Heterogeneity of stage IIIA endometrial carcinomas: implications for adjuvant therapy.

The purpose of this study was to evaluate overall survival (OS) and determine prognostic subclassifications for stage IIIA endometrial cancer. Stage IIIA endometrial cancer patients treated at M.D.

The activity of taxanes compared with bleomycin, etoposide, and cisplatin in the treatment of sex cord-stromal ovarian tumors.

Objective: We compared the efficacy and side effects of taxanes, with or without platinum, to bleomycin, etoposide, and cisplatin (BEP) in treating sex cord-stromal ovarian tumors.

Methods: We conducted a retrospective review of all patients with sex cord-stromal ovarian tumors seen at our institution from 1985 to 2002. Eligible patients were those who underwent pathologic confirmation, clinical evaluation, and treatment with a taxane or BEP for initial or recurrent disease.

Retrospective review: re-treatment of patients with ovarian cancer with carboplatin after platinum resistance.

The objective of the analysis was to determine the effectiveness of re-treating patients with ovarian cancer, primary peritoneal cancer, and fallopian tube cancer with carboplatin after being deemed platinum resistant. From a database period January 1, 1996, to December 12, 2002, 34 patients were identified who received nonplatinum agents before resuming treatment with carboplatin. The median age was 65 years, and a median of two nonplatinum chemotherapy (range 1-5) prior to re-treatment with carboplatin was received.

Gene expression profiles predict early relapse in ovarian cancer after platinum-paclitaxel chemotherapy.

Purpose: Women with advanced epithelial ovarian cancer are routinely treated with platinum-paclitaxel chemotherapy following cytoreductive surgery, yet only approximately 20% achieve long-term disease-free survival. We hypothesized that differences in gene expression before treatment could distinguish patients with short versus long time to recurrence after administration of platinum-paclitaxel combination chemotherapy.

Experimental Design: To test this hypothesis, gene expression profiling of 79 primary surgically resected tumors from women with advanced-stage, high-grade epithelial ovarian cancer was done using cDNA microarrays containing 30,721 genes.

Fertility-sparing surgery for malignancies in women.

Never before have women with newly diagnosed gynecologic malignancies had more options for preservation of fertility. Girls or women of childbearing age with several ovarian cancer subtypes have a high probability of unilateral ovarian involvement, and, thus, may be candidates for fertility-sparing surgery with preservation of a contralateral normal ovary and uterus. These subtypes include ovarian tumors of low malignant potential, malignant ovarian germ cell tumors, and ovarian sex cord-stromal tumors.

Risk factors for young premenopausal women with endometrial cancer.

Objective: Endometrial cancer is the most common gynecologic malignancy in the United States. The mean age at diagnosis is 61 years; however, 5-30% of women are aged younger than 50 years at the time of diagnosis. The objective of this study was to conduct a clinical and pathologic review of endometrial cancers diagnosed in premenopausal women aged younger than 50 years, to better identify the risk factors for this subgroup of women.

Gynecologic cancer as a "sentinel cancer" for women with hereditary nonpolyposis colorectal cancer syndrome.

Objective: Women with hereditary nonpolyposis colorectal cancer syndrome have a 40-60% lifetime risk for colon cancer, a 40-60% lifetime risk for endometrial cancer, and a 12% lifetime risk for ovarian cancer. A number of women with hereditary nonpolyposis colorectal cancer syndrome will have more than one cancer in their lifetime. The purpose of this study was to estimate whether women with hereditary nonpolyposis colorectal cancer syndrome who develop 2 primary cancers present with gynecologic or colon cancer as their "sentinel cancer.

Subcellular localization of p27kip1 expression predicts poor prognosis in human ovarian cancer.

Purpose: The cyclin-dependent kinase inhibitor p27(kip1) regulates cellular progression from G(1) to S phase. Several studies have shown that loss of p27(kip1) protein expression is associated with disease progression in various malignancies. The purpose of this study was to evaluate the subcellular localization of this cyclin-dependent kinase inhibitor in a large cohort of primary ovarian carcinomas and compare the results with clinicopathologic variables and overall survival.

The use of cytokeratin 7 and EMA in differentiating ovarian yolk sac tumors from endometrioid and clear cell carcinomas.

Yolk sac tumors (YSTs) have a variety of morphologic patterns, some of which can resemble either endometrioid adenocarcinoma (EAC) or clear cell carcinoma (CCC). Immunohistochemical staining for alpha-fetoprotein (AFP) is usually only focal and thus is not always helpful in the diagnosis of YST, and pancytokeratin (CK) is expressed by all three tumors. We studied a battery of immunohistochemical markers with specific attention to the utility of cytokeratin 7 (CK7) in differentiating YST from EAC and CCC.

An HSP90-mimic peptide revealed by fingerprinting the pool of antibodies from ovarian cancer patients.

To gain insight into the mechanisms of molecular recognition and humoral immune response in ovarian cancer, we used fingerprinting, a phage display-based combinatorial selection to isolate peptide ligands to tumor-related antibodies present in ascites from patients with advanced disease. First, we have isolated a consensus motif (sequence CVPELGHEC) in 86% of the peptides screened; this enriched motif was selected from a total of 10(8)-10(9) unique random sequences present in the library. Next, we identified the heat-shock protein 90 kDa (HSP90) as the native antigen mimicked by the motif.

Biological significance of focal adhesion kinase in ovarian cancer: role in migration and invasion.

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is activated by integrin clustering. There are limited data regarding the functional role of FAK in ovarian cancer migration and invasion. In the current study, FAK expression was evaluated in ovarian cell lines (nontransformed and cancer), 12 benign ovarian samples, and in 79 invasive epithelial ovarian cancers.

Expression of imatinib mesylate-targeted kinases in endometrial carcinoma.

Purpose: Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets c-Kit, Abl, and platelet-derived growth factor receptor (PDGFR). It has been shown to be an effective treatment for patients with chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). These cancers are characterized by activating mutations of the Abl and c-Kit tyrosine kinases, respectively.

Third-line chemotherapy in platinum- and paclitaxel-resistant ovarian, fallopian tube, and primary peritoneal carcinoma patients.

Ovarian carcinoma is a malignant disease with a high rate of recurrence, necessitating repeated chemotherapy treatments. We conducted a retrospective study in patients with platinum- and paclitaxel-resistant ovarian, fallopian tubes and primary peritoneal carcinoma patients treated at M.D.

The activity of taxanes in the treatment of sex cord-stromal ovarian tumors.

Purpose: To determine the efficacy and side effects of taxanes, with or without platinum, for the treatment of sex cord-stromal tumors of the ovary.

Patients And Methods: We conducted a retrospective review of all patients seen from 1985 to 2002 at The University of Texas M.D.

Serous carcinoma of the ovary, fallopian tube, or peritoneum presenting as lymphadenopathy.

The clinicopathologic features of 35 cases of serous carcinoma of the ovary, fallopian tube, or peritoneum presenting as lymphadenopathy are described. The cases were retrieved from the files of the Department of Pathology at the University of Texas M. D.

Synchronous primary cancers of the endometrium and ovary: a single institution review of 84 cases.

Objectives: Synchronous primary cancers of the endometrium and ovary are found in 10% of women with ovarian cancer and 5% of women with endometrial cancer. The purpose of this study was to characterize patients diagnosed with synchronous primary cancers of the endometrium and ovary with an emphasis on risk factors.

Methods: Between 1989 and 2002, 84 patients with synchronous primary cancers of the endometrium and ovary were identified.

A phase I study of Adp53 (INGN 201; ADVEXIN) for patients with platinum- and paclitaxel-resistant epithelial ovarian cancer.

Purpose: Adenoviral p53 (Adp53) is a replication-deficient adenovirus containing human p53 cDNA. This phase I study was designed as a toxicity study of multiple dosing of Adp53 administered by intraperitoneal (IP) delivery to patients with ovarian cancer.

Experimental Design: Eligibility criteria included patients with platinum- and paclitaxel-resistant metastatic epithelial ovarian cancer; a Zubrod performance status of 0, 1, or 2; and adequate bone marrow, liver, and renal function.

Her-2/neu overexpression and amplification in uterine papillary serous carcinoma.

Purpose: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer characterized by early metastasis, resistance to therapy, and a high mortality rate. Little is known about the biology of these tumors. Smaller studies suggest that Her-2/neu may be involved in the tumorigenesis of this disease.

Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis.

Purpose: Advanced-stage epithelial ovarian cancer has a poor prognosis with long-term survival in less than 30% of patients. When the disease is detected in stage I, more than 90% of patients can be cured by conventional therapy. Screening for early-stage disease with individual serum tumor markers, such as CA125, is limited by the fact that no single marker is up-regulated and shed in adequate amounts by all ovarian cancers.

Increased plasma levels of insulin-like growth factor 2 and insulin-like growth factor binding protein 3 are associated with endometrial cancer risk.

Circulating insulin-like growth factors (IGFs) and their binding proteins have been associated with increased risk of breast, prostate, colon, and lung cancer. To examine the association of IGFs and endometrial cancer risk, we measured the plasma levels of IGF-1, IGF-2, and IGF binding protein 3 (IGFBP-3) by ELISA in 80 women with endometrial cancer and 80 age-matched control subjects with no history of cancer. Mean plasma levels of IGF-2 were significantly higher in women with cancer versus controls (670 ng/ml versus 380 ng/ml, P < 0.

Analysis of 96 patients with advanced ovarian carcinoma treated with high-dose chemotherapy and autologous stem cell transplantation.

The purpose of this study was to identify characteristics significant to survival and progression-free survival in patients with advanced ovarian cancer receiving high-dose chemotherapy. In all, 96 patients received autologous stem cell transplantation. Regimens included paclitaxel with carboplatin (PC), topotecan, melphalan, cyclophosphamide (TMC) and cyclophosphamide, BCNU, thiotepa (CBT).

Functional role of matrix metalloproteinases in ovarian tumor cell plasticity.

Objective: We previously demonstrated that aggressive ovarian cancer cells are able to display in vitro vasculogenic mimicry, which is reflected by their ability to form vasculogenic-like networks in 3-dimensional cultures and to express vascular cell-associated markers. The goal of this study was to examine the functional role of specific matrix metalloproteinases in the formation of vasculogenic-like networks and extracellular matrix remodeling in vitro. We also investigated the clinical relevance of matrix metalloproteinase-2 and -9 and membrane type 1-matrix metalloproteinase in human ovarian cancers with evidence of tumor cell-lined vasculature.

Detection of residual subclinical ovarian carcinoma after completion of adjuvant chemotherapy.

Purpose: We sought to test the hypothesis that the presence of telomerase activity in peritoneal washings of patients treated for ovarian carcinoma is a sensitive and specific indicator of the presence of residual disease. We hypothesized that this test, if added to second-look procedure protocols, could help determine whether residual disease is present or not in patients who have completed their adjuvant chemotherapy for ovarian carcinoma.

Experimental Design: Peritoneal washings were obtained from 100 consecutive patients undergoing a second-look procedure after treatment for ovarian carcinoma (cases) and from 100 patients undergoing surgery for benign gynecological conditions (controls).

Grading ovarian serous carcinoma using a two-tier system.

In this study, we evaluate a two-tier system for grading ovarian serous carcinoma. This system is based primarily on the assessment of nuclear atypia with the mitotic rate used as a secondary feature. The study included 50 cases of low-grade ovarian serous carcinoma and 50 cases of high-grade ovarian serous carcinoma retrieved from the files of the Department of Pathology at the University of Texas M.