Rouba Ali-Fehmi

Wayne State University, Detroit, Michigan, United States

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Publications (90)293.86 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 03/2014; · 2.07 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the impact of race on the overall survival (OS) and progression-free survival (PFS) of white and African-American patients with uterine clear cell carcinoma (UCCC). A retrospective review was conducted of all primary UCCC cases treated at 1 of 4 major gynecologic cancer centers between 1982 and 2012. Patients and tumor characteristics were retrieved from the cancer databases of the respective institutions and based on a retrospective review of the medical records. Differences in the OS and PFS between African-American and white women were compared using the Kaplan-Meier curves and log-rank test for univariate analysis. Cox regression models for the multivariate analyses were built to evaluate the relative impact of the various prognostic factors. One hundred seventy women with UCCC were included in the study, including 118 white and 52 African-American women. Both groups were comparable with respect to age (P = 0.9), stage at diagnosis (P = 0.34), angiolymphatic invasion (P = 0.3), and depth of myometrial invasion (P = 0.84). In the multivariate analyses for known prognostic factors, OS and PFS were significantly different between white and African-American patients in the early-stage disease (hazard ratio [HR], 5.4; 95% confidence interval [CI], 1.2-23.2; P = 0.023 and HR, 3.5; 95% CI, 1.60-7.77; P = 0.0016, respectively) but not in the advanced-stage disease (HR, 0.83; 95% CI, 0.40-1.67; P = 0.61 and HR, 1.5; 95% CI, 0.84-2.78; P = 0.15, respectively). In the current study, African-American patients have a prognosis worse than that of white patients in early-stage UCCC. We could not prove the same difference in advanced-stage disease.
    International Journal of Gynecological Cancer 02/2014; · 1.94 Impact Factor
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    ABSTRACT: Objective Endometrial cancer mortality disproportionately affects black women and whether greater prevalence of obesity plays a role in this disparity is unknown. We examine the effect of race on post-surgical complications, length of stay, and mortality specifically in a morbidly obese population. Methods Black and white women with endometrial cancer diagnosed from 1996 to 2012 were identified from the University Pathology Group database in Detroit, Michigan, and records were retrospectively reviewed to obtain clinicopathological, demographic, and surgical information. Analysis was limited to those with a body mass index of 40 kg/m2 or greater. Differences in the distribution of variables by race were assessed by chi-squared tests and t-tests. Kaplan–Meier and Cox regression analyses were performed to examine factors associated with mortality. Results 97 white and 89 black morbidly obese women were included in this analysis. Black women were more likely to have type II tumors (33.7% versus 15.5% of white women, p-value = 0.003). Hypertension was more prevalent in black women (76.4% versus 58.8%, p-value = 0.009), and they had longer hospital stays after surgery despite similar rates of open vs minimally invasive procedures and lymph node dissection (mean days = 5.4) compared to whites (mean days = 3.5, p-value = 0.036). Wound infection was the most common complication (16.5% in whites and 14.4% in blacks, p-value = 0.888). Blacks were more likely to suffer other complications, but overall the proportions did not differ by race. In univariate analyses, black women had higher risk of endometrial cancer-related death (p-value = 0.090). No racial differences were noted in adjusted survival analyses. Conclusion A more complete investigation, incorporating socio-demographic factors, is warranted to understand the effects of morbid obesity and race on endometrial cancer.
    Gynecologic Oncology 01/2014; 133(1):38–42. · 3.93 Impact Factor
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    ABSTRACT: This article reviews the molecular features and pathogenesis of gynecologic malignancies. Understanding the molecular basis of endometrial carcinoma helps to provide an explanation for the prognosis of these tumors and opens up avenues for research into novel therapies that may prove beneficial.
    Clinics in laboratory medicine 12/2013; 33(4):911-925. · 1.17 Impact Factor
  • Sudeshna Bandyopadhyay, Rouba Ali-Fehmi
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    ABSTRACT: The most significant contribution of molecular subtyping of breast carcinomas has been the identification of estrogen-positive and estrogen-negative tumor subtypes, which are 2 distinct entities with differing prognoses and requiring different therapy. Molecular and genetic analyses can provide prognostic information; however, a thorough histopathologic evaluation with an evaluation of predictive biomarkers will provide similar information. Knowledge of genetic alterations in these tumors will help identify novel therapeutic targets, which might have an impact on prognosis. Understanding the progression pathways involved in the transition of in situ carcinoma to invasive carcinoma might lead to efficient risk stratification in these patients.
    Clinics in laboratory medicine 12/2013; 33(4):891-909. · 1.17 Impact Factor
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    ABSTRACT: A subset of uterine serous carcinoma (USC) may have better clinical behavior bringing up the possibility that there may be morphologic features, which would help in their categorization. The aim of this study is to evaluate the potential use of the MD Anderson Cancer Center 2-tier grading system for ovarian carcinoma in USC. Tumors assigned a combined score included in this analysis were 1) low-grade: tumors without marked atypia and 12 mitoses/10 high power field (HPF) and 2) high grade: tumors with severe nuclear atypia and >12 mitoses/10 HPF. Clinicopathologic parameters evaluated included patients' age, tumor size, myometrial invasion (MI), lymphovascular invasion (LVI), lymph node (LN), FIGO stage, and patient outcome. 140 patients with USC were included, 30 low grade uterine serous carcinoma (LGUSC) and 110 high grade uterine serous carcinoma (HGUSC). Of all parameters only 2 (MI and stage IA) reached statistical significance. 67% of LGUSC cases showed myometrial invasion versus 93.6% HGUSC cases (p=0.003). A higher percentage of LGUSC (63.3%) versus HGUSC (32.7%) were in stage IA (p=0.01). However, by multivariate analysis including age, LVI, stage and tumor grade only stage was an independent prognostic factor. The presence of atypia and mitosis across a uterine serous carcinoma is notoriously variable in magnitude and extent, potentially making evaluation of these features difficult and subsequent grading subjective. Our findings thus show that actual prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma may not be applicable.
    Gynecologic Oncology 11/2013; · 3.93 Impact Factor
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    ABSTRACT: Platelet-derived growth factor receptor alpha (PDGFRα) is believed to be associated with cell survival. We examined (i) whether PDGFRα blockade enhances the antitumor activity of taxanes in ovarian carcinoma and (ii) potential biomarkers of response to anti-PDGFRα therapy. PDGFRα expression in 176 ovarian carcinomas was evaluated with tissue microarray and correlated to survival outcome. Human-specific monoclonal antibody to PDGFRα (IMC-3G3) was used for in vitro and in vivo experiments with or without docetaxel. Gene microarrays and reverse-phase protein arrays with pathway analyses were performed to identify potential predictive biomarkers. When compared to low or no PDGFRα expression, increased PDGFRα expression was associated with significantly poorer overall survival of patients with ovarian cancer (P=0.014). Although treatment with IMC-3G3 alone did not affect cell viability or increase apoptosis, concurrent use of IMC-3G3 with docetaxel significantly enhanced sensitization to docetaxel and apoptosis. In an orthotopic mouse model, IMC-3G3 monotherapy had no significant antitumor effects in SKOV3-ip1 (low PDGFRα expression), but showed significant antitumor effects in HeyA8-MDR (high PDGFRα expression). Concurrent use of IMC-3G3 with docetaxel, compared with use of docetaxel alone, significantly reduced tumor weight in all tested cell lines. In protein ontology, the EGFR and AKT pathways were downregulated by IMC-3G3 therapy. MAPK and CCNB1 were downregulated only in the HeyA8-MDR model. These data identify IMC-3G3 as an attractive therapeutic strategy and identify potential predictive markers for further development.
    Gynecologic Oncology 10/2013; · 3.93 Impact Factor
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    ABSTRACT: Poorer survival from head and neck squamous cell carcinoma (HNSCC) in African Americans (AA) may be due to disparity in the prevalence of Human Papillomavirus (HPV) but earlier studies often failed to control other etiological factors. We aimed to elucidate whether racial disparities in HPV prevalence and overall survival were due to confounding from smoking or alcohol use. 385 patients with SCC of the mouth, pharynx, nose, or larynx who had surgical resection at Wayne State University affiliated hospitals were identified through a population-based cancer registry. Formalin fixed paraffin embedded tissue blocks were used to determine the presence of HPV DNA and its genotype using a sensitive broad-spectrum PCR technique. Patients' demographics, tumor characteristics and vital status were obtained through record linkage with the registry data and smoking and alcohol information was abstracted from medical record. Cox's proportional hazard model and unconditional logistic regression models were employed to analyze the overall survival and tumor HPV-positivity, respectively. HPV positivity in oropharyngeal cancer was substantially lower in AA than in other racial groups (odds ratio 0.14, 95% confidence interval (CI) 0.05-0.37) and adjustment for smoking or alcohol did not change this association. However, a significantly increased hazard ratio of death in AA oropharyngeal cancer patients (univariable hazard ratio (HR) 2.55, 95% CI 1.42-4.59) decreased to almost unity (HR 1.49, 95% CI 0.75-2.93) after adjustment for HPV and smoking. Lower HPV prevalence in AA largely accounts for their poorer survival from oropharyngeal cancer, but not other HNSSC.
    American journal of otolaryngology 09/2013; · 0.77 Impact Factor
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    ABSTRACT: The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 09/2013; · 2.07 Impact Factor
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    ABSTRACT: The purpose of this study was to examine predictors of lymph node (LN) metastases or extrauterine disease (ED) in low-grade (FIGO grade 1 or 2) endometrioid carcinoma (LGEC) in a multi-institutional setting. For LGEC with and without LN metastasis or ED, each of the 9 participating institutions evaluated patients' age, tumor size, myometrial invasion (MI), FIGO grade, % solid component, the presence or absence of papillary architecture, microcystic, elongated, and fragmented glands (MELF), single-cell/cell-cluster invasion (SCI), lymphovascular invasion (LVI), lower uterine segment (LUS) and cervical stromal (CX) involvement, and numbers of pelvic and para-aortic LNs sampled. A total of 304 cases were reviewed: LN or ED, 96; LN/ED, 208. Patients' ages ranged from 23 to 91 years (median 61 y). Table 1 summarizes the histopathologic variables that were noted for the LN or ED group: tumor size ≥2 cm, 93/96 (97%); MI>50%, 54/96 (56%); MELF, 67/96 (70%); SCI, 33/96 (34%); LVI, 79/96 (82%); >20% solid, 65/96 (68%); papillary architecture present, 68/96 (72%); LUS involved, 64/96 (67%); and CX involved, 41/96 (43%). For the LN/ED group, the results were as follows: tumor size ≥2 cm, 152/208 (73%); MI>50%, 56/208 (27%); MELF, 79/208 (38%); SCI, 19/208 (9%); LVI, 56/208 (27%); >20% solid, 160/208 (77%); papillary architecture present, 122/208 (59%); LUS involved, 77/208 (37%); CX involved, 24/208 (12%). There was no evidence of a difference in the number of pelvic or para-aortic LNs sampled between groups (P=0.9 and 0.1, respectively). After multivariate analysis, the depth of MI, CX involvement, LVI, and SCI emerged as significant predictors of advanced-stage disease. Although univariate analysis pointed to LUS involvement, MELF pattern of invasion, and papillary architecture as possible predictors of advanced-stage disease, these were not shown to be significant by multivariate analysis. This study validates MI, CX involvement, and LVI as significant predictors of LN or ED. The association of SCI pattern with advanced-stage LGEC is a novel finding.
    The American journal of surgical pathology 09/2013; · 4.06 Impact Factor
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    ABSTRACT: The miR-200 family is well known to inhibit the epithelial-mesenchymal transition, suggesting it may therapeutically inhibit metastatic biology. However, conflicting reports regarding the role of miR-200 in suppressing or promoting metastasis in different cancer types have left unanswered questions. Here we demonstrate a difference in clinical outcome based on miR-200's role in blocking tumour angiogenesis. We demonstrate that miR-200 inhibits angiogenesis through direct and indirect mechanisms by targeting interleukin-8 and CXCL1 secreted by the tumour endothelial and cancer cells. Using several experimental models, we demonstrate the therapeutic potential of miR-200 delivery in ovarian, lung, renal and basal-like breast cancers by inhibiting angiogenesis. Delivery of miR-200 members into the tumour endothelium resulted in marked reductions in metastasis and angiogenesis, and induced vascular normalization. The role of miR-200 in blocking cancer angiogenesis in a cancer-dependent context defines its utility as a potential therapeutic agent.
    Nature Communications 09/2013; 4:2427. · 10.02 Impact Factor
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    ABSTRACT: OBJECTIVE: We aimed to compare the differences in demographic features, clinicopathologic features, and survival in patients with vulvar/vaginal melanoma versus cutaneous melanoma with a special emphasis on race. MATERIALS AND METHODS: Data were obtained from the Surveillance Epidemiology and End Results database from 1973 to 2008. Kaplan-Meier curves and Cox multivariate model were used for statistical analysis. RESULTS: Seven hundred sixty-two patients with vulvar/vaginal melanoma and 55,485 patients with cutaneous melanoma patients were included in the study. Twenty-eight patients of the vulvar/vaginal group and 334 patients of the cutaneous group were black (3.6% vs 0.6%, respectively). The median age at the time of diagnosis was 68 years in the vulvar/vaginal group and 52 years in the cutaneous group (P < 0.0001). Three hundred fifty patients (45.9%) in the vulvar/vaginal and 46,499 patients (83.8%) in the cutaneous group presented with localized disease (P < 0.0001), whereas 64 patients (8.4%) in the vulvar/vaginal group and 1520 patients (2.7%) in cutaneous group presented with advanced disease (P = 0.0081). The median survival of the black patients was 16 months in the vulvar/vaginal group and 124 months in the cutaneous melanoma group (P < 0.0001). The median survival in the nonblack population was 39 months in the vulvar/vaginal group compared to 319 months in the cutaneous melanoma group (P <0.0001). In multivariate analysis performed for patients between 1988 and 2008, age, stage, and positive lymph nodes were negative independent prognostic factors for survival in vulvar/vaginal melanoma; whereas age, race, stage, radiation therapy, and lymph node positivity were negative prognostic factors in cutaneous melanoma. CONCLUSION: These findings emphasize that cutaneous and vulvar/vaginal melanomas have different clinicopathologic features and survival patterns.
    International Journal of Gynecological Cancer 06/2013; · 1.94 Impact Factor
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    ABSTRACT: The enhancer of zeste homolog 2 (EZH2) methyltransferase, which plays a key role in transcriptional gene repression, is abnormally elevated in epithelial ovarian cancer (EOC) patients and positively correlated with increasing stage of disease. We demonstrated that EZH2 depletion by RNA interference efficiently inhibited cell proliferation, colony formation, cell invasion, activated the apoptotic pathway, and enhanced chemosensitivity. Silencing of EZH2 resulted in re-expression of p21(waf1/cip1) on chromatin immunoprecipitation assay and concomitant down-regulation of trimethylated H3K27 and mutant p53 protein, contributing to attenuated EOC growth in SCID mice. Our findings suggest that EZH2-shRNA holds promise as a potential therapeutic modality for EOC.
    Cancer letters 04/2013; · 4.86 Impact Factor
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    ABSTRACT: OBJECTIVES: The objective of this study was to estimate the prevalence and prognostic impact of lymphadenectomy and lymph node involvement in patients with ovarian clear cell carcinoma (OCCC) grossly confined to the ovary. METHODS: Patients with a diagnosis of OCCC grossly confined to the ovary were identified from Surveillance, Epidemiology, and End Results program from 1988 to 2007. Only surgically treated patients were included. Statistical analysis using Student t test, Kaplan-Meier survival methods, and Cox proportional hazards regression were performed. RESULTS: One thousand eight hundred ninety-seven patients with OCCC who have undergone surgical treatment and deemed at time of the surgery to have disease grossly confined to the ovary were included: 538 (28.3%) had no lymphadenectomy (LND -1), and 1359 (71.7%) had lymphadenectomy. Of the 1359 patients who had lymphadenectomy, 1298 (95.5%) were International Federation of Gynecology and Obstetrics (FIGO) surgical stage I (LND +1), and 61 (4.5%) were upstaged to FIGO stage IIIC due to nodal metastasis (LND +3C). The 5-year disease-specific survival was 84.9% for LND -1, 88.0% for LND +1, and 65.0% for LND +3C (P < 0.001). Among those with histologically negative lymph nodes, the 5-year disease-specific survival was 85% for patients with 1 to 10 nodes removed, and 91% for those with more than 10 nodes removed (P = 0.054). On multivariate analysis after controlling for stage, age, and race, lymph node metastasis was an independent predictor of poor disease-specific survival (hazard ratio, 3.1; 95% confidence interval, 1.86-5.28; P < 0.001). On other hand, there was a trend toward an improved survival when more extensive lymphadenectomy is performed in patients with histologically negative nodes (1-10 vs >10 nodes), but it did not reach statistical significance (hazard ratio, 0.71; 95% confidence interval, 0.49-1.02; P = 0.064). CONCLUSIONS: Lymph node metastasis was uncommon in patients diagnosed with OCCC grossly confined to the ovary; however, patients with positive nodes were more likely to die compared to those with negative nodes. More extensive lymphadenectomy plays an important role in providing accurate staging and prognostic information.
    International Journal of Gynecological Cancer 02/2013; · 1.94 Impact Factor
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    ABSTRACT: The objective of this study was to analyze the clinical and pathologic factors in patients with uterine serous carcinoma confined to the endometrium. A total of 236 uterine serous carcinoma patients from the pathology databases of 4 large academic institutions were included in the study. Clinical and pathologic variables were analyzed, including patient demographics, tumor size (≤2 vs. >2 cm), myometrial invasion, lymphovascular invasion, lymph node status, tumor location (endometrium vs. polyp), cervical involvement, lower uterine segment involvement, FIGO stage, pelvic washings, recurrence, overall survival, and progression-free survival. Of 236 patients, 55 (23%) had tumors limited to the endometrium. Forty-four patients (80%) had Stage IA tumors. The tumor was confined to a polyp in 17 (30.9%) patients. Twenty patients (36.4%) had tumor sizes >2 cm and 12 (21.8%) exhibited lymphovascular invasion. Only 3 patients (5.4 %) had cervical stromal involvement. Thirty-three (66%) patients underwent pelvic and para-aortic lymphadenectomy with 2 positive para-aortic lymph nodes identified. Seven (12.7%) patients had positive washings, whereas 8 patients (14.5 %) had disease recurrence. At a median follow-up of 46 months, there was no difference in overall survival (P=0.216) or progression-free survival (P=0.063) between patients with tumors confined to a polyp, patients with tumors confined to the endometrium, and patients with tumors present in both polyp and the endometrium. Uterine serous carcinoma with only endometrial involvement, even when confined to a polyp, can be associated with poor prognosis, further stressing the importance of complete surgical staging and adjuvant treatment in this setting.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 01/2013; · 2.07 Impact Factor
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    ABSTRACT: OBJECTIVE: Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but ~40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor. METHODS: Clinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan Meier method; multivariate analysis was performed via cox-regression. RESULTS: The patients' mean age was 67.2years (range 40-91). Survival ranged from 0-184months (mean 42.8). We used a tumor size cut-off of 1cm and noted significant associations with myometrial invasion (p <0.0001), angiolymphatic invasion (p <0.0001), peritoneal washings (p=0.03), stage (p =0.015) and positive lymph nodes (p=0.05). Furthermore, recurrence was associated with larger tumors (p=0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors <1cm in both univariate and multivariate analysis. Conclusions Treatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The 1cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging.
    Gynecologic Oncology 11/2012; · 3.93 Impact Factor
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    ABSTRACT: Benign breast disease (BBD) is an established risk factor for breast cancer among Caucasian women, but less is known about BBD in African American (AA) women. As AA women suffer from disproportionate mortality due to breast cancer, special focus on pathological characteristics that may influence disease risk is warranted. Benign breast biopsies from AA women were identified by the University Pathology Group in Detroit, Michigan. AA women age 20 to 84 who underwent a breast biopsy from 1997 to 2000 were eligible for the study. Subsequent breast cancers were identified through a linkage with the Detroit SEER program. The first biopsy was reviewed by the pathologist, and lesions were classified following Dupont and Page criteria along with involution and other histologic features. Logistic regression was used to estimate the risk of developing a subsequent breast cancer with the histologic characteristics of BBD. 1,406 BBD biopsies from AA women were included in this study with a median follow-up of 10.1 years. The majority (68%) showed non-proliferative disease, 29% had proliferative disease without atypia, and 3% had proliferative disease with atypia. Subsequent incident breast cancers occurred in 55 women (3.9%). Women whose biopsies showed proliferative disease with atypia were over three-fold more likely to develop breast cancer as women who had non-proliferative disease (RR 3.29, 95% C.I. 1.21-8.93). Better characterization of the risk of breast cancer among women with BBD, considering both ethnicity and detailed molecular findings, can lead to better surveillance, earlier diagnosis, and, potentially, improved survival.
    Cancer Prevention Research 10/2012; · 4.89 Impact Factor
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    ABSTRACT: To describe the pattern and frequency of oncogene mutations in white and African American women with endometrial cancer and to determine if racial differences in oncogene mutations exist among women with pathologically similar tumors. Patients with endometrial cancer from a large urban hospital were identified through medical records, and representative formalin-fixed paraffin-embedded tumor blocks were retrieved. The study sample included 150 patients (84 African Americans) who underwent total abdominal hysterectomy for endometrial cancer. The Sequenom MassARRAY system and the OncoCarta Assay version 1.0 (Sequenom) were used to test for 238 mutations in 19 common oncogenes. The χ test and the Fisher exact test were used to assess differences in distribution of variables by race and oncogene mutation status. There were 20 mutations identified in 2 oncogenes (PIK3CA and KRAS) in tumors from 19 women (12.7%). Most of the mutations were found in PIK3CA (16/20). Thirteen percent of endometrioid tumors harbored mutations (11 PIK3CA and 2 KRAS) as did 29% of the malignant mixed Mullerian tumors (3 PIK3CA and 1 KRAS). There were no observed mutations in serous, clear cell, or mucinous tumor types. Among low-grade endometrioid cancers, tumors from African American patients were significantly associated with harboring either a KRAS or PIK3CA mutation (P = 0.04), with 7 PIK3CA mutations and all 4 KRAS mutations identified in African American women. This study provides preliminary evidence that oncogene mutation frequency of some subtypes of histologically similar endometrial carcinoma differ by race. Additional studies are needed to further explore this phenomenon in patients with endometrial carcinoma.
    International Journal of Gynecological Cancer 10/2012; 22(8):1367-72. · 1.94 Impact Factor
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    ABSTRACT: To investigate the possibility of inhibiting the progression of pancreatic ductal adenocarcinoma (PDAC) by facilitating the expression of E-cadherin through the enforced expression of microRNA-101 (miR-101). In situ hybridization was conducted with archival tissue using a double digoxigenin-labeled probe. Chromatin immunoprecipitation (ChIP) assay was conducted with EZ-Magna ChIPTM A. Gene profile analysis, Western blot, and immunoprecipitation assays were performed using standard protocols. We found that decreased miR-101 expression observed in archival patient tissues was significantly associated with poor prognosis indicated by low-intensity staining in high-grade tumors. ChIP assays using anti-enhancer of zeste homolog 2 (EZH2) antibodies indicated not only the interaction of EZH2 to the CDH1 (E-cadherin) promoter, but also that this interaction was significantly diminished in cells transfected with pre-miR-101. We observed a global downregulation of trimethylated lysine 27 of H3 histone (H3K27me3) along with upregulation of the enzymes histone deacetylase -1 and -2 with the re-expression of miR-101. Further, we observed lesser levels of transcriptional factors that inhibit the CDH1 promoter with pre-miR-101 treatment. Western blot analysis confirmed the enhanced E-cadherin expression. PANC-1 cells transduced with pre-miR-101 displayed markedly attenuated growth in SCID mice. These results suggest the potential therapeutic use of miR-101-enforced expression for inhibition of PDAC.
    Surgery 08/2012; 152(4):704-13. · 3.37 Impact Factor

Publication Stats

709 Citations
293.86 Total Impact Points

Institutions

  • 2003–2014
    • Wayne State University
      • • Department of Pathology
      • • Division of Gynecologic Oncology
      • • Department of Obstetrics and Gynecology
      Detroit, Michigan, United States
  • 2010–2013
    • University of Texas MD Anderson Cancer Center
      • • Department of Thoracic Head Neck Medical Oncology
      • • Department of Gynecologic Oncology
      Houston, TX, United States
  • 2004–2013
    • Harper University Hospital
      Detroit, Michigan, United States
  • 2012
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 2011
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
    • University of Washington Seattle
      • Department of Obstetrics and Gynecology
      Seattle, WA, United States
    • Henry Ford Hospital
      Detroit, Michigan, United States
  • 2005–2011
    • Karmanos Cancer Institute
      • Division of Hematology and Oncology
      Detroit, Michigan, United States