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Colleen M Feltmate

Publications and source records attributed to Colleen M Feltmate.

11 recordsLinked to original sources

Expression profiling of mucinous tumors of the ovary identifies genes of clinicopathologic importance.

PURPOSE: To elucidate the molecular mechanisms contributing to the unique clinicopathologic characteristics of mucinous ovarian carcinoma, global gene expression profiling of mucinous ovarian tumors was carried out. EXPERIMENTAL DESIGN: Gene expression profiling was completed for 25 microdissected mucinous tumors [6 cystadenomas, 10 low malignant potential (LMP) tumors, and 9 adenocarcinomas] using Affymetrix U133 Plus 2.0 oligonucleotide microarrays. Hierarchical clustering and binary tree prediction analysis were used to determine the relationships among mucinous specimens and a series of previously profiled microdissected serous tumors and normal ovarian surface epithelium. PathwayAssist software was used to identify putative signaling pathways involved in the development of mucinous LMP tumors and adenocarcinomas. RESULTS: Comparison of the gene profiles between mucinous tumors and normal ovarian epithelial cells identified 1,599, 2,916, and 1,765 differentially expressed in genes in the cystadenomas, LMP tumors, and adenocarcinomas, respectively. Hierarchical clustering showed that mucinous and serous LMP tumors are distinct. In addition, there was a close association of mucinous LMP tumors and adenocarcinomas with serous adenocarcinomas. Binary tree prediction revealed increased heterogeneity among mucinous tumors compared with their serous counterparts. Furthermore, the cystadenomas coexpressed a subset of genes that were differentially regulated in LMP and adenocarcinoma specimens compared with normal ovarian surface epithelium. PathwayAssist highlighted pathways with expression of genes involved in drug resistance in both LMP and adenocarcinoma samples. In addition, genes involved in cytoskeletal regulation were specifically up-regulated in the mucinous adenocarcinomas. CONCLUSIONS: These data provide a useful basis for understanding the molecular events leading to the development and progression of mucinous ovarian cancer.

Adenocarcinoma, Mucinous↗

Low risk of relapse after achieving undetectable HCG levels in women with partial molar pregnancy.

OBJECTIVE: We evaluated the risk of gestational trophoblastic neoplasia (GTN) for women with partial molar pregnancy whose human chorionic gonadotropin (hCG) levels fall spontaneously to undetectable levels using a sensitive hCG assay. METHODS: We analyzed data from the New England Trophoblastic Disease Center to estimate the risk of GTN among 284 women with partial molar pregnancy and at least 6 months of gonadotropin follow-up. RESULTS: None of the 238 women with complete gonadotropin follow-up and a spontaneous decline in serum hCG levels to undetectable levels subsequently developed GTN (95% confidence interval 0-1.6%). CONCLUSION: If these results are replicated at other institutions with longstanding experience managing partial molar pregnancies, it may be reasonable to abbreviate clinical follow-up for women with partial molar pregnancy whose serum hCG levels spontaneously decline to an undetectable level.

Adult↗

Postevacuation hCG levels and risk of gestational trophoblastic neoplasia among women with partial molar pregnancies.

OBJECTIVE: To develop human chorionic gonadotropin (hCG) criteria that determine a patient's risk of developing persistent gestational trophoblastic neoplasia (GTN) or achieving remission after partial mole evacuation. STUDY DESIGN: We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 284 women with partial molar pregnancies diagnosed between 1973 and 2003. RESULTS: An hCG level >199 mIU/mL in the third through eighth week following molar evacuation was associated with at least a 35% risk of GTN. CONCLUSION: Women with partial mole who have elevated hCG levels within the first few weeks after molar evacuation are at increased risk for developing GTN.

Biomarkers, Tumor↗

Clinical characteristics of persistent gestational trophoblastic neoplasia after partial hydatidiform molar pregnancy.

OBJECTIVE: To identify clinical characteristics associated with developing persistent gestational trophoblastic neoplasia (GTN) after partial hydatidiform molar pregnancy (PHM). STUDY DESIGN: Utilizing the Donald P. Goldstein in patients who developed persistence between 1973 and 1989. CONCLUSION: Older age at diagnosis and history of prior mole were significantly more common in women who developed persistence after partial molar pregnancy in referral of patients the earlier cohort but not in idefined clinical the recent cohort. In recent years no clinical factor was at increase their risk significantly associated with rsistence. database at the New England Trophoblastic Disease Center, 284 women with partial molar pregnancy diagnosed between 1973 and 2003 were characteristics identified. Clinical charac- for pe teristics, such as gravidity, parity, age, uterine size, gestational age at diagnosis, human chorionic gonadotropin levels at presentation and time to development of persistence (GTN) were analyzed. Data were also divided into 2 cohorts, an earlier one (1973-1989) and a later one (1990-2003), in order to look at potential changes over time. RESULTS: GTN developed in 5.6% of partial molar pregnancies. Older maternal age was significantly associated with development of persistent GTN in the earlier cohort but not in the recent cohort. Previous molar pregnancy was also statistically significantly more common the development of +/-after PHM.

Adult↗

Whole-genome allelotyping identified distinct loss-of-heterozygosity patterns in mucinous ovarian and appendiceal carcinomas.

PURPOSE: Mucinous adenocarcinoma of the ovary is one of the common histologic types of ovarian cancer. Its pathogenesis is largely unknown. In addition, the differential diagnosis of metastatic mucinous carcinomas to the ovaries, particularly those originating from the appendix, remains challenging. The purpose of this study is to identify molecular biomarkers for mucinous ovarian adenocarcinoma and compare them with those of appendiceal origin. EXPERIMENTAL DESIGN: Genome-wide loss-of-heterozygosity (LOH) analysis was done on DNA isolated from 28 microdissected primary mucinous ovarian carcinomas and five appendiceal adenocarcinomas. Markers from high-loss regions were selected for further analysis on a total of 32 ovarian and 14 appendiceal cancers. RESULTS: High levels of LOH rates (>40%) were detected on chromosome arms 9p, 17p, and 21q in mucinous ovarian carcinoma cases. The frequency of allelic loss was similar between high-grade and low-grade mucinous ovarian carcinoma cases but was significantly higher in ovarian versus appendiceal cases. In addition, LOH rates on five chromosomal loci were statistically different between ovarian and appendiceal carcinomas. CONCLUSION: A high frequency of LOH can be found in mucinous ovarian adenocarcinomas independent of grade. Despite histologic similarities between mucinous ovarian carcinomas and metastatic appendiceal carcinomas, they have distinct LOH profiles, which may be used for distinguishing the two diseases.

Adenocarcinoma, Mucinous↗

Whole-genome allelotyping using laser microdissected tissue.

Laser-based microdissection technologies have been recently developed and applied to procure homogenous populations of tumor cells from paraffin-embedded and frozen tissue sections. When combined with whole-genomic amplification techniques, sufficient amounts of DNA can be generated from a small number of tumor cells procured by laser-based microdissection. Amplified DNA can then be used to perform high-throughput genome-wide allelotyping using fluorescent-labeled microsatellite markers spanning the whole genome. Loss of heterozygosity can be assessed by Genescan and Genotyper software (ABI Prism).

Alleles↗

Human chorionic gonadotropin follow-up in patients with molar pregnancy: a time for reevaluation.

OBJECTIVE: To determine how often patients with molar pregnancy do not complete recommended follow-up and to identify factors that may predict failure to complete human chorionic gonadotropin (hCG) monitoring. This study also sought to determine how often patients with molar pregnancy who do not complete follow-up relapse after attaining at least one undetectable hCG value. METHODS: Four hundred randomly selected patients with molar pregnancy were analyzed regarding the serum hCG levels after molar evacuation. Demographic factors were determined for each patient: age, marital status, gravidity, parity, health insurance type, and distance from patient residence to trophoblastic center. RESULTS: Recommended hCG follow-up was completed in 63% of the uncomplicated 333 cases (n = 211). Three hundred twenty patients achieved at least one undetectable serum hCG level. Among the 320 patients, 33% achieved undetectable hCG values but did not complete recommended follow-up. However, none had any evidence of relapse. A distance of greater than 20 miles from the patient's residence to our center was associated with failure to complete hCG follow-up (P =.001). CONCLUSION: Because none of the 320 patients who achieved at least one undetectable hCG level has been diagnosed with gestational trophoblastic tumor relapse, it may be appropriate to reassess the duration of hCG monitoring for patients with molar pregnancy.

Adolescent↗

Osteopontin as a potential diagnostic biomarker for ovarian cancer.

CONTEXT: Development of new biomarkers for ovarian cancer is needed for early detection and disease monitoring. Analyses involving complementary DNA (cDNA) microarray data can be used to identify up-regulated genes in cancer cells, whose products may then be further validated as potential biomarkers. OBJECTIVE: To describe validation studies of an up-regulated gene known as osteopontin, previously identified using a cDNA microarray system. DESIGN, SETTING, AND PARTICIPANTS: Experimental and cross-sectional studies were conducted involving ovarian cancer and healthy human ovarian surface epithelial cell lines and cultures, archival paraffin-embedded ovarian tissue collected between June 1992 and June 2001, and fresh tissue and preoperative plasma from 144 patients evaluated for a pelvic mass between June 1992 and June 2001 in gynecologic oncology services at 2 US academic institutions. Plasma samples from 107 women selected from an epidemiologic study of ovarian cancer initiated between May 1992 and March 1997 were used as healthy controls. MAIN OUTCOME MEASURES: Relative messenger RNA expression in cancer cells and fresh ovarian tissue, measured by real-time polymerase chain reaction as 2(-DeltaDeltaCT)(a quantitative value representing the amount of osteopontin expression); osteopontin production, localized and scored in ovarian healthy and tumor tissue with immunohistochemical studies; and amount of osteopontin in patient vs control plasma, measured using an enzyme-linked immunoassay. RESULTS: The geometric mean for 2(-DeltaDeltaCT)for osteopontin expression in 5 healthy ovarian epithelial cell cultures was 4.1 compared with 270.4 in 14 ovarian cancer cell lines (P =.03). The geometric mean 2(-DeltaDeltaCT)for osteopontin expression in tissue from 2 healthy ovarian epithelial samples was 9.0 compared with 164.0 in 27 microdissected ovarian tumor tissue samples (P =.06). Immunolocalization of osteopontin showed that tissue samples from 61 patients with invasive ovarian cancer and 29 patients with borderline ovarian tumors expressed higher levels of osteopontin than tissue samples from 6 patients with benign tumors and samples of healthy ovarian epithelium from 3 patients (P =.03). Osteopontin levels in plasma were significantly higher (P<.001) in 51 patients with epithelial ovarian cancer (486.5 ng/mL) compared with those of 107 healthy controls (147.1 ng/mL), 46 patients with benign ovarian disease (254.4 ng/mL), and 47 patients with other gynecologic cancers (260.9 ng/mL). CONCLUSIONS: Our findings provide evidence for an association between levels of a biomarker, osteopontin, and ovarian cancer and suggest that future research assessing its clinical usefulness would be worthwhile.

Biomarkers, Tumor↗

Advances in the understanding of placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT) is the least common form of gestational trophoblastic disease. The tumor represents a neoplastic transformation of intermediate trophoblastic cells that normally play a critical role in implantation. PSTT can occur after a normal pregnancy, spontaneous abortion, termination of pregnancy, ectopic pregnancy or molar pregnancy. It displays a wide spectrum of behavior, and when metastatic, can be difficult to control even with surgery and chemotherapy. Because of PSTT's rarity, limited information is known about its natural history. Several recent studies have indicated that mitotic index is an important prognostic indicator. Advances in chemotherapeutic regimens have also improved clinical response in metastatic disease.

Cell Transformation, Neoplastic↗