Try a new search

Format these results:

Searched for:



Total Results:


The zinc finger gene ZIC2 has features of an oncogene and its overexpression correlates strongly with the clinical course of epithelial ovarian cancer

Marchini, Sergio; Poynor, Elizabeth; Barakat, Richard R; Clivio, Luca; Cinquini, Michela; Fruscio, Robert; Porcu, Luca; Bussani, Cecilia; D'Incalci, Maurizio; Erba, Eugenio; Romano, Michela; Cattoretti, Giorgio; Katsaros, Dionyssios; Koff, Andrew; Luzzatto, Lucio
PURPOSE: Epithelial ovarian tumors (EOT) are among the most lethal of malignancies in women. We have previously identified ZIC2 as expressed at a higher level in samples of a malignant form (MAL) of EOT than in samples of a form with low malignant potential (LMP). We have now investigated the role of ZIC2 in driving tumor growth and its association with clinical outcomes. EXPERIMENTAL DESIGN: ZIC2 expression levels were analyzed in two independent tumor tissue collections of LMP and MAL. In vitro experiments aimed to test the role of ZIC2 as a transforming gene. Cox models were used to correlate ZIC2 expression with clinical endpoints. RESULTS: ZIC2 expression was about 40-fold in terms of mRNA and about 17-fold in terms of protein in MAL (n = 193) versus LMP (n = 39) tumors. ZIC2 mRNA levels were high in MAL cell lines but undetectable in LMP cell lines. Overexpression of ZIC2 was localized to the nucleus. ZIC2 overexpression increases the growth rate and foci formation of NIH3T3 cells and stimulates anchorage-independent colony formation; downregulation of ZIC2 decreases the growth rate of MAL cell lines. Zinc finger domains 1 and 2 are required for transforming activity. In stage I MAL, ZIC2 expression was significantly associated with overall survival in both univariate (P = 0.046) and multivariate model (P = 0.049). CONCLUSIONS: ZIC2, a transcription factor related to the sonic hedgehog pathway, is a strong discriminant between MAL and LMP tumors: it may be a major determinant of outcome of EOTs.
PMID: 22733541
ISSN: 1078-0432
CID: 1934032

Long-term survival after fertility-sparing surgery for epithelial ovarian cancer

Schlaerth, Alan C; Chi, Dennis S; Poynor, Elizabeth A; Barakat, Richard R; Brown, Carol L
OBJECTIVE: To determine the long-term results of fertility-sparing surgery in the treatment of early-stage invasive epithelial ovarian cancer. METHODS: A retrospective review of 123 patients who underwent surgical staging for FIGO stage I epithelial ovarian cancer from November 1982 to July 2002. Demographics, stage, histopathology, adjuvant therapy, recurrence, and survival were compared for patients who had fertility-sparing surgery and for those having standard surgical staging. RESULTS: Twenty patients, with a median age of 27 years, had preservation of the uterus and contralateral ovary at the time of surgical staging. Platinum-based chemotherapy was administered to 50% of these patients postoperatively. Three patients (15%) recurred in the retained ovary at 9, 20, and 22 months, and all died of their disease. One patient was diagnosed with primary endometrial cancer at 15 months and was salvaged with hysterectomy. At a median follow-up of 122 months, 17 (85%) of 20 patients treated with fertility-sparing surgery were alive without disease. Of the 103 patients treated with removal of the uterus and both ovaries, 72% received adjuvant platinum chemotherapy. Twenty (19%) of the patients in the standard surgery group have recurred, and 17 have died of disease. At a median follow-up of 113 months, 78 (76%) of 103 patients treated with standard surgery were alive without disease. Five-year survival data showed no significant difference in the recurrence-free survival of the fertility-sparing and standard surgery groups (84% vs 78%) or overall survival (84% vs 82%). CONCLUSION: Fertility-sparing surgery is a reasonable alternative treatment for young women with stage I epithelial ovarian cancer desiring fertility preservation.
PMID: 19823055
ISSN: 1525-1438
CID: 1934042

CA125 level as a predictor of progression-free survival and overall survival in ovarian cancer patients with surgically defined disease status prior to the initiation of intraperitoneal consolidation therapy

Juretzka, Margrit M; Barakat, Richard R; Chi, Dennis S; Iasonos, Alexia; Dupont, Jakob; Abu-Rustum, Nadeem R; Poynor, Elizabeth A; Aghajanian, Carol; Spriggs, David; Hensley, Martee L; Sabbatini, Paul
OBJECTIVES: Recent data suggest that differences in CA125 levels within the normal range may predict progression-free survival (PFS), but limited information is available regarding the value of these differences in predicting overall survival (OS) in patients with epithelial ovarian cancer. The objective of this study was to determine whether CA125 is an independent predictor of OS in patients with surgically defined disease status at the end of primary therapy prior to intraperitoneal (IP) consolidation chemotherapy. A secondary objective was to assess the relationship of CA125 level to PFS. METHODS: Using data from a retrospective cohort of 433 patients who received intraperitoneal (IP) therapy following primary treatment for ovarian cancer between 1984 and 1998, we identified 241 patients with a complete clinical response and CA125 data at the time of second-look surgery prior to IP chemotherapy. Patient demographics and updated follow-up status were abstracted from medical records. Kaplan-Meier survival curves were compared using the log-rank test, and Cox regression models were used for multivariate analysis. RESULTS: The majority of patients had advanced stage III or IV disease (n=201, 83%) and high-grade histology (n=163, 68%). Taxane was used as part of primary platinum-based therapy in 56% (n=134) of patients, and subsequent IP chemotherapy was platinum-based in 85% (n=206). When considered as a continuous variable, CA125 was a predictor of OS (P=0.029). Using the median CA125 level in our study group as a cut-off, OS was increased in patients with CA125 < or =12 U/ml (median 5.8 years) compared with >12 (3.7 years) (P=0.0027). CA125 level was an independent predictor of OS (HR: 1.410; 95% CI, 1.044, 1.904, P=0.0248) in a multivariate model that included stage (P=0.0166), grade (P=0.0001), and findings at second-look surgery (P=0.0003). CA125 level was also a predictor of clinical PFS (radiographic or CA125 elevation criteria alone) in a subset of 161 patients as a continuous variable (P=0.0036), and when divided at the median (< or = or >12; median 2.8 years vs. 1.7 years; P=0.0017). CONCLUSIONS: In our study population, CA125 level at the end of primary therapy was a predictor of OS and PFS when considered as a continuous variable, or when divided at the median (< or = or >12 U/ml). Further prospective study is required to optimize clinically significant cut-off values within the normal range of CA125 levels for both OS and PFS endpoints.
PMID: 16996584
ISSN: 0090-8258
CID: 1934062

Clinicopathologic features of early adenocarcinoma of the cervix initially managed with cervical conization

Poynor, E A; Marshall, D; Sonoda, Y; Slomovitz, B M; Barakat, R R; Soslow, R A
OBJECTIVE: To evaluate the clinicopathologic features of microinvasive adenocarcinoma of the cervix in order to guide the management of patients with this disease. MATERIALS AND METHODS: A retrospective review was conducted of patients diagnosed with early invasive, 1 mm and 2 mm and 3 mm and 4 mm and
PMID: 16860853
ISSN: 0090-8258
CID: 1934182

The addition of extensive upper abdominal surgery to achieve optimal cytoreduction improves survival in patients with stages IIIC-IV epithelial ovarian cancer

Eisenhauer, Eric L; Abu-Rustum, Nadeem R; Sonoda, Yukio; Levine, Douglas A; Poynor, Elizabeth A; Aghajanian, Carol; Jarnagin, William R; DeMatteo, Ronald P; D'Angelica, Michael I; Barakat, Richard R; Chi, Dennis S
OBJECTIVES: To determine the survival impact of adding extensive upper abdominal surgical cytoreduction to standard surgical techniques for advanced ovarian cancer. METHODS: The records of all patients with stages IIIC-IV epithelial ovarian cancer who underwent primary surgery at our institution from 1998 to 2003 were reviewed. The cohort was divided into 3 groups. Group 1 patients required extensive upper abdominal surgery, such as diaphragm peritonectomy/resection, resection of parenchymal liver or porta hepatis disease and/or splenectomy with or without distal pancreatectomy, to achieve optimal cytoreduction (residual disease
PMID: 16890277
ISSN: 0090-8258
CID: 1934072

Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer

Sabbatini, Paul; Dupont, Jakob; Aghajanian, Carol; Derosa, Felicia; Poynor, Elizabeth; Anderson, Sybil; Hensley, Martee; Livingston, Phillip; Iasonos, Alexia; Spriggs, David; McGuire, William; Reinartz, Silke; Schneider, Sally; Grande, Cathy; Lele, Shashikant; Rodabaugh, Kerry; Kepner, James; Ferrone, Soldano; Odunsi, Kunle
PURPOSE: This open-label study assessed the safety and immunogenicity of two doses and two routes of the anti-idiotypic monoclonal antibody abagovomab (formerly ACA125) in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. EXPERIMENTAL DESIGN: Eligible patients from the three participating institutions were any stage at diagnosis, had relapsed, and had complete or partial response to additional chemotherapy. Patients were randomized to receive abagovomab at 2.0 versus 0.2 mg and i.m. versus s.c. for four immunizations every 2 weeks and then monthly for two additional immunizations. Planned evaluation included interval physical examinations and laboratory assessments with immune assessment, including HLA typing, human anti-mouse antibody, ELISA, and enzyme-linked immunospot. Patients were required to remain on study until week 10 (the first post-baseline Ab3 determination) to be considered for immunologic assessment. The primary end points were safety and immunogenicity primarily determined by Ab3 response. RESULTS: Forty-two patients received at least one vaccination and were eligible for safety analysis. Thirty-three patients were available for Ab3 analysis (removed for progression of disease, 6; withdrawal of consent, 2; unrelated adverse event, 1). The most common adverse events were self-limited pain at injection site, myalgia, and fever. No hematologic or nonhematologic toxicity grade>2 related to immunization was seen. Ab3 was detectable in all patients (median, 236,794 ng/mL); none of route of administration (P=0.6268), dose (P=0.4602), or cohort (P=0.4944) was statistically significant in terms of effect on maximum post-baseline Ab3 titer. Human anti-mouse antibody was not detectable at baseline but was present in all patients at week 16 (range, 488-45,000 ng/mL). CONCLUSIONS: Immunization with abagovomab is well tolerated and induced robust Ab3 responses at the two doses and routes tested. A phase III randomized study with abagovomab (2.0 mg s.c.) is warranted.
PMID: 17000686
ISSN: 1078-0432
CID: 1934052

Fifth International Conference on Ovarian Cancer: challenges and opportunities [Meeting Abstract]

Sood, Anil K; Abu-Rustum, Nadeem R; Barakat, Richard R; Bodurka, Diane C; Brown, Jubilee; Donato, Michele L; Poynor, Elizabeth A; Wolf, Judith K; Gershenson, David M
OBJECTIVE: This paper provides a summary of the presentations given at the Fifth International Conference on Ovarian Cancer in Houston, Texas on December 1-4, 2004. METHODS AND RESULTS: The focus of this meeting was to discuss the most current information regarding development, progression, diagnosis, and therapy of ovarian cancer. The presentations at this conference were grouped into 7 sessions, and are summarized in this paper as follows: ovarian cancer biology, novel therapeutic approaches, surgical and pathological controversies, quality of life/biobehavioral aspects of ovarian cancer, screening/prevention approaches, management of uncommon ovarian cancers, and treatment controversies. CONCLUSION: While many challenges remain in the overall management of ovarian carcinoma, the speakers at this conference reviewed the opportunities available to scientists and clinicians to work collaboratively to make advances.
PMID: 15907981
ISSN: 0090-8258
CID: 1934082

A fertility-sparing alternative to radical hysterectomy: how many patients may be eligible?

Sonoda, Yukio; Abu-Rustum, Nadeem R; Gemignani, Mary L; Chi, Dennis S; Brown, Carol L; Poynor, Elizabeth A; Barakat, Richard R
OBJECTIVE: To determine the percentage of patients with early-stage cervical cancer who may be eligible for fertility preservation with laparoscopic radical vaginal trachelectomy (LRVT). METHODS: We retrospectively reviewed the records of patients who underwent a radical hysterectomy for invasive cervical cancer at our institution from 12/85 to 8/01, before our use of LRVT at Memorial Sloan-Kettering Cancer Center. Institutional eligibility criteria for LRVT were applied. Patients > or =40 years of age were considered ineligible. RESULTS: We identified 435 patients who had undergone radical hysterectomy for cervical cancer; 186 were age < 40 at surgery and constituted our study population. Eighty-nine (48%) patients may have been eligible by our pathologic criteria. In 12 patients, LRVT may have been aborted or altered because of unexpected disease spread. CONCLUSION: A significant number of patients < 40 with early-stage cervical cancer may be pathologically eligible for LRVT and should be counseled on this preoperatively.
PMID: 15581959
ISSN: 0090-8258
CID: 1934092

Improved optimal cytoreduction rates for stages IIIC and IV epithelial ovarian, fallopian tube, and primary peritoneal cancer: a change in surgical approach

Chi, Dennis S; Franklin, Corinna C; Levine, Douglas A; Akselrod, Faina; Sabbatini, Paul; Jarnagin, William R; DeMatteo, Ronald; Poynor, Elizabeth A; Abu-Rustum, Nadeem R; Barakat, Richard R
OBJECTIVE: To determine the impact of the incorporation of extensive upper abdominal debulking procedures on the rates of optimal primary cytoreduction and complications in stages IIIC and IV epithelial ovarian, fallopian tube, and primary peritoneal carcinomas. METHODS: Two groups of patients were identified for comparison. Group 1, the control group, consisted of 70 consecutive patients who underwent "standard" primary cytoreductive surgery before May 2000. Group 2, the study group, was composed of 70 consecutive patients who underwent surgery after January 2001, during which time, a more comprehensive debulking of upper abdominal disease was used, including diaphragm stripping/resection, splenectomy, distal pancreatectomy, liver resection, resection of porta hepatis tumor, and cholecystectomy. RESULTS: The median age of the entire cohort was 60 years (range, 36-88 years). The majority had stage IIIC disease (86%) and serous histology (76%). Optimal cytoreduction (residual disease
PMID: 15350354
ISSN: 0090-8258
CID: 1934102

Gastrointestinal adenocarcinoma arising in a mature cystic teratoma of the ovary [Case Report]

Levine, Douglas A; Villella, Jeannine A; Poynor, Elizabeth A; Soslow, Robert A
BACKGROUND: Mature cystic teratoma of the ovary (MCTO) is the most common ovarian germ cell neoplasm and is usually diagnosed in early adulthood. Malignant transformation is rare, occurring in approximately 2% of all cases. Though malignant transformation can occur from any of the embryonic germ layers, the most common malignancy arising in these otherwise benign tumors is squamous cell carcinoma. CASE: We present a patient with a MCTO where malignant transformation of gastrointestinal epithelium resulted in moderately differentiated adenocarcinoma. After 3 years of follow-up, she remains free of disease. CONCLUSION: Although gastrointestinal epithelium is often found in MCTOs, adenocarcinoma arising from this cell type is uncommon. This is the third reported case of adenocarcinoma arising in gastrointestinal epithelium of a MCTO.
PMID: 15297213
ISSN: 0090-8258
CID: 1934112