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To evaluate incidence rates (IRs) of classic Kaposi's sarcoma (CKS) in Italy after the spread of AIDS, we distinguished CKS from AIDS-related KS (AKS) using an 'ad hoc' record linkage procedure between 15 Cancer Registries (CRs) (21% of the Italian population) and the national AIDS Registry. Between 1985 and 1998, 874 cases of CKS and 634 cases of AKS were diagnosed in the study areas. CKS accounted for 16 and 27% of KS cases below 55 years of age in men and women, respectively, but for 91 and 100% of those above age 55. The IRs for CKS were 1.0/ in men and 0.4/100,000 in women, but they varied between 0.3 in Umbria and 4.7 in Sassari in men, and between 0.1 in Parma and 1.7 in Sassari in women. IRs of CKS in both genders were stable between 1985-1987 and 1993-1998. In Northern and Central CRs the IR (adjusted for age and gender) for CKS was 0.5 in individuals born in the same area, but 1.6 in individuals born in Southern Italy or in the Islands (rate ratio = 3.2) suggesting that KS-associated herpesvirus, the cause of KS, is acquired early in life.

Malignant ovarian tumors have been continuously increasing in Western countries and represent the leading cause of death for gynecological cancer. In fact, the mortality for malignant ovarian tumors remains very high with a low percentage of 5-year survival in the advanced stage of disease. The aim of this study was to evaluate the incidence trend and epidemiological characteristics of malignant ovarian tumors in the Province of Sassari, Sardinia (Italy) in the period 1992-2001 and to report the variations in comparison to the 1974-1985 period. The analysis of our data regarding the period 1992-2001, if compared with those of the period 1974-85, showed an increase of malignant ovarian tumors which triplicated achieving an incidence of 11.99/100,000 vs 4.27/100,000. The analysis of our epidemiologic data showed an increase of the age of first diagnosis (mean 60.9 years for epithelial ovarian tumors), the occurrence of the cancer in women at low socio-economic levels and a family history of cancer among the patients with malignant ovarian tumors. These data suggest that both local environmental factors combined with genetic characteristics play a role in the pathogenesis of ovarian tumors. The genetic characteristics could be of particular interest because Sardinia has been through the centuries a geographical area with little population migration. The marked increase in the incidence of ovarian tumors in the last several years points out the need to organize systematic screening by ultrasonography in our population.

The aim of this study was to evaluate the incidence of malignant breast tumors in the Province of Sassari, Sardinia (Italy) in the period 1992-2002 and to report the variations in comparison to the 1974-1985 period. The analysis of our data showed that the overall number of malignant breast tumors was more than doubled from 1,139 cases in the period 1974-1985 to the 2,735 cases in the period 1992-2002, and the mean rate/100,000 changed from 43.4 to 106.0. The incidence in the age classes 45-64 years, which were at enhanced risk for breast cancer, was globally increased, changing from 143.6/100,000 to 198.7/100,000. On the other hand, the incidence in the youngest age classes (30-34 yrs) was reduced from 59.5% to 27.0%. The analysis of the histotypes showed a relative reduction of ductal carcinoma in the period 1992-2002 in comparison to the previous period 1974-1985 (65.2% vs 82.0%) whereas the incidence of anaplastic forms increased in advanced ages of life. We reported an important reduction of T0 tumors from 3.4% to 0.1%. These data could be due to the low diffusion of screening programs in Sardinia. Tumor metastases were more frequent in advanced age classes. In conclusion, the worrying data of the strong reduction of T0 cases, the increased age of first diagnosis and the advanced forms with positive nodal metastases showed that the prevention program has not been yet well organized.

Purpose: The h-prune gene is involved in cellular motility and metastasis formation in breast cancer through interacting with the nm23-H1 protein. The aim of this study was to better define the clinical and pathologic role of h-prune in breast cancer patients., Experimental Design: Using immunohistochemistry, we assessed h-prune and nm23-H1 protein expression in two series of breast cancer patients: (i) in 2,109 cases with pathologic reports on primary tumors and (ii) in 412 cases with detailed clinical information. To assess the role of DNA amplification in gene activation, the h-prune copy number was evaluated by fluorescence in situ hybridization analysis in 1,016 breast cancer cases., Results: In the patients tested (n = 2,463), 1,340 (54%) had an increased level of h-prune expression; a positive immunostaining for nm23-H1 was observed in 615 of 2,061 (30%) cases. Overexpression of h-prune was associated with multiple gene copy number at chromosome 1q21.3 in a very limited fraction of cases (68 of 1,016; 6.7%), strongly indicating that alternative pathways induce h-prune activation in breast cancer. Multivariate Cox regression analysis showed that neither h-prune overexpression nor decreased nm23-H1 immunostaining is independent prognostic factors. However, a significant association of h-prune overexpression with either advanced lymph node status (P = 0.017) or presence of distant metastases (P = 0.029) was observed., Conclusions: Although not significantly correlated with overall survival, positive h-prune immunostaining identifies subsets of breast cancer patients with higher tumor aggressiveness. Further investigations using larger collections of advanced breast cancer patients are required for assessing the predictive role of h-prune in breast cancer.

The normal duct-lobular system of the breast is lined by two epithelial cell types, inner luminal secretory cells and outer contractile myoepithelial cells. We have generated comprehensive expression profiles of the two normal cell types, using immunomagnetic cell separation and gene expression microarray analysis. The cell-type specificity was confirmed at the protein level by immunohistochemistry in normal breast tissue. New prognostic markers for survival were identified when the luminal- and myoepithelial-specific molecules were evaluated on breast tumor tissue microarrays. Nuclear expression of luminal epithelial marker galectin 3 correlated with a shorter overall survival in these patients, and the expression of SPARC (osteonectin), a myoepithelial marker, was an independent marker of poor prognosis in breast cancers as a whole. These data provide a framework for the interpretation of breast cancer molecular profiling experiments, the identification of potential new diagnostic markers, and development of novel indicators of prognosis.

The present paper analyses temporal trends for skin cancers including Kaposi's sarcoma in the data set of the Italian Network of Cancer Registries (pool AIRT), during 1986-1997. The estimated annual percent change (EAPC) of the standardised incidence rates for non-melanoma skin cancer (61,586 analysed cases), increased from 1986 to 1997 by 7.5%/year among males and by 5.2%/year among females. Melanoma (8,516 cases and 2,312 deaths) showed increasing incidence, 6.2%/year among males and 5.8%/year among females, and stable mortality. As regards Kaposis sarcoma (1,156 cases), incidence increased among males from 1986 to 1995 by about 13%/year, and then decreased; among females incidence was significantly increasing along the period.

14-3-3sigma is a candidate tumour suppressor gene transactivated by p53 in response to DNA damage. In gene expression analysis of normal luminal and myoepithelial cells, 14-3-3sigma was preferentially expressed by myoepithelial cells. This study has analysed the immunohistochemical distribution and subcellular localization of 14-3-3sigma in normal breast tissue and in a large series of benign and malignant breast lesions on whole tissue sections and by tissue microarray. Immunohistochemistry demonstrated that 14-3-3sigma was consistently expressed in the cytoplasmic compartment and occasionally in the nuclei of myoepithelial cells arranged as a continuous layer around normal ducts and lobular units, whereas luminal epithelial, stromal, endothelial, pericytic, lipomatous, and neural cells showed no staining. Myoepithelial cells of benign proliferations and pre-invasive lesions were consistently positive for 14-3-3sigma. Strong expression of 14-3-3sigma was evident in one case of ductal carcinoma in situ (5.5%) and in 105/554 invasive cancers (18.9%). Survival data were available for 452 patients with invasive breast carcinoma. 14-3-3sigma cytoplasmic subcellular localization was a statistically significant prognostic factor for the whole series of invasive carcinomas, as well as for those positive for oestrogen (ER) or progesterone receptors (PR). This analysis demonstrates the utility of 14-3-3sigma as a new adjunct antibody for characterization of myoepithelial cells and myoepithelial lesions and it may be a novel prognostic factor for breast cancer patients., (Copyright 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Purpose: Ocogenic activation of the BRAF gene has been demonstrated to be involved in the pathogenesis of malignant melanoma (MM). In this study, we investigated the contribution of BRAF to melanoma susceptibility, also making a comparison with frequency of CDKN2A germline mutations in MM patients from different areas in Italy., Patients and Methods: sing a combination of denaturing high-performance liquid chromatography analysis and automated sequencing on genomic DNA from peripheral blood or tumor tissue samples, 569 MM patients (211 from northern Italy and 358 from southern Italy) were screened for BRAF mutations., Results: Three BRAF germline sequence variants (M116R, V599E, and G608H) were identified in four (0.7%) of 569 MM patients. The most common BRAF mutation, V599E, was detected in one germline DNA sample only; M116R and G608H were newly described mutations. A high frequency (59%) of BRAF mutations was instead observed in tumor samples from patients also undergoing germline DNA analysis; at the somatic level, substitution of valine 599 was found to account for the majority (88%) of BRAF mutations. We then estimated the germline mutation rates in BRAF and CDKN2A among 358 consecutively collected patient samples originating in southern Italy; a low (2.5%) or very low (0.29%) prevalence of CDKN2A and BRAF mutations, respectively, was detected., Conclusion: utation analysis of either blood DNA from a large collection of MM patients or matched MM tissues from a subset of such patients revealed that BRAF is somatically mutated and does not play a major role in melanoma susceptibility. The present study further suggests that patient origin may account for different mutation rates in candidate genes.

The incidence of gynecologic tumors in the Province of Sassari in the period 1992-2000 has been studied in order to estimate their value and to make a comparison with the data of the period 1974-83. The analysis of our data regarding the period 1992-2000, if compared with those of the previous period 1974-83, showed a change in the percentage distribution of all gynecologic tumors, with an increase in the incidence of malignant tumors of the ovary (from 17.1% to 28.0%) and a reduction in the incidence of endometrial carcinoma (from 52.1% to 45.0%). Cervix cancer seemed stationary with a mild reduction (from 26.8% to 23.0%). The data showed, with regard to the incidence per 100,000, an increase of endometrial carcinoma (19.05 per 100,000 vs 11.99 per 100,000) and malignant ovarian tumor (11.99 per 100,000 vs 3.95 per 100,000). Our data reported a worrying increase of hormonal-dependent tumors in North Sardinia such as endometrial and ovarian cancer with the highest increase in malignant ovarian tumors. In comparison to the previous period we confirmed a historically low incidence of cervical and external genitalia tumors (vulva and vagina) in North Sardinia.

Several mutations in genes involved in Saccharomyces mating type switching may affect the homothallic behaviour in wine yeasts. In this study the semi-homothallic (Hq) segregation of a flor wine yeast strain was analysed. We aimed to understand the molecular basis of this behaviour in a flor autochthonous strain, verifying the MAT locus status by a PCR-based HO gene disruption and sequencing of the Y region of the HML, HMR and MAT loci, after nested PCR. Presence of ORFs a1 and a2 in the Y region of the HML locus was found. At the ORF a2 at HML locus, a mutation in the stop codon was found, so the a2 ORF contains 33 more bases.

A record linkage was carried out between the Italian National Registry of AIDS and 19 cancer registries. The aim was to evaluate the 1986 through 1998 trends in incidence rate (IR) of AIDS-defining cancers (ADCs) among persons with AIDS (PWA) in Italy overall and according to various characteristics. A steady decrease in IRs was found for Kaposi sarcoma (KS) in men between 1986-1992 (2.5 per 100 person-years [py]) and 1997-1998 (1.0 per 100 py). Conversely, the first decrease in IRs of KS in women (from 0.9 to 0.6 per 100 py) and of non-Hodgkin lymphoma in both genders (from 1.7 to 0.7 per 100 py) was seen between 1993-1996 and 1997-1998, thus pointing to a favorable impact of highly active antiretroviral therapies. The decline was consistent across different age and HIV transmission groups, but it was more marked in PWA with a CD4 count >50 cells/microL than in PWA with more severe immune suppression. As a proportion of AIDS cases, invasive cervical cancer increased from 1.5% in 1993-1996 to 2.4% in 1997-1998, but IRs after AIDS could not be evaluated. On account of the marked decline of KS in men in 1997-1998, the overall burden of ADCs in Italy became similar in both genders.

The SED1 gene (YDR077W), coding for the major cell wall glycoprotein of Saccharomyces cerevisiae stationary-phase cells, contains two blocks of tandem repeat units located within two distinct regions of the nucleotide sequence. A PCR survey of the SED1 open reading frames (ORFs) of 186 previously uncharacterized grape must isolates of S. cerevisiae yielded 13 PCR profiles arising from different combinations of seven SED1 length variants in individuals homozygous or heterozygous for the gene. Comparison of the nucleotide sequences of a group of representatives of each of the seven length variants with those of S288C and the type strain, CBS1171, unequivocally identified them as SED1 alleles and provided evidence for the presence of two minisatellite-like sequences, variable in length, within the ORF of an S. cerevisiae gene. The segregation analyses of the SED1 length variants and other genetic markers in 13 isolates representative of each PCR profile suggested that molecular mechanisms involved in minisatellite expansion and contraction may be responsible for SED1 heterozygosities within a population of homothallic must isolates of S. cerevisiae.

Sardinian sherry strains of S. cerevisiae form a biofilm on the surface of wine at the end of the ethanolic fermentation, when grape sugar is depleted and when further growth becomes dependent on access to oxygen. A point mutation in HSP12 or deletion of the entire gene results in inability to form this film. HSP12 encodes a heat-shock protein previously foundby others to be active during stationary phase, in cells depleted for glucose, and in cells metabolizing ethanol and fatty acids, all conditions associated with sherry biofilms., (Copyright 2002 John Wiley & Sons, Ltd.)

Early diagnosis of neoplastic diseases enjoined large popularity in the last two decades. In many countries or European regions, population-based cancer screening programs for breast, cervical and colorectal cancer are going on. Diagnostic tests, like the PSA test for prostate cancer, are not yet validated in terms of their efficacy in reducing specific mortality, but their spontaneous diffusion is changing the pattern of the disease incidence. In this contribution, we discuss briefly the survival trends for some tumours (breast, cervix, colorectal, melanoma and prostate cancer) for which the occurrence rates are modified by screening and for some of them we evaluate the possible impact of early diagnosis on survival rates.

In this study, three flor strains of Saccharomyces cerevisiae were genetically characterized. They were isolated from biofilms on Sardinian sherry-like wines produced at family-run wineries where pure cultures of yeasts were not used. The study aimed to investigate the life cycle of these naturally-occurring flor strains, using a genetic procedure supplemented by analysis of subsequent meiotic generations. A semi-homothallic life cycle was found in three strains that could be helpful in a genetic improvement programme.

The epidemiology of Salmonella infections in Sassari in the last four years was reported. The remarkable increase of gastroenteritis caused by uncommon Salmonella and by S. wien in 1975 and 1976 was point out: about all cases were related with 3 epidemic episodes in hospitalized patients that were notified as paratyphoid cases in 91% and as infancy's gastroenteritis in 9%. The 201 strains of Salmonella isolated from June 1975 to May 1976 belong for 91% to group B (for 80,5% to S. wien), for 2% to group C1, for 1,5% to group C2, for 5% to group D1 and for 0,5% to group E4. The hypothesis on introduction of S. wien in Sardinia were examined; the rules for limitation of Salmonella diffusion and for prevention of the endemicity of new imported strains, were examined.