Homozygous intragenic loss of the WT1 locus in a sporadic intralobar Wilms' tumor.
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Chromosome Deletion↗
Biomedical subjects
S Pilotti
Publications and source records attributed to S Pilotti.
trk and ret proto-oncogene expression in human neuroblastoma specimens: high frequency of trk expression in non-advanced stages.
Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto-oncogenes: trk, which encodes a tyrosine-kinase receptor for nerve growth factor (NGF) and ret, another receptor-type tyrosine kinase whose ligand is unknown. The mRNA expression of the trk gene was detected in 67.4% of cases, with increased frequency in I, II and IVs Evans' stages and in patients with favorable prognosis according to the Shimada classification. Moreover, trk expression inversely correlated with Nmyc-gene amplification. ret mRNA was found in 36.8% of cases and equally distributed in the different stages. In addition, ngfR (low-affinity NGF receptor)-gene expression was present in 9 out of 25 cases. The simultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF.
Adolescent↗
Combined analysis of ploidy and cell kinetics on fine-needle aspirates from breast tumors.
BACKGROUND: DNA ploidy and cell kinetics determined by flow-cytometric (FCM) analysis have provided relevant information on the natural history of breast cancer. These highly feasible and evaluable assays are particularly appropriate for small samples from fine-needle aspirates (FNA) to complement cytologic information for diagnosis of breast lesions. METHODS: DNA content and the percentage of cells in the cell cycle phases were evaluated on FCM DNA histograms from 281 consecutive FNA of benign and malignant breast lesions. RESULTS: FCM analysis was possible in 93% of FNA. Qualitative concordance in DNA content between FNA and surgical specimens was observed in 82% of the patients. Of the 145 aneuploid FNA, 144 (99%) were histologically diagnosed as carcinomas. The presence of only diploid clones was observed in 115 FNA: rapidly proliferating (S+G2M > 12%) diploid lesions proved to be histologically malignant in 67% of patients, and slowly proliferating diploid lesions were histologically benign in 79% of patients. False-positive results of ploidy and cell kinetics were observed in 1 and 10 patients, respectively. Of the 163 cancers evaluable for cytology and FCM, 158 were positive at cytology. The presence of aneuploid or of diploid rapidly proliferating clones in cytologically false-negative aspirates resulted in the detection of four additional cancers. CONCLUSIONS: Flow cytometric analysis of ploidy and cell kinetics on FNA could be a valuable tool complementary to cytology for breast cancer diagnosis.
Biopsy, Needle↗
Genetic changes in lung cancer.
In an attempt to define the type and temporal sequences of somatic genetic changes that precede the onset of invasive lung cancer, and to search for biological markers useful in screening multiple primary tumors of the upper aerodigestive tract, we have performed a cytogenetic and genetic study using normal bronchial epithelium and primary tumor specimens of 68 patients undergoing pulmonary resection for early stage lung cancer, and normal bronchial epithelium of 5 controls with metastatic sarcomas. Of the 68 lung cancer cases, 31 had a single tumor and 37 displayed multiple synchronous or metachronous tumors. Cytogenetic alterations were observed in 59% (23/39) of the evaluable tumor specimens with complex rearranged karyotypes, particularly involving chromosomes 3 (70%), 17 (39%), 11 (26%), 8, 9, 12 (22%), and 7 (17%). Gene alterations were also detected including overexpression of epidermal growth factor receptor (EGFR) in 63% (36/57), HER2/NEU in 21% (12/56), and p53 mutations in 50% (12/24). The overall frequency of genetic changes (any type) in the tumors was 76% (52/68). In the normal bronchial mucosa, we identified a rearranged karyotype in 20% of the evaluable cases (13/63); particularly simple rearrangements involving chromosomes 3p (6 cases), 7 (6 cases), 17 (3 cases), 9, 11 (2 cases), 8 (1 case); as well as overexpression of EGFR in 39% (20/51) and of HER2/NEU in 14% (7/51). The overall frequency of genetic changes (any type) in the normal epithelium was 46% (30/65). The presence of a rearranged karyotype in the bronchial mucosa was associated with a rearranged karyotype in the tumor sample. Other statistically significant correlations were found between histopathologic and clinical features and the occurrence of the different cytogenetic and genetic changes both in tumors and in the normal bronchial mucosa. No genetic abnormalities were found in the bronchial epithelium of the 5 controls.
Biomarkers, Tumor↗
"Occult" papillary carcinoma of the thyroid: a questionable entity.
A series of 72 cases of "occult" thyroid papillary cancer, i.e. tumours of less than 1.5 cm in diameter, was analysed. The patients--26 males and 46 females--were treated surgically, 25 by lobectomy and isthmusectomy and 47 by total thyroidectomy. In 51 cases nodal neck dissection was performed, bilateral in 2 cases. 9 thyroidectomised patients received radiometabolic therapy. Hormone therapy (T4) was continuously administered to 57 patients. The median duration of follow-up was 99 months (60-189). All the patients were alive (except one who died from other causes) and free of disease at last control. No relapses in the thyroid were observed in the conservatively treated patients. 2 patients of the 47 radically operated upon subsequently presented nodal metastasis and underwent neck dissection. The so-called "occult" thyroid papillary cancer does not differ from other papillary cancers with respect to morphological, clinical and prognostic factors--it differs only in size. Considering occult papillary tumours as an entity is questioned in this paper.
Adolescent↗
Papillomavirus, p53 alteration and primary carcinoma of the vulva.
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Carcinoma, Squamous Cell↗
Nodal neuroendocrine tumors.
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Carcinoma, Merkel Cell↗
Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland.
The p53 gene was analyzed in tumor specimens obtained from 52 patients with various types of carcinoma of the thyroid gland by a combined molecular and immunocytochemical approach. The histologic types included 37 well-differentiated papillary and follicular carcinomas, 8 poorly differentiated, and 7 undifferentiated carcinomas. The p53 gene was shown to be unaffected in all differentiated tumors by single-strand conformation polymorphism analysis. However, in two out of eight (25%) of poorly differentiated carcinomas and five out of seven (71%) undifferentiated carcinomas, p53 mutations were identified and subsequently characterized by DNA sequencing. One undifferentiated carcinoma displayed two areas with varying degrees of differentiation. The comparative analysis of the p53 gene, in both the more and the less differentiated area of this tumor, clearly showed that the p53 mutation was confined to the latter component of the tumor specimen. These results indicate that mutations of the p53 gene are associated with the most aggressive histologic types of thyroid tumors, such as the undifferentiated carcinoma and, to a certain extent, the poorly differentiated carcinoma, and that the alterations of this gene represent a late genetic event in human thyroid carcinogenesis.
Adult↗
HPV detection and p53 alteration in squamous cell verrucous malignancies of the lower genital tract.
We examined five cases of verrucous carcinoma (VC) and two cases of giant condyloma of Buschke-Löwenstein (GCBL) associated with invasive squamous cell carcinoma (ISCC), by immunocytochemistry and molecular techniques. Neither human papillomavirus (HPV) footprints nor p53-altered expression and/or mutation were observed among the cases of VC. By contrast, both cases of GCBL with ISCC turned out to be HPV 6 or 11 positive, showed overexpression of p53 and, one of the two, a mutation in the nucleotide sequence of this tumor suppressor gene. The results point out that VC and GCBL with ISCC, in spite of some morphologic similarities, are two distinct entities, the former being unrelated to both HPV and p53 inactivation and the latter related to both. Regarding p53, immunocytochemical and molecular data on GCBL with ISCC suggest a role of mutant p53 in the progression of malignancy into invasion.
Adult↗
Deletions of 17p and p53 mutations in preneoplastic lesions of the lung.
Cytogenetic and p53 mutation analysis in two cases of severe dysplasia of the bronchial epithelium in lung cancer patients and p53 immunostaining in a third one are reported. The finding of both chromosomal deletions of 17p and p53 mutation indicates that these changes may take place early in the process of lung carcinogenesis.
Base Sequence↗
Well-differentiated neuroendocrine carcinoma of the lung: a clinicopathologic and ultrastructural study of 10 cases.
The clinico-pathologic characteristics of 10 resected pulmonary tumors, which proved to be well-differentiated neuroendocrine carcinomas (WDNC) on the basis of light microscopic, immunocytochemical, ultrastructural and immunoelectron microscopic investigations, were evaluated. The tumors showed a wide spectrum of histologic features that could be referred to three basic patterns: 1) a carcinoid-like pattern; 2) an organoid pattern characterized by palisading cells at the edge of cellular areas, and 3) a prevalent adenocarcinoma-like pattern. The second pattern was the most distinct even though it often mimicked the small cell/large cell subtype of small cell carcinoma (SCC) owing to its association with marked atypia and poor differentiation. All but one of the patients were males and smokers. The mean age was 58 years. Half of the tumors were centrally located including those showing the adenocarcinoma-like pattern. Disease-free and overall survival and type of tumor dissemination in four patients were similar to those of SCC. Five evaluable patients were alive and disease-free after a mean follow-up of 74 months. Two of these were initially diagnosed as SCC. We conclude that, because of its impact on prognosis, the diagnosis of WDNC appears to be relevant although other factors able to adversely affect the clinical course remain undefined.
Adenocarcinoma↗
Cytogenetic and molecular genetic characterization of papillary thyroid carcinomas.
A combined cytogenetic and molecular analysis was performed on 11 cases of papillary thyroid carcinoma. A simple karyotypic abnormality was detected in five tumors, whereas six had no apparent chromosome change. In four of five rearranged cases the presence of a specific chromosomal abnormality involving chromosome 10 (cases 1 and 2) and chromosome 1 (cases 3 and 4) was associated with the rearrangement of two protooncogenes: RET and NTRKI (formerly trk), respectively, with different donor genes. Moreover, the chromosomal localization of the involved genes and the type of chromosomal change observed suggested that RET and NTRKI activation occurred by intrachromosomal rearrangements. The six cases with normal karyotype did not show RET or NTRKI activation. These findings suggest that a combined cytogenetic and molecular approach would be useful in understanding the pathogenesis of thyroid neoplasia.
Blotting, Southern↗
The role of fine needle aspiration in the diagnosis of thyroid nodules: analysis of 795 consecutive cases.
The utility of fine needle aspiration (FNA) and physical examination for selecting patients with palpable thyroid nodules for surgery was evaluated in 795 consecutive cases. Surgery was performed in 216 patients based upon the cytological diagnosis and clinical criteria. Excluding 42 patients who were lost to follow-up, the remaining 537 were regularly followed up (range, 2-10 years). Cytological findings were classified as malignant, histologic control recommended (suspicious), follicular tumor, benign, and unsatisfactory. Thirty-six aspiration biopsies were positive for malignancy and the diagnosis was confirmed histologically in 34 of them. In 65 patients with final histological diagnosis of malignancy, cytology was positive in 34, suspicious in 20, benign in 3 cases, and unsatisfactory in 8. All patients with cytological diagnosis of follicular tumor had a benign lesion at histology. There were two false positive and three false negative cytological results among the 216 histologically confirmed cases. Excluding unsatisfactory specimen sensitivity, specificity and the predictive value for a positive and a negative result were respectively 95%, 97.5%, 94.5%, and 97%. We conclude that FNA is a very reliable diagnostic test in the evaluation of thyroid nodules and is the best guidance in addition to clinical criteria for selecting patients to be submitted to surgery.
Adenoma↗
Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: long-term results.
Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.
Adolescent↗
A t(2;3)(q12-13;p24-25) in follicular thyroid adenomas.
We report the cytogenetic analysis of five cases of follicular thyroid adenoma. In two of them, we observed an identical t(2;3)(q12-13;p24-25) as a unique chromosome change. A third case showed a hyperdiploid karyotype with trisomies of chromosomes 7 and 12. Two cases had a normal diploid karyotype. These changes could define subgroups of follicular adenomas endowed with different malignant potential.
Adenocarcinoma↗
Simultaneous in situ hybridization for DNA and RNA reveals the presence of HPV in the majority of cervical cancer cells.
Thirteen cases of invasive squamous cell carcinoma of the uterine cervix containing HPV types 16 or 18 DNA sequences, as detected by Southern blot analysis, were investigated by in situ hybridization on routine paraffin sections, using 35S nick-translated DNA probes. Simultaneous in situ hybridization for DNA and RNA showed that in ten out of 13 cases (77%) the percentage of tumor cells containing HPV 16 or 18 varied from 75 to 100%. In one case, harboring both in situ and invasive carcinoma, the same type of HPV DNA was detected in both components. This finding suggests that neoplastic cells retained the viral genome during progression to invasiveness.
Carcinoma, Squamous Cell↗
Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters.
Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.
Biochemical Phenomena↗
HPV DNA in intraepithelial neoplasia and carcinoma of the vulva and penis.
Surgical specimens of 15 patients with early and 12 patients with advanced squamous cell carcinoma of the vulva and the penis were examined for the presence of human papillomavirus (HPV) type 6, 11, 16, and 18 DNA by Southern blotting (SB) and polymerase chain reaction (PCR) analysis. By SB, HPV type 16 DNA was detected in all early carcinomas and 2 of 12 cases of advanced squamous cell carcinoma (ISCC) of the vulva and penis. PCR revealed HPV DNA in four additional cases of vulvar and penile ISCC negative by SB. Three cases contained HPV16 and one HPV18. Two cases of vulvar and penile Buschke-Löwenstein (BL) tumor with malignancy and one case of vulvar verrucous carcinoma were also examined by both techniques. While BL tumors were associated with DNA of HPV6 or 11, no HPV association was found for verrucous carcinoma. Our results confirm that the detection rate of HPV DNA in early vulvar and penile carcinomas is much higher than in invasive carcinomas. In addition, we have shown that in the lower genital tract, 50% of cases of ISCC are HPV16 correlated. The absence of HPV DNA (types 6, 11, 16, and 18) in the remaining 50% of cases of ISCC thus suggests that vulvar and penile ISCC may have more than one pathogenetic pathway.
Base Sequence↗