Publications (16)43.5 Total impact
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Article: Immunohistochemical study of pElk-1 expression in human breast cancer: Association with breast cancer biologic profile and clinicopathologic features.
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ABSTRACT: BACKGROUND: Recently an increased interest on Elk1 protein and its role in breast cancer evolution has been noted. This protein is an element of the Ets family of transcription factors and it has been involved in a number of important cell processes through the activation of different genes, in a number of normal tissues as well as in many malignancies. METHODS: One hundred and seventy (n = 170) cases of operable breast cancer (invasive ductal, lobular and mixed type breast carcinomas) were randomly selected and investigated for the expression of pElk-1, Ki-67 and Cyclin D1 using immunohistochemistry .Our findings were correlated with tumors' clinicopathologic data and biologic profile. RESULTS: Activated Elk1 is positively associated with ER (p-value: 0.018) and also shows a positive association of with Cyclin D1 (p-value: <0.001). No relationship was noted between pElk1 and Ki67 (p-value: 0.213). Luminal A and B Her-2 positive breast cancer subtypes were showing greater pElk-1 immunoreactivity compared to Her-2 and Basal breast cancer subtypes, and also a higher staining intensity. No association of the molecule with other clinicopathologic characteristics (tumor size, stage, histological type or lymph node metastases) or disease adverse events (local recurrence, metastasis or death) was evidenced. CONCLUSIONS: Our findings offer a new perspective for the role of pElk-1 in breast neoplasia suggesting a direct relation of this molecule to tumor biology and a putative target of personalized breast cancer therapies, although its prognostic/discriminant role is not supported.Breast (Edinburgh, Scotland) 11/2012; · 2.09 Impact Factor -
Article: Her2 negative luminal breast carcinoma and Ki-67 evaluation.
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ABSTRACT: To determine the degree of inter-observer variability in defining the percentage of Ki-67 immunohistochemical expression in breast carcinoma cases and to investigate the validity of using the cut-point of 14% for the administration of adjuvant treatment in luminal B (Her2 negative) carcinomas. 99 ER, PR positive, Her2 negative breast carcinomas were consecutively selected from the Pathology files of "IASO" Women's Hospital. Ki-67 immunostaining was evaluated by four pathologists from four different institutions. Concerning the whole study group, the inter-observer agreement was substantial. Subgroup analysis upon the cases were at least one observer evaluated Ki-67 as being less than 14% showed that the inter-observer agreement was reduced to fair. Further analysis revealed that both below and above the clinicopathological limit of 14%, stands a "grey zone" of about ±7%, in which inter-observer agreement is weak. The administration of cytotoxic therapy in ER, PR positive, Her2 negative breast carcinomas featuring a Ki-67 labeling index of around 14, should be considered with caution. Probably decision-making should also take under consideration the whole morphological and biological profile of each tumor.Breast (Edinburgh, Scotland) 05/2012; 21(4):529-33. · 2.09 Impact Factor -
Article: Mucinous Epithelial Lesions in Endometrial Curettage Material: A Diagnostic Challenge.
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ABSTRACT: AIM:: To evaluate the immunohistochemical expression of several benign or malignant mucinous lesions that can be encountered in endometrial curettage material. MATERIALS AND METHODS:: Nineteen well-differentiated mucinous endometrial carcinomas, 12 papillary mucinous metaplasias, 11 cervical microglandular hyperplasias, 11 endocervical adenocarcinomas, 2 goblet cell metaplasias, 1 minimal-deviation adenocarcinoma, and 1 lobular endocervical glandular hyperplasia entered the study. Immunohistochemistry was performed with the following antibodies against: estrogen receptors, progesterone receptors, vimentin, p16, p63, carcinoembryonic antigen, and Ki-67. RESULTS:: Immunohistochemistry could easily distinguish endocervical adenocarcinoma of usual type from all other lesions under study. A Vim/p16/p63 signature was found to favor a cervical microglandular hyperplasia, whereas both mucinous endometrial carcinoma and mucinous papillary metaplasia would be preferentially characterized by a Vim/p16/p63 immunophenotype. A high Ki-67 expression would be of help in differentiating the latter 2 conditions. Statistically, the expression of estrogen receptors, progesterone receptors, and carcinoembryonic antigen did not aid in the differential diagnosis of these 3 conditions. For the 4 cases representing goblet cell metaplasia, minimal-deviation adenocarcinoma and lobular endocervical glandular hyperplasia, no results could be drawn. CONCLUSIONS:: In endometrial curettage material, the differential diagnosis of lesions comprising mucinous epithelium might be rendered by combining the immunohistochemical expression of vimentin, p16, p63, and Ki-67. Of all lesions, endocervical adenocarcinoma of usual type is the most easily identified.Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 04/2012; · 1.63 Impact Factor -
Article: Reply to the Letter to the Editor "Subgroup analysis and statistical power" by W.P. Martins and J.V.C. Zanardi.
European journal of obstetrics, gynecology, and reproductive biology 10/2011; · 1.97 Impact Factor -
Article: Immunohistochemical study of the angiogenetic network of VEGF, HIF1α, VEGFR-2 and endothelial nitric oxide synthase (eNOS) in human breast cancer.
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ABSTRACT: The role of Nitric Oxide (NO) in angiogenesis has not been fully clarified yet. A dual role for NO, either inductive or inhibitory, has been proposed on the basis of different effects that high or low concentrations of NO may exert on the angiogenic process. Additionally, it has been referred that NO may induce VEGF production, while VEGF may induce NO production via up-regulation of the endothelial nitric oxide synthase (eNOS), the two pathways being reverse. The aim of the current study was to investigate the expression of key molecules involved in these opposite pathways in primary breast cancer. Representative tumor samples from 242 patients with early-stage breast cancer (invasive ductal breast carcinomas) were investigated for the expression of VEGF, VEGFR-2, HIF1α, iNOS, and eNOS using immunohistochemistry. Endothelial NOS was found in 159 cases, VEGF in 131 cases, HIF-1α in 139 cases, VEGFR2 in 185 cases and inducible NOS (iNOS) in 22 cases. There was a significant correlation between the expression of VEGF and VEGFR-2, eNOS and VEGF, eNOS and VEGFR-2, eNOS and HIF1α. No statistically significant correlation was found between iNOS and the rest of the studied molecules. In breast cancer cases, the major molecules regulating NO and VEGF production can be co-expressed in the individual carcinomas implying a possibility for the relevant pathways to be active; however appropriate functional experiments remain to be conducted to prove such a hypothesis.Pathology & Oncology Research 06/2011; 18(1):33-41. · 1.37 Impact Factor -
Article: A systematic review and meta-analysis of randomized studies comparing misoprostol versus placebo for cervical ripening prior to hysteroscopy.
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ABSTRACT: Hysteroscopy is an effective method for examining the uterine cavity but has some limitations, including the occasional need for cervical dilatation. Misoprostol is routinely used for cervical dilatation in various procedures but has not gained wide acceptance for use before hysteroscopy. This review includes randomized controlled trials which compare the use of misoprostol versus placebo by different routes and doses before diagnostic or operative hysteroscopy. The MEDLINE database and the Cochrane Central Register of Controlled Trials were searched for articles published from January 1970 to April 2010. The outcome measures studied were related either to the facilitation of the hysteroscopic procedure (need for cervical dilatation, cervical width at the beginning of hysteroscopy, duration of the procedure and complications such as cervical tear and uterine perforation) or to the medication side-effects. With regard to side-effects, we studied the incidence of nausea, diarrhea, abdominal pain, bleeding, and fever. Vaginal misoprostol reduced the need for cervical dilatation in the total population of pre- and post-menopausal women to a statistically significant degree. In the subgroup of operative hysteroscopy the need for dilatation and the duration of the procedure were also significantly reduced. Most other outcomes relating to the facilitation of the procedure did not reach statistical significance. The side effects in the misoprostol group were significantly more frequent than in the placebo group. There is insufficient evidence to recommend the routine use of misoprostol before every hysteroscopy. As the lack of serious benefit from misoprostol is unlikely to be due to type II error, its use should be reserved for selected cases.European journal of obstetrics, gynecology, and reproductive biology 05/2011; 158(1):17-23. · 1.97 Impact Factor -
Article: MELF invasion in endometrial cancer as a risk factor for lymph node metastasis.
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ABSTRACT: To investigate whether the microcystic, elongated and fragmented (MELF) pattern of myometrial invasion encountered in certain endometrioid endometrial carcinomas can be considered as a risk factor for lymph node metastasis. A total of 351 cases of total abdominal hysterectomy and bilateral salpingo-oophorectomy with/without lymphadenectomy or lymph node sampling, performed for endometrioid endometrial adenocarcinoma, were included in this study. The existence of MELF invasion, vascular invasion, fibromyxoid stromal reaction and lymph node metastasis were recorded. Immunohistochemistry for endothelial and epithelial markers was performed on selected cases. MELF invasion was identified in 20 (10.81%) and 13 cases (13.13%) treated without and with lymphadenectomy, respectively. All these cases were either well or moderately differentiated carcinomas, stages IA-II (without considering lymph node status). Positive lymph nodes were detected in seven of 13 MELF-positive (53.84%) and six of 86 MELF-negative cases (6.97%) This observation was statistically significant. Of the seven MELF-positive tumours with lymph node metastasis, three cases exhibited intravascular tumour emboli while four showed a fibromyxoid stromal reaction. MELF pattern invasion was found to be related statistically to lymph node metastasis. Nevertheless, further studies are needed in order to evaluate the clinical significance of this observation.Histopathology 03/2011; 58(6):966-73. · 3.08 Impact Factor -
Article: MicroRNA expression analysis in triple-negative (ER, PR and Her2/neu) breast cancer.
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ABSTRACT: miRNAs are small, regulatory molecules approximately 21-24 nucleotides in length. They function at the post-transcriptional level by controlling the expression of more than 50% of human protein-coding genes and play an essential role in cell signaling pathways. The objective of the present study was to explore the expression profile of oncomiRs and tumor-suppressor miRs, and to define their possible correlations in triple-negative (ER, PR and Her2/neu) primary breast cancers. Forty-nine primary triple-negative breast cancer cases, along with 34 matched tumor-associated normal samples were investigated for the expression of 9 miRNAs using qPCR. Relationships between the expression of miR-10b, miR-21, miR-122a, miR-145, miR-205, miR-210, miR-221, miR-222 and miR-296 and the pathologic features of the tumors were examined, as were the influences of miR expression on patient overall and cancer-specific survival. miR-21, miR-210 and miR-221 were significantly overexpressed, whereas miR-10b, miR-145, miR-205, miR-122a were significantly underexpressed in the triple-negative primary breast cancers. Significant correlations among all of the studied miRs were scored both in the breast cancer and control tissue. Expression of miR-222 and miR-296 did not exhibit any significant difference between the breast cancer and normal tissue. There was a non-significant trend for high expression levels of the microRNAs, miR-21, miR-210, miR-221 and miR-222, to be associated with worse patient disease-free and overall survival. miR-21, miR-210 and miR-221 expression plays a significant role in triple- negative primary breast cancers.Cell cycle (Georgetown, Tex.) 02/2011; 10(3):507-17. · 5.36 Impact Factor -
Article: Primary atypical carcinoid of the breast: a case report and brief overview of evidence.
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ABSTRACT: Primary atypical carcinoid of the breast is rare. Herein we present a case of atypical carcinoid of the breast treated with surgery. The management plan is commented. Moreover an overview of the current evidence is presented. All the evidence is classified as level IV (opinion-based evidence) since there is no satisfactory case series to support a certain therapeutic decision. The treatment for an atypical carcinoid of the breast is the same one offered in patients diagnosed with primary infiltrating breast cancer. A multi-centric approach is needed in order to gather enough data to confidently support a certain management plan for these patients.World Journal of Surgical Oncology 01/2011; 9:52. · 1.12 Impact Factor -
Article: PTEN-loss and nuclear atypia of EIN in endometrial biopsies can predict the existence of a concurrent endometrial carcinoma.
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ABSTRACT: The objective of the present study was to evaluate whether nuclear atypia or PTEN-loss in endometrial intraepithelial neoplasia (EIN), could help to predict in endometrial curettage material, the prevalence of concurrent carcinoma in hysterectomy specimens. This retrospective single-institution study included women who were diagnosed with endometrial hyperplasia (simple or complex) and underwent hysterectomy within 12weeks from the initial diagnosis without interval treatment. All endometrial curettage slides were reviewed by three experienced pathologists and only cases that fulfilled the criteria of EIN were used for further analysis. For each case, the nuclear atypia and the immunohistochemically detected expression of PTEN were evaluated. The hysterectomy slides were also reviewed and the findings were used in the subsequent analysis. Out of 83 cases that were enrolled in the study, 33 (39.76%), had a concurrent endometrial carcinoma. Nuclear atypia in EIN cases with a final histology of endometrial cancer was found in 31 out of 33 cases (93.94%) but only in 27 out of 50 benign cases (54%). There was no PTEN-loss in 8 out of 33 EIN cases (24.24%) that proved to be cancer and 22 out of 50 EIN cases (44%) that proved to be benign. Either atypia or PTEN-loss or both were found in 33/33 (100%) cancer cases and in 39/50 (78%) benign cases; this difference was statistically significant (Fisher exact test, p < 0.05). PTEN-loss, as an independent variable, was not found to be a predictor of endometrial cancer in the final histology. However, biopsies presented with EIN, featuring nuclear atypia and recognized as PTEN-null are more likely to be finally diagnosed with endometrial cancer.Gynecologic Oncology 12/2010; 119(3):516-9. · 3.89 Impact Factor -
Article: The role of stress in female reproduction and pregnancy: an update.
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ABSTRACT: Life exists by establishing a balanced equilibrium, called homeostasis, constantly challenged by adverse stimuli, called stressors. In response to these stimuli, a complex neurohormonal reaction exerted by the activation of the so-called stress system is initiated. The latter is activated in a coordinated fashion, leading to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chance for survival. The stress system suppressive effects on female reproduction involve suppression of the hypothalamic-pituitary-ovarian axis at the hypothalamic, pituitary, ovarian, and uterine levels. Experimental and human data suggest that adverse prenatal stimuli, of either maternal or fetal origin, acting in the developing embryo in utero, can lead to the development of short- and long-term health disorders. These include preterm birth of the offspring, low birth weight, and the development of adult diseases ranging from the metabolic syndrome to several neurodevelopmental disorders.Annals of the New York Academy of Sciences 09/2010; 1205:69-75. · 3.15 Impact Factor -
Article: Increased apoptosis of neutrophils in induced sputum of COPD patients.
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ABSTRACT: The aim of the current study was to evaluate apoptosis in induced sputum neutrophils and to investigate the relationship between the number of apoptotic cells and clinical parameters in COPD patients. Twenty-four COPD ex-smoker patients and 10 healthy controls were included in the study. All subjects underwent clinical evaluation and sputum induction. Sputum cell in situ apoptosis was identified using white light microscopy and TUNEL assay technique. Apoptosis of neutrophils obtained by sputum induction was expressed as apoptotic rate (AR=percentage of apoptotic neutrophils over the number of neutrophils measured). TUNEL assay revealed statistically significant higher AR in COPD patients than controls (p=0.004). Patients with FEV(1)<50%pred had significantly higher median (IQR) AR (%) compared to patients with FEV(1)>or=50% [26.3 (16-29) vs 13.1 (8.6-21), p=0.01]. No significant association was found between the number of apoptotic cells and age, symptoms or medication used. The significantly increased apoptotic rate of neutrophils that were found in COPD patients with advanced disease compared to controls might reflect either a deregulation of apoptosis of neutrophils or, a reduced clearance of apoptotic neutrophils from the airways. The pathophysiologic significance of the observed phenomenon has to be further explored.Respiratory medicine 04/2009; 103(8):1130-5. · 2.33 Impact Factor -
Article: The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions.
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ABSTRACT: To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. 78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF), smooth muscle actin (SMA) and CD34, while microvessel density (MVD) was counted using the anti-CD31 antibody. VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma. Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma.BMC Cancer 02/2008; 8:88. · 3.01 Impact Factor -
Article: Erythropoietin and its receptor in breast cancer: correlation with steroid receptors and outcome.
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ABSTRACT: Autocrine/paracrine erythropoietin (EPO) action, promoting cell survival and mediated by its receptor (EPOR) in various solid tumors, including breast carcinoma, questions about the prognostic and therapeutic interest of this system. The expression of EPO/EPOR is steroid dependent in some tissues; however, a clear relationship of EPO/EPOR and steroid receptors in breast cancer has not been established thus far. Recently, the field of steroid receptors has expanded, including rapid effects mediated by membrane-associated receptors, regulating cell survival or apoptosis. The aim of this study was to evaluate EPO/EPOR and membrane-associated steroid receptor expression in breast carcinoma, in view of their prognostic significance, compared with other established markers [estrogen receptor (ER)-progesterone receptor (PR) status and Her2 expression] and hypoxia-induced factor 1 nuclear localization in 61 breast cancer specimens followed for <or=90 months. We report that EPO-EPOR were expressed in 80% and 84% of samples, although 8% and 2% of nontumoral fields expressed EPO/EPOR too. Membrane-associated receptors for estrogen (mER), progesterone (mPR), and androgen (mAR) were expressed in 96%, 94%, and 93% of cases. Significant correlations between EPO-hypoxia-induced factor 1alpha, mER-ER, mER-EPO, mAR-EPOR, and mER-mPR-Her2 were found. Finally, EPO, EPOR, and mAR are inversely related to disease-free and overall survival. However, in view of the above correlations, we conclude that EPO/EPOR and membrane steroid receptors are not independent prognostic markers as they are closely related to other established markers. In contrast, they may represent possible new therapeutic targets.Cancer Epidemiology Biomarkers & Prevention 10/2007; 16(10):2016-23. · 4.12 Impact Factor -
Article: Safety issues of hysteroscopic surgery.
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ABSTRACT: The term hysteroscopy is used to determine the procedure during which an endoscopic view of the endometrial cavity is achieved with the help of a type of endoscopic device called "the hysteroscope." Hysteroscopy is used to assist the diagnosis for a series of female pathology. Apart from its diagnostic value, hysteroscopy can also be used for operative procedures including ablation and resection. Both diagnostic and operative hysteroscopy have been used for a number of years and various studies have been published to describe their success and complication rates throughout this period. Diagnostic hysteroscopy is relatively safe, whereas complications occur more frequently when operative hysteroscopy is used. These complications include uterine perforation, hemorrhage, fluid overload, gas embolization, and hyponatremia. The rate in the appearance of these complications is dependent on the type of the hysteroscopic procedure, the distending medium, and the experience of the hysteroscopist. To avoid any problems concerning the application of hysteroscopic procedures, it is important to take the necessary precautions both preoperatively and intraoperatively. For example, the preoperative use of thinning agents of the endometrium and the reduction of the operating time, or the avoidance of cutting too deeply into the myometrium, are some of the parameters to be considered when hysteroscopy is in argument.Annals of the New York Academy of Sciences 01/2007; 1092:229-34. · 3.15 Impact Factor -
Article: Greek experience in the use of Thermachoice for treating heavy menstrual bleeding: prospective study.
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ABSTRACT: Heavy menstrual bleeding (HMB) occurs in a considerable percentage of the general population and is one of the main causes due to which a patient is referred to health services. Despite the efforts for pharmaceutical interventions, the symptom usually persists, therefore operative techniques are needed to control the bleeding. Today, apart from the choice of hysterectomy, other less aggressive techniques have been invented. The first results of the Greek Study Group on Gynecological Endoscopy regarding the use of the Thermachoice device are hereby presented. One hundred patients suffering HMB were treated with the Thermachoice device following a standard protocol designed by the Study Group. The follow-up meetings with the patients were held at 3, 6, 12, 24, and 36 months. It seems that the overall effectiveness rate (96%) is satisfactory and it is similar to the overall effectiveness rate reported in other relevant studies upon the Thermachoice device.Annals of the New York Academy of Sciences 01/2007; 1092:460-5. · 3.15 Impact Factor
Top co-authors
Top Journals
Institutions
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2011–2012
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University of Crete
- • Department of Surgical Oncology
- • Department of Pathology
Réthymnon, Kriti, Greece
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2010
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National and Kapodistrian University of Athens
- Division of Internal Medicine II
Athens, Attiki, Greece -
University of Ioannina
- Τμήμα Ιατρικής
Ioánnina, Ipeiros, Greece
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2008
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Harokopion University of Athens
Athens, Attiki, Greece
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