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Biomedical subjects

F Tanda

Publications and source records attributed to F Tanda.

At least 19 recordsLinked to original sources
PubMed2005

Epidemiological aspects of ovarian malignancies in North Sardinia in the period 1992-2001.

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.

Adenocarcinoma, Mucinous↗
PubMed2005

Epidemiology of malignant breast tumors in the province of Sassari (Sardinia, Italy) in the period 1992-2002.

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.

Adult↗
PubMed2004

The incidence of female genital tumors in the Province of Sassari in the period 1992-2000.

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.

Adolescent↗
PubMed2003

Microsatellite instability and mutation analysis among southern Italian patients with colorectal carcinoma: detection of different alterations accounting for MLH1 and MSH2 inactivation in familial cases.

BACKGROUND: Microsatellite instability (MSI) is due to defective DNA mismatch repair (MMR) and has been detected at various rates in colorectal carcinoma (CRC). The role of MSI in colorectal tumorigenesis was assessed further in this study by both microsatellite analysis of two CRC subsets [unselected patients (n = 215) and patients <50 years of age (n = 95)], and mutation screening of the two major MMR genes MLH1 and MSH2 among familial CRC cases. PATIENTS AND METHODS: PCR-based microsatellite analysis was performed on paraffin-embedded tissues. In CRC families, MLH1/MSH2 mutation analysis and MLH1/MSH2 immunostaining were performed on germline DNA and MSI+ tumour tissues, respectively. RESULTS: The MSI+ phenotype was detected in 75 (24%) patients, with higher incidence in early-onset or proximally located tumours. Among 220 patients investigated for family cancer history, MSI frequency was markedly higher in familial [18/27 (67%)] than in sporadic [32/193 (17%)] cases. Three MLH1 and six MSH2 germline mutations were identified in 14 out of 36 (39%) CRC families. Prevalence of MLH1/MSH2 mutations in CRC families was significantly increased by the presence of: (i) fulfilled Amsterdam criteria; (ii) four or more CRCs; or (iii) one or more endometrial cancer. While MSH2 was found mostly mutated, almost all [8/9 (89%)] familial MSI+ cases with loss of the MLH1 protein were negative for MLH1 germline mutations. CONCLUSIONS: Both genetic (for MSH2) and gene-silencing (for MLH1) alterations seem to be involved in CRC pathogenesis.

Adult↗
PubMed2003

The role of (99m)Tc-tetrofosmin pinhole-SPECT in breast cancer non palpable axillary lymph node metastases detection.

AIM: We evaluated the usefulness of (99m)Tc-tetrofosmin axillary pinhole (P)-SPECT in breast cancer (BC) non palpable axillary lymph node metastasis detection compared with conventional planar and SPECT scintimammography. METHODS: We studied prospectively 188 consecutive patients with suspected primary BC, negative at axillary clinical examination. Ten minutes after 740 MBq (99m)Tc-tetrofosmin injection, planar and SPECT scintimammography were acquired, followed by axillary P-SPECT imaging. RESULTS: At histology, 12 patients had benign mammary lesions and 176 had BC. Axillary lymph node dissection (ALND) was performed in all BC patients, bilaterally in 3 cases: 74/179 axillae had metastases. P-SPECT showed a significantly higher overall sensitivity than SPECT and planar (93.2% vs 85.1% and 36.5%, respectively; p<0.05 and p<0.0005, respectively) and was false negative in 5 patients with 1 metastatic node each, micrometastatic in 4/5 cases; SPECT and planar were also false negative in these 5 cases and in 6 and in 42 further cases, respectively. P-SPECT added important prognostic information by distinguishing single from multiple and pound 3 from >3 nodes; only P-SPECT defined the exact number of nodes in 15/25 patients with 2-4 nodes. P-SPECT showed the highest accuracy and NPV: 92.7% and 95%, respectively (SPECT 90.5% and 90%, respectively; planar 73.2% and 68.9%, respectively). CONCLUSION: (99m)Tc-tetrofosmin axillary P-SPECT appears highly accurate in BC non palpable axillary lymph node metastasis detection and significantly more sensitive than both planar and SPECT, its few false negative results predominantly concerning micrometastases; moreover, only P-SPECT gave additional important prognostic information. Given its very high NPV, P-SPECT could also be used to better select patients who might avoid ALND.

Adult↗
PubMed2002

Chromosomal abnormalities and microsatellite instability in sporadic endometrial cancer.

Defective DNA mismatch repair and nonfunctional mechanisms controlling the proper progression of the cell cycle have been proposed as being responsible for the genomic instability and accumulation of karyotypic alterations in endometrial cancer (EC). To assess whether numerical chromosomal anomalies (aneuploidy) and microsatellite instability (MSI) might be representative of distinctive tumour behaviour, paraffin-embedded tissue samples from 86 patients with sporadic EC were evaluated by both fluorescence in situ hybridisation (FISH) and microsatellite analysis, using free nuclei and genomic DNAs (respectively). Approximately one-third of the tumours analysed (24/74; 32%) exhibited MSI, whereas 38/86 (44%) of the EC samples displayed aneuploidy. The majority of the unstable cases (15/24; 63%) were from advanced-stage patients. Conversely, 23 (61%) out of the 38 tumours with aneuploidy were from early-stage patients. No apparent correlation was found between MSI and aneuploidy, whereas the immunohistochemical (IHC) analysis revealed that inactivation of the MLH1 mismatch repair gene may be involved in the majority of the MSI+ sporadic ECs. No genetic or cytogenetic alteration analysed here seems to add any significant predictive value to the stage of disease.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Prevalence and prognostic role of microsatellite instability in patients with rectal carcinoma.

BACKGROUND: Association between microsatellite instability (MSI) and favorable postoperative survival in patients with colorectal cancer receiving adjuvant chemotherapy has been indicated. To evaluate whether an analogous positive prognostic role of MSI could be present in rectal carcinoma (RC; most RC patients receive adjuvant radiotherapy), PCR-based microsatellite analysis of archival RCs and statistical correlation with clinico-pathological parameters were performed. PATIENTS AND METHODS: DNA from paraffin-embedded paired samples of tumors and corresponding normal tissue from 91 RC patients was analyzed for MSI using five microsatellite markers (tumors were classified as MSI(+) when two or more markers were unstable). RESULTS: Seventeen (19%) RC patients exhibited a MSI(+) phenotype. Prevalence of instability was found in patients with earlier RC onset (28% in cases with diagnosis age < or =55 years versus 15% in cases >55 years), whereas similar MSI frequencies were observed in patients with different disease stage or receiving different adjuvant therapies. While MSI was detected in seven (64%) of 11 familial patients, a remarkably lower MSI incidence was observed in sporadic cases (10/80; 12.5%). A significant association with better disease-free survival (DFS) and overall survival (OS) was found for MSI(+) patients (median DFS/OS, 30/32 months) in comparison to MSI(-) ones (median DFS/OS, 18/21 months) (P <0.001). CONCLUSIONS: MSI was demonstrated to be a strong molecular prognostic marker in rectal carcinoma, independent of the administered treatment (radiotherapy, chemotherapy or both).

Adenocarcinoma↗
PubMed2002

BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling.

BACKGROUND: The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC). PATIENTS AND METHODS: Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes. RESULTS: Three BRCA1/2 germline sequence variants were identified. While BRCA2-Ile3412Val is a missense variant with unknown functional significance, BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in seven families (15%). BRCA2-8765delAG was found in six of eight (75%) BRCA1/2-positive families and seven of 501 (1.4%) unselected and consecutively collected BC patients. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P <0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC. CONCLUSIONS: Identification of such features should address BC patients and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this is the first report of a detailed BRCA1/2 mutation screening in Sardinia, having immediate implications for the clinical management of BC families.

Adult↗
PubMed2001

Detection of occult melanoma cells in paraffin-embedded histologically negative sentinel lymph nodes using a reverse transcriptase polymerase chain reaction assay.

PURPOSE: Detection of occult metastasis before the development of clinical disease could allow more accurate staging, appropriate follow-up procedures, and adjuvant therapies in patients with malignant melanoma (MM). The sentinel lymph node (SLN) has been proposed as a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. In this study, we screened both paraffin-embedded SLNs and peripheral-blood (PB) samples from MM patients at various stage of disease using a multimarker reverse transcriptase polymerase chain reaction (RT-PCR) assay. The prognostic significance of the presence of PCR-positive markers was also evaluated. PATIENTS AND METHODS: Total RNA was obtained from paraffin-embedded SLN sections and PB samples of 75 MM patients. RT-PCR was performed using tyrosinase and MelanA/MART1 as melanoma-associated markers. Radiolabeled PCR products were analyzed on denaturing polyacrylamide gels. RESULTS: Good sensitivity of the RT-PCR assay on archival tissues was demonstrated after comparison of RT-PCR results on frozen and paraffin-embedded SLNs from 16 MM patients. Significant correlation between the disease stage and marker expression in both PB and SLN samples was observed; the highest value was for patients who were positive for both markers in SLN (P =.006). Progression of disease was significantly associated with the total number of PCR-positive markers in both PB (P =.034) and SLN (P =.001) samples. CONCLUSION: Although sensitivity is lowered by the use of paraffin-embedded specimens, our data indicate that RT-PCR analysis of serial sections from archival SLNs may be helpful in improving detection of occult micrometastases, thus improving staging of patients with melanoma.

Biomarkers, Tumor↗
PubMed2001

Clinical significance of PCR-positive mRNA markers in peripheral blood and regional nodes of malignant melanoma patients. Melanoma Cooperative Group.

Reverse-transcriptase polymerase chain reaction (RT-PCR) with multiple markers has been demonstrated to be highly sensitive in detecting metastatic cells in peripheral blood of malignant melanoma (MM) patients, and the circulating MM cells to be significantly correlated with disease stages. We further evaluated the presence of specific PCR-positive mRNA markers in peripheral blood as well as in regional nodes as an expression of tumor progression. Peripheral blood samples from 317 MM patients with either localized (n = 219) or metastatic (n = 98) disease were processed to obtain total cellular RNA. RT-PCR was performed using tyrosinase (TYR), p97, and MelanA/MART1 as mRNA markers. PCR products were analyzed by gel electrophoresis and Southern blot hybridization. In addition, paraffin-embedded samples of histologically proven tumor-negative lymph nodes from the subset of patients with localized disease were analyzed by RT-PCR, using radiolabeled primers for TYR and MelanA/MART1. The presence of mRNA markers was significantly correlated with tumor burden with a good correlation between risk of recurrence (evaluated in stage I-III patients) and increasing number of PCR-positive markers (p = 0.0002). Currently, for each patient, PCR results obtained at different times during follow-up are being analyzed, and any variation in the number of PCR-positive markers is being correlated to the clinical status. Molecular screening of histologically negative nodes for the presence of metastatic MM cells is also under evaluation. Preliminary assessment of a subset of MM patients with higher risk of recurrence will require longer follow-up in order to define the role of RT-PCR in monitoring these patients.

Biomarkers, Tumor↗
PubMed2000

Microsatellite analysis at 10q25-q26 in Sardinian patients with sporadic endometrial carcinoma: identification of specification patterns of genetic alteration.

BACKGROUND: Loss of heterozygosity (LOH) at chromosome 10q25-q26 has been reported previously in endometrial carcinoma (EC), suggesting the presence of tumor suppressor gene(s). Nevertheless, frequency of genome-wide microsatellite instability (MSI) has been demonstrated higher in EC than in other common malignancy, mostly due to defective DNA mismatch repair. The authors further evaluated the role of the chromosome 10q25-q26 in endometrial tumorigenesis as well as the clinical significance of any observed genetic alteration in sporadic EC. METHODS: Paired normal and tumor samples from 94 Sardinian patients with sporadic EC at various stages of disease were screened by polymerase chain reaction (PCR)-based microsatellite analysis. Genomic DNA was isolated from paraffin embedded tissues and amplified by PCR using microsatellite markers spanning approximately 14 cM at 10q25-q26. Microsatellite instability was studied at four loci mapping to different chromosomal locations. RESULTS: Thirty-two (34%) EC patients were found negative for genetic alterations within the 10q25-q26 region. Among the remaining 62 (66%) EC cases, the authors identified 1) a minimum consensus region of LOH of approximately 1 cM, between D10S610 and D10S542 markers; and 2) a subset of tumors with prevalence of instability at 10q25-q26 (10qMI+), as expression of the presence of a MSI+ phenotype. CONCLUSIONS: The authors' data establish the existence of significant correlations between disease stages and 10qMI+ (with or without MSI+). However, longer follow-up and additional studies are required to define the clinical significance of these findings as prognostic factors. Moreover, the minimum region of LOH at 10q25-q26 will be further analyzed for identifying the putative tumor suppressor gene involved in EC pathogenesis.

Adult↗
PubMed2000

Identification of a founder BRCA2 mutation in Sardinia.

Sardinian population can be instrumental in defining the molecular basis of cancer, using the identity-by-descent method. We selected seven Sardinian breast cancer families originating from the northern-central part of the island with multiple affected members in different generations. We genotyped 106 members of the seven families and 20 control nuclear families with markers flanking BRCA2 locus at 13q12-q13. The detection of a common haplotype shared by four out of seven families (60%) suggests the presence of a founder BRCA2 mutation. Direct sequencing of BRCA2 coding exons of patients carrying the shared haplotype, allowed the identification of a 'frame-shift' mutation at codon 2867 (8765delAG), causing a premature termination-codon. This mutation was found in breast cancer patients as well as one prostate and one bladder cancer patient with shared haplotype. We then investigated the frequency of 8765delAG in the Sardinian breast cancer population by analysing 270 paraffin-embedded normal tissue samples from breast cancer patients. Five patients (1.7%) were found to be positive for the 8765delAG mutation. Discovery of a founder mutation in Sardinia through the identity-by-descent method demonstrates that this approach can be applied successfully to find mutations either for breast cancer or for other types of tumours.

BRCA2 Protein↗
PubMed2000

Definition of the role of chromosome 9p21 in sporadic melanoma through genetic analysis of primary tumours and their metastases. The Melanoma Cooperative Group.

Malignant melanoma (MM) is thought to arise by sequential accumulation of genetic alterations in normal melanocytes. Previous cytogenetic and molecular studies indicated the 9p21 as the chromosomal region involved in MM pathogenesis. In addition to the CDKN genes (p16/CDKN2A, p15/CDKN2B and p19(ARF), frequently inactivated in familial MM), widely reported data suggested the presence within this region of other melanoma susceptibility gene(s). To clearly assess the role of the 9p21 region in sporadic melanoma, we evaluated the presence of microsatellite instability (MSI) and loss of heterozygosity (LOH) in primary tumours as well as in synchronous or asynchronous metastases obtained from the same MM patients, using 9 polymorphic markers from a 17-cM region at 9p21. LOH and MSI were found in 27 (41%) and 11 (17%), respectively, out of 66 primary tumours analysed. In corresponding 58 metastases, MSI was found at higher rate (22; 38%), whereas a quite identical pattern of allelic deletions with 27 (47%) LOH+ cases were observed. Although the CDKN locus was mostly affected by LOH, an additional region of common allelic deletion corresponding to marker D9S171 was also identified. No significant statistical correlation between any 9p21 genetic alteration (LOH, MSI or both) and clinicopathological parameters was observed.

Adolescent↗
PubMed1999

A case of primary hydatidosis of the thyroid gland.

A 54-year-old woman presented with an expansive mass in the anterior cervical region (front of the neck) with abscess. Laboratory tests and thyroid profile proved normal. Surgical exploration revealed a hydatid cyst in the left lobe of the thyroid gland with parasitic metastasis of the left lateral cervical lymph node chain. Postoperative examination of the nodule showed it to be a solitary primary thyroid hydatid cyst.

Diagnosis, Differential↗