Biomedical subjects

S Sulfaro

Publications and source records attributed to S Sulfaro.

At least 19 recordsLinked to original sources

PubMed1999

Loss of heterozygosity at 10q in tumors of the upper respiratory tract is associated with poor prognosis.

Frequent loss of a specific chromosomic region in cancers is often associated with inactivation of a tumor-suppressor gene. The long arm of chromosome 10 is deleted in several types of tumor, among them squamous-cell carcinomas of the head and neck (HNSCC). To determine the role of 10q deletions in the tumorigenesis of the upper respiratory tract, 47 HNSCCs were examined for loss of heterozygosity (LOH) at 10q: 43% of the cases analyzed showed LOH at 10q, and 2 distinct hot spots of deletion were identified, at 10q22-23 and 10q25-26. The possible involvement of pTEN/MMAC1, a tumor-suppressor gene mapped at 10q23, was also evaluated. No mutation, homozygous deletion or loss of expression of pTEN/MMAC1 was detected, indicating that inactivation of this gene plays a minor role in HNSCC development. Interestingly, the frequency of deletion at 10q was greater in invasive carcinoma than in adjacent carcinoma in situ, and a significant association between LOH and poor prognosis was observed. Taken together, our results suggest the presence in the long arm of chromosome 10 of (a) tumor-suppressor gene(s) other than pTEN/MMAC1 and presumably involved in the malignant progression of tumors of the upper respiratory tract. Int. J. Cancer (Pred. Oncol.) 84:432-436, 1999.

Blotting, Southern↗

PubMed1998

Microsatellite instability in squamous cell carcinomas of the head and neck related to field cancerization phenomena.

Patients affected by squamous cell carcinoma of the head and neck (HNSCC) show frequent occurrence of multiple cancers and widespread precancerous lesions in the mucosa of the upper respiratory tract, a phenomenon known as field cancerization. In this study, we investigated the role of genetic instability in the development of HNSCC and in particular in tumour multiplicity phenomena of the upper respiratory tract. For this purpose, we analysed microsatellite instability (MI) and loss of heterozygosity (LOH) at 20 loci mapping on five chromosomal arms in 67 HNSCC patients, 45 of whom had a single cancer and 22 had multiple primary tumours. The possible involvement of the hMLH1 gene in genetic instability and as a potential target of 3p21 deletion phenomena in head and neck cancers was also investigated. Our data indicate that mismatch repair-related genetic instability plays a minor role in the carcinogenesis of HNSCC and in tumour multiplicity of the head and neck region. Moreover, our results exclude a role for the hMLH1 gene as a determinant of MI and as a specific gene target of deletion at 3p21 in HNSCC. We conclude that presumably other genetic mechanisms, such as those hypothesized for MI-negative hereditary non-polyposis colorectal cancer patients, may play a major role in the carcinogenesis of the mucosa of the upper respiratory tract.

Alleles↗

PubMed1997

Overexpression of CDC25A and CDC25B in head and neck cancers.

The deregulation of several cell cycle-related genes participates in neoplastic transformation. Cell cycle progression is driven by cyclin-dependent kinases, which are positively regulated by association with cyclins and negatively regulated by binding to inhibitory subunits. The activity of cyclin-dependent kinases is also regulated by the phosphorylation status, which is controlled by the antagonistic action of wee1 kinase and CDC25 phosphatases. Three CDC25 genes are present in human cells: CDC25A, CDC25B, and CDC25C. These three genes function at different phases of the cell cycle. Whereas CDC25A and CDC25B are expressed throughout the cell cycle, with peak expression in G1 for CDC25A and in both G1-S-phase and G2 for CDC25B, CDC25C is predominantly expressed in G2. Several lines of evidence suggest a role for CDC25s as oncogenes. CDC25A and CDC25B cooperate with Ha-ras or loss of Rb1 in the oncogenic transformation of rodent fibroblasts. Moreover, they are transcriptional targets of c-myc, and CDC25A in particular plays an important role as a mediator of myc functions. On the basis of the evidence that CDC25 phosphatases can act as oncogenes, we analyzed the expression of CDC25A, CDC25B, and CDC25C genes in 20 squamous cell carcinomas of the head and neck by quantitative reverse transcription-PCR. Our results show that whereas CDC25C is expressed at a low level with no relevant differences between neoplastic tissue and normal mucosa, CDC25A and CDC25B are overexpressed in a large fraction of tumors.

Carcinoma, Squamous Cell↗

PubMed1996

Chromosome 13q deletion mapping in head and neck squamous cell carcinomas: identification of two distinct regions of preferential loss.

Heal and neck squamous cell carcinomas show frequent cytogenetic alterations involving the long arm of chromosome 13. To define the extent of 13q deletions and to identify the minimal areas of chromosome loss, 48 primary squamous cell carcinomas of the head and neck were analyzed for loss of heterozygosity using 11 different polymorphic loci. About 67% of the tumors displayed loss of genetic material at 13q. Most of the cases showed loss of the entire long arm of the chromosome. However, the presence of partial deletions in 10 cases provided evidence of the existence of two preferential sites of chromosome loss at 13q32-ter and 13q14.2-q14.3. The colocalization of the 13q14 minimal region of deletion with the retinoblastoma (RB) gene, which has been proposed as an oncosuppressor in diverse tumor types, prompted us to verify the involvement of this gene in the development of head and neck cancer. No significant variation in RB protein or RB mRNA expression was detected, thus excluding a role for such a gene in the genesis of this type of tumor. Taken together, our data suggest the existence of two new tumor suppressor genes (one close to and one distal to RB), which play a role in the development and/or progression of head and neck squamous cell carcinomas.

Base Sequence↗

PubMed1996

Diagnostic utility of cell-block from bronchial washing in pulmonary neoplasms.

In order to evaluate the usefulness of cell-block (CB) bronchial washing in the diagnosis of pulmonary neoplasms, we examined cytological samples of 1,145 bronchoscopies; CBs could be prepared in 777 cases (67.9%) and 201 cases, positive or suspicious for malignancy, were selected for the study (173/201 smears: 86.1%; 174/201 CBs: 86.6%). CBs were positive in 12 cases while the corresponding smears were negative (10 cases) or suspicious (2 cases); 2 cases had suspicious CBs with negative smears. Thus, the use of CBs increased the positive diagnosis from 173 to 185 cases, for an increase of 6.5%. We can conclude that CB could be a routine, inexpensive method, helpful in pulmonary neoplasm's diagnosis; moreover, CB has the advantage of being an histologic specimen, often the only one, useful for other diagnostic procedures.

Bronchoalveolar Lavage↗

PubMed1995

Recurrences and second primary tumours in the head and neck region: differentiation by p53 mutation analysis.

BACKGROUND: Patients with head and neck cancer are at high risk of developing additional primary tumours in the aerodigestive tract as a result of field cancerization phenomena. In this context, the appearance of a new neoplasm often poses a problem of differential diagnosis between recurrence and new primary tumour. The differentiation between the two entities in essentially clinical and conventionally based on the histological and spatio-temporal relations between the two lesions; however, the validity of these criteria has still to be assessed. DESIGN: To evaluate whether field cancerization phenomena may affect the clinical diagnosis of relapse/metastasis in the head and neck region, p53 mutation pattern was analysed in a series of primary tumours and corresponding recurrences/metastases. The rationale was that, since p53 mutations are a very early and polymorphic phenomenon, a recurrence/metastasis must retain the same mutation as the the primary tumour, whereas independent tumours are likely to display a different p53 gene status. RESULTS: Molecular analysis provided conclusive results in 9 of 12 cases analysed. The clinical diagnosis of recurrence was confirmed by molecular analysis in 4 of these cases. In contrast, a differential p53 mutation pattern supported an independent origin for 3 presumed local recurrences and 2 lung lesions. CONCLUSIONS: The use of p53 mutation analysis as a clonality marker allowed us to ascertain the inadequacy of the current diagnostic criteria for the differentiation between a new independent tumour and recurrence/metastasis. These findings substantiate the relevance of field cancerization phenomena in the head and neck region and prompt the use of p53 mutation analysis as a fundamental tool to improve the diagnosis and management of head and neck cancers.

Adult↗

PubMed1995

Brief report: prognostic importance of cellular DNA content in T1-2 N0 laryngeal squamous cell carcinomas treated with radiotherapy.

One hundred fifty-two unselected, consecutive patients with T1-2N0 laryngeal squamous cell carcinoma received radical radiation therapy at the Division of Radiotherapy, Centro di Riferimento Oncologico, Aviano, Italy. Thirty-one (20.4%) of the patients showed disease recurrence or persistence (R/P) after radiotherapy. Flow-cytometric DNA ploidy measurements were performed in 72 cases; 20 had tumor R/P and 52 did not. Tumor R/P occurred more frequently (in 17 [85%] of 20 cases) in patients with diploid tumors. The hazard ratio of recurrence in diploid tumors as compared with aneuploid tumors, after inclusion of all the other significant prognostic factors in a Cox proportional hazards model, was 8.9 (P < .01). Therefore DNA ploidy seems to be an important marker of tumor R/P in patients with T1-2N0 laryngeal carcinoma after radiotherapy.

Carcinoma, Squamous Cell↗

PubMed1994

Low-grade malignant lymphoma, hepatitis C virus infection, and mixed cryoglobulinemia.

Because a close relationship has been established between mixed cryoglobulinemia and hepatitis C virus (HCV) infection, the clinical, histologic, and virologic findings of 31 patients affected by mixed cryoglobulinemia have been determined. HCV infection was investigated by the presence of anti-HCV antibodies and by polymerase chain reaction (PCR) amplification of the 5' untranslated region (5'UTR), and the genotype of HCV was also determined according to Okamoto et al (J Gen Virol 73:673, 1992). A bone marrow (BM) biopsy was performed in all patients, and liver and kidney biopsies were performed when indicated. The prevalence of anti-HCV antibodies was high (83.9%); polymerase chain reaction amplification of the 5' untranslated region was positive in 26 subjects (83.9%), and Core region amplification in 26 of 27 subjects (96.2%). A high prevalence of genotype II was found (76.6%). Chronic liver disease was present in 15 (48%) patients. BM biopsy specimens showed the presence of low-grade non-Hodgkin's lymphomas in 12 cases (38.7%), whereas, in 11 patients (35.5%), the BM infiltration was not monoclonal (reactive). Mixed cryoglobulinemia is closely associated with HCV infection. Apparently, only 1 patient was not infected by the virus. Several HCV genotypes are involved in the pathogenesis of mixed cryoglobulinemia. The disease is associated with a high prevalence of low-grade non-Hodgkin's lymphomas.

Aged↗

PubMed1993

Three discrete regions of deletion at 3p in head and neck cancers.

Alteration of the short arm of chromosome 3 is one of the most consistent cytogenetic abnormalities found in human head and neck cancers. These alterations, composed of translocations and deletions, have been associated with the presence of a tumor suppressor gene(s), but no clear evidence of the location of this presumptive gene(s) was available. We performed a molecular analysis of the 3p region using a polymerase chain reaction-based approach. Twenty-eight of the 38 cases analyzed (74%) showed the presence of single or multiple areas of allelic loss. Three commonly deleted regions, tentatively mapped to 3p24-ter, 3p21.3, and 3p14--cen, were identified. Our results suggest that at least three oncosuppressor genes mapping on 3p may be involved in head and neck cancer development and support a common oncogenic pathway with squamous cell lung cancer, for which a similar pattern of 3p deletion has been described recently.

Base Sequence↗

PubMed1989

A pathologic assessment of tumor residue and stromal changes after intraarterial chemotherapy for head and neck carcinomas. A study on serial sections of the whole surgical specimen.

Thirty-one patients with advanced, biopsy-proven squamous cell carcinoma (SCC) of the head and neck were treated with intraarterial chemotherapy (IAC) and subsequent radical surgery. Cisplatin at 25 mg/d (4 hours of infusion) and bleomycin at 15 mg/d (20 hours of infusion) were administered for 10 consecutive days. Radical surgery was performed after clinical evaluation 2 weeks later. Clinical tumor regression (total disappearance or shrinkage of the tumor mass by more than 50%) was recorded in 28 of 31 (90.3%) patients. Tumor regression was then assessed pathologically using a procedure based on examination of large serial histologic sections of the whole surgical specimen. Tumor residue was classified pathologically according to the TNM categories: RO, no residual tumor (five cases [16.1%]); R1, microscopic residual tumor (tumor residue detectable only at the microscopic level; 12 cases [38.7%]); and R2, macroscopic residual tumor (tumor mass detectable also on the fresh or fixed specimen and/or by the naked eye on the stained tissue sections; 14 cases [45.2%]). Moreover, tumor cell and/or stromal changes possibly associated with tumor regression were found in 77.4% of the cases. Metastatic lymph nodes were found in 12 cases (38.7%), and regression changes were observed in most lymph node metastases. Only standardized, prospective pathologic protocols for the analysis of whole specimens by serial sections permit the assessment of existing tumor residue. The TNM classification of pathologic tumor residue and definitions that we used appear feasible and reliable enough in evaluating postchemotherapeutic tumor regression.

Bleomycin↗

PubMed1989

Pathologic assessment of computerized tomography accuracy for the evaluation of the laryngeal cartilaginous framework in laryngopharyngeal carcinomas.

Sixty-six whole-organ sectioned laryngopharyngectomy specimens removed for cancer during a seven-year period were uniformly examined to determine the accuracy of preoperative high resolution computerized tomography (CT) for detection of cartilaginous involvement. Our results indicate that CT has a high overall specificity (88.2%) but a low sensitivity (47.1%); we observed a high false-negative rate (26.5%) and a fairly low false-positive rate (5.9%). Massive cartilage destruction was easily assessed by CT, whereas both small macroscopic and microscopic neoplastic foci of cartilaginous invasion were missed on CT scans. Moreover, false-positive cases were mainly due to proximity of the tumor to the cartilage. Clinical implications of these results are discussed.

Carcinoma↗

PubMed1989

T staging of the laryngohypopharyngeal carcinoma. A 7-year multidisciplinary experience.

Sixty-six whole-organ sectioned, nonirradiated, laryngopharyngectomy specimens that were removed because of cancer during a 7-year period were uniformly examined to determine the accuracy of perioperative T staging by high-resolution computed tomography (CT) and clinical evaluation (indirect-direct laryngoscopy) by comparing this preoperative staging with the postsurgical pathologic staging. The accuracy of the clinical vs CT staging for laryngeal carcinomas was 58.8% vs 70.6%, whereas the accuracy of the staging by combination of the two modalities was 88.2%. Combined staging modalities showed the same accuracy for laryngeal and hypopharyngeal carcinomas (88.2%), whereas clinical staging accuracy for hypopharyngeal carcinomas was lower (52.9%) and CT accuracy was higher (82.4%) than that observed for laryngeal carcinomas. In the majority of the cases that were staged inaccurately, the error was one of under-estimation: in particular, tumors confined to the mucosa and early infiltration of laryngeal fat spaces were not detected by CT.

Adult↗

PubMed1989

Dipeptidylaminopeptidase IV activity in T lymphocyte subsets in B cell non-Hodgkin's lymphomas.

The total T cell population and T cell subsets in ten lymph nodes with reactive lymphoid hyperplasia (RLH) and 23 specimens (21 lymph nodes, one stomach, and one small bowel) involved by histologically and immunohistologically diagnosed B cell non-Hodgkin's lymphomas (NHLs) were determined by reactivity with monoclonal antibodies Leu 4-CD3, Leu 3-CD4, and Leu 2-CD8 in cytospin preparations from cell suspensions. T cell populations were also investigated for the coexpression of dipeptidylaminopeptidase IV (DAP IV) activity, which was visualized simultaneously with cell surface immunostaining by a combined cytochemical and immunocytochemical method. The mean absolute percentage of Leu 4-CD3+ (total T) and Leu 3-CD4+ cell populations was significantly lower in B cell NHL cases than in RLH cases (35% v 54%, P less than .001; 29.5% v 44.4%, P less than .01). No difference in the mean absolute percentage of the Leu 2-CD8+ T cell subset was found between the RLH cases and the B cell NHL cases classified as other than category A as described by the Working Formulation (WF) of NHLs. The relative percentage of Leu 4-CD3+ and Leu 2-CD8+ cells coexpressing DAP IV reactivity was lower in B cell NHL cases than in RLH cases (27.3% v 39.5%, P less than .05; 13.5% v 24.4%, P less than .10). There was no difference in the proportion of Leu 3-CD4+ cells expressing DAP IV reactivity between the NHL and RLH groups (34.5% v 36.1%). Since the mean relative percentage of Leu 2-CD8+ cells expressing DAP IV reactivity in the B cell NHL group in the other than category A according to the WF was lower than that of the RLH group (12.5% v 24.4%), and whereas the mean absolute percentage of total Leu 2-CD8+ cells was similar in the two groups (16.6% and 16.6%), a possible defective role of this Leu 2-CD8+ DAP IV+ subset, at least in B cell NHLs in the other than category A according to the WF, may be hypothesized.

Antibodies, Monoclonal↗

PubMed1989

Intermediate lymphocytic lymphoma encompassing diffuse and mantle zone pattern variants. A distinct entity among low-grade lymphomas?

Intermediate lymphocytic lymphoma has been operationally included among low-grade lymphomas, but few clinical data appeared to support definitely such an inclusion. The clinicopathologic features of 13 out of 14 cases of intermediate lymphocytic lymphoma either encompassing diffuse or mantle-zone pattern variants (ILL or MZL, respectively), diagnosed by conventional histology according to established criteria, are reported. Frozen section immunophenotypic analysis was also performed in 10 cases and enzyme studies were done in five. The 14 cases formed 6.9% of 203 non-Hodgkin's lymphomas (NHL) histologically diagnosed over a 2-year period. Among the 13 cases studied, there were nine males (five with ILL and four with MZL) and four females (one with ILL and three with MZL). Median age was 59 years. Splenomegaly (46%), high stage diseases (100%), involvement of bone marrow (92%) and peripheral blood (38%), and diffusion to and/or involvement of extranodal sites (38%), all were common findings at presentation. The 34 low-grade NHL of the total series classified according to the Working Formulation did not significantly differ from the ILL/MZL group in terms of frequency of involvement of bone marrow (69%) and peripheral blood (56%) as well as diffusion to and/or involvement of extranodal sites (26%). In ILL/MZL, therapy modalities were not uniform and the short follow-up time precluded firm conclusions on prognosis. Immunohistology demonstrated that ILL/MZL diagnosed by adequate morphologic criteria is a fairly homogeneous entity, also sharing most of its consistent immunological features with low-grade NHL. Thus, ILL/MZL is a relatively frequent and consistently recognizable clinical and pathological entity that may deserve a distinct place among NHL according to the Working Formulation. Proper clinical studies are needed to establish on a firmer basis the prognosis and optimal treatment of ILL/MZL.

Adenosine Triphosphatases↗

PubMed1989

A method for routine approach to laryngeal and hypopharyngeal surgical specimens by whole organ sections in the horizontal plane.

A procedure of pathological analysis of laryngopharyngeal specimens by whole organ sections in the horizontal plane was developed and evaluated. The use of a fast decalcifying and fixative solution allowed both an easier sectioning of the whole organ and thin (5-6 microns) histological whole organ sections of laryngo pharyngectomy specimens. The complete procedure required 5 to 10 days for each case. A preliminary examination of 39 surgical laryngopharyngectomy specimens with laryngeal or hypopharyngeal carcinomas showed that most of the normal structures were histologically identifiable on whole organ horizontal histological sections. The data of the local neoplastic spread related to the main sites of origin were in accordance with the results obtained by other studies using whole organ sections in the coronal or vertical planes. In conclusion, with this procedure it is possible to obtain, in a reasonably short time, thin histological horizontal whole organ sections allowing an adequate and complete assessment of the microscopic characteristics of the tumor and of the tridimensional relationships of the neoplasm with the host organ; moreover, by this procedure pathological data may be compared with preoperative CT or MR scans in patients with laryngeal and hypopharyngeal carcinomas.

Histocytochemistry↗

PubMed1989

A combined cytochemical and immunocytochemical method for simultaneous visualization of cytoplasmic enzyme reactivity and cell surface antigens in cell suspensions.

Immunocytochemical methods were used in combination with enzyme cytochemistry to visualize simultaneously cytoplasmic enzyme reactivity (for dipeptidyl[amino]peptidase [DAP IV], acid phosphatase [AcP], chloroacetyl esterase [CAE]) and cell surface antigens (Leu-3a, Leu-4, Leu-14, Leu-M1, OKT4, OKT8, OKB7) in cytospin preparations from cell suspensions of human reactive lymphoid tissues (four lymph nodes and three tonsils). Different fixative solutions were tested. Enzyme and immunocytochemical reactions were carried out in different orders of sequence to establish which was the better direction for the combination of the two methods. The following immunocytochemical methods were tested: three stages, avidin-biotin complex, peroxidase-antiperoxidase, alkaline phosphatase-antialkaline phosphatase (APAAP) (using both peroxidase and alkaline phosphatase as labeling enzyme). Acetone or buffered formalin acetone gave the best results both for cytochemical and immunologic reactions. DAP IV and AcP reactivities could be visualized only when cytochemical reactions were performed before immunocytochemistry. CAE reactivity could be demonstrated either before or after immunocytochemistry. Cell surface antigens could be demonstrated with most immunocytochemical methods: however, the APAAP method was preferred for its sensitivity and effectiveness when combined with enzyme cytochemistry. By this approach, cells expressing only immunologic markers and cells expressing only cytochemical markers could easily be distinguished from those coexpressing both markers, because cytochemistry and immunocytochemistry could be combined without affecting the reactivity of each marker, and the reaction products did not hamper the interpretation of preparations.

Antigens, Surface↗

PubMed1988

Dendritic reticulum cell pattern as a microenvironmental indicator for a distinct origin of lymphoma of follicular mantle cells.

Follicular dendritic reticulum cells (DRCs) are known to be normally present in primary follicles and both follicular centres and mantle zones of secondary follicles of peripheral lymphoid tissue. Involved frozen biopsy tissue specimens from eight cases of intermediate lymphocytic lymphoma/mantle zone lymphoma (ILL/MZL); eight cases of follicular centre cell lymphomas (FCCL) of the centroblastic/centrocytic type; and seven cases of well-differentiated lymphocytic lymphoma (WDLL) consistent with chronic lymphocytic leukaemia (CLL) were analysed immunohistologically with R4/23 (DRC-1) monoclonal antibody reactive with 'bystander' DRCs. As opposed to FCCL and most WDLL/CLL cases, the DRCs consistently formed a loose, ill-defined meshwork with a radiating or blurred outline in all MZL cases and one ILL. On the basis of the observed findings as well as from those reported in literature, the hypothesis is proposed that ILL/MZL originates from the follicular mantle zone and represents a distinct lymphoma entity owing to its peculiar immunostaining pattern of DRCs that allows it to be separated from both FCCL and WDLL/CLL. Moreover, the absence of DRCs in the microenvironment of other B-cell malignancies such as prolymphocytic leukaemia and hairy cell leukaemia, analogously with most CLL cases, would speak in favour of their different--possibly extrafollicular--compartment of origin within lymphoid tissue.

Dendritic Cells↗

PubMed1988

Superficial extending carcinoma of the larynx.

Superficial extending carcinoma of the hypopharynx is a recently recognized form of carcinoma regarded as a possible pharyngeal counterpart to early gastric cancer and superficial esophageal carcinoma. In this study we report the radiological, clinical, and pathological features of three carcinomas of the larynx, which show architectural and histopathological features similar to those previously described in superficial extending carcinoma of the hypopharynx. These cases were singled out from a series of 37 consecutive laryngectomy specimens of primary infiltrating laryngeal carcinomas that were uniformly studied by means of a whole-organ sections technique. Pathologically, these cases showed a clearly invasive growth through the basal membrane into the lamina propria and an entire or predominant, extensive, superficial type of spread; infiltration of underlying muscle or gland structures was restricted to a few microscopic foci, regardless of the presence of lymph node metastases. The present study demonstrates that infiltrating carcinomas with a preferential superficial type of growth may also be encountered in the larynx. Differences between the histological features of these carcinomas of the larynx and the histopathological spectrum of so-called early laryngeal cancer are emphasized.

Aged↗