Taddei Gl

HERG potassium channels are more frequently expressed in human endometrial cancer as compared to non-cancerous endometrium

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.

Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer.

PURPOSE The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P < .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.

Ten-year results of a prospective study on the prognostic role of ploidy in endometrial carcinoma: dNA aneuploidy identifies high-risk cases among the so-called 'low-risk' patients with well and moderately differentiated tumors.

To improve the outcome of endometrial cancer patients, a more accurate prognostic assessment is mandatory. The aims of the study were to evaluate the role of flow cytometric DNA ploidy as an independent prognostic factor in patients with endometrial cancer and to verify if ploidy was able to distinguish patients with different prognosis into homogeneous subgroups for grade of differentiation and stage.

Testosterone maintenance therapy : Effects on vulvar lichen sclerosus treated with clobetasol propionate

OBJECTIVE To evaluate the possible effects of topical testosterone as maintenance therapy after clobetasol propionate treatment. STUDY DESIGN Thirty-two patients with biopsy-proven vulvar lichen sclerosus (LS), after 24 weeks of treatment with 0.05% clobetasol propionate cream, were randomly distributed into two groups of 16 each and treated for a further length of time (24 weeks) with testosterone 2% ointment or a cream-based preparation (placebo). The patients were examined before and after treatment for symptoms, gross aspects and histologic features. RESULTS With clobetasol propionate all patients had a marked improvement (P < .001) in both clinical and histologic parameters. After clobetasol propionate therapy, the 16 testosterone-treated patients had significant worsening of their symptoms (P < .05%) and no evident changes in gross aspects (P = NS). The placebo-treated group had good symptomatic control of their disease, with no significant changes in symptoms or gross aspects (P = NS). CONCLUSION After the good results obtained with clobetasol propionate, treatment with testosterone appeared to have a negative effect, while a regularly provided emollient cream was useful in symptom control.

Hormonal patterns, steroid receptors and morphological pictures of endometrium in hyperstimulated IVF cycles

OBJECTIVE The purpose of this contribution is to investigate the pathophysiology of the abnormal endometrial development in hyperstimulated IVF cycles. STUDY DESIGN In 12 IVF-patients who did not have embryo transfer because of failure of oocyte fertilization, serum values of 17 beta-estradiol, progesterone, FSH, LH, total and free testosterone, and androstenedione were measured on the pick-up day and were evaluated with respect to the values normally expressed in the day of ovulation; in the endometrial specimens collected 2 days later, at the time of embryo replacement, estrogen and progesterone receptors were immunohistochemically determined and dating by the Noyes method was performed. RESULTS 17 beta-Estradiol values are constantly higher, and progesterone levels are, only in four cases, higher than expected for the day of ovulation in a natural cycle. These hormonal patterns can only partially explain the pattern of steroid receptors: progesterone receptors are expressed sparsely both in glands and stroma, while estrogen receptors are abundant in the glands and absent in the stroma. In 11 of 12 patients an abnormal endometrial development with stromal advancement was observed: this morphological picture of the endometrium could partially be explained only in the four cases presenting high progesterone levels by serum values and endometrial receptor content of estrogen and progesterone. CONCLUSIONS The abnormal endometrial development in hyperstimulated IVF cycles could only in part be explained by estrogen and progesterone, and other factors have to be considered.

Cerebellar liponeurocytoma. Case report with considerations on prognosis and management.

Summary.Summary. Background: Cerebellar liponeurocytoma has only recently been recognized as a distinct clinicopathological entity. Although the few cases described in literature support the relatively benign nature of this lesion, optimum treatment strategy and long term behaviour still have to be defined. Clinical Presentation: This 61-year-old man came under our observation with unspecific signs of intracranial hypertension and a symptomathology revealing a probable posterior fossa lesion. Imaging studies showed a cerebellar mass lesion with prevalent adipose content. Intervention: Gross total tumour removal was performed. The pathological examination revealed a lesion composed of medulloblastoma-like cells with prominent areas of lipidisation. A review of literature has been made in an attempt to investigate on recurrence patterns, importance of the extent of removal and the usefulness of radiotherapy. Conclusion: The few cases reported in literature so far seem to confirm the relatively benign nature of cerebellar liponeurocytoma. No radiotherapy was given in our case and the reasons for this decision are reported.

KRAS Mutations Testing in Colorectal Carcinoma Patients in Italy: From Guidelines to External Quality Assessment

Background Monoclonal 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 Findings In 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. Conclusions The 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.

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.

Liquid‐based endometrial cytology: its possible value in postmenopausal asymptomatic women

The incidence of endometrial adenocarcinoma in asymptomatic women is low. Nevertheless, some of these women might require endometrial surveillance. In this study, we evaluated the accuracy of liquid-based endometrial cytology compared to biopsy in asymptomatic postmenopausal women. Three hundred twenty women scheduled for hysteroscopy were enrolled for this study. After hysteroscopy, patients were submitted to endometrial cytology and to biopsy. Two hundred ninety-three (92%) women had sonographically thickened endometrium (>5 mm), 53 (17%) were on tamoxifen, and 16 (5%) were on hormonal substitutive treatment. The evaluation of the biopsies determined that six (2%) women had adenocarcinoma, one (<1%) had adenomatous atypical hyperplasia, and eight (3%) had simple nonatypical hyperplasia. Endometrial cytology evidenced 5 (2%) neoplastic cases, 2 (<1%) hyperplastic with atypia cases, and 25 (8%) hyperplastic without atypia cases. Two hundred twenty-two biopsies (69%) and 17 (5%) cytologies were inadequate. One adenocarcinoma and one simple nonatypical hyperplasia were underrated by cytology resulting, respectively, as atypical hyperplasia and as negative. Four cases were false positive (simple nonatypical hyperplasias on cytology, negative on biopsy). The sensitivity and specificity were estimated, respectively, at 94% and 95%; the positive and negative predictive value were estimated, respectively, at 80% and 99%. Endometrial cytology provided sufficient material more often than biopsy (P < 0.01). We suggest to introduce liquid-based endometrial cytology in the management of some subpopulations of asymptomatic postmenopausal women. Particularly, the combination of liquid-based endometrial cytology and transvaginal sonography may improve their diagnostic accuracy and reduce unnecessary more invasive and expensive procedures.

I. Aging of the human endometrium: a basic morphological and immunohistochemical study

OBJECTIVE To evaluate if human endometrium presents morphological variations suggestive of an age-related decline in endometrial receptivity. STUDY DESIGN Peri-implantation endometrium of younger (<30 years of age: n = 13) and older (>40 years of age: n = 17) normally menstruating women was studied. Endometrial specimens were routinely fixed in buffered formalin and embedded in paraffin. Sections (5 mu m) were stained with hematoxylin-eosin, periodic acid-Schiff (PAS) and Trichrome conforming to Masson according to conventional histologic examination. Several consecutive sections were used for the following immunohistochemical study: vascular localization (CD34), cellular proliferation index (PCNA), progesterone and estrogen receptors. RESULTS Using both the traditional morphological evaluation and monoclonal antibodies, no significant differences were found between the endometria of women <30 years of age and those of women >40. CONCLUSIONS Our results suggest that human endometrium does not age, at least while cyclic hormonal stimulation and menstruation are present.