Nicolas Samartzis

University of Zurich, Zürich, Zurich, Switzerland

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Publications (7)17.04 Total impact

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    ABSTRACT: Class I histone deacetylases (HDACs-1-3) play an important role in steroid hormone-dependent gene expression and in modulating cell survival and proliferation. We analyzed their expression in a tissue microarray including 74 endometriosis samples and 30 normal endometrium controls. The mean HDAC-1 immunoreactivity score (IRS ± standard deviation) was 7.6 ± 2.5 in endometriosis and 5.3 ± 2.3 in normal endometrium (P < .001). In contrast, the IRSs of HDAC-2 and -3 were 11.7 ± 0.7 and 11.8 ± 1.1 in endometriosis and 11.6 ± 1.0 and 11.9 ± 0.4 in normal endometrium (P = .7 and P = .2), respectively. Significant correlations were found between HDAC-1 and estrogen (-alpha/-beta) and progesterone receptor expression. In conclusion, HDAC-1, but not HDAC-2/-3, was significantly increased in endometriosis and associated with steroid hormone receptor expression that may reflect interdependence. In context with the literature, specific inhibitors of HDAC-1 may have inhibitory activities similar to those of broad-spectrum HDAC inhibitors and may be clinically tolerated, which would increase their chance as an option in the treatment of endometriosis.
    Reproductive sciences (Thousand Oaks, Calif.) 05/2013; · 2.31 Impact Factor
  • Reproductive Sciences 05/2013; · 2.06 Impact Factor
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    ABSTRACT: The G protein-coupled estrogen receptor (GPER) is thought to be involved in non-genomic estrogen responses as well as processes such as cell proliferation and migration. In this study, we analyzed GPER expression patterns from endometriosis samples and normal endometrial tissue samples and compared these expression profiles to those of the classical sex hormone receptors. A tissue microarray, which included 74 samples from different types of endometriosis (27 ovarian, 19 peritoneal and 28 deep-infiltrating) and 30 samples from normal endometrial tissue, was used to compare the expression levels of the GPER, estrogen receptor (ER)-alpha, ER-beta and progesterone receptor (PR). The immunoreactive score (IRS) was calculated separately for epithelium and stroma as the product of the staining intensity and the percentage of positive cells. The expression levels of the hormonal receptors were dichotomized into low (IRS < 6) and high (IRS > =6) expression groups. The mean epithelial IRS (+/-standard deviation, range) of cytoplasmic GPER expression was 1.2 (+/-1.7, 0-4) in normal endometrium and 5.1 (+/-3.5, 0-12) in endometriosis (p < 0.001), of nuclear GPER 6.4 (+/-2.6, 0-12) and 6.8 (+/-2.9, 2-12; p = 0.71), of ER-alpha 10.6 (+/-2.4, 3-12) and 9.8 (+/-3.0, 2-12; p = 0.26), of ER-beta 2.4 (+/-2.2; 0-8) and 5.6 (+/-2.6; 0-10; p < 0.001), and of PR 11.5 (+/-1.7; 3-12) and 8.1 (+/-4.5; 0-12; p < 0.001), respectively. The mean stromal IRS of nuclear GPER expression was 7.7 (+/-3.0; 2-12) in endometrium and 10.8 (+/-1.7; 6-12) in endometriosis (p < 0.001), of ER-alpha 8.7 (+/-3.1; 2-12) and 10.6 (+/-2.4; 2-12; p = 0.001), of ER-beta 1.8 (+/-2.0; 0-8) and 5.4 (+/-2.5; 0-10; p < 0.001), and of PR 11.7 (+/-0.9; 8-12) and 10.9 (+/-2.0; 3-12; p = 0.044), respectively. Cytoplasmic GPER expression was not detectable in the stroma of endometrium and endometriosis. The observed frequency of high epithelial cytoplasmic GPER expression levels was 50% (n = 30/60) in the endometriosis and none (0/30) in the normal endometrium samples (p < 0.001). High epithelial cytoplasmic GPER expression levels were more frequent in endometriomas (14/20, 70%; p = 0.01), as compared to peritoneal (9/18, 50%) or deep-infiltrating endometriotic lesions (7/22, 31.8%). The frequency of high stromal nuclear GPER expression levels was 100% (n = 74/74) in endometriosis and 76.7% (n = 23/30) in normal endometrium (p < 0.001). The frequency of high epithelial nuclear GPER expression levels did not differ between endometriosis and normal endometrium. The present data indicate a unique GPER expression pattern in endometriosis, especially in endometriomas as compared to the normal endometrium. The overexpression of GPER in endometriotic lesions suggests a potential role for GPER in the hormonal regulation of endometriosis, which should be taken into consideration for future hormonal treatment strategies.
    Reproductive Biology and Endocrinology 04/2012; 10:30. · 2.41 Impact Factor
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    ABSTRACT: Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n=136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n=3/20, 15%) and one deep-infiltrating endometriosis sample (n=1/22, 5%), but in none of the peritoneal endometriosis (n=0/16) and eutopic endometrium samples (n=0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (P<0.0005), as well as peritoneal (P=0.003) and deep-infiltrating endometriosis (P=0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied.
    Modern Pathology 02/2012; 25(6):885-92. · 5.25 Impact Factor
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    ABSTRACT: To determine whether the outpatient loop electrosurgical excision procedure (LEEP) conization (out-LEEP) is as effective and safe as inpatient LEEP conization (in-LEEP) with regard to the complete removal of cervical dysplasia, recurrence-free survival and post-operative morbidity. 233 patients were included in this retrospective cohort study from January 2002 to December 2007. 181 had outpatient treatment and 52 inpatient treatment. We used Mann-Whitney U test, two-sided Fisher's exact test, Chi-square test, log rank test and Kaplan-Meier curve. Incomplete excision was found in 16/52 (30.8%) cases in the inpatient group and 46/181 (25.4%) in the outpatient group (P = 0.48). Six patients had post-operative complications: two cases of secondary haemorrhage in each group (in-LEEP 3.8%, out-LEEP 1.1%, P = 0.22) and two cases of cervical stenosis amongst inpatients (3.8%, P = 0.049). Alteration of specimen by thermal artifact were reported in 4/52 (7.7%) of in-LEEP cones and 10/181 (5.5%) of out-LEEP cones (P = 0.52). Measurements of cones in both groups were comparable with a mean depth of 9.35 mm (±5.5 mm) and 8.4 mm (±3.4 mm), respectively. Our results suggest that efficacy and safety of ambulatory LEEP conization is comparable as in inpatient procedure.
    Archives of Gynecology 11/2011; 285(5):1441-5. · 0.91 Impact Factor
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    ABSTRACT: Epigenetic regulation is an important mechanism leading to cancer initiation and promotion. Histone acetylation by histone deacetylases (HDACs) represents an important part of it. The development of HDAC inhibitors has identified the utility of HDACs as a therapeutic target. Little is known about the epigenetic regulation of vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell cancer (VSCC). In this study, the expression of class I HDACs (HDAC 1, 2 and 3) was compared in a series of VIN and VSCC tissues. A tissue micro array (TMA) with specimens from 106 patients with high-grade VIN and 59 patients with vulvar cancer was constructed. The expression of HDACs 1, 2 and 3 were analyzed with immunohistochemistry (IHC). The nuclear expression pattern was evaluated in terms of intensity and percentage of stained nuclei and was compared between vulvar preinvasive lesions and vulvar cancer. HDAC 2 expression was significantly higher in VIN than in VSCC (p < 0.001, Fisher's test). Also, 88.7% (n = 94/106) of VIN samples and only 54.5% (n = 31/57) of VSCC samples were scored at the maximum level. Conversely, HDAC 3 expression was significantly higher in VSCC (93%, 53/57) compared to VIN (73.6%, 78/106, p = 0.003), whereas only a small difference in the expression of HDAC 1 was found between these two entities of vulvar neoplasia. These results suggest that epigenetic regulation plays a considerable role in the transformation of VIN to invasive vulvar neoplasia.
    BMC Cancer 01/2011; 11:463. · 3.33 Impact Factor
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    ABSTRACT: To determine characteristics and clinical course of high-grade anogenital intraepithelial neoplasia (AIN) in human immunodeficiency virus (HIV)-infected women. HIV-positive women with biopsy-proven high-grade (II and III) vulvar (VIN), vaginal (VAIN) or perianal intraepithelial neoplasia (PAIN) were identified in the electronic databases of 2 colposcopy clinics. A total of 31 patients were identified from 1992 to 2007, of which 30 had a mean follow-up of 47.7 months (SD = 46.0; range, 2.6-166.2). Of the patients, 77.4% had VIN, 12.9% VAIN and 9.7% PAIN at first diagnosis. Age at diagnosis of IN was 36.2 years (SD +/- 5.2; range, 23.5-47.0). Ninety percent of patients received antiretroviral therapy at first diagnosis of IN; 65% (13 of 20) of patients with a follow-up of > 2 years required a second treatment, and 2 developed invasive vulvar cancer (10%). AIN among HIV-positive women shows a high relapse rate despite treatment modality used and a substantial invasive potential.
    The Journal of reproductive medicine 12/2008; 53(12):947-51. · 0.75 Impact Factor