Metsovo Lung: History of Population Environmental Exposure

The historical course of the Metsovo Lung phenomenon began to be investigated in the 1980s when extensive pleural calcifications causing malignant mesothelioma appeared at a high frequency beyond expectation. It was not possible to explain their frequency. This finding reasonably raised the question of whether it was indeed tuberculous pleurisy or something else. The biopsies carried out confirmed that these were tremolite asbestos fibres. These fibres were derived from a shielding material containing asbestos. This is a global phenomenon according to which the entire population of Metsovo was exposed to asbestos, without knowing it, from a traditional shielding material. The abandonment of the material and its non-use brought about a gradual reduction of the phenomenon, which also marks the reduction of mesothelioma

The clinical and diagnostic impact of using standard criteria of adequacy assessment and diagnostic terminology on thyroid nodule fine needle aspiration

The study was aimed to investigate the impact of using standard criteria for assessing specimen adequacy and diagnostic terminology (CAST) on fine-needle aspiration (FNA) diagnosis and clinical management of thyroid nodules. The study included similar numbers of FNAs performed in 2 year before (group A) and 1.5 year after (group B) implementing the standard CAST. In comparison to group A, group B showed a significantly lower rate of nondiagnostic specimens (RND) (16.1% vs. 21.6%, P ≤ 0.01) and rate of descriptive diagnoses (RDD) (3.8% vs. 14.5%, P ≤ 0.001) and greater non-neoplastic (70.0% vs. 64.1%, P < 0.05) and follicular cell lesions (7.4% vs. 4.3%, P < 0.05) but a similar percentage of neoplastic diagnoses. The rate of surgical follow-up (RSF) was significantly higher in group B than in group A, overall (21.6% vs. 17.0%, P < 0.05), or in subgroups of non-neoplastic (12.6% vs. 5.4%, P < 0.01) and neoplastic categories (81.0% vs. 61.0%, P < 0.05). The rate of cytohistologic concordance was higher in group B although the difference was not statistically significant. We concluded that use of the standard CAST on FNA diagnosis of thyroid nodules significantly reduced RND and RDD, providing more consistent diagnoses among the pathologists as well as better and more uniform communication between the pathologists and the clinicians. Furthermore, the cytohistological concordance was slightly better after CAST implementation, indicating that the improvement of diagnostic consistency among pathologists did not sacrifice the diagnostic accuracy. Diagn. Cytopathol. 2008;36:161–166. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58042/1/20762_ftp.pd

Cytological Results of Ultrasound-Guided Fine-Needle Aspiration Cytology for Thyroid Nodules: Emphasis on Correlation with Sonographic Findings

PURPOSE: To compare the cytological results of ultrasound-guided fine-needle aspiration (US-FNA) cytology of thyroid nodules to sonographic findings and determine whether US findings are helpful in the interpretation of cytological results. MATERIALS AND METHODS: Among the thyroid nodules that underwent US-FNA cytology, we included the 819 nodules which had a conclusive diagnosis. Final diagnosis was based on pathology from surgery, repeated FNA cytology or follow-up of more than one year. Cytological results were divided into five groups: benign, indeterminate (follicular or Hurthle cell neoplasm), suspicious for malignancy, malignant, and inadequate. US findings were categorized as benign or suspicious. Cytological results and US categories were analyzed. RESULTS: Final diagnosis was concluded upon in 819 nodules based on pathology (n=311), repeated FNA cytology (n=204) and follow-up (n=304), of which 634 were benign and 185 were malignant. There were 560 benign nodules, 141 malignant nodules, 49 nodules with inadequate results, 21 with indeterminate results, and 48 that were suspicious for malignancy. The positive and negative predictive values of the US categories were 59.1% and 97.0%, and those of the cytological results were 93.7% and 98.9%. The US categories were significantly correlated with final diagnosis in the benign (p=0.014) and suspicious for malignancy (p<0.001) cytological result groups, but not in the inadequate and indeterminate cytological results groups. The false positive and negative rates of cytological results were 1.9% and 3.2%. CONCLUSION: Sonographic findings can be useful when used alongside cytological results, especially in nodules with cytological results that are benign or suspicious for malignancy.ope

The expression of HSP27 is associated with poor clinical outcome in intrahepatic cholangiocarcinoma

<p>Abstract</p> <p>Background</p> <p>The heat shock proteins (HSPs) 27-kDa (HSP27) and 72-kDa (HSP72), are ubiquitous chaperone molecules inducible in cells exposed to different stress conditions. Increased level of HSPs are reported in several human cancers, and found to be associated with the resistance to some anticancer treatments and poor prognosis. However, there is no study of the relationship between HSPs expression and patient's prognosis in intrahepatic cholangiocarcinoma (IHCCA). In this exploratory retrospective study, we investigated the expressions of HSP27 and HSP72 as potential prognostic factors in IHCCA.</p> <p>Methods</p> <p>Thirty-one paraffin-embedded samples were analyzed by immunohistochemical methods using HSP27 and HSP72 monoclonal antibodies. Proliferation rate was assessed in the same specimens by using monoclonal antibody against phosphorylated histone H3 (pHH3). Fisher's exact test was used to assess the hypothesis of independence between categorical variables in 2 × 2 tables. The ANOVA procedure was used to evaluate the association between ordinal and categorical variables. Estimates of the survival probability were calculated using the Kaplan-Meier method, and the log rank test was employed to test the null hypothesis of equality in overall survival among groups. The hazard ratio associated with HSP27 and HSP72 expression was estimated by Cox hazard-proportional regression.</p> <p>Results</p> <p>The expression of HSP27 was related to mitotic index, tumor greatest dimension, capsular and vascular invasion while the expression of HSP72 was only related to the presence of necrosis and the lymphoid infiltration. Kaplan-Maier analysis suggested that the expression of HSP27 significantly worsened the patients' median overall survival (11 ± 3.18 vs 55 ± 4.1 months, P-value = 0.0003). Moreover HSP27-positive patients exhibited the worst mean survival (7.0 ± 3.2 months) in the absence of concomitant HSP72 expression.</p> <p>Conclusion</p> <p>The expression of HSP27, likely increasing cell proliferation, tumor mass, vascular and capsular invasion, might promote aggressive tumor behaviour in IHCCA and decrease patients' survival. Immunohistochemical detection of HSP27 on routine sections may provide a reliable prognostic marker for IHCCA able to influence the therapeutic strategies for this cancer.</p

Role of Versican, Hyaluronan and CD44 in Ovarian Cancer Metastasis

There is increasing evidence to suggest that extracellular matrix (ECM) components play an active role in tumor progression and are an important determinant for the growth and progression of solid tumors. Tumor cells interfere with the normal programming of ECM biosynthesis and can extensively modify the structure and composition of the matrix. In ovarian cancer alterations in the extracellular environment are critical for tumor initiation and progression and intra-peritoneal dissemination. ECM molecules including versican and hyaluronan (HA) which interacts with the HA receptor, CD44, have been shown to play critical roles in ovarian cancer metastasis. This review focuses on versican, HA, and CD44 and their potential as therapeutic targets for ovarian cancer

Investigation a) disturbances of cell cycle, apoptosis, b) prototype of angiogenesis c) presence of structural and numerical abnormalities in normal, hyperplastic and malignant endometrium.

The aim of this study was the investigation of: a) disturbances of expression of the cell cycle proteins, apoptosis, b) prototype of angiogenesis c) presence of structural and numerical abnormalities in normal, hyperplastic and malignant endometrium. Materials and Methods: In the present work were studied, formalin fixed, paraffin-embedded tissue sections from 31 (21.1%) cases of normal endometrium (16 cases of secretory and 15 cases of proliferative), 36 (24.5%) cases of hyperplastic endometrium (19 simple and 16 complex hyperplasia) and 80 (54.4%) cases of endometrial cancer, for the immuneohistochemical expression of : 1) hormonal receptors ER and PR, 2) proteins of cell cycle and/or apoptosis (Ki67/MIB1, p53, Rb and bcl-2), 3) regulating proteins of angiogenesis (VEGF, VEGFR-1[kai] vegfr-2) and 4) the HER2/neu protein. Moreover, was studied HER2/neu gene amplification with the method of fluorescence in-situ hibridization (FISH). Finally, microvessel density (MVD), was evaluated after detection of immunohistochemical expression of the protein CD34. The results were connected with clinicopathological parameters. Results: During the multistep process of endometrial carcinogenesis was observed an important increase of the immunohistochemical expression of the proteins that were studied, from normal, to hyperplastic and carcinomatous endometrium, concretely: Ki67/MIB1 (p=0.003 and p=0.05 respectively), p53 (p=0.006 and p=0.002 respectively), VEGF (p=0.003 and p<0.0001 respectively), VEGFR-1 (p=0.05 and p<0.0001 respectively) and MVD (p<0.0001 και p<0.0001 respectively). The expression of bcl-2 protein was considerably higher in hyperplastic, concerning the normal and carcinomatous endometrium (p<0.0001 and p<0.0001 respectively). Was elected cross-correlation of expression of VEGF of epithelial cells with: the 1) MVD of normal, hyperplastic and carcinomatous endometrium (p<0.0001), 2) the 132 in endometrioid carcinomas and was higher in high comapared with low grade carcinomas, while the expression of p53, VEGF proteins and ΜVD was higher in low compared with high grade carcinomas (p<0.0001, p=0.008 and p=0.013, respectively). expression of VEGFR-1 receptor of normal, hyperplastic and carcinomatous endometrium (p<0.0001), the expression of VEGFR-2 receptor of carcinomatous endometrium (p=0.05), 4) the expression of proliferation index Ki67/MIB1 of hyperplastic and carcinomatous endometrium (p=0.01 and p=0.05 respectively) and 4) the expression of the protein p53 of carcinomatous endometrium (p=0.01). There was not observed immunohistochemical expression of HER2/neu protein or gene amplification. Loss of Rb expression was observed in a small number of endometrial carcinomas. The immunohistochemical expression of the proteins Ki67/MIB1, p53 and VEGF was higher in serous papillary compared to endometrioid carcinomas (p=0.002, p<0.0001 and p=0.06 respectively), Bcl-2 immunohistochemical expression was higher in endometrioid compared with serous papillary carcinomas (p=0.04). Immunohistochemical expression of ER and PR receptors was observed exclusively Conclusions: Our results suggest that in the pathogenesis of endometrial carcinomas important is the role of the proteins p53, bcl-2 and VEGF while on the contrary it does not appear important the role of proteins Rb and HER2/neu. The VEGF, that is produced by the epithelial cells of endometrium has probably double action 1) induce the stromal angiogenesis of normal, hyperplastic and carcinomatous endometrium (paracrine action) and 2) induce the cellular proliferation of epithelial cells of the hyperplastic and carcinomatous endometrium (autocrine action). The expression of VEGF of epithelial cells of endometrium it is probably regulated immediately by p53 gene.Σκοπός της παρούσας μελέτης ήταν η διερεύνηση α) διαταραχών της έκφρασης πρωτεϊνών του κυτταρικού κύκλου ή/και της απόπτωσης β) του προτύπου αγγειογέννεσης και γ) της παρουσίας αριθμητικών ανωμαλιών του γονιδίου Her2/neu στο φυσιολογικό, υπερπλαστικό και καρκινωματώδες ενδομήτριο. 128 Υλικό και μέθοδοι: Στην παρούσα εργασία μελετήθηκαν 31 περιπτώσεις φυσιολογικού ενδομητρίου (16 εκκριτικού και 15 παραγωγικού), 36 περιπτώσεις υπερπλαστικού ενδομητρίου (19 απλής και 16 σύνθετης υπερπλασίας) και 80 περιπτώσεις καρκινωματώδους ενδομητρίου για την ανοσοϊστοχημική έκφραση: 1) των ορμονικών υποδοχέων ΕR και PR, 2) των πρωτεϊνών του κυτταρικού κύκλου ή/και της απόπτωσης (Ki67/MIB1, p53, Rb και Bcl-2), 3) των ρυθμιστικών πρωτεϊνών της αγγειογένεσης (VEGF, VEGFR-1και VEGFR-2) και 4) της πρωτεΐνης HER2/neu. Επιπλέον, μελετήθηκε πιθανή ενίσχυση του γονιδίου HER2/neu με την μέθοδο του φθορίζοντος in-situ υβριδισμού (FISH). Τέλος αξιολογήθηκε η μικροαγγειακή πυκνότητα (MVD) των ιστών μετά από ανίχνευση της ανοσοϊστοχημικής έκφρασης της πρωτεΐνης CD34. Tα αποτελέσματα συσχετίστηκαν με κλινικοπαθολογικές παραμέτρους. Αποτελέσματα: Κατά την πολυσταδιακή διαδικασία της καρκινογένεσης του ενδομητρίου παρατηρήθηκε σημαντική αύξηση της ανοσοϊστοχημικής έκφρασης των πρωτεϊνών που μελετήθηκαν, από το φυσιολογικό στο υπερπλαστικό και καρκινωματώδες ενδομήτριο, συγκεκριμένα: Ki67/MIB1 (p=0.003 και p=0.05, αντίστοιχα), p53 (p=0.006 και p=0.002, αντίστοιχα), VEGF (p=0.003 και p<0.0001, αντίστοιχα), VEGFR-1 (p=0.05 και p<0.0001, αντίστοιχα) και της MVD (p<0.0001 και p<0.0001, αντίστοιχα). Η έκφραση της πρωτεΐνης Bcl-2 ήταν σημαντικά υψηλότερη στο υπερπλαστικό, σε σχέση με το φυσιολογικό και το καρκινωματώδες ενδομήτριο (p<0.0001 και p<0.0001, αντίστοιχα). Αναδείχτηκε συσχέτιση της έκφρασης του VEGF των επιθηλιακών κυττάρων με: 1) την MVD του φυσιολογικού, υπερπλαστικού και καρκινωματώδους ιστού (p<0.0001), 2) την έκφραση του υποδοχέα VEGFR-1 του φυσιολογικού, υπερπλαστικού και καρκινωματώδους ενδομητρίου (p<0.0001), 3) την έκφραση του υποδοχέα VEGFR-2 του 129 καρκινωματώδους ενδομητρίου (p=0.05), 4) τον δείκτη πολλαπλασιασμού Ki67/MIB1 του υπερπλαστικού και καρκινωματώδους ενδομητρίου (p=0.01 και p=0.05, αντίστοιχα) και 4) την έκφραση της πρωτεΐνης p53 του καρκινωματώδους ενδομητρίου (p=0.01). Δεν παρατηρήθηκε υπερέκφραση της πρωτεΐνης και ενίσχυση του γονιδίου HER2/neu. Απώλεια της πρωτεΐνης Rb ανευρέθηκε σε μικρό αριθμό καρκινωμάτων. Η έκφραση των πρωτεϊνών Ki67/MIB1, p53 και VEGF ήταν υψηλότερη στα ορώδη θηλώδη σε σχέση με τα ενδομητριοειδή καρκινώματα (p=0.002, p<0.0001 και p=0.06, αντίστοιχα), ενώ η έκφραση της Bcl-2 ήταν υψηλότερη στα ενδομητριοειδή σε σχέση με τα ορώδη θηλώδη καρκινώματα (p=0.04). Έκφραση των ER και PR ανιχνεύθηκε αποκλειστικά σε καρκινώματα ενδομητριοειδούς τύπου

Clinicopathological study of metallothionein immunohistochemical expression, in benign, borderline and malignant ovarian epithelial tumors

Metallothioneins (MTs) are a family of cystein-rich metal-binding proteins, which are expressed in normal cells during fetal and postnatal life but also in a variety of human neoplasms. MT expression in human tumors has been linked to resistance to anticancer drugs and differentiation and progression in some types of tumors. This study examined the immunohistochemical expression of MTs in benign, borderline and malignant tumors of ovarian surface epithelium and the possible correlations with clinicopathological parameters and survival. A total of 87 cases with diagnosis of ovarian surface epithelial tumors were included. Specifically, 21 cases of benign cystadenomas (11 serous and 10 mucinous), 14 borderline (low malignant potential tumors, 8 mucinous and 6 serous) and 52 cases of ovarian cancer were analysed. Immunohistochemical expression of MT (cut-off level >10% of tumor cells) was clearly associated with malignancy. A statistically significant correlation was found between the expression of MT in cancer cases and benign tumors (p<0.0001) and cancer cases and borderline tumors p= 0.003. In cancer cases a difference was observed between grade I and III (p=0.002). There was no correlation of MT overexpression with survival in the small number of ovarian carcinoma patients where it was analysed. MT constitutes a marker that characterizes aggressiveness and a high malignant potential in ovarian epithelial tumors. In diagnostic problems MT may help distinguish between benign, borderline and malignant tumors