Squamous Cell Carcinoma Of Supraglottic Larynx Research Articles

Treatment discordance in the utilization of neck dissection for stage I-II supraglottic tumors.

In 2018, the National Comprehensive Cancer Network treatment guidelines began recommending the use of neck dissection during surgical management of stage I-II supraglottic laryngeal squamous cell carcinoma (LSCC). Trends and factors associated with the use of neck dissection during larynx-preserving surgery for patients with cT1-2, N0, M0 supraglottic LSCC in the National Cancer Database (2004-2020) were evaluated using multivariable-adjusted logistic regression. Of the 2080 patients who satisfied study eligibility criteria, 633 (30.4%) underwent neck dissection. Between 2018 and 2020, the rate of neck dissection was 39.0% (114/292). After multivariable adjustment, academic facility type, undergoing biopsy prior to surgery, and more radical surgery were significant predictors of receiving neck dissection. The results of this national analysis suggest that the utilization of guideline-concordant neck dissection for management of stage I-II supraglottic LSCC remains low and highlight the need to promote the practice of neck dissection for this patient population.

Reliability and outcomes of lymph nodes biopsy in cT1-cT2 N0 supraglottic laryngeal squamous cell carcinoma.

In oral and oropharyngeal squamous cell carcinoma (SCC), sentinel node biopsy (SNB) was described as a reliable and reproductive alternative to elective neck dissection for the staging of clinical N0 T1-T2 patients. The SNB technique in supraglottic laryngeal SCC was successfully described in small series. The aim of this study is to analyze retrospectively the results of SNB technique in supraglottic SCC in CHU Godinne, to determine if the technique is reliable and may be proposed in a future multicentral prospective trial. The study involved a retrospective analysis of 39 patients who underwent surgery between 2003 and 2019 at CHU Godinne. All patients presented with clinical N0 neck status. The SNB procedure included general anesthesia, 99-technetium colloid peritumoral injection, and lymphoscintigraphy. The hand-held gamma probe was utilized for SNB after tumoral resection during the same operating session. Out of 39 patients, 36 underwent SNB as the sole staging tool, while 3 patients received SNB in combination with elective neck dissection. Primary outcome was the 2-years neck recurrence-free survival (RFS). Secondary outcomes were the 2- and 5-years disease-specific survival (DSS). Additionally, sensitivity and negative predictive value (NPV) of the SNB technique were analyzed. Sentinel nodes were successfully identified in all 39 patients. An average of 4 nodes excised per patient. Positives SN were detected in 23% (9 in 39) cases, leading to subsequent selective neck dissection. Two cases of neck recurrence were observed, both considered as false negatives, occurring after an average of 3.5 months. Th median follow-up period was 48 months with a 2-year RFS of 95%. Sensitivity and NPV of the SNB technique were found to be 82% and 94%, respectively. Two and five years DSS were 84% and 71.7%, respectively. The results suggest that SNB in T1-T2 supraglottic SCC is a feasible and reliable technique for managing the neck in N0 early-stage patients. However, to establish its oncological equivalence with selective node dissection, further prospective and comparative studies are warranted. The findings of this study underscore the importance of ongoing research in refining and validating the role of SNB in the management of supraglottic SCC, potentially paving the way for more widespread adoption in clinical practice.

The minimal number of examined lymph nodes for accurate nodal staging and favorable prognosis in T1-2 supraglottic laryngeal squamous cell carcinoma

ObjectiveThe study aimed to investigate the minimal number of examined lymph nodes (ELNs) for accurate assessment of lymph node status and favorable prognosis in patients with stage T1-2 supraglottic laryngeal squamous cell carcinoma (LSCC) who received radical resection. MethodsPatients with stage T1-2 supraglottic LSCC from the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese Academy of Medical Sciences, Cancer Hospital/National Cancer Center (NCC) were reviewed. The association of the ELN count with the identification of nodal metastasis and overall survival (OS) was analyzed using a multivariate regression model. Locally weighted scatterplot smoothing fitting curve and the ‘changepoint’ package were adopted to identify the optimal cut points using R. ResultsA total of 429 patients from the SEER database and 53 patients from NCC were enrolled. The probability of identifying nodal metastasis was positively related to the ELN count. For patients diagnosed with pathological stage N0 (pN0) disease, the mortality risks rapidly decreased when the amount of ELNs exceeded ten, and those with ELNs >10 had better OS. ConclusionAn adequate amount of ELNs benefits precise nodal staging in patients with stage T1-2 supraglottic LSCC. Ten lymph nodes are the minimum number of ELNs. For pN0 patients, an ELN count ≤10 is an unfavorable prognostic factor.

Treatment and outcome among patients with laryngeal squamous cell carcinoma in Stockholm-A population-based study.

Survival of patients with advanced laryngeal squamous cell carcinoma (LSCC) remains poor and management protocols warrant further development. We thus investigated treatment and outcome-related factors for LSCC in Stockholm, Sweden. In a retrospective setting, 520 patients with LSCC diagnosed during 2000-2014, were included. Data on stage, treatment, and outcome were correlated with recurrence-free and overall survival (RFS and OS, respectively). Five-year OS for all patients was 65%. Five-year RFS for T1a, T1b, T2, T3, and T4 glottic LSCC was 90%, 91%, 77%, 47%, and 80%, respectively. The corresponding figures for T1, T2, T3, and T4 supraglottic LSCC were 64%, 66%, 64%, and 86%. Patients with a T3 glottic LSCC had unexpectedly poor survival, especially when compared with patients with a T4 tumor. Patients with T4 disease were primarily treated with laryngectomy and postoperative radiotherapy (RT)/chemoradiotherapy (CRT), while most patients with T3 LSCC were treated with RT/CRT.

A Predictive Nomogram for Lymph Node Metastasis in Supraglottic Laryngeal Squamous Cell Carcinoma.

PurposeLymph node metastasis (LNM) has a negative impact on the survival of patients with laryngeal squamous cell carcinoma (LSCC). Supraglottic LSCC is the most common cause of cervical lymph node metastases due to the extensive submucosal lymphatic plexus. The accurate evaluation of LNM before surgery can inform improved decisions in the clinic. In this study, we aimed to construct a nomogram to predict LNM in primary supraglottic LSCC patients.MethodsThe data from 314 patients with clinico-pathological confirmed supraglottic LSCC who underwent partial or total laryngectomy in our department from 2016 to 2020 were retrospectively analyzed (243 cases in the training set and 71 cases in the validation set). A multivariate logistic regression model was used to screen out independent risk factors and a nomogram was established. The accuracy and discrimination ability of the nomogram was evaluated using a consistency index and calibration curves.ResultsTumor size, tumor differentiation degree and LMR (lymphocyte-monocyte ratio) were selected to construct the nomogram. The C-index was 0.731 in the training set and 0.707 in the validation set. The calibration curves of the training and validation group both exhibited close agreement between the predicted and the actual presence of LNM.ConclusionsA nomogram was established based on routinely measured pretreatment variables and the predicted results improved the management of patients with LNM.

Early death in supraglottic laryngeal squamous cell carcinoma: A population-based study.

Supraglottic laryngeal squamous cell carcinoma (LSCC) is the second most common type of laryngeal cancer with a poor prognosis. Current population-based estimates of the early death rate and associated factors for early death of supraglottic LSCC are lacking. The purpose of this study was to assess the early death rate and related factors for early death in patients with supraglottic LSCC. We identified 3733 adult patients diagnosed with supraglottic LSCC between 2010 and 2017 for whom the vital status at 3months was known from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were staged according to the seventh edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. The early death (survival time ≤ 3months) rate was calculated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with the early death rate. 313 (8.38%) of the 3733 patients died within 3months of diagnosis of supraglottic LSCC. Of these, 225 patients died from cancer-specific causes. Multivariate logistic regression analyses confirmed that advanced age, male sex, advanced T stage, advanced N stage, advanced M stage, and not undergoing treatment (surgery, radiotherapy, and chemotherapy) had significant correlations with all-cause early death in supraglottic LSCC. In addition, advanced age, advanced T stage, advanced N stage, advanced M stage, and not undergoing treatment (surgery, radiotherapy, and chemotherapy) were significantly correlated with cancer specificity in supraglottic LSCC. When a tumor is newly diagnosed, we should pay close attention to sex, age, unmarried status and AJCC TNM staging to quickly detect supraglottic LSCC patients with a tendency toward early death. These findings have implications for precise prognosis prediction and individualized and personalized patient counseling and therapy.

En Bloc Resection of Supraglottic Carcinomas with Transoral Laser Microsurgery.

Objective:Complete en bloc supraglottic tumor excision with transoral laser microsurgery (TLM) can be achieved with good postoperative outcomes. We report surgical feasibility and the postsurgical outcomes of en bloc resection of supraglottic laryngeal squamous cell carcinomas (LSCC) with TLM.Methods:Seventeen patients who underwent TLM for supraglottic laryngeal cancer were included in the study. Demographic and pathological data, clinic and follow-up outcomes of the patients were reviewed and analyzed.Results:Type 1 TLM was performed in three patients, type 2a in one patient, type 3b in 12 patients, and type 4b in one patient. Negative surgical margins were achieved in all of the cases. Re-excision or any adjuvant treatment for positive resection margins was not required in any of the cases. Eight patients received adjuvant radiotherapy due to lymph node metastasis. Mean follow-up time was 33.8±15.7 months (range: 10–65 months). None of the patients had recurrence or distant metastasis.Conclusion:The transoral approach with the use of CO2 laser and microscopy offers complete tumor excision for treating supraglottic LSCC. The three-dimensional structure of the supraglottis can be achieved with adequate exposure. En bloc resection is possible with safe margins.

Pre-Treatment Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Occult Cervical Metastasis in Clinically Negative Neck Supraglottic and Glottic Cancer.

Background. Among patients with diagnosis of Laryngeal Squamous Cell Carcinoma (LSCC), up to 37.5% of cases may have occult metastasis (OM), and this feature is linked to poor prognosis and high rate of local recurrence. The role of elective neck dissection (END) in clinically negative neck (cN0) LSCC remains controversial. It is of great value to search for low-cost and easily detectable indicators to predict the risk of OM in laryngeal cancer. Recent reports have shown that high values of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) represent a negative prognostic factor in head and neck cancers. The aim of our study has been to investigate the value of pre-treatment NLR and PLR with regard to predicting occult cervical metastasis in cN0 supraglottic and glottic LSCC. Materials and methods. Data of patients affected by LSCC, who had been surgically treated by means of laryngectomy (total, horizontal partial and supracricoid) and END between January 2006 and January 2021, were retrospectively reviewed, using information retrieved from a database dedicated to such procedures in a single tertiary care referral institute. Results. A total of 387 patients were treated for LSCC at our Institute from 2006 to 2021, but only 108 of them met the inclusion criteria. The median age at the time of diagnosis was 64 years (range, 39–89 years). All the tumors were treated with a laryngectomy and an END. A total of 27.7% of patients were found positive for neck node metastasis (the pN+ group), while 78/108 (72.3%) patients were found to be negative for the presence of neck metastasis (the pN0 group). High values of NLR, but not PLR, significantly correlated with the probability of OM, and according to the iterative algorithm of Newton–Raphson, an NLR value of 2.26 corresponds to a probability of OM of 20%. Conclusion. Our analysis revealed a statistical correlation between high NLR pre-treatment values and positive neck OM in patients with LSCC.

Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients.

BackgroundAberrant expression of exosomal miRNAs has emerged as a research hotspot. However, no studies have been conducted on the dysregulation of exosomal miRNAs derived from cancer‐associated fibroblasts (CAFs) in supraglottic laryngeal squamous cell carcinoma (SLSCC).MethodsCancer‐associated fibroblasts and paired normal fibroblasts (NFs) from SLSCC patients were cultured, and exosomes in the culture supernatants were collected and identified. Exosomal miRNA expression was compared in each pair of CAFs and NFs by next‐generation sequencing, and expression of selected exosomal miRNAs was validated by reverse transcription‑quantitative PCR. Four online bioinformatic algorithms predicted the potential target genes of aberrantly expressed miRNAs, while gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment and network analysis identified downstream target genes and their interactions.ResultsThree pairs of CAFs and NFs were successfully cultured and purified. CAF‐derived exosomal miRNAs were mostly downregulated and included miR‐656‐3p, miR‐337‐5p, miR‐29a‐3p and miR‐655‐3p; however, some, including miR‐184‐3p, miR‐92a‐1‐5p, miR‐212‐3p and miR‐3135b, were upregulated. Bioinformatics analysis revealed involvement of these miRNAs in biological processes, cellular components and molecular functions. KEGG analysis revealed the top 30 pathways involvement in cancer initiation and progression and in cell cycle regulation. An interaction network showed miR‐16‐5p, miR‐29a‐3p, miR‐34c‐5p, miR‐32‐5p and miR‐490‐5p as the top five miRNAs and CCND1, CDKN1B, CDK6, PTEN and FOS as the top five target genes.ConclusionsSLSCC patients showed aberrant expression of CAF‐derived exosomal miRNAs. The top five miRNAs and their target genes may jointly constitute a carcinogenic tumour microenvironment and act as biomarkers for SLSCC intervention.

Induction Chemotherapy Plus Simultaneous Modulated Accelerated Radiation Therapy in Non-operative Hypopharyngeal and Supraglottic Laryngeal Squamous Cell Carcinoma: Long-Term Outcome of a Prospective Phase 2 Study.

Background: To evaluate the toxicities and long-term outcomes of induction chemotherapy (ICT) plus simultaneous modulated accelerated radiation therapy (SMART) in non-operative hypopharyngeal and supraglottic laryngeal squamous cell carcinoma (SCCH/L).Materials and Methods: This was a prospective phase 2 study. Patients diagnosed with SCCH/L, aged from 18 to 75, staged from III to IVB in accordance with the AJCC 2010 criteria, and refusing surgery were eligible. The patients were treated with 2–3 cycles of docetaxel-cisplatin-based ICT and SMART combined with 2–3 cycles of cisplatin-based concurrent chemotherapy. The prescription dose to the primary tumor and metastatic nodes was 69 Gy in 30 fractions. Acute and late toxicities were assessed according to the established Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria, and long-term outcomes were analyzed.Results: Between February 2013 and June 2015, 55 newly diagnosed SCCH/L patients were enrolled. No grade 2 or worse acute xerostomia was noted. The incidences of grade 3 acute dermatitis, oral mucositis, and pharyngoesophagitis were 12.7, 3.6, and 12.7%, respectively. The median follow-up time was 48 months (range 5.5–74 months). The main late toxicity was hoarseness or sore throat, with an incidence of 32.7%. The 5-year functional larynx-preservation survival was 51.5%. The 3- and 5-year locoregional control and overall survival were 58.2, 51.5, 63.6, and 54.1%, respectively.Conclusions: The ICT plus SMART with a regimen of 69 Gy/30 F for the treatment of SCCH/L demonstrated acceptable severe toxicity, satisfactory long-term outcomes, and laryngeal function preservation.

Integrated analysis revealing genome-wide chromosomal copy number variation in supraglottic laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a genetically complex tumor type and one of the leading causes of cancer-associated disability and mortality. Genetic instability, such as chromosomal instability, is associated with the tumorigenesis of LSCC. Copy number variations (CNVs) have been demonstrated to contribute to the genetic diversity of tumor pathogenesis. Comparative genomic hybridization (CGH) has emerged as a high-throughput genomic technology that facilitates the aggregation of high-resolution data of cancer-associated genomic imbalances. In the present study, a total of 38 primary supraglottic LSCC cases were analyzed by high-resolution array-based CGH (aCGH) to improve the understanding of the genetic alterations in LSCC. Additionally, integration with bioinformatic analysis of microarray expression profiling data from the Gene Expression Omnibus (GEO) database provided a fundamental method for the identification of putative target genes. Genomic CNVs were detected in all cases. The size of net genomic imbalances per case ranged between a loss of 682.3 Mb (~24% of the genome) and a gain of 1,958.6 Mb (~69% of the genome). Recurrent gains included 2pter-q22.1, 3q26.1-qter, 5pter-p12, 7p22.3p14.1, 8p12p11.22, 8q24.13q24.3, 11q13.2q13.4, 12pter-p12.2, 18pter-p11.31 and 20p13p12.1, whereas recurrent losses included 3pter-p21.32, 4q28.1-q35.2, 5q13.2-qter, 9pter-p21.3 and monosomy 13. Gains of 3q26.1-qter were associated with tumor stage, poor differentiation and smoking history. Additionally, through integration with bioinformatic analysis of data from the GEO database, putative target oncogenes, including sex-determining region Y-box 2, eukaryotic translation initiation factor 4 gamma 1, fragile X-related gene 1, disheveled segment polarity protein 3, defective n cullin neddylation 1 domain containing 1, insulin like growth factor 2 mRNA binding protein 2 and CCDC26 long non-coding RNA, and tumor suppressor genes, such as CUB and sushi multiple domains 1, cyclin dependent kinase inhibitor 2A, protocadherin 20, serine peptidase inhibitor Kazal type 5 and Nei like DNA glycosylase 3, were identified in supraglottic LSCC. Supraglottic LSCC is a genetically complex tumor type and aCGH was demonstrated to be effective in the determination of molecular profiles with higher resolution. The present results enable the identification of putative target oncogenes and tumor suppressor gene mapping in supraglottic LSCC.

Serum levels of microRNA-21 and microRNA-10a can predict long-term prognosis in laryngeal cancer patients: a multicenter study

BackgroundLaryngeal squamous cell carcinoma (LSCC) ranks as the second most common subtype of squamous cell sarcoma (SCC) of the head and neck. In clinical practice, more tools are required to assist doctors in identifying patients who are at risk of poor prognosis at an early stage. Many studies have shown that microRNA-21 plays an important role in LSCC. MicroRNA-10a has also been found to be differentially expressed in squamous cell carcinomas of the head and neck. This study aimed to test whether circulating microRNA-21 and microRNA-10a could serve as prognostic predictors for patients with LSCC.MethodsBetween May 2009 and Jan 2015, laryngeal cancer patients who were treated at three medical centers were enrolled based on inclusion and exclusion criteria. Baseline blood samples were obtained before surgery, chemotherapy, or radiotherapy. MicroRNA array was used to detect the microRNAs that were differently expressed between the LSCC patients and healthy controls. The serum levels of selected microRNAs were tested in each patient using qRT-PCR. Clinical information was acquired from the patients’ clinic or in-hospital records and all of the patients were followed-up.ResultsA total of 236 patients (average age, 59.4±10.7 years; male, 223; 33.5% with supraglottic LSCC, and 66.5% with glottis LSCC) were enrolled into the final analysis. MicroRNA array showed that the serum level of microRNA-21 was higher and that of microRNA-10a was lower in the LSCC patients compared with the healthy controls. Patients at T I/II stage, N0 stage, M0 stage had lower serum level of microRNA-21 and higher serum level of microRNA-10a. Serum level of microRNA-21 and microRNA-10a both differed significantly between patients with LSCC of well, moderate and poor differentiation. Cox proportional hazards model revealed that T stage, N stage, M stage, age, and ratio of serum level of microRNA-21 and microRNA-10a were risk factors associated with 5-year survival rate in patients with LSCC. Kaplan Meier survival analysis revealed that lower baseline ratio of serum level of microRNA-21 and microRNA-10a predict better 5 years survival. The receiver-operating characteristic curve demonstrated the ratio had a good ability to discriminate patients survive at the end of five years follow-up, with an area under the curve (AUC) of 0.8965 (95% CI: 0.7849–0.9811).ConclusionsThe serum levels of microRNA-21 and microRNA-10a are associated with long-term prognosis in laryngeal cancer patients. Lower serum level of microRNA-21 and higher serum level of microRNA-10a predict better prognosis in LSCC patients.

High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy.

ObjectivesMost early stage laryngeal squamous cell carcinomas (LSCC) are treated with radiotherapy. Discovery of new biomarkers are needed to improve prediction of outcome after radiotherapy and to identify potential targets for systemic targeted therapy. The ataxia telangiectasia mutated (ATM) gene plays a critical role in DNA damage response induced by ionizing radiation.MethodsThe prognostic value of immunohistochemical expression of pATM, pChk2, and p53 were investigated in 141 patients with T1‐T2 LSCC curatively treated with external beam radiotherapy. Uni‐ and multivariable Cox regression analyses were performed to examine the relation between expression levels of markers and local control.ResultsLocal control was significantly worse in cases with high levels of pATM (HR 2.14; 95% CI, 1.08–4.24; P = .03). No significant associations with local control were found for pChk2 and p53 expression. The association of high pATM expression with poor local control was only found for supraglottic LSCC (HR 10.9; 95% CI, 1.40–84.4; P = .02).ConclusionOur findings suggest a potential role for ATM in response to radiotherapy in early stage supraglottic LSCC and imply ATM inhibition as a possibility to improve response to radiotherapy.Level of Evidence NA Laryngoscope, 130: 1954–1960, 2020

Screening of molecular markers of induced chemotherapy in supraglottic laryngeal squamouscell carcinoma.

ObjectiveTo investigate the expressions of MAPK10, c-Jun and Itga6 in laryngeal carcinoma and its influence on the sensitivity to docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy.MethodsFifty-seven patients with supraglottic squamous cell carcinoma, who were treated by two cycles of TPF induction chemotherapy in our hospital, were enrolled in this study and divided into groups by chemotherapy resistance or chemotherapy sensitivity. The expressions of mRNA and protein of MAPK10, c-Jun and Itga6 in tumor tissues were evaluated by immunohistochemistry. The consistency of mRNA and protein expressions was tested, and the relation with the clinicopathological features was analyzed.ResultsThe positive rates of MAPK10 andc-Jun in the tumor tissues of the sensitive group were significantly higher than those of there assistant group, which was 90.48% and 100.00%, respectively. The expression rate of Itga6 was significantly higher in the resistant group, which was 83.33% (P < 0.05). The mRNA levels of MAPK10 and c-Jun were significantly lower in the resistant group than in the sensitive group, whilethemRNA levelof Itga6was significantly higher in the resistant group (P < 0.05). The protein expressions of MAPK10, c-Jun and Itga6 were consistent with their mRNA expressions (P < 0.05). The expressions of MAPK10, c-Jun and Itga6 were not correlatedwithage, gender and tumor diameter (P > 0.05). However, the expressions of MAPK10 and c-Jun were negatively correlated withclinical stage and pathological grading (P < 0.05). Negative correlations between MAPK 10 and Itga6, and between c-Jun and Itga6in tumor tissues were found by Spearman'srank correlation coefficient (P < 0.05). The correlation was also negative in the resistant tumor tissues (P < 0.05).ConclusionThe MAPK10 and c-Jun expressions were down-regulated, while the Itga6 expression was up-regulated in the chemo-resistant laryngeal carcinoma, and the expression levels of different factors were correlated witheach other. These factorsmight be important biomarkers for predicting outcomes of TPF chemotherapy in laryngeal carcinoma in the future.

Clinical significance of matrix metalloproteinase (MMP)-2 and MMP-9 expression in laryngeal squamous cell carcinoma

Background/Aim. The previous researches suggest that matrix metalloproteinases (MMPs) have the ability to degrade extracellu-lar matrix components and play an important role in malignant tumour progression and metastasis. The aim of this study was to investigate MMP-2 and MMP-9 expression in the tissue of laryn-geal squamous cell carcinoma (LSCC) and to evaluate their clini-cal significance. Methods. In this prospective study the samples of tumour tissue of seventy patients with LSCC (45 glottic and 25 supraglottic), and samples of laryngeal mucosa of 70 patients with chronic laryngitis were immunohistochemically stained for MMP-2 and MMP-9. We studied the relationships between MMPs tissue expression and clinical and histological characteris-tics of the patients with LSCC in comparison to the patients with chronic laryngitis. Results. MMP-2 and MMP-9 expression was significantly higher in the tissue of both glottic and supraglottic LSCC than in chronically inflamed laryngeal mucosa (p &lt; 0.001 and p &lt; 0.001, respectively). There were positive correlations be-tween epithelial MMP-2 expression and the presence of perineu-ral invasion (r = 0.515, p &lt; 0.008), lymphovascular invasion (r = 0.559, p &lt; 0.004) and disease recurrence (r = 0.415, p &lt; 0.039) in supraglottic LSCC, as well as between MMP-2 expression and the presence of the exophytic type of tumour growth (r = 0.347, p &lt; 0.020) in glottic LSCC. Epithelial MMP-9 expression was as-sociated with lymphovascular invasion (r = 0.331, p &lt; 0.026) and the presence of the exophytic tumour growth (r = 0.474, p &lt; 0.001) in glottic LSCC. Conclusion. MMP-2 and MMP-9 can be used as potential biomarkers for the assessment of LSCC progression.

Distinct Biomarker Profiles and Clinical Characteristics in T1-T2 Glottic and Supraglottic Carcinomas.

BackgroundIn early stage laryngeal squamous cell carcinoma (LSCC) radiotherapy with curative intent is a major treatment modality. TNM classification is used to define patients eligible for radiotherapy. Studies in early stage glottic LSCC identified several predictive biomarkers associated with local control. However, we recently reported that this predictive value could not be confirmed in supraglottic LSCC.ObjectiveTo examine whether clinical behavior and protein expression patterns of these biomarkers differ between glottic and supraglottic LSCC.Study DesignRetrospective cohort study.MethodsTumor tissue sections of 196 glottic and 80 supraglottic T1‐T2 LSCC treated primarily with RT were assessed immunohistochemically for expression of pAKT, Ki‐67 and β‐Catenin. Expression data of HIF‐1α, CA‐IX, OPN, FADD, pFADD, Cyclin D1, Cortactin and EGFR in the same cohort of glottic and supraglottic LSCC, were retrieved from previously reported data. The relationship between glottic and supraglottic sublocalization and clinicopathological, follow‐up, and immunohistochemical staining characteristics were evaluated using logistic regression and Cox regression analyses.ResultsGlottic LSCC were correlated with male gender (P = .001), hoarseness as a primary symptom (P < .001), T1 tumor stage (P < .001), negative lymph node status (P < .001), and an older age at presentation (P = .004). Supraglottic LSCC patients developed more post‐treatment distant metastasis when adjusted for gender, age, and T‐status. While supraglottic LSCC was associated with higher expression of HIF‐1α (P = .001), Cortactin (P < .001), EGFR (P < .001), and Ki‐67 (P = .027), glottic LSCC demonstrated higher expression of CA‐IX (P = .005) and Cyclin D1 (P = .001).ConclusionDifferences in clinicopathological and immunohistochemical staining characteristics suggest that T1‐T2 glottic and supraglottic LSCC should be considered as different entities.Level of EvidenceN/A. Laryngoscope, 2020

Management of the N0 neck in patients with laryngeal squamous cell carcinoma

Background: Neck lymph node status is the chief prognostic index in patients with head and neck squamous cell carcinoma (SCC), yet the management of a clinically negative neck in this setting is still controversial, especially in patients with laryngeal SCC (LSCC).Objectives: To evaluate the efficacy of selective neck dissection (SND) to control occult disease in patients with LSCC and clinically negative (cN0) necks.Materials and methods: Medical records of 1476 patients with cN0 LSCC were analyzed. In conjunction with primary treatment, 126 (8.5%) underwent at least unilateral elective neck dissection, whereas most 1350 (91.5%) followed a wait-and-see protocol. Prognostic significance was indicated by the Kaplan–Meier survival estimates.Results: The rate of occult neck disease was 15%. Five-year overall and disease-free survival rates were 74.4% and 66.7%, respectively. Prognosis was closely related to T stage, preoperative tracheotomy, and postoperative recurrence. There was no significant correlation with age, sex, or preoperative neck dissection; but in patients with supraglottic LSCC, the relation between prognosis and preoperative neck dissection was significant, with fewer neck and local recurrences than the wait-and-see group (p < .05).Conclusions and significance: Selective neck dissection is serving as an accurate prognostic tool in patients with supraglottic laryngeal cancers.

PTEN Is Associated With Worse Local Control in Early Stage Supraglottic Laryngeal Cancer Treated With Radiotherapy.

ObjectivesThe aim of this study was to establish the prognostic value of the epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on local control in patients with early stage supraglottic laryngeal squamous cell carcinoma (LSCC) treated with radiotherapy only.Study designRetrospective cohort study.MethodsImmunohistochemical staining for EGFR and PTEN was performed on pretreatment biopsies of a selected well‐defined homogeneous group of 52 patients with T1–T2 supraglottic LSCC treated with radiotherapy between 1990 and 2008. Kaplan–Meier analysis and univariate and multivariate Cox Regression analyses were performed to correlate clinical data and expression levels of EGFR and PTEN with local control.ResultsKaplan–Meier survival analysis and Cox Regression analysis showed a significant association between PTEN expression and local control (hazard ratio [HR] = 3.26, 95% confidence interval [CI] = 1.14–9.33, P = .027) and between lymph node status and local control (HR = 3.60, 95% CI = 1.26–10.31, P = .017). Both were independent prognostic factors in a multivariate analysis (HR = 3.28, 95% CI = 1.14–9.39, P = .027 and HR = 3.62, 95% CI = 1.26–10.37, P = .017, respectively). There was no significant association between EGFR expression and local control (HR = 1.32, 95% CI = 1.17–10.14, P = .79).ConclusionThis study showed an association between both high PTEN expression and the presence of lymph node metastasis and deteriorated local control in early stage supraglottic LSCC treated with radiotherapy.Level of EvidenceNA

Oncological outcomes of surgical treatment for T3 supraglottic laryngeal squamous cell carcinoma patients

Background: T3 supraglottic laryngeal carcinoma (LC) is a common advanced laryngeal cancer.Objective: This study was conducted to assess the clinical results of pathological T3 (pT3) supraglottic LC patients who were amenable to laryngectomy treated with primary surgery and postoperative therapy.Methods: Retrospective review of 202 pT3 cases of supraglottic laryngeal squamous cell carcinoma.Results: The five-year cancer specific survival (CSS) rate was 63.7% and the overall survival rate (OS) was 62.8%. For T3 supraglottic patients who underwent total laryngectomy, the five-year disease-free survival (DFS) was 51.8%, and the CSS was 62.5%. For patients who underwent partial laryngectomy, the five-year DFS was 72.2%, and the CSS was 79.0%. High lymph node and stage status are predictors of mortality for these patients. No difference was found in the DFS and CSS rates between patients with negative margins and those with positive margins following postoperative radiotherapy and chemotherapy.Conclusion: Surgical treatment of T3 supraglottic LC patients achieved satisfactory results. Postoperative radiotherapy and chemotherapy are an effective method of treatment for T3 supraglottic LC patients, especially for those with a positive margin.

Expression and clinical significance of long non-coding RNA LINC00520 in laryngeal squamous cell carcinoma

Objective:To investigate the expression of LINC00520 in laryngeal squamous cell carcinoma(LSCC),and analyze its relevance and roles in carcinogenesis and development of LSCC.Method:The expression of LINC00520 in laryngeal squamous cell carcinoma tissue and paired adjacent normal tissue was determined by real-time PCR.The relationship between the expression of LINC00520 and the clinicopathological characteristics including clinical stage,pathological type,histological grade and lymph node metastasis of LSCC was analyzed.Result:(1)The LINC00520 expression level was significantly upregulated in LSCC tissues compared to that of paired adjacent normal tissues(P<0.000 1).(2)There were no statistical differences of the LINC00520 expression level among supraglottic,glottic and subglottic LSCCs(P>0.05).The LINC00520 expression level had no significant changes in poorly differentiated LSCC compared with that of well and moderately differentiated counterparts(P>0.05).Moreover,the expression of LINC00520 had no significant difference between T1+T2 stage and T3+T4 stage LSCC tissues(P>0.05).Interestingly,the LINC00520 level in LSCC with lymph node metastasis was significantly higher than that in patients without lymph node metastasis(P<0.01).Conclusion:Upregulation of LINC00520 in LSCC may contribute to its metastasis.