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Endometriosis is a common gynecologic disease, which generally follows a benign course. Notwithstanding, several clinical and histologic studies as well as molecular data show that endometriosis could be a precursor of sporadic endometrioid and clear cell carcinomas at extrauterine loci. Several reports have implicated alterations of the hMLH1 and p16 ink4a (p16) genes, in particular hypermethylation of the promoter region, and of the PTEN gene, principally genetic mutations, in endometrial and ovarian cancers and have indicated that these alterations are already present in precancer conditions. In this report, we analyzed the methylation status of hMLH1 and p16 and the protein expression of PTEN and hMLH1 in 46 cases of endometriosis stages III and IV to better define the possible involvement of these genes in the malignant transformation of endometriosis. We found abnormal methylation of hMLH1 in 4 of the 46 cases (8.6%). In addition, these cases had no detectable hMLH1 protein expression. Regarding patients with hMLH1 alterations, 2 were classified as stage IV and 2 showed coexistent endometriosis and carcinoma. Only 1 case of endometriosis (2.17%), classified as atypical, showed abnormal methylation of p16. Reduced PTEN protein expression was detected in 7 of 46 cases (15.21%): 5 were clinically classified as stage IV, and the other 2 presented both cancer and hypermethylated hMLH1. Our preliminary study suggests that reduced expression of both hMLH1 and PTEN may be involved in the malignant evolution of endometriosis and should be used as markers of neoplastic transformation in aggressive endometriosis with elevated tumor markers. The term endometriosis strictly indicates the presence of ectopic endometrial glands and stroma outside the uterus. When endometrial tissue is instead located within the myometrium, the conventional term is adenomyosis. Endometriosis is an important clinical condition, whose principal symptoms are dysmenorrhea, deep dyspareunia and chronic pelvic pain. There is a high prevalence of endometriosis, ranging between 20% and 90%, in women with pelvic pain and/or infertility, while among multiparous women, the prevalence is very low (3.7%). 1-5 Even if endometriosis generally follows a benign course, it may show some malignant features, such as invasiveness and metastatic capacity. 6 In addition, a strict relationship between endometriosis and extrauterine clear cell and endometrioid carcinomas has been suspected as evidenced by their frequent coexistence in surgical specimens (17%). 7-9 The risk factors for endometriosis and ovarian malignancy are similar and include early menarche, regular periods, short menstrual cycles and low parity. Tubal ligation is protective for endometrioid and clear cell carcinomas of the ovary but not for serous and mucinous carcinomas. 9 Several molecular data indicate the malignant precursor role of endometriosis. Endometriosis exhibits LOH at 1 or more chromosomal loci (5q, 6q, 9p, 11q and 22q) in about 82% of cases. 10,11 Analysis of clonality in endomet...

Even if the etiology of pelvic prolapse is poorly defined and multifactorial, aging risk factors, such as biomechanical abnormalities in connective tissue composition, hormonal deficiency, and irregular tissue metabolism, are nonmodifiable and therefore largely stated in clinical practice. Regardless of future developments, based on the reported findings, prolapse therapy will be more influenced by genetics, biological pelvic changes, changes in tissue homeostasis, and topical hormones, rather than general pelvic corrective surgical anatomy.

Abstract. HPV involvement in head and neck (HN) cancer is still under active investigation. Fresh frozen and archival clinical samples from 115 patients affected by HN carcinomas were analysed by PCR-based methods and direct sequencing. HPV types, intra-type variants, physical status, viral load and viral transcript presence were determined. HPV positivity was correlated with the main clinical-pathological features, including smoker and drinker status, and the clinical outcome. Twenty-one tumours were HPV positive (18.3%) with HPV16 being the most frequent type (n=14) followed by HPV6 (n=4), HPV33, HPV35, and HPV58 (n=1, each type). Tonsil carcinomas contained more high-risk HPV types (6/8; 75%) than all other sites (p=0.0004). HPV16 genome was integrated in all analysed tumours, as pure integrated form or mixed with concomitant episomal forms (4 cases). The viral load showed a wide variability (range, 0.7-485 copies per cell) with the highest value detected in a larynx tumour and the lowest one in a case of cancer of the oral cavity. In 9 HPVpositive samples where mRNA was available, transcripts of viral early oncogenes originating by integrated, episomal or mixed forms of the viral genome were found. A statistically significant correlation was evidenced between HPV and tumour differentiation, being the virus more associated with tumour grade G3/G4. Multivariate Cox regression analysis revealed that lymph-node and grade status were significant independent factors for a worse disease-free survival and overall survival, whereas the HPV status was associated with a better overall survival (OR, 0.33; 95% CI, 0.13-0.81; p=0.01). Taken together these results indicate that distinct pathological mechanisms for the malignant transformation in each single HN subsite should be taken in account; HPV molecular analyses should be considered a valid tool to distinguish subsets of oropharyngeal tumours and HPV presence could be useful for the prognostic assessment of HNSCC. IntroductionTumours of the oral cavity and pharynx have been estimated at 643,000 cases for 2002, with 349,000 deaths (1). The incidence of these cancers is traditionally found to be very high in some areas of the world (e.g., France and South India), but in the last decade other areas (e.g., Eastern Europe and Japan) reported an increasing incidence of head and neck (HN) squamous cell carcinomas (SCC) (2). HN cancer constitutes one of the most difficult pathologies to eradicate. Recurrences are frequent and about a half of patients die (1). The heterogeneity of treatment response and the lack of prognostic factors could be the main causes of the adverse clinical outcome. Moreover, the behaviour variability of each individual tumour has also emphasized the difficulties of managing these tumours.Life habits such as the intake of toxic agents present in tobacco smoke, alcohol drink and betel chewing, or poor hygiene remain major risk factors for these tumours. However, the fraction of HN cancers attributable to these risk factors is close to 80-90%, while the...

Very long follow-up is recommended for AF lesions, due to the risk of recurrence and malignant change into AFS. Segmental resection is the most recommended therapy for AFS.