoplastic and neoplastic endometrium. Non-neoplastic endometrial cells were exclusively characterized by euploid nuclear DNA content. The NP content may vary significantly in relation to the proliferative stage as reflected by a 2-3-fold increase NP/DNA ratio in growing as compared to growth arrested cells.

The effect of labetalol on contractility of human myometrial preparations.

Because of results in animal experiments which demonstrated a partial beta 2-adrenoceptor activity of labetalol on rat uterine smooth muscle the present study was conducted in human preparations. The following results were obtained: 1. Rhythmic uterine contractions with a defined steady-state amplitude and frequency were elicited spontaneously and after methylergometrine.

Combined morphologic and cytochemical grading of serous ovarian tumors.

The potentiality of DNA analysis to complement morphologic evaluation in classifying serous ovarian tumors as adenoma, borderline malignancy, or invasive adenocarcinoma was investigated in a series of 54 tumors. The DNA analyses were performed on histologic tumor sections. The primary diagnoses were borderline tumor in 24 cases and invasive adenocarcinoma in 30 (World Health Organization classification).

The prognostic significance of DNA measurements in endometrial carcinoma.

DNA analysis was performed in 71 cases of endometrial carcinoma, selected from a retrospective series of 445 cases registered at the Department of Gynecology, Radiumhemmet, Karolinska Hospital, Stockholm, during 1973-1975. The histological material from 37 patients surviving more than eight years was compared with that from those who died from cancer within two years. The prognostic value of the DNA distribution pattern of the tumors in relation to the clinical stage and the histological grade of the tumors was evaluated.

Prognostic significance of nuclear DNA content in serous ovarian tumors.

Specimens from 73 serous ovarian cancers were examined with respect to DNA content of the tumor cells. The prognostic value of DNA analysis, as reflected in patient survival, was retrospectively compared with that of conventional histological assessment of cancer. DNA in individual tumor cells was measured in sections from the original paraffin-embedded specimens.