Publications (6)22.55 Total impact
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Article: Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy.
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ABSTRACT: Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92-1.00] and an estimated specificity of 0.71 [95% CI = 0.62-0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81-0.89). The per-patient and per-site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.International Journal of Cancer 03/2011; 128(5):1151-68. · 5.44 Impact Factor -
Article: Diagnosis of vulvar lesions by non-invasive optical analysis: a pilot study.
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ABSTRACT: A procedure that could allow an early in vivo and non-invasive detection of vulvar lesions would be extremely useful. We tested an innovative optical method (Optiprobe), which uses a harmless, visible light source for the in vivo, on-line detection of minimal alterations in the structure of vulvar epithelium. A group of 3 female volunteers without gynecological symptoms were first screened to evaluate optical properties of normal vulvar tissue. Next, a group of 16 patients undergoing gynecological examination for vulvar lesions was evaluated by the Optiprobe at suspected sites before these sites were biopsied for histological analysis. Adjacent, non-involved sites were also measured to provide internal controls. Histological analysis of the biopsies identified one case that did not show obvious alterations, 4 cases of high-grade vulvar intraepithelial neoplasia (VIN), 5 cases of vulvitis, and 6 cases of lichen sclerosis (LS).The optical properties of the VIN cases were significantly different from those of controls, due to a decrease in the absorption spectra and an increase in the scattering spectra. In contrast, a significant increase in the absorption spectra and a decrease in the scattering spectra were observed in the cases of vulvitis. In the LS cases, the absorption spectra were as in controls, whereas the scattering spectra were significantly decreased. We conclude that the Optiprobe provides a useful tool for a rapid and non-invasive detection of vulvar alterations. The method should contribute to reduce the number of biopsies and to facilitate the long-term follow-up of vulvar lesions.Rare tumors 01/2009; 1(1):e8. -
Article: Moving toward individualized therapy based on NER polymorphisms that predict platinum sensitivity in ovarian cancer patients.
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ABSTRACT: Platinum-based chemotherapy exerts its cytotoxic effect by forming DNA adducts and subsequently inhibiting DNA replication. Removing platinum DNA adducts requires the nucleotide excision repair (NER) pathway. The xeroderma pigmentosum (XP) complementation group of genes plays an essential role in the NER pathway. We hypothesized that genetic polymorphisms in XP genes may predict clinical response to platinum chemotherapeutic treatment and survival in women with gynecological cancers. We genotyped 146 cases of advanced epithelial ovarian cancer for XP gene polymorphisms using the PCR-RFLP method. Kaplan-Meier plots and the log-rank test were used to assess associations between survival and recurrence-free interval and the XP gene polymorphisms. Hazard ratio of response was estimated from an adjusted multivariate Cox proportional hazard model. Women with a heterozygous variant XPA allele had shorter median survival (21.5 months, P=0.03) and shorter median time to recurrence (11.3 months, P=0.05) than women with the homozygous wild-type allele (37.9 and 13.9 months, respectively). Women with a homozygous variant XPG allele had significantly shorter median survival (8.3 months, P=0.006) compared with women with the homozygous XPG wild-type allele (24.6 months). Polymorphisms in XPC, XPD exon10, and XPD exon23 were associated with a decreased risk of recurrence and death, but were not statistically significant. This study suggests that NER gene polymorphisms may correlate with recurrence and patient survival. A larger sample size is needed to assess platinum chemotherapy response with these polymorphisms. These findings may help identify subgroups of cancer patients likely to benefit from individualized treatment strategies. Our next study will examine NER gene polymorphisms in cervical cancer patients.Gynecologic Oncology 11/2007; 107(1 Suppl 1):S223-9. · 3.89 Impact Factor -
Article: Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis.
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ABSTRACT: Mutations in tumor-suppressor gene BARD1 have been found in inherited and spontaneous breast, ovarian and uterine cancers. BARD1 plays a critical role in DNA repair and ubiquitination as binding partner of BRCA1, with which it colocalizes to nuclear dots. Independently of BRCA1, BARD1 can induce p53-dependent apoptosis in response to genotoxic stress. Therefore, BARD1 or p53 might be defective in cancer cells spared from apoptosis. We investigated BARD1 and p53 expression in ovarian, breast and non-small-cell lung cancers. BARD1 expression was highly upregulated and cytoplasmic in most cancer cells, while weak nuclear staining was observed in the surrounding normal tissue. Maximal BARD1 expression was associated with the most malignant ovarian cancer, clear cell carcinoma. In breast cancer, BARD1 expression was correlated with poor differentiation and large tumor size, established factors of poor prognosis, as well as short disease-free survival. In contrast to breast and ovarian cancers, no correlation of BARD1 expression with either grade or stage could be determined for lung cancer. RT-PCR, performed on 10 ovarian cancers, revealed absence of the 5' portion of the BARD1 transcript in 7 tumors, and sequencing of the remaining 3 identified a missense mutation (A1291G) resulting in an amino acid change of glutamine 406 to arginine. These data suggest that genetic and epigenetic changes might lead to elevated cytoplasmic expression of BARD1 and that cytoplasmic BARD1 might be a poor prognostic factor for breast and ovarian cancers.International Journal of Cancer 04/2006; 118(5):1215-26. · 5.44 Impact Factor -
Article: Cervical chromosome 9 polysomy: validation and use as a surrogate endpoint biomarker in a 4-HPR chemoprevention trial.
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ABSTRACT: Several genetic alterations have been described in cervical cancers including: human papillomavirus (HPV) E6 and E7 oncoproteins, subtle sequence changes, alterations in chromosome number, chromosome translocations, and gene amplifications. This report focuses on establishing chromosome 9 polysomy as a cervical biomarker of chromosome instability and using it in a chemoprevention trial. Chromosomal instability is a feature of most human cancers and is probably an early event in the process. We used 37 cervical cone specimens to validate chromosome 9 polysomy as a biomarker and then tested its modulation in a randomized clinical trial of 4-hydroxyphenylretinamide (4-HPR) in 39 patients with three blinded histopathologic reviews. No confounders were identified. In the present study, immunohistocytochemical analysis of Chromosome 9 polysomy was carried out and quantitatively measured. The Cell Index, the ratio of the number of total chromosome 9 copies to the total number of ells, increases significantly in archival samples as the cervix changes from normal to CIN to invasive cancer. In the chemoprevention trial, chromosome 9 polysomy was used as a biomarker and supported the histological analysis showing that 4-HPR impaired the natural regression response. Chromosome 9 polysomy appears to be a marker of genetic instability that can be used in chemoprevention trials as a surrogate endpoint biomarker. In this randomized trial of 4-HPR, the chromosome 9 polysomy measurements supported the clinical histopathologic reading in a quantitative manner suggesting that 4-HPR at 200 mg/day may have been inhibiting the regression seen in the placebo arm by inducing genetic instability.Gynecologic Oncology 01/2006; 99(3 Suppl 1):S32-7. · 3.89 Impact Factor -
Article: Quantitative histopathology and chromosome 9 polysomy in a clinical trial of 4-HPR.
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ABSTRACT: This trial examined the use of 4-hydroxyphenyl-retinamide (4-HPR), demonstrated to be a potent inhibitor of carcinogenesis in vitro and in animal models, in patients with cervical intraepithelial neoplasia (CIN) grades 2 to 3. Quantitative pathology and chromosome 9 polysomy were used to understand the biology and quantify the clinical histopathologic changes observed. Patients were randomized to 4-HPR or placebo for 6 months and followed for six more months. Cervical biopsies were obtained at baseline, 6 months, and 12 months; the biopsies were read blinded three times by the study pathologist. Feulgen-stained sections were also obtained and analyzed using computer-assisted image cytometry. Chromosome 9 polysomy was performed on tissue slices using in situ hybridization and measured quantitatively. Statistical analyses were carried out in S-Plus (Insightful Corporation, Seattle, WA) and R. The interim analysis, planned for 40 patients, was carried out on 39. The 6- and 12-month analyses showed a statistically significant difference between the two study arms. When code was broken, the 4-HPR-treatment arm was found to have fared less well than placebo. Analyses of Feulgen-stained sections provided a quantitative measure of the increase of DNA content and texture features. Chromosome 9 polysomy was also measured using image analysis. The changes observed were consistent with those of cells displaying cancerous changes, indicating a lack of response. 4-HPR is not active at 200 mg/day. The interim analysis was helpful in directing the study; and, in this case, ending it. The intermediate endpoint biomarkers of quantitative histomorphometry and chromosome 9 polysomy yielded quantitative and repeatable results consistent with the findings of the clinical pathologist.Gynecologic Oncology 09/2004; 94(2):296-306. · 3.89 Impact Factor
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Institutions
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2004
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Hôpitaux Universitaires de Genève
Genève, GE, Switzerland -
University of Texas MD Anderson Cancer Center
- Biomedical Engineering
Houston, TX, USA
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