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S Pilotti

Publications and source records attributed to S Pilotti.

At least 19 recordsLinked to original sources
PubMed1996

Aberrant FHIT transcripts in Merkel cell carcinoma.

Merkel cell carcinoma is a rare neuroendocrine carcinoma of the skin which shares several features with small cell lung carcinoma. In a previous study, we reported a high frequency of abnormalities of the FHIT gene, located at 3p14.2, in small cell lung tumors. To determine the role of the FHIT gene in small cell neuroendocrine malignancies, 14 cases of Merkel cell carcinoma were analyzed by reverse transcription of FHIT mRNA followed by PCR amplification and sequencing of products. Eight of 14 tumors (57%) displayed abnormal FHIT products that lacked three or more exons of the FHIT gene. The pattern of abnormal transcripts was similar to that observed in small cell lung tumors, suggesting that FHIT abnormalities might be a common genetic marker of these two types of neuroendocrine tumors.

Acid Anhydride Hydrolases↗
PubMed1996

Microsatellite alterations in bronchial and sputum specimens of lung cancer patients.

Early diagnosis of lung cancer based on conventional screening procedures has been unable thus far to decrease lung cancer mortality. We explored the possibility of using microsatellite instability in the detection and screening of early phases of lung carcinogenesis. We studied tumor, histopathologically normal bronchial mucosa, and cytological specimens of 51 lung cancer patients for the presence of clonal variations at microsatellite polymorphisms. Microsatellite alterations were found in tumor, normal bronchial mucosa and cytological specimens of 25 of 51 (49%) of the patients. The detection of microsatellite alterations in histopathologically normal bronchial specimens and cytological clinical samples with minimal atypia suggests a possible application of this genetic marker in early diagnosis of precancerous lesions and lung cancer.

Adenocarcinoma↗
PubMed1996

The FHIT gene 3p14.2 is abnormal in lung cancer.

To determine the role of the FHIT gene, which encompasses the fragile site at 3p14.2, we analyzed 59 tumors of the small cell and non-small cell type by reverse transcription of FHIT mRNA, followed by PCR amplification and sequencing of products. Allelic losses affecting the gene were evaluated by microsatellite polymorphism analysis and genomic alterations by hybridization using cDNA and genomic probes. Small cell lung tumors (80%) and non-small cell lung cancers (40%) showed abnormalities in RNA transcripts of FHIT, and 76% of the tumors exhibited loss of FHIT alleles. Abnormal lung tumor transcripts lack two or more exons of the FHIT gene. Small cell lung cancer tumors and cell lines were analyzed by Southern blotting and showed rearranged BamHI fragments. These data suggest a critical role of the FHIT gene in lung carcinogenesis.

Amino Acid Sequence↗
PubMed1996

A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma.

The p53 protein is a multifunctional transcriptional regulator involved in cellular response to DNA damage and has been implicated as a putative determinant of sensitivity of tumor cells to cytotoxic agents. Since the p53 gene becomes inactivated in over one-half of advanced ovarian carcinoma, in this study we have examined the relationships between p53 gene alterations, p53 immunoreactivity, and response to cisplatin-based chemotherapy in ovarian cancer patients. All patients had advanced (FIGO stage III or IV) ovarian carcinoma and, with one exception, were untreated at the time of collection of tumor specimens. After initial debulking surgery, patients received high-dose cisplatin therapy. Tumor samples were analyzed for p53 gene mutations and for p53 protein accumulation, and the findings were correlated with tumor responsiveness. Of the 33 tumors examined, p53 gene mutations were found in 20 cases, including 15 missense mutations, 2 deletions, 2 nonsense mutations, and a base substitution at splice site. Twenty tumors showed positive immunostaining for p53. Only missense mutations were associated with positive immunostaining. In addition, p53 overexpression was detected in five tumors in the absence of mutations. Most (12 of 14) of the missense mutations associated with p53 protein stabilization were found refractory to therapy, as well as tumors overexpressing wild-type p53 (4 of 5). A significant correlation has been found between p53 accumulation, type of mutation (i.e., missense mutations), and pathological response to cisplatin-based therapy. In conclusion, the present results are consistent with a role of p53 as a determinant of chemosensitivity of ovarian carcinoma.

Alleles↗
PubMed1996

Variant translocation t(6;10)(p21;q22) in pulmonary chondroid hamartoma.

Banding cytogenetics and fluorescence in situ hybridization analysis of a pulmonary chondroid hamartoma (PHC) showed the presence of a t(6;10)(p21;q22). A cytogenetically identical translocation has previously been found in another case of PHC, suggesting that it could represent a variant form of the standard t(6;14)(p21;q24).

Chromosome Banding↗
PubMed1996

Age-related activation of the tyrosine kinase receptor protooncogenes RET and NTRK1 in papillary thyroid carcinoma.

Oncogenic rearrangements of RET and NTRK1 proto-oncogenes are frequently detected in papillary thyroid carcinomas. Several studies have shown an association between ionizing radiation and development of this tumor type. In addition in vitro irradiation of tumor cell lines induced rearrangements of RET similar to those observed in human papillary thyroid carcinomas. These two observations could be related to the reported increased incidence of papillary thyroid carcinomas in children living in contaminated areas around Chernobyl, given that it has been demonstrated that about 60% of them presents a RET oncogenic activation. However, this high frequency of RET positivity in radiation exposed children does not rule out the possibility that age could also play a role in the development of RET positive tumors. To assess this possibility we looked for a relationship between the presence of RET and NTRK1 oncogenic rearrangements and age at surgery in a sample of 92 consecutive patients. Our results show that, in papillary thyroid carcinoma, the frequency of RET and NTRK1 activation is significantly higher in the group of patients aged 4-30 years, thas supporting the concept that age could be contributing to this thyroid specific carcinogenic process.

3T3 Cells↗
PubMed1995

Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident.

Since the Chernobyl nuclear reactor accident, a striking increase of thyroid carcinoma has been reported in children exposed to radiation in Belarus. Because of its unprecedented scale and its emotional implications, this finding has raised concern and called the attention of the scientific community to this major health problem. Although epidemiologically documented, a direct correlation between thyroid cancer and radiation exposure has not been definitely proven at the molecular level. On the assumption that ionizing radiation could cause specific and common cancer-associated genetic lesions, an analysis of oncogene activation and/or tumor suppressor gene inactivation would help to define radiation-induced thyroid carcinomas. Therefore, we have analyzed by different molecular approaches, including Southern blotting, DNA transfection assay on NIH-3T3 cells, and reverse transcription-PCR analysis, six papillary carcinomas from children living in the region of Belarus at the time of the Chernobyl nuclear accident to identify tumor-specific gene rearrangements of the proto-oncogenes RET and TRK, previously found activated in a tumor type-specific manner in papillary thyroid carcinoma. Using Southern blot analysis in four cases, we could detect specific rearranged bands indicating an oncogenic activation of RET that in three cases resulted in rearranged sequences provided by the same activating gene. Moreover, the DNA of the last three cases showed a biological activity in transforming NIH-3T3 cells after the DNA-mediated transfection assay, and the respective NIH-3T3 transfectants were found to express the oncogenic fusion transcripts. These results support the possibility that RET oncogenic activation could represent a major genetic lesion associated with thyroid carcinoma in children exposed to the Chernobyl nuclear accident.

3T3 Cells↗
PubMed1995

Contribution of ploidy and cell kinetics from fine-needle aspirates for the diagnosis of breast lesions: study of 606 consecutive cases.

A total of 606 consecutive patients with palpable breast lesions underwent physical examination, mammography, and fine-needle aspiration for cytologic and flow-cytometric (FCM) DNA analyses. FCM determinations included DNA ploidy and the fraction of cells in S + G2 + M phases. Aneuploid clones were considered indicative of malignancy; diploid, rapidly proliferating (S+G2+M>12%) clones were considered suggestive of malignancy; and diploid, slowly proliferating clones were considered indicative of benignancy. Sensitivity, specificity, and the predictive accuracy for positive or negative results of FCM information were 82%, 90%, 93.1% and 69.8%, respectively. These values were lower than those observed for the three conventional diagnostic assays owing to the presence of false-positive results (in 23 cases) or unassessable DNA plots (in 90 cases). FCM information alone detected five cases in which the other tests gave inconclusive results and in association to the conventional diagnostic triple test, increased the incidence of positive conclusive cases from 97.9% to 99.2%. However, further refinements are needed before this approach can be used as a routine diagnostic tool.

Adult↗
PubMed1995

Allelotyping in Wilms tumors identifies a putative third tumor suppressor gene on chromosome 11.

An analysis of loss of heterozygosity for markers on both the short and the long arm of chromosome 11 was performed in 24 sporadic Wilms tumors. Six cases (25%) showed allelic losses involving the entire chromosome. In one case (4%) the loss was restricted solely to the WT1 gene on band p13. Two cases (8%) displayed allelic losses for WT1 and for markers on band p15.5, where the putative tumor suppressor gene WT2 has been mapped, but retained heterozygosity for markers on the long arm. In three tumors (13%) the loss of heterozygosity involved markers mapped to chromosomal regions p15.5 and q23.3-qter, but did not affect WT1 and markers on q12-q13. Altogether, the proportion of cases showing allelic losses at the distal region of 11q (37%) was comparable to that of cases with LOH affecting the WT1 (37%) or the WT2 (46%) loci, thus suggesting the existence of a third chromosome 11 tumor suppressor gene involved in the pathogenesis of Wilms tumors.

Alleles↗
PubMed1995

Genetic evidence for an independent origin of multiple preneoplastic and neoplastic lung lesions.

Patients with a primary cancer in the lung or in the upper aerodigestive tract have an increased risk of developing synchronous or metachronous second primary lung tumors. This phenomenon has been related to the chronic exposure of the bronchial tree to carcinogens through a so-called "field cancerization" process. This study was designed to investigate at the somatic level the genetic basis of the field cancerization effect in patients having multiple simultaneous neoplastic and preneoplastic lesions of the lung. The pattern of specific genetic changes occurring with high frequency and in early stages of lung carcinogenesis including p53 mutations, deletions of chromosome 3p, and K-ras mutations, was investigated by immunocytochemical, cytogenetic, and molecular approaches in 11 synchronous lesions of five patients with multiple lung cancers. Different genetic lesions were observed in all of the pathological specimens analyzed from each patient. The pattern of these changes was different both in topographically distant or adjacent lesions and in tumors with the same histopathological diagnosis supporting their independent origin. The present data provide further evidence of the clinical relevance of the field cancerization process, and support the use of genetic markers in the differential diagnosis of recurrence or metastasis versus second primaries of the lung.

Adenocarcinoma↗
PubMed1995

Involvement of chromosomes 17 and 22 in dermatofibrosarcoma protuberans.

Literature on the cytogenetics of dermatofibrosarcoma protuberans (DFSP) is limited; only 10 cases with chromosome aberrations have been reported. They are karyotypically characterized by the presence of supernumerary ring(s), either as the sole cytogenetic abnormality or together with a few additional structural or numerical changes. We report the cytogenetic and fluorescence in situ hybridization (FISH) analysis of three new DFSP, one primary and two recurrent tumors. In two cases we found a supernumerary ring as the sole change, whereas the third had two copies of a marker chromosome and monosomy of chromosome 22. Sequences of chromosomes 17 and 22 were identified by FISH in the supernumerary rings and in the markers. The fluorescence pattern suggested that additional sequences were present in the two rings, but showed that the marker chromosomes were entirely painted by chromosome 17 and 22 probes. The findings indicate that juxtaposition and/or amplification of chromosome 17 and 22 sequences could be crucial in the pathogenesis of DFSP.

Adult↗
PubMed1995

Analysis of estrogen and progesterone receptors on preoperative fine-needle aspirates.

For 56 cases of carcinoma of the breast, results of the immunocytochemical assay for estrogen and progesterone receptors performed on preoperative fine-needle aspirates were compared with those obtained on scraping material from the same tumors. The value and usefulness of this last analysis was demonstrated in a previous study. The level of agreement between the two cytological techniques was assessed by the k statistic. A high level of agreement was found, with k values of 0.909 and 0.889 for estrogen and progesterone receptors, respectively. The results reported here revealed the reliability of steroid receptor determination on fine-needle aspiration biopsies, provided that sufficient cellularity was available. This technique can replace the open biopsy procedure, in as much as it represents a rapid, almost painless, and easily repeated method for the assessment of the receptor status, and is useful for treatment decisions at any time during the course of the disease.

Biopsy, Needle↗
PubMed1995

An I.T.M.O. group study on second-line treatment in advanced epithelial ovarian cancer: an attempt to identify clinical and biological factors determining prognosis.

The aim of the present study was to determine the activity of a combined regimen of mitoxantrone (DHAD) and ifosfamide (IFO) and identify clinical and biological factors with prognostic importance for the second-line treatment of ovarian cancer. The following factors were investigated for their prognostic importance: age, disease sites, platinum responsiveness, histological grade, the presence of clinically/radiologically detectable versus not detectable disease, residual disease volume after first surgery, p53 protein, c-erbB-2 oncoprotein and laminin receptor. 72 patients entered the trial. DHAD and IFO therapy led to a 15% response rate among the 47 cases with clinically/radiologically detectable disease (1 complete and 6 partial responses), with a median response duration of 4 months. The response rate was significantly different according to platinum responsiveness (4% objective responses in platinum-resistant versus 27% in platinum-sensitive disease). The time to treatment failure (TTF) and overall survival (OS) were affected by the presence of clinically detectable disease at study entry (median TTF 4 months in the presence of clinically/radiologically detectable disease versus 9 months if the disease was not similarly detectable, P = 0.02; median OS 10 months versus 21 months, P = 0.01). Initially overexpressed in only a few tumours, the c-erbB-2 oncoprotein became overexpressed in 36% of platinum-resistant tumours; this modulation did not occur in platinum-sensitive tumours. Furthermore, laminin receptor was expressed in 77% of platinum-sensitive versus 39% of platinum-resistant patients. There were no differences in p53 protein expression according to drug responsiveness.

Adult↗
PubMed1995

Papillomavirus, p53 alteration, and primary carcinoma of the vulva.

Twenty-nine samples from 28 cases of vulvar squamous cell carcinoma, of which 13 fulfilled the criteria of the bowenoid subtype (mean age 45 years, range 31-68) and 16 of the usual subtype of invasive squamous cell carcinoma (ISCC) (mean age 67.5 years, range 34-83) were investigated for human papillomavirus (HPV) DNA, TP53 alterations, and mdm2 and bcl-2 gene product deregulation. Microscopically all the bowenoid subtype cases (group I) showed a high-grade intraepithelial (VIN 3, carcinoma in situ) lesion associated with early invasive carcinoma in six cases and overt invasive carcinoma in one. By contrast, no evidence of early carcinoma was present in the ISCCs (group II). By in situ hybridization and/or Southern blot hybridization or polymerase chain reaction (PCR), HPV DNA was detected in all cases of group I and in four of 16 cases (25%) of group II, two only by Southern blot after PCR. By single-strand conformation polymorphism and immunocytochemistry only wild-type TP53 and absence of detectable p53 product, respectively, were found in all cases of group I, i.e., in high-risk HPV-positive carcinomas, whereas mutations and/or p53 overexpression accounted for 75% in group II, i.e., in mainly HPV-negative carcinomas. The TP53 gene mutations observed in invasive carcinomas were significantly related to node-positive cases (p = 0.04). Taken together and in agreement with in vitro data, these results support the view that an alteration of TP53, gained either by interaction with viral oncoproteins or by somatic mutations, is a crucial event in the pathogenesis of vulvar carcinomas, but that TP53 mutations are mainly associated with disease progression. Finally, a preliminary immunocytochemical analysis seems to speak against the possible involvement of both MDM2 and BCL-2 gene products in the development of vulvar carcinoma.

Adult↗