Metastasis Of Laryngeal Carcinoma Research Articles

Pattern of Neck Node Metastasis in Laryngeal Carcinoma

Background: Cancer continues to be a major health problem despite advances in medical technology for its diagnosis and treatment. Cancer of the larynx is the eleventh most common cancer in the world. Carcinoma larynx is a multifactorial disease. Smoking, betel-nut, betel-leaf chewing habit and drinking alcohol are the most important factors associated with carcinoma larynx.
 Objective: To detect the rate and level of cervical lymph node metastasis in laryngeal carcinoma
 Methods: Detailed information was obtained in each cases according to protocol. Complete history was taken from accompanying attendants. Thorough clinical examination was done. All the information’s were recorded in the fixed protocol. Patients were randomly assigned to one of three groups by card sampling. Collected data were classified, edited, coded and entered into the computer for statistical analysis by using updated computerized program SPSS-19
 Results: Out of 50 cases the mean average age was found 58.5±11.9 years with range from 39 to 78 years. Majority (70.0%) patients presented with supraglottic carcinoma followed by 13(26.0%) glottic carcinoma and 2(4.0%) subglottic carcinoma. More than three fourth (78.0%) patients had difficulty in swallowing followed by 17(34.0%) had hoarseness of voice, 12(24.0%) had discomfort in throat, 10(20.0%) had earache, 6(12.0%) had hemoptysis and 4(8.0%) had cough. Majority (42.0%) patients were found N0 followed by 15(30.0%) N1, 13(26.0%) N2 and 1(2.0%) N3 of neck node. Majority (42.0%) patients was found in stage T3 followed by 7(14.0%) in stage T1, 18(36.0%) in stage T2 and 4(8.0%) in stage T4. Majority (56.0%) patients was found in level-II of neck nodes followed by 12(24.0%) level III, 4(8.0%) level IV, 3(6.0%) level II+III, 2(4.0%) level III+IV and 1(2.0%) level III+IV+V of neck nodes.
 Conclusion: Laryngeal carcinoma is a common clinical entity in otolaryngology practice. Male were more predominant and the highest age group was 51-60 years. In our study most common Laryngeal carcinoma was supraglottic in nature. T3 was the commonest stage of involvement. Common clinical presentation was difficulty in swallowing and hoarseness of voice. N 0 and N1 was the most common pattern of neck node metastasis. In our series majority of them were in level II
 Bangladesh J of Otorhinolaryngology; October 2018; 24(2): 115-124

Pepsin promotes IL-8 signaling-induced epithelial\u2013mesenchymal transition in laryngeal carcinoma

BackgroundLaryngopharyngeal reflux (LPR), with its increasing morbidity, is attracting considerable attention. In recent years, the causal role between LPR and laryngeal carcinoma has been debated. The main harmful component of LPR is pepsin, which has been shown to induce mucosal inflammation by damaging the mucous membrane. Thus, pepsin is linked to an increased risk of laryngeal carcinoma, although the potential mechanism remains largely unknown.MethodsThe human laryngeal carcinoma cell lines Hep-2 and Tu212 were exposed to different pepsin concentrations and the morphology, proliferation, migration, secretion of inflammatory cytokines, and epithelial–mesenchymal transition (EMT) of the cells were assessed. To evaluate whether interleukin-8 (IL-8) had a causal relationship with pepsin and EMT, an IL-8 inhibitor was used to suppress IL-8 secretion during pepsin exposure and the expression of EMT markers, cell proliferation, and migration were analyzed.ResultsPepsin promoted proliferation, colony formation, migration, and IL-8 secretion of Hep-2 and Tu212 cells in vitro. Furthermore, increased pepsin concentrations changed the morphology of Hep-2 and Tu212 cells; levels of the epithelial marker E-cadherin were reduced and those of mesenchymal markers vimentin and β-catenin and the transcription factors snail and slug were elevated. A similar effect was observed in laryngeal carcinoma tissues using immunohistochemistry. IL-8 level was reduced and EMT was restored when pepsin was inhibited by pepstatin. EMT was weakened after exposure to the IL-8 inhibitor, with significant reduction in pepsin-induced cell proliferation and migration.ConclusionsPepsin may induce EMT in laryngeal carcinoma through the IL-8 signaling pathway, which indicates that it has potential role in enhancing cell proliferation and metastasis of laryngeal carcinoma.

The effects of β-elemene on rabbit VX2 laryngeal carcinoma and factors associated with tumor growth and metastasis

To investigate the inhibition effect of β-elemene on the growth and metastasis of laryngeal carcinoma and the underlying mechanism. Sixty-six rabbits were vaccinated with suspension of VX2 cancer tissues to establish a rabbit laryngeal carcinoma model and then they were randomly treated with the injection of 0.9% sodium chloride solution (as a control), cisplatin, or β-elemene from the seventh day after vaccination. The rabbits were sacrificed three weeks after vaccination. The laryngeal tumor was dissected. and the volume of tumor and the inhibitory rate of tumor growth were measured. The expressions of PCNA (proliferation cell nuclear antigen), Bcl-2 (B-cell lymphoma-2) and VEGF-D (vascular endothelial growth factor D) in tumor were semiquantitatively examined by immunohistochemistry. The inhibition rates of tumor growth in β-elemene-treated group and the cisplatin-treated group were 48.5% and 51.4%, respectively. The expressions of Bcl-2 in β-elemene-treated group and cisplatin-treated group were significantly lower than the control (P<0.05), but with no significant difference between β-elemene-treated group and cisplatin-treated group. The expression of PCNA in β-elemene-treated group was significantly decreased compared to control group (P<0.05). The expression of VEGF-D in β-elemene-treated group was lower than that in control group or the cisplatin-treated group (P<0.05). β-elemene can inhibit the growth of rabbit VX2 laryngeal tumor, which may be associated with the inhibition of factors related to tumor growth and metastasis.

Neuromedin U expression related to the occurrence of laryngeal carcinoma and the regional lymph node metastasis

Objective:Research Institute of OtolaryngologyHead and Neck Surgery, Renmin Hospital of Wuhan University Neuromedin U(NMU) plays important role in immune regulation in a variety of tissues and organs, and this study intends to explore the correlation between the local metastasis of laryngeal cancer and the expression of NMU.Method:A retrospective analysis was made on 240 cases of laryngeal carcinoma in our hospital. The expression of NMU was detected by immunohistochemistry. Microassay tissue(TMA) was used to further analyze the correlation of NMU protein expression with T, N and M stage in laryngeal carcinoma.Result:Cervical lymph node metastasis was present in 51.4% of 240 laryngeal carcinoma patients. The expression of NMU was significantly higher in the patients with local metastasis than those without metastasis. And along with tumor progression, NMU expression increased significantly.Conclusion:The expression of NMU in laryngeal carcinoma was significantly correlated with the metastasis of laryngeal carcinoma and TNM stage, which indicated that NMU may be involved in the development of laryngeal carcinoma metastasis.

Hypoxia promotes the invasion and metastasis of laryngeal cancer cells via EMT.

The purpose of this study is to explore the role of hypoxia on the invasion and metastasis of laryngeal carcinoma. The invasion and migration ability of laryngeal cancer SCC10A cell was detected by transwell assay. Western blot was applied to analyze the expression of EMT-related proteins. Fifty-seven samples from postoperative patients with laryngeal cancer were collected to study. Immunohistochemistry was used to examine the expression of GLUT-1 and EMT-related proteins (Vim, E-cad, N-cad) in normal laryngeal squamous epithelial tissue, laryngeal cancer adjacent tissues and laryngeal squamous cell carcinoma tissues. Hypoxia promoted laryngeal cancer cell invasion and migration. Hypoxia also enhanced the expression of GLUT-1, vimentin and N-cad, which exist statistically significant correlation with the clinical staging and lymph node metastases (P<0.05). The expression of GLUT-1 is positively correlated with Vim and N-cad expression in laryngeal squamous cell carcinoma tissues, but negatively correlated with E-cad expression. The patient survival rate with the positive expression of GLUT-1, Vim and N-cad becomes much shorter compared with those with negative expression of GLUT-1, Vim and N-cad (P<0.05). Hypoxia promoted laryngeal cancer cell invasion and migration via EMT.

Quantitative Proteomics Approach to Screening of Potential Diagnostic and Therapeutic Targets for Laryngeal Carcinoma

To discover candidate biomarkers for diagnosis and detection of human laryngeal carcinoma and explore possible mechanisms of this cancer carcinogenesis, two-dimensional strong cation-exchange/reversed-phase nano-scale liquid chromatography/mass spectrometry analysis was used to identify differentially expressed proteins between the laryngeal carcinoma tissue and the adjacent normal tissue. As a result, 281 proteins with significant difference in expression were identified, and four differential proteins, Profilin-1 (PFN1), Nucleolin (NCL), Cytosolic non-specific dipeptidase (CNDP2) and Mimecan (OGN) with different subcellular localization were selectively validated. Semiquantitative RT-PCR and Western blotting were performed to detect the expression of the four proteins employing a large collection of human laryngeal carcinoma tissues, and the results validated the differentially expressed proteins identified by the proteomics. Furthermore, we knocked down PFN1 in immortalized human laryngeal squamous cell line Hep-2 cells and then the proliferation and metastasis of these transfected cells were measured. The results showed that PFN1 silencing inhibited the proliferation and affected the migration ability of Hep-2 cells, providing some new insights into the pathogenesis of PFN1 in laryngeal carcinoma. Altogether, our present data first time show that PFN1, NCL, CNDP2 and OGN are novel potential biomarkers for diagnosis and therapeutic targets for laryngeal carcinoma, and PFN1 is involved in the metastasis of laryngeal carcinoma.

Identification of a differential expression signature associated with tumorigenesis and metastasis of laryngeal carcinoma

ObjectivesMetastasis is the most significant prognostic factor for laryngeal carcinoma which necessitates the identification of molecular alterations associated with metastasis. The identification of such molecular alterations will not only prove useful in treatment but also provide insight into mechanisms of cancer metastasis. The studies conducted so far have not specifically focused on metastasis or invasion pathways. Therefore we investigated the expression profiles with a pathway focused approach. Materials and methodsTotal RNA was extracted from 36 laryngeal tumors and paired cancer free tissue. Expression levels of 88 genes were determined using a PCR array system following cDNA synthesis. Obtained data was used for the calculation of altered expression levels, facilitating relevant algorithms. Significant alterations were determined according to their p-value obtained by Student's t-test. ResultsSixteen genes have shown altered expression when compared with adjacent cancer-free tissue. 2 of these 16 genes have shown differential expression in tumors with neck metastasis in respect to non-metastatic tumors. ConclusionWe found that TGFB1, TIMP1, c-Myc, SPARC, COL4A2 and SOX4 show altered expression in laryngeal tumors. c-Myc and SOX4 expression is decreased as laryngeal tumors switch to metastatic phenotype.

The utility of elastography and CEUS for the differentiation between benign and malignant cervical lymphadenopaty. Three cases report

The differentiation between benign and malignant cervical lymph nodes is a frequent challenge for the clinician. We present the cases of three patients with cervical lymphadenopathy (inflammatory lymph node, lymphoma, and metastasis of laryngeal carcinoma) in which the use of elastography and contrast enhanced ultrasonography had substantial contribution to the correct final diagnosis.

Laryngeal carcinoma metastasis to the orbit: case report

We present the first report in the all English literature of a case of laryngeal squamous cell carcinoma metastasis to the orbit. Case report of orbital metastasis from laryngeal carcinoma; clinical, radiological and pathological findings are discussed. A 75-year-old man presented to the ENT department with a five-week history of left orbital pain, swelling and reduced vision. Past medical history included laryngectomy, bilateral neck dissection and post-operative radiotherapy for T4 N2c M0 squamous cell carcinoma of the supraglottis, 10 months earlier. Imaging showed an orbital mass extending along the roof and lateral aspect of the orbit into the optic canal and superior orbital fissure, and further posteriorly into the left cavernous sinus with meningeal enhancement in the left anterior cranial fossa. Histopathological analysis after biopsy showed the mass to be consistent with metastatic poorly differentiated squamous cell carcinoma. After searching the all English literature, we report what is, to our best knowledge, the first case of laryngeal carcinoma metastasis to the orbit. Despite its rarity and poor prognosis, such a metastasis should be considered as part of the differential diagnosis of an orbital mass, as timely recognition can improve the patient's quality of life.

The Relationship between the Extracellular Matrix and the Angiogenesis and Metastasis of Laryngeal Carcinoma

Aims: We studied the relationships between the growth, metastasis and angiogenesis of laryngeal carcinoma and extracellular matrix protein-1 (ECM1) and hyaluronan (HA). Methods: Thirty-three cases of benign and malignant laryngeal tumors were included. Using immunohistochemical staining, we examined the expression of ECM1 and HA in tumors and metastatic lymph nodes and correlated it with counts of microvessel density. Results: The expression of ECM1 (p = 0.004) and HA (p = 0.036) was significantly different between benign and malignant tumors. The expression of ECM1 was strongly associated with microvessel density (Spearman’s ρ = 0.513, p = 0.017), with the strongest expression present within caner nests. With respect to HA, expression was significantly associated with more advanced clinical TNM stage (Spearman’s ρ = 0.521, p = 0.015). The link was stronger in cases where metastasis or recurrence occurred than in those without complication (p = 0.014). No significant relationship was found between ECM1 and HA expression among malignant samples (Spearman’s ρ = 0.383, p = 0.087). Conclusions: ECM1 has a high association with the growth, metastasis and angiogenesis of laryngeal carcinoma. An increased level of HA expression was related to the process of laryngeal carcinogenesis. Specifically, carcinoma cells with high levels of HA secretion had a higher potential for metastasis. No significant relative expression of ECM1 and HA was found.

Study of the SH3-domain GRB2-like 2 gene expression in laryngeal carcinoma

Laryngeal carcinoma is a common malignant tumor of the upper respiratory tract, and in 95% of cases the tumor is laryngeal squamous cell carcinoma (LSCC). The abnormity of SH3-domain GRB2-like 2 (SH3GL2) gene was found in LSCC. In order to clarify the relationship between SH3GL2 gene and LSCC, we evaluated the expression of the SH3GL2 gene in LSCC. Real-time PCR, immunohistochemistry and Western blotting were used to detect the mRNA and protein expression and find the various rules of SH3GL2 gene in LSCC. The result of real-time PCR showed that the expression level of SH3GL2 mRNA in LSCC tissue was apparently down-regulated; immunohistochemical analysis showed that SH3GL2 protein was mainly located in cytoplasm, the rate of positive cells and SH3GL2 protein expression level were fluctuated with the pathological classification of LSCC; the result of Western blotting showed that SH3GL2 protein was down-regulated significantly in LSCC samples, especially in metastatic lymph nodes. These results suggest that SH3GL2 is a LSCC related gene and its expression level is fluctuated with the pathological classification which indicate that SH3GL2 participates in the development and progression of LSCC. And it may be considered as a novel tumor marker to find both a new anti-oncogene and relative factors of invasion and metastasis of laryngeal carcinoma.

Relationship between the expression of CD44v6 and development, progress, invasion and metastasis of laryngeal carcinoma.

The expression of CD44v6 and its relationship with the development, progress, invasion and metastasis of laryngeal carcinoma was investigated. The expression and content of CD44v6 mRNA in tissuess were detected by both RT-PCR and FCM which were respectively extracted from normal laryngeal mucosa, leukoplakia of larynx, laryngeal papilloma, polyp of vocal cord, tissues of laryngeal carcinoma, metastatic and nonmetastatic lymph nodes of neck, and tissues close to carcinoma. The outcome of RT-PCR indicated that the expression rate of CD44v6 mRNA involved in tissues of laryngeal carcinoma and metastatic lymph nodes of neck was the highest (90%-100%) compared with that of leukoplakia of larynx, laryngeal papilloma, tissues close to carcinoma by 0.5 cm (55.56%-60.00%) and that of normal laryngeal mucosa, polyp of vocal cord, nonmetastatic lymph nodes and tissues close to carcinoma by 1.0 cm was the lowest (13.33%-20%). The result from FCM was highly consistent with that from RT-PCR. It was suggested that CD44v6 was closely related with the development, progress, invasion and metastasis of laryngeal carcinoma. The outcome from the tissues close to carcinoma by different distance could do help to the determination of incisal edge in surgery abstractly.

The expression of matrix metalloproteinases in supraglottic carcinoma and its clinical implication for estimating lymph node metastases

Abstract Introduction: There has been no effective method to predict the lymph node metastasis of laryngeal carcinoma so far. The present study attempts to establish an effective molecular pathologic method to detect occult lymph node metastases in supraglottic carcinoma. Methods: Included in this study were thirty-two patients with supraglottic SCC, undergone supraglottic horizontal partial laryngectomy and neck dissection. Matched primary cancer and the corresponding adjacent non-neoplastic tissues were selected to detect the expression of matrix metalloproteinases (MMPs) at protein and mRNA level respectively by immunohistochemical technique and semiquantitative RT-PCR, meanwhile its cervical lymph nodes were examinated by routine histopathology to determine if there were any evidences of node metastasis. Results: In primary cancer tissues, the expression of MMP-1, MMP-2, MMP-7, MMP-8, MMP-9 and MMP-10 at protein level was 37.3%, 62.5%, 59.4%, 18.8%, 62.5% and 25.0% respectively, and at mRNA level was 43.8%, 75.0%, 65.6%, 15.6%, 75.0% and 34.4% respectively. In the corresponding adjacent non-neoplastic tissues, however, only six positive expressions were observed. At protein level one case was MMP-7 and the other MMP-9, and at mRNA level one case was MMP-2, one case MMP-7, and other two MMP-9. Multivariate logistic regression analysis suggested that the positive expressions of MMP-2, MMP-7 and MMP-9 were closely related with the lymph node micrometastasis in supraglottic carcinoma. Conclusions: The expression of MMPs genes is upregulated significantly in supraglottic carcinoma, especially that of MMP-2, MMP-7 and MMP-9. There may be lymph nodes micrometastasis present when any two of the above three MMPs, or all of them, are positively expressed simultaneously.

Microvessel density as a marker of regional metastasis in laryngeal carcinoma

Microvessel density as a marker of regional metastasis in laryngeal carcinoma

Alteration of P53 protein expression and p53 gene in laryngeal carcinoma

To study the prevalence of P53 protein expression and p53 gene mutation in laryngeal carcinoma. Using immunohistochemistry P53 expression was detected in 31 patients with laryngeal carcinoma. In 11 P53 negative patients,microdissection-PCR-HA technique was used to determine mutation in p53 exon 5, 6, 7, 8. Among the 31 patients tested with immunostaining, the overall average positive rate was 64.5%. Positive rates for T3 and T4 tumors were 86.7% vs 43.8% in T1 and T2 tumors.The positive rate was 91.7% in those with cervical node metastasis compared with 47.4% in those without lymph node metastasis. The positive P53 immunostaining was more frequently found in poor differentiated carcinoma (87.5%) and moderate-differentiated carcinoma (66.7%),than in well differentiated carcinoma (45.5%). The abnormal exon 5 or 7 of p53 gene were detected in 2 out of 11 cases, in which P53 was negative. P53 gene mutation is related with TNM grading and cervical lymph node metastasis in laryngeal carcinoma. P53 mutation tents to be correlated to pathologic grading.

An unusual metastatic site of laryngeal carcinoma: scapular muscles

It is well known that in advanced cervical metastatic disease of head and neck squamous cell carcinoma, the incidence of distant metastasis is high. A case of distant metastasis to the scapular muscles from an uncontrolled cervical metastasis of laryngeal carcinoma is presented. Other unusual metastatic sites are reviewed and the possible mechanism of the spread is discussed.

Expression of Membrane type 1-Matrix Metalloproteinase in Laryngeal Carcinoma

Membrane type 1-matrix metalloproteinase (MT1-MMP) is a member of the recently identified unique membrane-type subgroup in the matrix metalloproteinase (MMP) family. MT1-MMP has proteolytic activity against components of the extracellular matrix and activates progelatinase A (MMP-2) at the cell surface. In this study, we analyzed the expression of MT1-MMP mRNA in 45 cases of laryngeal carcinoma by RT-PCR and investigated the relationship between MT1-MMP expression and survival in 18 cases. The result showed that the expression of MT1-MMP mRNA was higher in tumor tissue than in corresponding normal tissue. The tumoral expression in clinical stage III was higher than in stage II. The tumoral expression level of MT1-MMP mRNA in patients with lymph node metastasis was signigicantly higher than those with negative lymph nodes. The patients with high expression level showed significantly poorer 5 year survival than those with low expression level. Collectively, our findings suggest that the high level of MT1-MMP expression is closely related to the invasion and metastasis of laryngeal carcinoma, and indicates poorer prognosis. Copyright 1999 W.B. Saunders Company Ltd on behalf of the Arányi Lajos Foundation