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Laryngeal Squamous Cell Carcinoma (laryngeal + squamous_cell_carcinoma)
Selected AbstractsThe Expression of Proto-Oncogene eIF4E in Laryngeal Squamous Cell Carcinoma,THE LARYNGOSCOPE, Issue 7 2003Zhou Liang MD Abstract Objectives/Hypothesis The translation initiation factor eukaryotic initiation factor 4E (eIF4E) binds to the cap of messenger RNA in the first step of messenger RNA recruitment. Overexpression of eIF4E results in the upregulation of specific angiogenic factor basic fibroblast growth factor (bFGF). The study aims to demonstrate that the overexpression of eIF4E could facilitate recognizing initiation start sites for the translation of bFGF and play an important role in the tumorigenesis of laryngeal squamous cell carcinoma. Study Design Retrospective. Methods Paraffin-embedded sections of 37 samples of laryngeal squamous cell carcinoma, 10 samples of vocal cords polyps, and 20 fresh samples of laryngeal squamous cell carcinoma were analyzed using immunohistochemical streptavidin peroxidase technique, Western blot analysis, and reverse transcriptase,polymerase chain reaction. Results The overexpression of eIF4E was observed in all 37 paraffin-embedded samples of laryngeal squamous cell carcinoma, whereas no staining was noticed in vocal cords polyps samples. There were significant correlations between the overexpression of protein eIF4E and TN stages, histological grades, local recurrence, and the states of metastasis (P <.01). Moreover, the overexpressions of both bFGF protein and bFGF messenger RNA correlated with the histological grades and the states of metastasis (P <.01), but the overexpression of eIF4E and bFGF did not correlate with age, sex, and tumor sites (P >.05). Conclusions Eukaryotic initiation factor 4E can enhance the expression of bFGF at translation level. The eIF4E and bFGF collaborate in tumorigenesis, development, invasion, and metastasis of laryngeal squamous cell carcinoma, in view of which the former can be considered as a tumor molecular marker and an independent prognostic molecular marker of laryngeal squamous cell carcinoma. [source] Prognostic Significance of p53/bcl-2 Co-expression in Patients With Laryngeal Squamous Cell CarcinomaTHE LARYNGOSCOPE, Issue 8 2000Martin C. Jäckel MD Abstract Objective The p53, bcl-2, and bax genes are known to be involved in control of cell cycle progression and regulation of apoptotic cell death. Although they are frequently altered in laryngeal squamous cell carcinoma, their clinical relevance is not yet fully understood. In the present study, individual and combined expressions of these genes were related with patient survival as well as with proliferative and apoptotic activity. Design Retrospective study. Methods Paraffin-embedded tissue sections of 88 laryngeal squamous cell carcinomas that were diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. Apoptotic cells were visualized using the nick end labeling method. To assess proliferative activity of tumors, mitotic indices were determined. Results Age of patients, advanced disease (stages III and IV), high mitotic activity, positive bcl-2 expression, high level of p53 expression, and p53/bcl-2 co-expression were significantly associated with shortened overall survival in univariate analysis. In multivariate analysis, only age and p53/bcl-2 co-expression had independent prognostic value. Other combinations of genes, i.e., bcl-2-to-bax and p53-to-bax ratios, were not associated with patient outcome. A significant positive correlation was found between apoptotic and mitotic activity. However, protein levels of p53, bcl-2, and bax were unrelated to proliferation and apoptosis of tumor cells. Conclusions The co-expression of p53/bcl-2 was an independent predictor of patient outcome and had a prognostic value superior to both parameters considered separately. The rate of apoptosis mainly counterbalanced proliferative activity but appeared not to be significantly influenced by p53, bcl-2, and bax. [source] Telomerase Activity Is Upregulated in Laryngeal Squamous Cell Carcinoma,THE LARYNGOSCOPE, Issue 3 2000Aongus J. Curran MB, FRCSI Objective/Hypothesis The immortalizing enzyme telomerase has been linked to carcinogenesis and is being targeted as a novel molecular marker. This study investigated telomerase expression in patients with laryngeal squamous cell carcinoma and correlated telomerase activity with conventional prognostic parameters. Study Design A consecutive series of patients with laryngeal squamous cell carcinoma undergoing surgical salvage for persistent or progressive disease after failed radiation therapy. Methods Twenty patient samples of laryngeal squamous cell carcinoma and 20 adjacent histologically normal mucosal samples were assayed using the telomeric repeat amplification protocol (TRAP) method for detection of telomerase activity. The leukemic cell line, K562, acted as a positive control and the human fibroblast line, Hs21Fs, as a negative control. A sample was classified as telomerase positive when an RNase-sensitive hexameric repeat ladder was observed. Absence of laddering was considered a negative result. Results Seventeen of 20 (85%) tumor samples and 4 of 20 (20%) adjacent histologically normal samples were telomerase positive. No statistically significant difference was observed when densitometric readings were compared by T category, tumor grade, or site (by ANOVA). Conclusions Although telomerase activity is present in laryngeal cancer, levels of activation do not correlate with conventional parameters used for prognostication. Our study indicates that the marker may be a useful adjunctive method in the diagnosis of malignancy after radiation failure. [source] Genetic polymorphism of N -acetyltransferase 2 in the susceptibility to laryngeal squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2005Murat Ünal MD Abstract Background. The purpose of this study was to investigate whether polymorphism of N -acetyltransferase 2 (NAT2) genotypes are associated with the risk of laryngeal squamous cell carcinoma (SCC). Methods. The study group consisted of 45 white patients with laryngeal SCC (42 men, with a mean age of 54 years [range, 37,70 years] and three women, with a mean age of 47 years [range, 32,55 years]) and 104 control subjects (68 men and 36 women; mean age, 50 years; range, 28,73 years). All of the patients were primarily treated with surgical intervention. Blood samples (5 mL) were obtained before surgery or from the patients under follow-up to 5 years after surgery (mean follow-up, 27 months; range, 6,48 months). DNA was extracted from the lymphocytes by high pure template preparation kit. NAT2*5A, NAT2*6A, NAT2*7A/B, and NAT2*14A were detected by use of LightCycler- NAT2 mutation detection kit by real-time polymerase chain reaction with Light Cycler instruments. The association between NAT2 polymorphisms and laryngeal SCC was prospectively modeled through multivariate logistic regression analysis. Results. We found that the risk of laryngeal SCC was 7.3-fold higher in individuals with NAT2*5 mutant allele, 3.8-fold higher in subjects with NAT2*6 heterozygote allele, and 38.3-fold higher in NAT2*6 mutant allele. We also found that individuals with NAT2*7 heterozygote allele had a 0.2-fold less risk for the development of laryngeal SCC (p = .018). Conclusion. In this population, patients with NAT2*5 mutant and *6 heterozygous and mutant genotypes had a significantly higher risk for development of laryngeal SCC. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Routine inclusion of level IV in neck dissection for squamous cell carcinoma of the larynx: Is it justified?HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2004Avi Khafif MD Abstract Background. Dissection of levels II,IV as part of an elective or therapeutic neck dissection is common practice during laryngectomy for laryngeal squamous cell carcinoma (SCC). The necessity of routine dissection at level IV has recently been questioned. The purpose of this study was to find the incidence of level IV metastases in patients with transglottic and supraglottic SCC who underwent neck dissections. Methods. The charts of 71 suitable patients were reviewed. Forty-two had supraglottic primary cancers, and 29 had transglottic primary tumors. Levels II,IV had been removed in them all, and their neck specimens were marked according to the levels of the neck. The surgical specimens were pathologically diagnosed. Results. Of 43 patients who underwent elective lateral neck dissection, the only one (2.3%) with level IV metastases also showed metastases at level II. Nine (32%) of the other 28 patients with clinical adenopathy had level IV metastases. Conclusions. Dissection of level IV as part of a therapeutic neck dissection for supraglottic and transglottic SCC is recommended for patients with clinically enlarged lymph nodes, but its necessity in the absence of detectable adenopathy is challenged. © 2004 Wiley Periodicals, Inc. Head Neck26: 309,312, 2004 [source] Human papillomavirus infection and cyclin D1 gene amplification in laryngeal squamous cell carcinoma: Biologic function and clinical significance,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2002Giovanni Almadori MD Abstract Background Human papillomavirus (HPV) infection is suspected to be a risk factor for head and neck, and in particular for laryngeal, carcinogenesis. Cyclin D1 gene (CCND1) overexpression and amplification have been shown to play a role as prognostic factors in many human cancers, among which are head and neck cancers. Methods A literature review of the role in head and neck cancers of HPV infection and CCND1 overexpression and amplification was undertaken. We have evaluated the extent of the current knowledge in this field under the light of recent acquisitions, in particular, about a correlation between HPV infection, a suspected risk factor, and CCND1 amplification, a frequent mutation (about 20% of laryngeal cancers) and a prognostic factor in laryngeal SCC. Results and Discussion The significant correlation between HPV infection and CCND1 amplification supports the hypothesis of the involvement of HPV infection in laryngeal carcinogenesis and suggests that HPV positive laryngeal cancers may constitute a different subset of tumors with a peculiar molecular pattern and thus with a different clinical behavior. HPV infection may be considered a synergistic risk factor with smoking and/or alcohol consumption to be investigated in heavy smokers and drinkers, thus contributing to the identification of patient at high-risk for the development of laryngeal cancer who should undergo strict follow-up and primary and secondary prevention. © 2002 Wiley Periodicals, Inc. Head Neck 24: 597,604, 2002 [source] Prognostic significance of Bcl-2 and p53 expression in advanced laryngeal squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2001Michael Friedman MD Abstract Background Proteins regulating the cell cycle and cell death are frequently abnormally expressed in cancer. Several of these, particularly p53 and Bcl-2, have been widely suggested as possible prognostic markers in diverse human malignancies. Their role in predicting outcome in squamous cell carcinomas of the head and neck is unclear and may depend on the location, stage, and treatment of the tumor. Methods To assess this question specifically for advanced squamous cell carcinoma of the larynx, we studied 69 patients with stage III or IV tumors, all but 6 of whom were treated with surgery plus postoperative irradiation by a single physician. We studied the patients retrospectively to test the association between expression of Bcl-2 and p53, as assessed by immunohistochemistry, with treatment outcome and survival. Results Twenty of the 69 patients died from their tumor (poor outcome); the rest were alive and tumor free at the last follow-up or died of unrelated causes without clinical tumor recurrence (good outcome). Fourteen tumors had detectable Bcl-2 expression, including 8 scored as overexpressors. Thirty-nine tumors overexpressed p53. Expression of neither Bcl-2 nor p53 was associated with outcome, overall survival, or disease-free survival. Only tumor stage was significantly associated with outcome and disease-free survival. Conclusion These data indicate that assessing expression of p53 or Bcl-2 is unlikely to be prognostically useful for surgically treated advanced laryngeal carcinoma. © 2001 John Wiley & Sons, Inc. Head Neck 23: 280,285, 2001. [source] Annexin A1 subcellular expression in laryngeal squamous cell carcinomaHISTOPATHOLOGY, Issue 6 2008V A F Alves Aims:, Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. Methods and results:, Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. Conclusions:, ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases. [source] Leptomeningeal carcinomatosis from squamous cell carcinoma of the supraglottic larynxJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2003Stephen R Thompson Summary Leptomeningeal carcinomatosis is an uncommon but devastating form of metastatic spread. To our knowledge, only 16 cases originating from a head and neck cancer have been reported. We describe the first case of a patient with leptomeningeal carcinomatosis arising from a laryngeal squamous cell carcinoma. Shortly after completing treatment for an advanced supraglottic laryngeal cancer, this 63-year-old man presented with lower limb neurological symptoms and signs. Radiological and cytological evidence of leptomeningeal carcinomatosis of the distal spinal canal was identified. He was treated with intrathecal methotrexate and palliative radiotherapy. Although his pain improved, his lower limb weakness worsened. He died 3 weeks after completing radiotherapy. Presumed mode of spread was via the haematogenous route. The natural history and management of leptomeningeal carcinomatosis are discussed. Clinicians should be aware of the uncommon possibility of leptomeningeal carcinomatosis in a patient presenting with an appropriate constellation of symptoms and signs, and a past history of cancer. [source] Association between human papillomavirus infection and laryngeal squamous cell carcinomaJOURNAL OF MEDICAL VIROLOGY, Issue 6 2010Kamal Morshed Abstract The aim of this study was to compare the prevalence of human papillomavirus (HPV) infection in laryngeal squamous cell carcinoma using two methods: PCR-DNA enzyme immunoassay (PCR/DEIA) and immunohistochemistry (IHC) for detection of HPV in specimens of laryngeal squamous cell carcinoma and to correlate the presence of HPV with the epidemiological and clinicopathological features of recurrence and survival. HPV DNA was amplified from 93 paraffin-embedded laryngeal squamous cell carcinoma tissue specimens by the short PCR fragment (SPF 10) primer set using PCR/DNA method. HPV detection using monoclonal anti-human papilloma virus antibodies Clone K1H8 for IHC reaction was performed on 130 specimens. HPV was identified in 35.5% of patients with laryngeal squamous cell carcinoma using PCR/DEIA and 27.7% using IHC. There was no statistically significant association between the presence of HPV and the epidemiological and clinicopathological features and recurrence. There was no statistically significant association between the presence of HPV and overall survival nor disease specific survival. Statistically significant correlation between HPV detection using PCR/DEIA technique and IHC technique was found. The presence of HPV infection in 27.7% and 38.9% of the patients suggests a possible role in the etiology of laryngeal squamous cell carcinoma. The SPF10 PCR/DEIA technique is the most accurate method for detection of HPV in laryngeal squamous cell carcinoma. J. Med. Virol. 82:1017,1023, 2010. © 2010 Wiley-Liss, Inc. [source] Soluble Fas (sFas) and soluble Fas ligand (sFas-L) balance in laryngeal carcinoma before and after surgical treatmentJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2003Lorenzo Pignataro MD Abstract Background and Objectives Fas and its specific ligand (Fas-L), both of which are involved in apoptosis, exist in membrane-bound and soluble forms. The soluble forms (sFas and sFas-L) have been observed in various tumours, but their clinical significance has not yet been clarified. The aim of this study was to assess serum sFas and sFas-L levels in patients with laryngeal squamous cell carcinoma (LSCC) and their possible correlations with surgical treatment. Methods Serum sFas and sFas-L levels were determined by ELISA in samples taken from 26 LSCC patients on the day before surgery (T0), and 2 weeks (T1) and 6 months after surgery (T2), and in samples taken from 35 healthy volunteers. Results The mean serum sFas levels in the 35 healthy volunteers and the 26 LSCC patients at T0 were respectively 5941,±,411 pg/ml and 6290,±,652 pg/ml (P,=,0.63), and the mean serum sFas-L levels were 0.1,±,0.05 ng/ml and 2.95,±,0.8 ng/ml (P,<,0.0001). After surgery, there was a statistically significant decrease in sFas at both T1 (P,<,0.05) and T2 (P,<,0.01), and in sFas-L at T2 (P,<,0.01). Conclusions The decrease in sFas and sFas-L levels after surgery suggest that they may be produced by or closely linked to tumour cells. Larger prospective clinical studies of patients with LSCC will be needed to establish the clinical significance of sFas and sFas-L, as reported for other neoplasms. J. Surg. Oncol. 2003;83:112,115. © 2003 Wiley-Liss, Inc. [source] The Effect of treatment on survival in patients with advanced laryngeal carcinoma,THE LARYNGOSCOPE, Issue 7 2009Christine G. Gourin MD Abstract Objectives/Hypothesis: Over the last 2 decades, survival from laryngeal cancer has decreased. We sought to identify factors associated with decreased survival in laryngeal cancer. Methods: Patients diagnosed with laryngeal squamous cell carcinoma from 1985 to 2002 were retrospectively reviewed. Results: A total of 451 patients met study criteria. Five-year survival rates were 85% for stage I, 77% for stage II, 51% for stage III, and 35% for stage IV disease. Survival for patients with stage I,III disease was similar for patients treated operatively or nonoperatively (P = .4). However, patients with stage III disease treated nonoperatively had worse survival with radiation alone (XRT) compared to chemoradiation (CR) (P = .006). Patients with stage IV disease had significantly better survival with surgery (49%) than CR (21%) or XRT alone (14%) (P < .0001). Analysis by primary tumor stage demonstrated that survival for T1,T3 disease was independent of treatment modality (P = .2); however, for T4 patients, operative treatment was associated with significantly better survival (55%) than CR (25%) or XRT (0%) (P < .0001). Proportional hazards models confirmed significantly worse survival for stage IV, T4, N2 or N3 disease, and nonoperative treatment. For T4 disease, after controlling for nodal status, nonoperative treatment was the only significant predictor of worse survival. Conclusions: Primary surgical treatment is associated with improved survival for patients with stage IV disease and specifically T4 primary tumors. These data suggest that the observed national decrease in survival from laryngeal cancer may be due to a shift toward nonoperative treatment in that subset of patients with advanced primary disease. Laryngoscope, 2009 [source] Activation of Signal Transducers and Activators of Transcription 3 and Overexpression of its Target Gene CyclinD1 in Laryngeal Carcinomas,THE LARYNGOSCOPE, Issue 11 2008Bin Liu MD Abstract Objectives/Hypothesis: Constitutive activation of signal transducers and activators of transcription (STAT) 3 has been observed in many solid tumors including head and neck squamous cell carcinoma. Expression and activation of STAT3 in laryngeal carcinoma have not been fully understood. The study aims to investigate the expression and activation of STAT3 in laryngeal carcinoma, the relationship between activated STAT3 and its downstream target gene CyclinD1 and the related clinicopathological factors of activated STAT3. Study Design: Prospective. Methods: Sixty-four samples of laryngeal squamous cell carcinoma and 12 samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and reverse transcriptase-polymerase chain reaction. Statistical analysis was performed using SPSS. Results: The overexpression of both STAT3 and CyclinD1 mRNA was observed in all samples of laryngeal squamous cell carcinoma. The mRNA levels of STAT3 and CyclinD1 in carcinoma tissue were 2.1- and 2.3-fold higher than those in control mucosa, respectively; the differences were statistically significant (P < .01). The overexpression of STAT3, p-STAT3, and CyclinD1 protein was also observed in all tumor samples. The protein levels of STAT3, p-STAT3, and CyclinD1 in carcinoma tissue were 1.6-, 4.5-, and 2.0-fold higher than those in control mucosa respectively; the differences were statistically significant (P < .01). There was a positive correlation between p-STAT3 protein and CyclinD1 mRNA (Pearson correlation coefficient = 0.827, P < .01). There were significant correlations between the overexpression of p-STAT3 protein and clinical T stage (P < .01), and tumor size (P < .05). The p-STAT3 protein level of patients in T1, T2 was higher than that of patients in T3, T4. The p-STAT3 protein level of patients with tumor size within 20 mm was higher than that of patients with tumor size more than 20 mm. Conclusions: High expression and activation of STAT3 exist in laryngeal carcinomas. Activated STAT3 may take effect on promoting transcription of its downstream target gene CyclinD1. The role of activation of STAT3 in laryngeal carcinogenesis needs further research. [source] Laryngeal Cancer in the United States: Changes in Demographics, Patterns of Care, and SurvivalTHE LARYNGOSCOPE, Issue S111 2006FACS, Henry T. Hoffman MD Abstract Background: Survival has decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this same period, there has been an increase in the nonsurgical treatment of laryngeal cancer. Objective: The objectives of this study were to identify trends in the demographics, management, and outcome of laryngeal cancer in the United States and to analyze factors contributing to the decreased survival. Study Design: The authors conducted a retrospective, longitudinal study of laryngeal cancer cases. Methods: Review of the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985 and 2001. Analysis of these case records addressed demographics, management, and survival for cases grouped according to stage, site, and specific TNM classifications. Results: This review of data from the NCDB analysis confirms the previously identified trend toward decreasing survival among patients with laryngeal cancer from the mid-1980s to mid-1990s. Patterns of initial management across this same period indicated an increase in the use of chemoradiation with a decrease in the use of surgery despite an increase in the use of endoscopic resection. The most notable decline in the 5-year relative survival between the 1985 to 1990 period and the 1994 to 1996 period occurred among advanced-stage glottic cancer, early-stage supraglottic cancers, and supraglottic cancers classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in the 1994 to 1996 period resulted in poor 5-year relative survival for those receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when compared with that of patients after surgery with irradiation (65.2%) and surgery alone (63.3%). In contrast, identical 5-year relative survival (65.6%) rates were observed during this same period for the subset of T3N0M0 glottic cancers initially treated with either chemoradiation or surgery with irradiation. Conclusions: The decreased survival recorded for patients with laryngeal cancer in the mid-1990s may be related to changes in patterns of management. Future studies are warranted to further evaluate these associations. [source] Aberrant EGFR and Chromosome 7 Associate with Outcome in Laryngeal Cancer,THE LARYNGOSCOPE, Issue 7 2005Larry E. Morrison PhD Objectives/Hypothesis: Epidermal growth factor receptor (EGFR) over-expression has been reported as a prognostic indicator in laryngeal cancer; however, the association with disease outcome has been inconsistent among studies. Here, we use fluorescence in situ hybridization (FISH) in addition to immunohistochemistry to assess laryngeal squamous cell carcinoma (SCC) to determine whether FISH can better predict patient outcome. Study Design: Retrospective study on 59 patients presenting with advanced disease. Methods:EGFR and chromosome 7 genomic statuses were measured using FISH, and EGFR expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded specimens and correlated with outcome in the 59 patients. Results: EGFR expression was marginally associated with outcome, whereas both EGFR and chromosome 7 FISH status were significantly associated with outcome, and the combination of EGFR and chromosome 7 FISH status provided the strongest association of any two combined parameters (P = .0004). Combining EGFR expression with EGFR and chromosome 7 FISH status provided further improvement (P > .0001). Conclusions: Measurements of EGFR and chromosome 7 FISH status, and to a lesser extent EGFR expression, have potential value in treatment planning for patients with laryngeal SCC. [source] The Expression of Proto-Oncogene eIF4E in Laryngeal Squamous Cell Carcinoma,THE LARYNGOSCOPE, Issue 7 2003Zhou Liang MD Abstract Objectives/Hypothesis The translation initiation factor eukaryotic initiation factor 4E (eIF4E) binds to the cap of messenger RNA in the first step of messenger RNA recruitment. Overexpression of eIF4E results in the upregulation of specific angiogenic factor basic fibroblast growth factor (bFGF). The study aims to demonstrate that the overexpression of eIF4E could facilitate recognizing initiation start sites for the translation of bFGF and play an important role in the tumorigenesis of laryngeal squamous cell carcinoma. Study Design Retrospective. Methods Paraffin-embedded sections of 37 samples of laryngeal squamous cell carcinoma, 10 samples of vocal cords polyps, and 20 fresh samples of laryngeal squamous cell carcinoma were analyzed using immunohistochemical streptavidin peroxidase technique, Western blot analysis, and reverse transcriptase,polymerase chain reaction. Results The overexpression of eIF4E was observed in all 37 paraffin-embedded samples of laryngeal squamous cell carcinoma, whereas no staining was noticed in vocal cords polyps samples. There were significant correlations between the overexpression of protein eIF4E and TN stages, histological grades, local recurrence, and the states of metastasis (P <.01). Moreover, the overexpressions of both bFGF protein and bFGF messenger RNA correlated with the histological grades and the states of metastasis (P <.01), but the overexpression of eIF4E and bFGF did not correlate with age, sex, and tumor sites (P >.05). Conclusions Eukaryotic initiation factor 4E can enhance the expression of bFGF at translation level. The eIF4E and bFGF collaborate in tumorigenesis, development, invasion, and metastasis of laryngeal squamous cell carcinoma, in view of which the former can be considered as a tumor molecular marker and an independent prognostic molecular marker of laryngeal squamous cell carcinoma. [source] Prognostic Significance of p53/bcl-2 Co-expression in Patients With Laryngeal Squamous Cell CarcinomaTHE LARYNGOSCOPE, Issue 8 2000Martin C. Jäckel MD Abstract Objective The p53, bcl-2, and bax genes are known to be involved in control of cell cycle progression and regulation of apoptotic cell death. Although they are frequently altered in laryngeal squamous cell carcinoma, their clinical relevance is not yet fully understood. In the present study, individual and combined expressions of these genes were related with patient survival as well as with proliferative and apoptotic activity. Design Retrospective study. Methods Paraffin-embedded tissue sections of 88 laryngeal squamous cell carcinomas that were diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. Apoptotic cells were visualized using the nick end labeling method. To assess proliferative activity of tumors, mitotic indices were determined. Results Age of patients, advanced disease (stages III and IV), high mitotic activity, positive bcl-2 expression, high level of p53 expression, and p53/bcl-2 co-expression were significantly associated with shortened overall survival in univariate analysis. In multivariate analysis, only age and p53/bcl-2 co-expression had independent prognostic value. Other combinations of genes, i.e., bcl-2-to-bax and p53-to-bax ratios, were not associated with patient outcome. A significant positive correlation was found between apoptotic and mitotic activity. However, protein levels of p53, bcl-2, and bax were unrelated to proliferation and apoptosis of tumor cells. Conclusions The co-expression of p53/bcl-2 was an independent predictor of patient outcome and had a prognostic value superior to both parameters considered separately. The rate of apoptosis mainly counterbalanced proliferative activity but appeared not to be significantly influenced by p53, bcl-2, and bax. [source] Telomerase Activity Is Upregulated in Laryngeal Squamous Cell Carcinoma,THE LARYNGOSCOPE, Issue 3 2000Aongus J. Curran MB, FRCSI Objective/Hypothesis The immortalizing enzyme telomerase has been linked to carcinogenesis and is being targeted as a novel molecular marker. This study investigated telomerase expression in patients with laryngeal squamous cell carcinoma and correlated telomerase activity with conventional prognostic parameters. Study Design A consecutive series of patients with laryngeal squamous cell carcinoma undergoing surgical salvage for persistent or progressive disease after failed radiation therapy. Methods Twenty patient samples of laryngeal squamous cell carcinoma and 20 adjacent histologically normal mucosal samples were assayed using the telomeric repeat amplification protocol (TRAP) method for detection of telomerase activity. The leukemic cell line, K562, acted as a positive control and the human fibroblast line, Hs21Fs, as a negative control. A sample was classified as telomerase positive when an RNase-sensitive hexameric repeat ladder was observed. Absence of laddering was considered a negative result. Results Seventeen of 20 (85%) tumor samples and 4 of 20 (20%) adjacent histologically normal samples were telomerase positive. No statistically significant difference was observed when densitometric readings were compared by T category, tumor grade, or site (by ANOVA). Conclusions Although telomerase activity is present in laryngeal cancer, levels of activation do not correlate with conventional parameters used for prognostication. Our study indicates that the marker may be a useful adjunctive method in the diagnosis of malignancy after radiation failure. [source] Mutant p53 and cyclin A1 protein expression in primary laryngeal squamous cell carcinomas do not correlate to second primary tumours of the head and neck,ANZ JOURNAL OF SURGERY, Issue 1-2 2009Ross D. Farhadieh Abstract Background:, Field cancerization is a feature of head and neck squamous cell carcinoma. No biological marker in the index tumour has been correlated to the development of second primary tumours (SPT). Cyclin A1 is a cell cycle regulator and a downstream target of p53. This study assessed predictive correlation of cyclin A1 and mut-p53 with clinicopathological parameters and occurrence of (SPT) 7in the head and neck. Methods:, Using immunohistochemistry 106 patients treated for primary laryngeal squamous cell carcinoma were investigated for expression of cyclin A1 and mut-p53. Results:, Expression of cyclin A1 and mut-p53 were noted in 83 of 106 (78.3%) and 25 of 106 (23.6%) patients. There was a weak but significant correlation between mut-p53 and cyclin A1 (r = 0.301, P = 0.002) expression. During the follow-up period (median 41.0 months (range 1,205 months)), 21 of 106 (19.8%) patients developed an SPT. There was no statistically significant correlation between the markers investigated and disease recurrence, SPT diagnosis or clinicopathological parameters. Conclusion:, Second primary tumours are an intriguing problem in treatment of HNSCC and a predictive marker identifying those greatest at risk would be a leap forward. [source] Validation of the composite laryngeal recurrence staging systemCANCER, Issue 4 2004Peter D. Lacy M.D. Abstract BACKGROUND The Composite Laryngeal Recurrence Staging System (CLRSS) has been described recently as an improved alternative to the retreatment TNM system (rTNM) for staging patients with recurrent laryngeal squamous cell carcinoma. The objectives of this study were to validate the CLRSS and compare its use with the rTNM system. METHODS A retrospective chart review was conducted of 67 patients with recurrent laryngeal squamous cell carcinoma who had their initial treatment between 1980 and 1992. The external validity of the CLRSS was assessed, and its ability to stage patients and to predict survival was compared with the rTNM system. RESULTS The overall 2-year survival rate was 51% (34 of 67 patients). The rTNM system was unable to stage 12 patients (18%), whereas all patients could be staged using the CLRSS. The CLRSS predicted survival better than the rTNM system (c-statistic = 0.79). CONCLUSIONS The newer CLRSS staging system for recurrent laryngeal carcinoma outperformed the rTNM system in its ability to stage more patients and to predict survival. Cancer 2004. © 2004 American Cancer Society. [source] A systematic review of case,control studies of human papillomavirus infection in laryngeal squamous cell carcinomaCLINICAL OTOLARYNGOLOGY, Issue 4 2004L. Rees A role for human papillomavirus (HPV) has been suggested in laryngeal squamous cell carcinoma (LSCC). In order to quantitate the available evidence, we reviewed studies examining the risk of laryngeal cancer-associated HPV. PubMed was searched for case,control studies conducted worldwide and published in any language since 1966. Relevant papers were hand-searched and cross-referenced. Six studies met the inclusion criteria. The studies are heterogeneous in the methods used to harvest tissue samples and techniques for detecting the virus within the tissue. HPV-16 positivity among cases ranged from 2.7% to 46.9% and 0,5.7% among controls. Two studies showed a significantly increased risk of LSCC if HPV-16 was present (OR 18.5, 95% CI 2.2,154.8, OR 2.6, 95% CI 1.1,6.0). An increased risk was also observed for glottic versus supraglottic cancer in one study (OR 9.69, 95% CI 1.47,64.04). The direction of effect is towards an increase in risk of LSCC in people with evidence of HPV-16 infection. There is marked heterogeneity in the methods used to detect the virus and frequency with which it is detected. An adequately powered study using a reliable detection technique is required to confirm and quantify this risk and to examine effect modification. [source] Annexin A1 subcellular expression in laryngeal squamous cell carcinomaHISTOPATHOLOGY, Issue 6 2008V A F Alves Aims:, Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. Methods and results:, Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. Conclusions:, ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases. [source] Frequent high telomerase reverse transcriptase expression in primary oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2007Kolja Freier Background:, Gene copy number gain of chromosomal arm 5p is frequently found in oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes. TERT is a candidate gene encoding for human telomerase reverse transcriptase (hTERT). The aim of the present study was to elucidate the relevance of TERT copy number gain and high hTERT expression in OSCC. Methods:, Fluorescence in situ hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were performed to analyze TERT copy numbers and hTERT expression, respectively, on tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal and laryngeal squamous cell carcinomas (PSCC/LSCC). Results:, Increased hTERT protein expression was more frequently found in OSCC (71.1%, 155/218) than in PSCC/LSCC (36.0%, 35/89) (P < 0.001). By contrast, specific TERT amplifications were less common in OSCC (2.1%, 4/191) compared with PSCC/LSCC (9.9%, 8/81) (P = 0.047). Conclusions:, High hTERT expression is a frequent finding in OSCC. It might be a promising target for the development of specific anti-neoplastic therapy approaches. [source] The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neckJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2000Karin Nylander Abstract: Despite intense research, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (SCCHN) is still low. Several different factors have been studied in the search for one or more factors that give important prognostic information at the time of diagnosis. Many recent studies have focused on the TP53 tumour suppressor gene, analysing its gene status and protein status. When looking at p53 protein expression, using immunohistochemistry, no correlation to patient outcome has been seen for the whole group of SCCHN. However, a significant association between p53 expression and poor patient outcome was found when looking only at patients with laryngeal squamous cell carcinomas. Also, in oral premalignant lesions, expression of p53-positive cells in the suprabasal layers of the epithelium has been seen as an indication of impending malignant development. Concerning the prognostic significance of mutations in the TP53 gene, results differ. But when restricting analysis to tumours with mutations causing an obvious change in protein, TP53 mutation was found to be a strong and independent variable for prognosticating survival. This review article gives an up-to-date overview of the p53 molecule and evaluates its possible prognostic role in SCCHN. Today it is clear that the p53 pathway is very important in SCCHN biology and potentially in its treatment. The function and importance of a few other cell cycle proteins connected to p53 are also discussed. [source] Prognostic Significance of p53/bcl-2 Co-expression in Patients With Laryngeal Squamous Cell CarcinomaTHE LARYNGOSCOPE, Issue 8 2000Martin C. Jäckel MD Abstract Objective The p53, bcl-2, and bax genes are known to be involved in control of cell cycle progression and regulation of apoptotic cell death. Although they are frequently altered in laryngeal squamous cell carcinoma, their clinical relevance is not yet fully understood. In the present study, individual and combined expressions of these genes were related with patient survival as well as with proliferative and apoptotic activity. Design Retrospective study. Methods Paraffin-embedded tissue sections of 88 laryngeal squamous cell carcinomas that were diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. Apoptotic cells were visualized using the nick end labeling method. To assess proliferative activity of tumors, mitotic indices were determined. Results Age of patients, advanced disease (stages III and IV), high mitotic activity, positive bcl-2 expression, high level of p53 expression, and p53/bcl-2 co-expression were significantly associated with shortened overall survival in univariate analysis. In multivariate analysis, only age and p53/bcl-2 co-expression had independent prognostic value. Other combinations of genes, i.e., bcl-2-to-bax and p53-to-bax ratios, were not associated with patient outcome. A significant positive correlation was found between apoptotic and mitotic activity. However, protein levels of p53, bcl-2, and bax were unrelated to proliferation and apoptosis of tumor cells. Conclusions The co-expression of p53/bcl-2 was an independent predictor of patient outcome and had a prognostic value superior to both parameters considered separately. The rate of apoptosis mainly counterbalanced proliferative activity but appeared not to be significantly influenced by p53, bcl-2, and bax. [source] Prevalence of Herpes Simplex Virus in Malignant Laryngeal Lesions,THE LARYNGOSCOPE, Issue 2 2000Anna M. Pou MD Abstract Objective: To determine the prevalence of herpes simplex virus (HSV) in malignant laryngeal lesions. Study Design: Retrospective review. Materials and Methods: Paraffin-embedded, histologically confirmed specimens containing benign laryngeal lesions, squamous cell carcinoma of the larynx, and squamous cell carcinoma of the oral cavity were identified from archived surgical specimens. Biopsies of normal-appearing oral cavity tissue were also obtained from fresh-frozen cadavers. These tissues were analyzed for the presence of HSV DNA using polymerase chain reaction techniques. Patient charts were reviewed for patient demographics, risk factors, stage, clinical course, treatment, and outcome. Results: HSV was detected in nine laryngeal squamous cell carcinomas (75%) and in none of the benign laryngeal lesions (P = .0001). HSV was also found in three oral cavity squamous cell carcinomas (25%) and in none of the controls (P = .049). Conclusion: HSV is more prevalent in squamous cell carcinoma of the larynx and oral cavity than in their respective control groups, suggesting a role for carcinogenesis. HSV is more prevalent in squamous cell carcinoma of the larynx than of the oral cavity. Further studies to determine the role of HSV as a cocarcinogen and its interrelationship with other environmental factors in laryngeal cancer are warranted. [source] Mutant p53 and cyclin A1 protein expression in primary laryngeal squamous cell carcinomas do not correlate to second primary tumours of the head and neck,ANZ JOURNAL OF SURGERY, Issue 1-2 2009Ross D. Farhadieh Abstract Background:, Field cancerization is a feature of head and neck squamous cell carcinoma. No biological marker in the index tumour has been correlated to the development of second primary tumours (SPT). Cyclin A1 is a cell cycle regulator and a downstream target of p53. This study assessed predictive correlation of cyclin A1 and mut-p53 with clinicopathological parameters and occurrence of (SPT) 7in the head and neck. Methods:, Using immunohistochemistry 106 patients treated for primary laryngeal squamous cell carcinoma were investigated for expression of cyclin A1 and mut-p53. Results:, Expression of cyclin A1 and mut-p53 were noted in 83 of 106 (78.3%) and 25 of 106 (23.6%) patients. There was a weak but significant correlation between mut-p53 and cyclin A1 (r = 0.301, P = 0.002) expression. During the follow-up period (median 41.0 months (range 1,205 months)), 21 of 106 (19.8%) patients developed an SPT. There was no statistically significant correlation between the markers investigated and disease recurrence, SPT diagnosis or clinicopathological parameters. Conclusion:, Second primary tumours are an intriguing problem in treatment of HNSCC and a predictive marker identifying those greatest at risk would be a leap forward. [source] | |||||||||||||||||||||||||