Summary The expression of α -methylacyl-coenzyme-A racemase (AMACR) has previously been reported in 75% to 100% of urethral/bladder clear cell carcinomas, tumors that are known to display broad ...phenotypic overlap with their identically named müllerian counterparts. Herein, we assess the utility of AMACR in distinguishing endometrial clear cell carcinomas (CCCs) from endometrial serous carcinomas (ESCs) and endometrial endometrioid carcinomas (EECs). A total of 111 endometrial carcinomas in a tissue microarray, including 49 CCCs, 13 ESCs, and 49 EECs, were assessed for AMACR immunoreactivity, with results scored semiquantitatively (scores 0, 1+, 2+, 3+ for 0%, 1%-5%, 6%-50%, >50% immunoreactive cells, respectively). Fifty (45%) of the 111 carcinomas were AMACR positive, with the following score distribution: CCC: 0 (n = 12), 1+ (n = 12), 2+ (n = 3), 3+ (n = 22); EEC: 0 (n = 38), 1+ (n = 4), 2+ (n = 4), 3+ (n = 3); ESC: 0 (n = 11), 1+ (n = 1), 2+ (n = 0), 3+ (n = 1). AMACR expression was significantly more frequent in CCC (75%) than in ESC (15%) or EEC (22%); P < .0001. The sensitivity and specificity of AMACR expression in classifying a carcinoma as CCC were 0.75 (95% confidence interval CI, 0.61-0.86) and 0.79 (95% CI, 0.66-0.88), respectively, with an odds ratio of 11.62 (95% CI, 5-28; P < .001) and an area under the curve of 0.79 (95% CI, 0.68-0.88). These findings indicate that AMACR expression is strongly associated with CCC and displays a relatively robust diagnostic test performance. However, its practical utility may be limited by the focal nature of its expression in 32% of the AMACR-positive CCC cases as well as its expression in 15% to 22% of the non-CCC histotypes.
Summary Phenotypic differences between otherwise similar tumors arising from different gynecologic locations may be highly significant in understanding the underlying driver molecular events at each ...site and may potentially offer insights into differential responses to treatment. In this study, the authors sought to identify and quantify phenotypic differences between ovarian clear cell carcinoma (OCCC) and endometrial clear cell carcinoma (ECCC) using a proteomic approach. Tissue microarrays were constructed from tumor samples of 108 patients (54 ECCCs and 54 OCCCs). Formalin-fixed samples on microarray slides were analyzed by matrix-assisted laser desorption/ionization mass spectrometry, and 730 spectral peaks were generated from the combined data set. A linear mixed-effect model with random intercept was used to generate 93 (12.7%) peaks that were significantly different between OCCCs and ECCCs at the fold cutoffs of 1.5 and 0.667 and an adjusted P value cutoff of 1.0 × 10−10 . Liquid chromatography–tandem mass spectrometry was performed on selected cores from each group, and peptides identified therefrom were compared with lists of statistically significant peaks from the aforementioned linear mixed-effects model to find matches within 0.2 Da. A total of 53 candidate proteins were thus identified as being differentially expressed in OCCCs and ECCCs, 45 (85%) of which were expressed at higher levels in ECCCs than OCCCs. These proteins were functionally diverse and did not highlight a clearly dominant cellular theme or molecular pathway. Although ECCCs and OCCCs are very similar, some phenotypic differences are demonstrable. Additional studies of these differentially expressed proteins may ultimately clarify the significance of these differences.
Summary Insulin-like growth factor-II messenger RNA–binding protein 3 (IGF2BP3 or IMP3) is a biomarker whose expression has been found to be a negative prognostic factor in several neoplasms ...including ovarian clear cell carcinoma (CCC). In this study, we analyzed the frequency and clinicopathologic significance of IMP3 expression, as assessed by immunohistochemistry and as scored using a modified H-score system, in a cohort of 50 endometrial CCCs. Cases with scores of 0 to 100, 101 to 200, and 201 to 300 were classified as negative/mildly positive (n = 17), moderately positive (n = 20), and strongly positive (n = 13), respectively. A distinctive pattern of increased staining at the myoinvasive front (relative to the main tumor) was evident in 46% of the cases with evaluable foci of myometrial invasion. Moderate/strong IMP3 staining was associated with a tumor architectural pattern that has been reported to be of poor prognostic significance: at least 10% of the tumor composed of solid architecture or individual infiltrating tumor cells ( P = .01). Increasing levels of IMP3 expression showed a trend toward decreasing relapse-free survival (RFS; median survival, 75.6, 81.3, and 48.4 months for the negative/mildly, moderately, and strongly positive groups, respectively P = .09). However, IMP3 expression was not significantly associated with reduced overall survival or RFS in a multivariate analytic model. The finding in a subset of our cases of increased IMP3 expression at the tumoral myoinvasive front is consistent with a role for IMP3 in invasiveness, as is the trend toward reduced RFS in cases expressing IMP3 at high levels. These preliminary findings suggest that IMP3 expression may be involved in the pathogenesis of CCC and is worthy of further exploration.
Objective Disorders that lead to preterm delivery influence the fetal inflammatory response. Study Design We calculated odds ratios of elevated concentrations of 25 blood proteins on the first ...postnatal day in 798 infants born before the 28th week and classified by the pregnancy disorder that lead to preterm delivery. Results Concentrations of cytokines (IL-1β, IL-6, TNFα), cytokine receptors (IL-6R, TNF-R1, TNF-R2), systemic inflammatory proteins (CRP, SAA, MPO), chemokines (IL-8, MCP-1, MCP-4, MIP-1β, RANTES, I-TAC), adhesion molecules (ICAM-1, ICAM-3, VCAM-1, E-selectin), and metalloproteinases (MMP-1, MMP-9) were elevated in children delivered after preterm labor, membrane rupture, abruption, and cervical insufficiency, whereas such a pattern was not seen after preeclampsia or fetal indication/growth restriction. Inflammatory profiles were also associated with maternal vaginitis. Conclusion The patterns of blood proteins in the newborn support the division of pregnancy disorders that lead to preterm delivery into those associated, and those not associated, with inflammation.
Colonization of second-trimester placenta parenchyma Onderdonk, Andrew B., PhD; Hecht, Jonathan L., MD, PhD; McElrath, Thomas F., MD, PhD ...
American journal of obstetrics and gynecology,
07/2008, Letnik:
199, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Objective The overtly healthy, nonpregnant uterus harbors bacteria, Mycoplasma and Ureaplasma . The extent of colonization remains elusive, as are relationships between isolated microorganisms, ...preterm labor and fetal inflammation. Study Design Biopsy specimens of chorion parenchyma from 1083 placentas delivered before the beginning of the 28th week of gestation were cultured, and the placentas were examined histologically. The frequencies of individual microorganisms and groups of microorganisms were evaluated in strata of processes leading to preterm delivery, routes of delivery, gestational age, and placenta morphology. Results Placentas delivered by cesarean section with preeclampsia had the lowest bacterial recovery rate (25%). Preterm labor had the highest rates, which decreased with increasing gestational age from 79% at 23 weeks to 43% at 27 weeks. The presence of microorganisms in placenta parenchyma was associated with the presence of neutrophils in the fetal stem vessels of the chorion or in the vessels of the umbilical cord. Conclusion The high rate of colonization appears to coincide with phenomena associated with preterm delivery and gestational age. The presence of microorganisms within placenta parenchyma is biologically important.
Objectives To assess antenatal and early postnatal antecedents of attention problems identified by the Child Behavior Checklist in extremely preterm children. Study design In a cohort of 826 children ...born between 23 and 27 weeks' gestation, we collected demographic, birth, and postnatal information. We then identified behavior problems by using parent ratings from the Child Behavior Checklist at 2 years' adjusted age. We created time-oriented logistic regression risk models to identify significant risk factors for attention problems and Diagnostic and Statistical Manual of Mental Disorders –compatible attention deficit/hyperactivity problems (ADHPDSM ). Results Children were at increased risk of both attention problems if they were born to a woman who had no formal education beyond high school and/or a woman who was exposed to secondhand smoke. Recovery of a single organism from the placenta was associated with increased risk of an attention problem, and fetal stem vessel thrombosis and recovery of Mycoplasma species were associated with increased risk of ADHPDSM . Infants of multifetal gestations were at reduced risk of both attention problems. The only postnatal risk factor for an attention problem was recovery of bacteria from a tracheal aspirate. Conclusion Among extremely preterm infants, several potentially modifiable antenatal and perinatal antecedents are associated with increased risk for attention problems and ADHPDSM at 2 years adjusted age.
The aim of this study was to assess potential quality assurance (QA) issues in the diagnosis and characterization of adnexal masses on pelvic computed tomographic (CT) and magnetic resonance (MR) ...imaging studies.
Images from 128 women who had oophorectomies during a 16-month period with CT and/or MR studies within 5 years of surgery (145 CT scans from 103 women and 49 MR studies from 42 women, with 17 having both MR and CT studies) were reviewed by three radiologists who assigned QA scores of 0 (no QA issue), 1 (minor issue with minimal impact on clinical care), or 2 (major issue with potential impact on clinical care). The difficulty of diagnosis was assigned a score of 0 (very difficult diagnosis to make), 1 (difficult but possible to make the diagnosis), or 2 (diagnosis should be made). The incidence of adnexal QA issues was calculated using total CT and MR pelvic examinations performed on women during the interval.
Twenty-nine QA issues were identified in 28 women in 17 of 145 CT studies (11.7%) and 12 of 49 MR examinations (24.5%) in women having adnexal surgery (17 of 11,194 0.15% of female pelvic CT studies and 12 of 603 2.0% of female pelvic MR studies performed in the time interval). Issues included missed lesions, lesions misidentified as leiomyomas, fat described in the lesion but not seen histologically, postmenopausal status of patient not considered, ultrasound correlation not recommended, and confusion of right and left sides.
Errors in CT and MR studies regarding the diagnosis and characterization of adnexal masses in a highly enriched population of women undergoing adnexal surgery are common. Knowledge of the types of QA issues found in CT and MR studies of adnexal masses should aid in decreasing future errors.
Summary Plasma cells are the hallmark of chronic endometritis but are not specific for upper tract infection. Plasma cells have also been noted in hormonally mediated endometrial disorders in ...association with gland architectural changes (“disordered proliferative” and “anovulatory” patterns), and stromal breakdown. We reviewed benign endometrial biopsies diagnosed at Beth Israel Deaconess Medical Center over a 2-year period described as disordered/anovulatory patterns ± stromal breakdown. Cases were excluded if tissue was not available; women were younger than 50 years where most diagnoses were atrophic or cancer; or diagnoses were secretory, menstrual endometrium, or polyps. The remaining 61 cases were compared to 33 samples of unremarkable proliferative endometrium. Plasma cells were quantified on hematoxylin and eosin–stained sections and using a histochemical stain methyl green pyronin. The indication for biopsy was an abnormal pattern of bleeding in 34 cases, infertility workup in 7, incidental part of workup for pain, or other findings in 5. The majority of disordered proliferative endometrium had plasma cells (61% grade 1, 17% grade 2) all seen on methyl green pyronin staining only. Two thirds of proliferative endometrium with breakdown showed plasma cells (19% grade 1, 39% grade 2, 10 % grade 3). Plasma cells were rare in inactive endometrium and noted in only 18% of unremarkable proliferative endometrium, all grade 1. Plasma cells are commonly present in the endometrium of women with dysfunctional uterine bleeding and focal stromal breakdown. Given the lack of clinical evidence for infection, the inflammation likely represents a physiologic process.
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