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The cellular tumor suppressor protein pl61NK4a (p16) has been identified as a biomarker for transforming human papilloma virus (HPV) infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell cycle and cell proliferation by inhibiting cell cycle G1 progression.To confirm the role of p16 as biomarker for transforming HPV infections and possible clinical applications in histological samples from the uterine cervix.The subject of this study included 56 biopsies of the cervical canal collected from January 2012 to September 2012 in the Institute of Pathology of the University of Sassari. The search for HPV immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while for the detection of p16 was used CINtecTM p16 (INK4a) histology kit.In 56 biopsies performed in women aged between 23 and 69 years, the authors highlighted, by histological analysis, 24 cases of low-grade squamous intraepithelial lesion (LSIL) - cervical intraepithelial neoplasia (CIN1) and 31 cases of high-grade squamous intraepithelial lesion (HSIL) - CIN2/3); 15 CIN2, 14 CIN3, and two cervical squamous cell carcinoma in situ (SCIS). One case was an infiltrating squamous cell carcinoma (ISC). In 24 CIN1, there was a 16.67% positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2 the percentage of positivity for p16 was considerably increased (73.33%), unlike the search for HPV which had a positivity rate of 20%. Finally, in 14 cases of CIN3, and in three carcinomas, the positivity for p16 was equal to 100%, however the search for HPV positivity was between 0% and 7.14%.These results demonstrated that p16 was a highly sensitive marker of cervical dysplasia. The authors have shown that p16 overexpression increased with the severity of cytological abnormalities and that had a greater ability to identify the viral infection compared to the classical immunohistochemical staining for HPV.

Le voragini con funzione di inghiottitoio hanno costantemente impegnato il Gruppo Speleologico Neretino (GSN) da circa trentacinque anni a questa parte. Le attività di esplorazione, disostruzione e rilievo degli ipogei sono state affiancate da osservazioni e studi sui tributari idrologici, dapprima per la necessaria sicurezza della progressione nelle cavità e, in seguito, per la comprensione delle caratteristiche geomorfologiche dei sistemi. Nondimeno, anche la divulgazione dei risultati di esplorazioni e ricerche ha costituito una delle principali attività del gruppo. Sono state così svolte azioni di protezione idrogeologica ante litteram, prima cioè della definizione e diffusione dei concetti di difesa del territorio e delle attività umane dai dissesti naturali o indotti. In questa nota si intende sottolineare l'incidenza dell'intervento umano, sia nel determinare l'assetto idrografico dei sistemi fluvio-carsici che nell'esporre risorse naturali, ecosistemi, infrastrutture ed attività al rischio idrogeologico, come dedotto dalle attività svolte nei territori di Nardò, Mesagne e Surano negli ultimi tre anni.

Alcune grotte del Distretto Preistorico di Nardò contengono manufatti musteriani riferibili al Riss finale. Numerosi siti ipogei del Salento conservano depositi con industrie, in alcuni casi anche reperti osteologici, di Homo neandertaliensis del Pleistocene Superiore, che costituiscono una importante registrazione geologica benché l'inquadramento cronologico non è ancora definito. Considerando lo stato dell'arte di varie discipline, si pongono le basi per definire gli indicatori geologici paleoclimatici del Tirreniano e del Würm e si delineano scenari ambientali di fasi cruciali delle parabola esistenziale di Homo neandertaliensis.

The Apulia region of southern Italy is one of the most important italian karst areas, due to widespread presence of carbonate rocks over its entire extension. Surface and subsurface karst morphologies characterize it, with particular diffusion of landforms as dolines and sinkholes. Since the first occupation of this land by man, some of the karst landforms have been used and partly modified (if not cancelled) to several aims: draining the surface waters, discharging floods, and reclaiming marsh lands, among the others. Southern Apulia, in particolar, hosts a large number of dolines, producing at the ground similar morphologies (abrupt shafts in a generally flat terrain) but which might be originated by different processes (collapse, solution, soffusion, etc.). This contribution examines the territory of Mesagne, in the Brindisi province: even if characterized by mostly flatland, the Mesagne area presents some tens of water sinks, most of which correspond to dolines. Drainage works today visible at the sites derive from a multi-secular anthropogenic activity. Some of the dolines have been recognized as produced by collapse, through progressive detachment of the vault of an original underground cavern, or favoured by the erosion of low cemented sandy and silty deposits covering the underlying carbonate rocks. Likely, many other dolines might share the same origin. At Mesagne, as in large areas of Salento (the southern part of Apulia), a Quaternary sequence transgressively overlies the Cretaceous carbonate bedrock with an unconformable contact. The Quaternary sequence consists of calcarenites and intervening clayey deposits. The bottom calcarenite can be correlated to the Pleistocene Calcarenite di Gravina formation; above it, an intermediate unit, made of argillaceous silts with sandy intercalations, is present. The top unit is again formed by calcarenites with subordinate calcirudites, related to the Terraced Marine Deposits Auct. Due to this geological configuration, the hydrogeology of the area shows two distinct aquifers: the shallow aquifer is represented by the top calcarenites. Water from this aquifer is generally used for irrigation. The aquifer lower limit is given by the impervious layers in the argillaceous silts, which act as a barrier of low permeability. The deep aquifer, on the other hand, is contained within the Cretaceous limestones, and represents the only local supply of drinkable water. From the hydrogeological point of view, the territory of Mesagne, which is considered as representative of large areas in southern Apulia, is highly vulnerable to the following hazards: (i)flooding, favoured by the overall flat topography, and the presence of geological formations with low permeability in the first meters of the subsoil; (ii)development of collapse dolines, or sinkholes; (iii) groundwater pollution, regarding both the shallow and the deep aquifer. Safeguard of the hydric resources, and mitigation of the risk related to natural and anthropogenic hazards in this fragile karst area, may be pursued only through knowledge of the physical features of the territory and the correct management of its natural resources.

Le Vore di Barbarano sono due delle più ampie cavità carsiche, a prevalente sviluppo verticale, del Salento. Esse risultano morfologicamente più complesse di altre cavità analoghe, quali le Vore di Spedicaturo e le Grotte della Poesia. Le osservazioni speleologiche, geomorfologiche, stratigrafiche, idrogeologiche e biologiche, permettono di individuare i meccanismi speleogenetici all'origine delle vore. Sono state così individuate le fasi evolutive dalla formazione delle protogrotte sino alle aperture degli accessi.

Numerosi e frequenti crolli di blocchi di roccia interessano la falesia di Roca Vecchia e gli ipogei delle Grotte della Poesia. Le ricerche condotte hanno individuato i processi ed evidenziato le differenti azioni carsiche attive all'origine dei fenomeni gravitativi. In particolare, il mescolamento delle acque dolci meteoriche e di falda con quelle marine è causa di ipercarsismo chimico, molto aggressivo sul calcare. Altri processi ipercarsici derivano dall'idrodinamismo costiero che causa, specie nel sopratidale e intertidale, variazioni di umidità e salinità. Importanti risultano anche le azioni di bioerosione esercitate da organismi, specie in corrispondenza del solco di battente alla base della falesia. Di modesta entità risultano invece gli effetti delle azioni meccaniche dovute all'idrodinamismo costiero. Il carsismo contribuisce significativamente a determinare il "rapido" arretramento della linea di costa.

Aim. We report our experience on the management of Hurthle cell neoplasms (HCNs) of the thyroid and a review of the literature in order to describe the most relevant clinical, diagnostic, biologic and therapeutic aspects. Materials and Methods. We retrospectively reviewed the clinical records of 15 consecutive patients with HCN. The male/female ratio was 1:4 and the mean age was 53.8 years. Fourteen patients underwent total thyroidectomy and one patient lobectomy. Two patients were lost to follow up. The mean follow up time was 54 months. Results. Eleven Hurthle cell adenomas and 4 carcinomas were found. At the time of initial surgical evaluation 9 patients (60%) were symptomatic, with hyperthyroidism and dysphagia being the most frequent manifestations. Only in 6 (40%) cases the diagnosis was obtained by preoperative fine needle aspiration biopsy. Among patients with Hurthle cell adenoma and carcinoma the mean age was 51 and 62 years respectively and the mean lesion size 1.6 and 3.8 cm respectively. No cases of death or recurrence were registered. Conclusions. Clinical manifestations are similar to those for other differentiated thyroid neoplasms. Patients with Hurthle cell carcinoma presented a mean age and a mean tumor size greater than those with Hurthle cell adenoma. Our data suggest that adenomas have not a malignant potential; nevertheless surgical resection is necessary to obtain a precise evaluation of eventual infiltrative events. Surgical resection is also the treatment of choice for the treatment of carcinomas with total thyroidectomy representing the best surgical option. Obiettivo. Riportiamo in questo articolo la nostra esperienza nel management delle neoplasie a cellule di Hurthle (HCNs) ed una revisione della letteratura allo scopo di sottolineare i più importanti aspetti clinici, diagnostici, biologici e terapeutici. Materiali e metodi. Abbiamo esaminato i dati clinici di 15 pazienti consecutivi con HCN. L’età media dei pazienti era di 53,8 anni e il rapporto maschi/femmine 1:4. Quattordici pazienti sono stati sottoposti a tiroidectomia totale ed uno a lobectomia. Due pazienti sono stati persi al follow up. Il tempo medio di follow up era di 54 mesi. Risultati. Undici pazienti sono stati trovati affetti da adenoma a cellule di Hurthle e 4 da carcinoma. Nove pazienti (60%) erano sintomatici, e solo in 6 (40%) casi la diagnosi è stata ottenuta tramite biopsia con ago aspirato. L’età media dei pazienti affetti da adenoma era 51 anni e di quelli con carcinoma 62. La dimensione media delle lesioni era superiore nei pazienti con carcinoma (3,8 cm verso 1,6 in quelli con adenoma). Non sono stati osservati decessi o recidive. Conclusioni. Abbiamo osservato una differenza di età e di dimensione delle lesioni tra i pazienti affetti da adenoma e quelli affetti da carcinoma. I nostri dati suggeriscono che gli adenomi a cellule di Hurthle non hanno potenziale maligno, tuttavia l’asportazione chirurgica è necessaria per la valutazione di eventuali eventi infiltrativi. Il trattamento chirurgico con tiroidectomia totale o resezioni più ampie ove necessario rappresenta il trattamento di scelta per i carcinomi.

Early and certain diagnoses of endometriosis are mandatory to begin the correct treatment and to exclude the risk of endometriosis-associated ovarian carcinoma (EOC) and endometrial stromal sarcoma (ESS).To assess the immunohistochemical expression of Ber-Ep4, an epithelial antigen, and CD10 in endometriosis.Forty-eight women underwent laparoscopic surgery for endometriosis and endometriotic samples were recovered for histology. In all surgical specimens Ber-Ep4 and CD10 were searched by an immnohistochemical method. The authors evaluated the correlations among the immunohistochemical positivity and the location of endometriosis.Most cases (40/48 83.34%) were represented by ovarian endometriotic cyst. Among the eight remaining cases, three (3/48, 6.25%) were pelvic endometriotic lesions, two (2/48, 4.17%) peritoneum of vesico-uterine pouch, one vaginal lesion (2.08%), one salpinx lesion (2.08%), and one inguinal location (2.08%). Ber-Ep4 and CD10 were expressed in 90% and in 100% of the ovarian lesions, respectively. In pelvic lesions Ber-Ep4 and CD10 showed both 66.67% of positivity and had the same pattern in peritoneal, salpinx, vaginal, and inguinal lesions (50%, 100%, 100%, 100%, respectively). Ber-Ep4 was negative in 6/48 (12.5%) cases whereas CDO10 was negative in 2/48 (4.17%) cases of endometriosis. The sensitivity of Ber-Ep4 and CD10 for endometriosis diagnosis were 87.50% and 95.83%, respectively. Immunohistochemistry for Ber-Ep4 showed positivity in all cases of endometriosis with typical cubic epithelium, whereas CD10 was positive in 1/2 (50%) atypical case.Immunohistochemical expression of Ber-Ep4 and CD10 was positive in most cases of endometriosis and was useful in differential diagnosis with mesothelial cysts. Ber-Ep4 was negative in cases of hyperplastic epithelium or cytological atypia; these cases are not well-differentiated and could be optimally treated by surgery and not by hormonal therapy because of the risk of cancer degeneration.

To assess the immunohistochemical expression of Ber-EP4, a new epithelial antigen in ovarian cancer.We studied 25 cases of ovarian cancer in which Ber-EP4, CEA and CA 125 were investigated by an immunohistochemical method. We evaluated the correlations between immunohistochemical positivity and grading, histotype and stage of disease.CEA was positive in 5 out of 25 cases (20%), CA-125 in 17 out of 25 cases (68%) and Ber-EP4 in 14 out of 25 cases (56%). Ber-EP4 was mainly present in mucinous tumors in comparison to serous tumors (78.6% vs. 50%). Ber-EP4, as well as CA-125, were directly proportional to tumor differentation (70% of positivity in G1 vs 37.5% in G3 for the former and 80% in G1 vs 50% in G3 for the latter, respectively), whereas CEA showed no relevant difference regarding the grading. There were no differences among the three antigens studied with regard to clinical stage.In our study Ber-EP4 was positive in 14 out of 22 cases (63.6%) of the primary epithelial ovarian cancers studied. The presence of this antigen seems to be related to histotype and grading but not to clinical stage.

Endometrial stromal sarcomas (ESSs) are rare neoplasms, which are currently treated by surgery, whereas effective adjuvant therapies have not yet been established. Recently, epidermal growth factor receptor (EGFR) expression has been described in ESS, and a potential role of EGFR-targeted adjuvant therapies has been proposed. The aim of this study was to analyze EGFR status in an ESS series and to evaluate their potential role as molecular targets.EGFR status was investigated in a total of ten cases of ESS, which included seven low-grade ESS and three undifferentiated ESS cases. EGFR expression levels were assessed by immunohistochemistry, and gene amplification analysis was performed with dual-color fluorescence in situ hybridization (FISH).Nine out of ten ESS cases showed positive immunostaining, whereas FISH analysis demonstrated constantly negative results.This study confirmed that EGFR is frequently overexpressed in ESS. FISH analysis did not show EGFR amplification in any of the tumors, therefore EGFR expression in ESS should be related to different genetic mechanisms.

Various authors have investigated the pathological findings of penile tissue after chronic arterial obstruction, but the significance of these changes in the corpora cavernosa remains unclear. In order to evaluate the possible damages in the erectile tissue after chronic arterial obstruction at different levels, we utilized an experimental model in rats to determine the changes in smooth muscle cells and elastic fibers of the erectile tissue by microscopic immunohistochemical and ultrastructural studies.Twelve adult male Wistar rats were employed in this study. Ten were used for the experiments and two as control. The rats were anaesthetized with ether and intraperitoneal 10\% chloral hydrate. Microsurgical isolation of the involved vessels was performed with the aid of a Zeiss dissecting microscope. Partial stenosis was achieved with 11/0 nylon and amputation of the penis was performed at previously established time periods. The partial stenosis was carried out at the level of the aortic below the renal vessels (Group A), the common iliac artery on both sides (Group B) and the hypogastric artery on the left side (Group C). Arterial obstruction was maintained in each group for 50, 40 and 25 days, respectively.In comparison with normal controls, the histological findings revealed discrete and diffuse interstitial hyalinosis with reducted elastic fibers, while dilated vascular lacunae were also present on TEM (Transmission Electron Microscope) and SEM (Scanning Electron Microscope) examination. The greatest ultrastructural damages were observed in the group with obstruction of the common iliac artery on both sides. The foregoing confirms that an eventual chronic obstruction of these arteries does not allow the formation of collateral vessels for the corpora cavernosa.

To assess the immunohistochemical expression of p53 protein, a tumour suppressor gene of the oncogene c-erb-B2 and MIB-1 proliferation marker (Ki-67 antigen) in endometrial carcinoma.We studied 29 cases of endometrial carcinoma in which the p53, c-erb-B2 and MIB-1/Ki-67 antigens were investigated by an immunohistochemical method. We evaluated the correlations among the immunohistochemical positivity and the grading, depth of myometrial invasion, stage of the neoplasia and follow-up.Both p53 and c-erb-B2 were positive in 16 out of 29 cases (55.2%), whereas MIB-1 was positive in 19 out of 29 cases (65.5%). All these three antigens showed a positive correlation with the grading, myometrial invasion and FIGO stage. Regarding follow-up, p53, c-erb-B2 and MIB-1 were, respectively, positive in 100%, 83.4% and 66.7% of neoplasias of patients who died of disease whereas they were positive in 40%, 40% and 60%, respectively, of tumours of patients with no evidence of disease.The overexpression of p53, c-erb-B2 and MIB-1 seem to indicate a more malignant tumour phenotype.

Based on hospital discharges in 1001-2010, we calculated risk of tumours with an elevated occupational and environmental etiological fraction by health district of residence within the Local Health Unit (LHU) N. 8 of Sardinia. With reference to the age and gender-specific hospitalization rates of the whole LHU, residents in the urban Cagliari health district showed an excess risk of haemolymphopoietic cancer (RR = 1.07; 95% CI 1.03-1.12) and bladder cancer (RR = 1.10; 95% CI 1.05-1.16); in both instances, risks were higher among female residents. The highest excess risk for lung cancer was observed among residents in the Quartu-Parteolla health district (RR = 1.13; 95% CI 1.05-1.21), and it was slightly higher among male residents. The results appear to confirm the role of urban factors in increasing cancer risk.

Background Human Papillomavirus (HPV) infection is one of the most important causes of cancer. It can play a role in cervical and extra-cervical cancers. Penile cancer is rare, even if an increasing trend was recently reported. Aim of the present study was to assess the prevalence and distribution of HPV genotypes in cases of penile cancer diagnosed in Sardinia, Italy. Surrogate markers of HPV infection (i.e., E6 and p16 genes) were also evaluated in all cases. Methods An observational, retrospective study which recruited all cases of penile cancer diagnosed between 2002 and 2019 at a tertiary care hospital in Sardinia, Italy, was carried out. HPV-DNA detection and genotyping were performed by Real-time PCR. Specimens were tested for oncogene E6 mRNA and for p16(INK4a) expression. Results HPV prevalence was 28.1% (9/32); HPV-16 was the most prevalent genotype (7/9, 77.8%). p16INK4a positivity was found in 66.7% of the samples with a statistically significant difference between HPV-positive and -negative groups. E6-transcript was detected in 71% of the HPV-16 positive samples. The overall survival was not statistically different between HPV-positives and -negatives. Discussion The present study confirms the etiologic role of HPV in penile cancer and supports the adoption of vaccination strategies in men and women. Further studies should clarify the diagnostic and prognostic role of E6 and p16 proteins. Conclusion HPV infection can favor the occurrence of penile cancer, whose diagnosis and prognosis could be improved with the implementation of validated molecular techniques.

Objectives: Anal cancer is a rare disease. However, its incidence is increasing in some population groups. Infection caused by Human Papillomavirus (HPV) is strongly associated with the risk of anal cancer, whose variability depends on samples, histology, and HPV detection methods. The aim of the study was to assess prevalence and distribution of HPV genotypes in patients diagnosed with anal carcinoma. Methods: An observational, retrospective study was carried out in a tertiary care hospital in North Sardinia, Italy. Specimens of anal cancer diagnosed from 2002&ndash, 2018 were selected. Demographic, epidemiological, and clinical variables were collected to assess their relationship with the occurrence of anal cancer. Results: The overall HPV positivity was 70.0% (21/30), with HPV-16 being the predominant genotype (~85%). The highest prevalence of anal cancer was in patients aged &ge, 55 years. HPV positivity was higher in women (p-value &gt, 0.05) and in moderately differentiated samples (G2) (p-value &lt, 0.05). p16INK4a and E6-transcript positivity were found in 57% and 24% of the HPV positive samples, respectively. The OS (overall survival) showed a not statistically significant difference in prognosis between HPV positive sand negatives (10, 47.6%, vs. 4, 44.4%, p-value = 0.25). Conclusions: HPV-DNA and p16INK4a positivity confirmed the role of HPV in anal carcinoma. Our findings could support the implementation and scale-up of HPV vaccination in males and females to decrease the incidence of HPV-associated cancers. Further studies are needed to better clarify the prognostic role of HPV/p16 status.

Background: Human Papilloma virus (HPV) is recognized as the etiological agent of benign and malignant ano-genital lesions. The most prevalent genotypes associated with cervical carcinoma are HPV-16 and -18 worldwide. However, recent studies have emphasized the role of other genotypes, such as HPV-51, in the pathogenesis of cervical dysplasia. The aim of the study was to estimate the burden of HPV-51 infection in invasive cervical malignant lesions in Northern Sardinia, Italy. Methods/Principal Findings: An observational, retrospective, prevalence, mono-center study was carried out to evaluate the presence of HPV genotypes in tissues biopsies of cervical lesions (CIN-1, CIN-2, CIN-3 and invasive carcinoma) gathered from 1996 to 2009. Biological samples were collected from women admitted consecutively to a tertiary university hospital situated in Sassari, Italy. Molecular methods were used to identify 28 oncogenic HPV types. A total of 155 formalin-fixed and paraffin-embedded cervical tissue samples were analyzed. Approximately half of the cervical lesions were classified as invasive carcinoma. HPV-DNA was detected in 71% of the samples, with a higher frequency (100%) in those categorized as invasive neoplasia. Mono- or co-infections were demonstrated in 45.8% and 25.8% of the cervical samples, respectively. Overall, the most prevalent HPV types were -16 (49%) and -51 (19.4%), with an increased frequency of detection associated with the severity of the cervical lesions. Conclusions/Significance: This survey highlights for the first time the relevant role of HPV-51 infection in the pathogenesis of invasive cervical cancer prior to the introduction of a vaccination program. Although a selection bias could have influenced the results, other recent studies have described the impact of HPV-51. This remarkable epidemiological element should be carefully evaluated, particularly in the view of opting for preventive vaccines, whose cross-protection patterns determine their efficacy in protecting against infection from HPV types that are not included in the vaccine itself.

Background: Human papillomavirus (HPV) has been associated with several disorders of the genital tract, skin and oropharynx. The aims of our study were to evaluate the prevalence of HPV infection in women between 15 and 54 years of age in North Sardinia, Italy, to identify the prevalence of High Risk - Human papillomaviruses (HR-HPV) genotypes and to establish a correlation between molecular and cytological results. Methods: From 2007 to 2009 we consecutively enrolled women aged 15-54 years admitted to public and private outpatient settings. All the participants filled in a questionnaire about the socio-cultural state, sexual activity and awareness about HPV. 323 cervical specimens were tested for HPV-DNA and HPV genotypes with INNO-LiPA HPV Genotyping CE Amp kit. Samples showing positivity to some HPV genotypes were re-tested using “in house” quantitative Real-Time PCR assays. Results: Overall HPV-DNA positivity was detected in 35.9% of the women. The prevalence of HR-HPV infection among HPV positive samples was 93.1% with a specific prevalence of HPV 16, 51, 31, 53 and 18 of 54.3%, 37.9%, 10.3%, 6.9% and 5.2%, respectively. Co-infection with any HPV, HR-HPV, LR-HPV and HR/LR-HPV type was 18.3%, 14.9%, 0.9% and 2.5%, respectively; HPV 16/51 co-infection was detected in 64.6% of the HR-HPV co-infection group. The most frequent HPV-genotypes detected were 16 (32.5%) and 51 (22.7%). Among the 57 patients harboring mono-infection the most prevalent HPV genotypes were 16 (38.6%) and 31(10.5%). A multivariate analysis identified a statistical significant association between HPV infection and age and between HPV infection and previous sexual transmitted diseases. A statistically significant association between cytological cervical lesions and generic HPV exposure was identified. Conclusions: To our knowledge, this is the first survey evaluating the prevalence of HPV infection in Northern Sardinia and drawing attention to the unusual high proportion of genotype HPV 51. Given the recent implementation of a widespread immunization program with vaccines not containing HPV 51, it has been relevant to prove the high prevalence of this HPV genotype from the start of the vaccination campaign, in order to avoid in the future attributing to the vaccination program a possible selection effect (HPV replacement).