Cumulative prognostic value of p16/CDKN2 and p53 oncoprotein expression in premalignant laryngeal lesions.
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Adult↗
Biomedical subjects
O Gallo
Publications and source records attributed to O Gallo.
Cyclooxygenase and lipoxygenase metabolite generation in nasal polyps.
A role of prostaglandins (PGs) and leukotrienes (LTs) in the pathogenesis of nasal polyps has been recently suggested. Cyclooxygenase (CO) products (thromboxane B2, PGE2 and 6-keto PGF1 alpha) and lipoxygenase (LO) products (LTB4 and LTC4) were investigated by radioimmunoassay in polyps, hypertrophic turbinates and nasal mucosa from 14 patients with non-allergic (n = 6), allergic chronic rhinitis (n = 6) and aspirin-sensitive asthma (ASA) (n = 2), who underwent polypectomy. In all tissues CO metabolite levels were found higher than LO products (P < 0.01). Nasal polyps showed a significantly lower (P < 0.05) arachidonic acid (AA) metabolism in comparison to nasal mucosa. In polyps of allergic patients significantly higher LTB4 levels (P < 0.001) and a tendency to produce higher amounts of CO products in comparison to non-allergic subjects were observed, whereas in turbinates of non-allergic patients LT levels were significantly higher in comparison to those of allergic ones (P < 0.01). In ASA patients a decreased CO/LO ratio was found supporting the hypothesis of an imbalance of AA metabolism in this syndrome. These findings seem to indicate that the occurrence of nasal polyps may represent the result of different chronic inflammatory stimuli, regulated in part by AA metabolites.
6-Ketoprostaglandin F1 alpha↗
Immunohistochemical vs molecular biology methods. Complementary techniques for effective screening of p53 alterations in head and neck cancer.
The purpose of this study was to correlate p53 gene alterations and their expression in 85 head and neck squamous cell carcinomas. Genomic p53 was amplified with the polymerase chain reaction (PCR) from formalin-fixed, paraffin-embedded tissues. Exons 5 through 8 were screened for mutations by means of non-isotopic single-strand conformation polymorphism (SSCP) analysis. p53 expression was detected by means of immunohistochemistry (IHC) with the p53 monoclonal antibody DO-7. Twenty-three lesions (27%) showed both SSCP variants and DO-7 immunostaining, whereas 37 (44%) demonstrated both SSCP normal patterns and negative staining. Twenty-five lesions (29%) were discordant, including 12 IHC-positive (14%) and 13 SSCP-positive (15%) lesions. However, discordant IHC-negative, SSCP-positive lesions could have been easily interpreted after sequencing of the abnormal samples. Had these been screened with IHC only, all nonsense or frameshift p53 mutations would have been missed. IHC-positive, SSCP-negative lesions were interpreted in light of current models of p53 immunodetection. Had these been screened with SSCP or sequencing only, a sizeable number of tumors expressing p53 protein abnormalities would have been undetected. Therefore, simultaneous use of both methods increases the number of p53 abnormalities detected, and is warranted.
Antibodies, Monoclonal↗
Warthin's tumour associated with autoimmune diseases and tobacco use.
To better clarify the possible role of immune mechanisms in the pathogenesis of Warthin's tumour (WT), we performed a retrospective study of patients with WT surgically treated at the Institute of Otolaryngology Head and Neck Surgery, University of Florence, during a 25-year period; looking for a possible association with autoimmune pathologies. The retrospective analysis of clinical records of 140 WT patients compared with those of 380 patients with pleomorphic adenoma revealed a higher incidence of autoimmune disorders, particularly organ-specific disease (i.e. insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, autoimmune hyperthyroidism and hypothyroidism) in WT patients than in pleomorphic adenoma (PA) patients (23% vs 3%; R.R.: 8.69; p < 0.0001). Moreover, we demonstrate a positive smoking history in 87% of WT patients compared to only 38% of PA subjects (p < 0.001). Because of the well-known possible association among multiple immune disorders, our data support the hypothesis of an immune pathogenesis of WT and also suggest the possible role of tobacco smoke in facilitating such immune reactions responsible for the lympho-epithelial coexistence of WT.
Adenolymphoma↗
Potential biomarkers in predicting progression of epithelial hyperplastic lesions of the larynx.
Factors contributing to malignant transformation of laryngeal pre-neoplastic lesions remain largely unknown. Potential etiologic factors may be related to a genetically controlled sensitivity to environmental carcinogens. In this study, we investigated bleomycin-induced chromosome fragility in 15 patients with laryngeal keratoses who experienced a malignant transformation of pre-neoplastic lesions during follow-up, as compared with chromosome fragility in 15 historical controls with no progression of laryngeal keratoses during a 10-year follow-up, in a match-paired analysis. Chromosomal analysis demonstrated a higher sensitivity to clastogens in patients with malignant progression of laryngeal pre-neoplastic lesions than that of control patients with no evolution of their original laryngeal keratoses (p < 0.01). Furthermore, in the attempt to identify possible prognostic markers we studied proliferative activity (MIB-1 expression) and p53 gene aberration in biopsy samples from non-invasive and invasive laryngeal lesions in both groups. p53 immunostaining was observed in 10/15 (66.7%) of pre-neoplastic lesions and in 11/15 (73.3%) of metachronous laryngeal cancers. No differences in terms of p53 expression were noted between transformed and not-transformed lesions. Mutations at p53 gene were observed in 3/15 (20%) of pre-invasive biopsies and in 4/5 (80%) of the laryngeal cancers analyzed. Our data suggest that p53 alteration is an early event in the genesis of a subset of laryngeal carcinomas and that there is no conclusive data about the possible clonal development of metachronous laryngeal carcinoma from a p53 mutated pre-invasive disease in the same patient. MIB-1 expression was found to progressively increase with degree of epithelial hyperplasia and dysplasia in both transformed (p = 0.007) and not-transformed (p < 0.1) lesions. Surprisingly, pre-invasive lesions with tumor evolution showed a lower proliferative activity when compared with laryngeal lesions without malignant transformation (p = 0.013). These data suggests that subjects with pre-neoplastic laryngeal lesion showing an increased susceptibility to carcinogens and with less proliferative disease could be at a higher risk for development of laryngeal carcinoma.
Antigens, Nuclear↗
Increased mutagen-induced chromosome damage in patients with transformed laryngeal pre-cancerosis.
Factors that contribute to malignant transformation of laryngeal pre-neoplastic lesions remain largely unknown. Potential etiological factors may be related to a genetically controlled sensitivity to environmental carcinogens. In this study, we investigated bleomycin-induced chromosome damage in 15 patients who experienced a malignant transformation of preneoplastic laryngeal lesions during follow-up, as compared with chromosome fragility in 30 historical controls with no progression of keratoses during a 10-year follow-up, in a match-paired analysis. Chromosomal analysis demonstrated higher sensitivity to clastogens in patients with malignant progression of laryngeal pre-neoplastic lesions than that of control patients with no evolution of their original laryngeal keratoses (p = 0.003). Furthermore, among the study patients, chromosome sensitivity was most apparent in non-tobacco users with malignant transformation of laryngeal disease. Our data suggest that subjects with pre-neoplastic laryngeal lesion showing increased susceptibility to carcinogens could be at higher risk for development of laryngeal carcinoma.
Adult↗
Prognostic implications of Sialosyl-Tn antigen expression in sinonasal intestinal-type adenocarcinoma.
The expression of the mucin antigen sialosyl-Tn (S-Tn) was evaluated immunohistochemically in a series of 30 intestinal type adenocarcinomas of the nasal cavities and paranasal sinuses to assess the relationship between the histological features of the lesions and their clinical behaviour. In grades 1 and 2 adenocarcinomas, the staining localised at the apical pole or within the cytoplasm of neoplastic cells, and in the content of glandular structures. Grade 3 adenocarcinomas had a very scanty expression of the antigen. Mucinous adenocarcinomas showed an intense immunoreaction within the cell cytoplasm and in the extracellular mucous pools. Conversely, non-neoplastic sinonasal mucosa had a very focal distribution of the antigen. Immunostaining was scored according to the percentage of low power microscopic fields showing positivity. Twenty-one adenocarcinomas (70%) were considered positive. No significant relationship was found between S-Tn positivity and the histological degree of differentiation of the lesion. The 5-year survival rate and disease-free interval of patients with S-Tn positive adenocarcinomas were significantly lower than those with negative adenocarcinomas (17.8% versus 72%, P = 0.0001; 16.6% versus 40%, P = 0.0001, respectively). These results indicate that S-Tn immunostaining appears to be a significant prognostic factor in patients with sinonasal intestinal type adenocarcinoma.
Adenocarcinoma↗
Increasing evidence that Epstein-Barr virus may be involved in the pathogenesis of undifferentiated carcinoma of the salivary glands.
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Carcinoma↗
Carcinoma of the anterior commissure of the larynx: II. Proposal of a new staging system.
On the basis of embryology and clinical experience, we have defined here an anterior commissure (AC) subsite of the human larynx and have addressed the issue as to whether the degree of involvement of this subsite is related to the outcome of glottic cancer, in terms of local control within 5 years of therapy. Retrospective analysis of 534 patients included 1) classification of patients according to the TNM, 2) actuarial evaluation of the outcome, 3) reclassification of patients according to the involvement of the AC subsite, and 4) reevaluation of the outcome according to this latter classification. The results showed that the outcome was not well correlated with TNM classification, whereas patients with progressively heavier involvement of the AC subsite had a progressively worse outcome. On the basis of these data, we suggest that TNM classification of cancer involving the AC be implemented by and AC classification, in order to better forecast the prognosis and design specific conservative surgery.
Adult↗
Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination.
The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.
Antigens, Nuclear↗
bcl-2 protein expression correlates with recurrence and survival in early stage head and neck cancer treated by radiotherapy.
Inherent cellular radioresistance plays a critical role in the failure of radiation therapy (RT). The proto-oncogene bcl-2 encodes a protein that inhibits apoptosis, a common mechanism of cell death induced by several genotoxic agents, including gamma-radiation. Thus, it is likely that bcl-2 gene expression could be involved in the complex mechanisms of radioresistance in human tumors with some prognostic implications. In this study, we analyzed the predictive relevance of bcl-2 expression on 5-year disease-free and overall survival in patients with early stage squamous cell carcinoma of the head and neck (SCCHN) primary treated with RT. The expression of bcl-2 was analyzed by immunohistochemistry on paraffin-embedded sections from 71 consecutive stage I-II SCCHN patients treated with curative RT. We detected bcl-2 protein in 21% of SCCHN studied. A suggestive association was observed between tobacco exposure and bcl-2 protein expression (P < 0.1); this association was stronger in those patients who failed primary RT (P = 0.03). Moreover, we documented a higher rate of bcl-2 immunoreactive tumors in postirradiated biopsies from relapsed patients than in preirradiated ones (P = 0.03). In both univariate and multivariate analyses, bcl-2 expression was the most important indicator for disease-free survival (P = 0.08 and P = 0.01, respectively) and overall survival (P = 0.004 and P = 0.05) within 5 years of RT. The present study indicates that the proto-oncogene bcl-2 is abnormally expressed in some SCCHN, and its expression may prove to be a useful tool in selecting patients for conventional RT with clear prognostic implications.
Adult↗
Loss of p53 gene mutation after irradiation is associated with increased aggressiveness in recurring head and neck cancer.
The p53 gene plays a pivotal role in the control of a checkpoint during G1 and in the apoptotic program. It has been postulated that alterations of p53 may influence radio-sensitivity and prognosis in several malignancies. We studied the p53 gene status of 35 consecutive head and neck cancer patients who failed primary radiotherapy (RT) in preirradiated and postirradiated tumor samples using DNA single-strand conformational polymorphism analysis. Sixteen of 35 (46%) preirradiated samples presented with band shifts suggestive of point mutations in one or two exons. Eleven of these tumors (69%) showed the same shift even in the postirradiated samples. Exons 5 and 8 were prevalently affected in this group. Five tumors (31%) lost the mutation following RT. The missed mutations clustered in exon 7. All mutations were confirmed by sequencing. Actuarial analysis demonstrated increased survival in patients with tumors bearing a p53 gene mutation in both preirradiated and postirradiated samples (P = 0.05 and P = 0.01, respectively). We also found that loss of p53 gene mutation in postirradiated cancers is associated with a significantly shorter disease-free interval (P < 0.02) and a worse prognosis (P < 0.05). A possible explanation in such cases is clonal selection by RT of more aggressive and radioresistant cell subpopulations, which are wild-type for the p53 gene. Taken together, our data suggest that not only p53 gene status but also the pattern of mutations could modulate the response of tumor cell to RT in vivo.
DNA Mutational Analysis↗
Bcl-2 overexpression and smoking history in head and neck cancer.
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Carcinoma, Squamous Cell↗
p53 oncoprotein expression in parotid gland carcinoma is associated with clinical outcome.
BACKGROUND: Recent studies of the molecular biology of cancer have demonstrated that p53 tumor suppressor gene aberration is associated with the development and progression of several different cancer types. METHODS: To analyze the expression of the p53 oncoprotein in parotid gland neoplasms, 72 parotid gland tumors (including 46 malignant and 26 benign cases) were studied immunocytochemically using the murine monoclonal DO-7 anti-p53 antibody. In parotid gland cancers, no and low expression (-/+) or moderate and high expression (++/+++) of the p53 oncoprotein were examined for correlation with patient survival and other clinicopathologic features, including clinical stage, tumor size, regional lymph node status, facial nerve paralysis, local infiltration, and distant failures. RESULTS: Positive staining was observed focally in 3 of 26 (11%) benign tumors and in 31 (67%) of 46 malignant tumors. Cancers showing moderate and high expression of p53 tended to be more advanced and larger than those with no expression or low expression, and presented at diagnosis more frequently, with signs of local aggressiveness. Tumors with moderate and high expression of p53 were associated more frequently with regional and distant metastases (P = 0.07 and P = 0.004, respectively). Multiple logistic regression analysis showed that regional and distant metastases were associated independently with p53 expression (P = 0.068 and P = 0.047, respectively). Moreover, patients whose cancers had moderate or high p53 expression had lower disease free and overall actuarial survival rates than those with no or low p53 expression (P = 0.021 and P = 0.033, respectively). Univariate and multivariate analysis confirmed the independent predictive prognostic value of p53 expression in patients with parotid gland cancer (P = 0.044 and P = 0.039, respectively). Furthermore, p53 expression did not correlate positively with patients' smoking habits in this series. CONCLUSION: The p53 tumor suppressor gene may be involved in salivary gland carcinogenesis, and its oncoprotein expression is an independent indicator of clinical aggressiveness in patients with carcinoma of the parotid gland.
Gene Expression↗
Prognostic significance of clinically false positive cervical lymph nodes in patients with laryngeal carcinoma.
BACKGROUND: A significant proportion of clinically positive palpable cervical lymph nodes in patients with head and neck cancer are histologically benign. The biologic and prognostic significance of this reactive lymph node enlargement has not been fully clarified. METHODS: In this study, the incidence of clinically positive microscopically negative cervical lymph nodes in a series of 902 patients who had neck procedures as a part of their primary treatment for N0-2 laryngeal cancer was analyzed and survival rates of 342 patients with true negative lymph nodes (N0- necks) were compared with those of 106 patients with clinically false positive lymph nodes (N1-2b- necks). In 86 patients with false positive lymph nodes, a histopathologic analysis was performed to determine the histomorphologic pattern of the enlarged lymph nodes and to evaluate which parameters, if any, correlated with 5-year patient survival. RESULTS: Overall actuarial survival did not differ significantly in the two groups. However, the actuarial survival curves in the false positive group were clearly better compared with those of the true negative group with more advanced laryngeal cancers, particularly T4 lesions (P < 0.05). Interestingly, the analysis of pattern of recurrence showed a higher incidence of distant metastases in false positive patients with advanced stage laryngeal cancer than in true negative subjects. In addition, the histologic examination of 375 enlarged hyperplastic cervical lymph nodes from 86 neck specimens showed the prevalence of sinus histiocytosis in the false positive group and its favorable prognostic significance. No statistically significant differences with regard to the number and size of enlarged lymph nodes were found. On the contrary, lymph node location seems to have a prognostic impact on survival and the reactive benign enlargement of a digastric lymph node is a possible poor prognostic factor. CONCLUSIONS: Survival of patients with clinically false positive, histologically benign hyperplastic cervical lymph nodes who have more advanced laryngeal carcinoma is higher than clinically negative patients, suggesting that the presence of palpable benign nodes may be a sign of the host's immune activation, with favorable prognostic significance.
Actuarial Analysis↗
Interleukin-6 and acute-phase proteins in head and neck cancer.
The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), alpha 1-antitrypsin (ATT), alpha 1-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx (n = 9), oral cavity (n = 4), oropharynx (n = 3) and hypopharynx (n = 2). Proteins were measured at three time points before and three time points after surgery. Significant (P < 0.0001) relationships were found between IL-6 and CRP (r = 0.69), and fibrinogen (r = 0.51), whereas no correlation was found with AAT (r = 0.13, P = 0.56), AAG (r = 0.38; P = 0.07) and HPT (r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies.
Acute-Phase Proteins↗
p53 expression: a potential biomarker for risk of multiple primary malignancies in the upper aerodigestive tract.
The concept of field cancerisation assumes that in head and neck cancer patients (HNCP) with multiple malignancies the second primary cancers may arise independently from the entire upper aerodigestive tract as a consequence of massive exposure to common carcinogens. Since mutations and/or overexpression of the p53 tumour suppressor gene represent a genetic alteration frequently occurring in HNCP, we analysed immunocytochemically p53 oncoprotein expression in first primary, second primary cancers and in macroscopically uninvolved normal epithelium from different sites of the upper aerodigestive tract from 12 HNCP with multiple malignancies, in comparison with p53 expression in biopsy specimens of the upper aerodigestive tract from 5 non-neoplastic heavy smokers, as controls. In patients with multiple malignancies 6 cases (50%) showed positive staining of both first and second primaries, whereas 3 (25%) had positive labelling of first primary cancer but not of the subsequent second primary, 2 (17%) patients showed p53 expression only in the second primary cancer, and finally only 1 patient (8%) showed no p53 immunoreactivity in both first and second primary tumours. Moreover, 10 out of 12 (83%) HNCP with multiple cancers showed p53-positive staining in the normal epithelium from different sites of the upper aerodigestive tract, also at a significant distance from the site of first and second primary malignancies. contrast, sporadic p53 immunostaining was observed only in three out of 35 (8.5%) specimens from non-neoplastic controls. In addition, in 4 HNCP with multiple tumours the histological examination of apparently normal epithelium from the upper aerodigestive tract revealed signs of moderate or severe dysplasia, and in 1 case an in situ carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
New insights into the pathogenesis of Warthin's tumour.
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Adenolymphoma↗