Summary HERG K + channels, besides contributing to regulate cardiac and neuronal excitability, are preferentially expressed in tumour cell lines of different histogenesis, where their role in the development and maintenance of the neoplastic phenotype is under study. We show here that both herg gene and HERG protein are expressed with high frequency in primary human endometrial cancers, as compared to normal and hyperplastic endometrium. RT-PCR and immunohistochemistry, using specific anti-HERG antibodies developed in our laboratory, were applied to tissue specimens obtained from 18 endometrial cancers and 11 non-cancerous endometrial tissues. herg RNA and HERG protein are expressed in 67% and 82%, respectively, of cancerous, while in only 18% of non-cancerous tissues. In particular, no expression was found in endometrial hyperplasia. Moreover, electrophysiological experiments confirmed the presence of functioning HERG channels on the plasma membrane of tumour cells. On the whole, these data are the first demonstration of the presence of HERG channels in primary human neoplasias, and could candidate HERG as a potential tool capable of marking cancerous versus hyperplastic endometrial growth.
Liquid-based endometrial cytology: cyto-histological correlation in a population of 917 women Objective: Liquid-based cytology, because of its capacity to reduce the obscuring factors and to provide thin-layer specimens, represents an opportunity to reevaluate endometrial cytology. In order to assess the utility of the liquid-based method in endometrial diagnosis, we evaluated its accuracy in comparison with histology. Methods: Nine hundred and seventeen women scheduled for hysteroscopy were enrolled in the study. After providing informed consent, all the women proceeded sequentially to hysteroscopy, endometrial cytology and then biopsy endometrial sampling. Results: Cyto-histological correlations were possible in 519 cases (57%): in 361 (39%) cases the biopsy was inadequate, in 15 (2%) the cytology was inadequate, and in 22 (2%) both were inadequate. At biopsy 25 (3%) women had adenocarcinoma, 5 (1%) had adenomatous atypical hyperplasia and 21 (2%) had simple non atypical hyperplasia. At cytology two adenocarcinomas and one adenomatous atypical hyperplasia were underrated as atypical hyperplasias and as non-atypical hyperplasia; two simple non-atypical hyperplasias were reported as negative; and eight cases were false positive (non-atypical hyperplasia at cytology, negative at biopsy). In our population, the cytology provided sufficient material more often than biopsy (P < 0.04). Sensitivity was estimated at 96%, specificity at 98%, positive predictive value at 86% and negative predictive value at 99%. Conclusions: We concluded that endometrial cytology may be an efficient diagnostic method. It could be applied to selected patients solely or in association with ultrasonography. The combination of these two noninvasive procedures may improve their diagnostic accuracy and reduce unnecessary hysteroscopies, thereby producing benefits for women and society.Keywords: endometrial neoplasms, uterine neoplasms, cytodiagnosis, cytological techniques, ThinPrep, LBC, liquid-based cytology IntroductionEndometrial adenocarcinoma ranks fifth in incidence among malignancies in women, and it is the most frequent malignancy of the female genital tract in developed countries. The majority of the cases are sporadic whereas about 10% are hereditary. Most important among the latter, is the autosomal dominantly inherited non-polyposis colorectal cancer caused by mutation of a DNA mismatch repair gene that determines constitutive microsatellite instability and Cowden syndrome in patients with germ line PTEN inactivation. Two subtypes of endometrial carcinoma, named type I and type II, have been described on the basis of their different age of development, aetiopathogenesis, histopathological features and prognosis. Type I adenocarcinoma, which accounts for most cases (approximately 80%), occurs in peri-menopausal women, is oestrogen dependent, more often well differentiated and endometrioid, and has a favourable behaviour with appropriate therapy. Conversely, the rare type II endometrial adenocarcinoma affects older postmenopausal wo...
No external funding was either sought or obtained for this study. The authors have no conflicts of interests to declare.
BackgroundMonoclonal antibodies directed against the epidermal growth factor receptor (EGFR) have been approved for the treatment of patients with metastatic colorectal carcinoma (mCRC) that do not carry KRAS mutations. Therefore, KRAS testing has become mandatory to chose the most appropriate therapy for these patients.Methodology/Principal FindingsIn order to guarantee the possibility for mCRC patients to receive an high quality KRAS testing in every Italian region, the Italian Association of Medical Oncology (AIOM) and the Italian Society of Pathology and Cytopathology -Italian division of the International Academy of Pathology (SIAPEC-IAP) started a program to improve KRAS testing. AIOM and SIAPEC identified a large panel of Italian medical oncologists, pathologists and molecular biologists that outlined guidelines for KRAS testing in mCRC patients. These guidelines include specific information on the target patient population, the biological material for molecular analysis, the extraction of DNA, and the methods for the mutational analysis that are summarized in this paper. Following the publication of the guidelines, the scientific societies started an external quality assessment scheme for KRAS testing. Five CRC specimens with known KRAS mutation status were sent to the 59 centers that participated to the program. The samples were validated by three referral laboratories. The participating laboratories were allowed to use their own preferred method for DNA extraction and mutational analysis and were asked to report the results within 4 weeks. The limit to pass the quality assessment was set at 100% of true responses. In the first round, only two centers did not pass (3%). The two centers were offered to participate to a second round and both centers failed again to pass.ConclusionsThe results of this first Italian quality assessment for KRAS testing suggest that KRAS mutational analysis is performed with good quality in the majority of Italian centers.
The morphological and functional aspects of the endometrium were investigated in 28 asymptomatic post-menopausal women to evaluate the ageing phenomenon of this tissue. Haematoxylin-eosin staining showed an atrophic endometrium in 12 cases and a hyperplastic endometrium in the other 16 cases. Masson's trichrome identified moderate fibrosis in all post-menopausal endometrial stroma. Immunohistochemical analyses were performed on the endometrial specimens to evaluate the distribution of the capillary system, the cellular proliferation index and the presence of oestrogen and progesterone receptors. Our data showed a discrepancy between the morphological pictures and the functional aspects of the post-menopausal endometrium. In fact, the morphological pictures suggested an involution of this tissue according to the increase in collagen fibres, the decrease in vascular distribution and the frequent atrophic patterns. On the other hand, data from steroid receptors and the cell proliferation index suggest that post-menopausal endometrium is an active structure. So, endometria from normal post-menopausal women appear to be in a more quiescent state than in a really atrophic condition. This leads to the question: does the endometrium really age?
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