Recurrent Laryngeal Squamous Cell Carcinoma Research Articles

Protein expression analysis for predicting recurrent laryngeal squamous cell carcinoma.

The expression of a number of proteins plays a major role in predicting recurrent laryngeal squamous cell carcinoma (LSCC). Thus, the aim of the present study was to investigate the expression of 16 selected proteins as prognostic indicators for recurrent and non-recurrent LSCC. Samples from a total of 41 patients with LSCC were investigated by immunohistochemistry. Digital image analysis was performed, and various associated factors were calculated. Histoscore (H-score) and receiver operating characteristic curves were used to divide protein expression in high and low for predicting disease recurrence. Disease-free survival (DFS) curves, crude hazard ratios (HRs) and adjusted HRs were analyzed and compared. Significantly different H-scores were found between the recurrent and non-recurrent groups in terms of pRb and c-Met expression. pRb was expressed at high levels in recurrent LSCC, while c-Met was expressed at low levels. Patients with low pRb expression had a longer DFS than those with high pRb expression (log-rank χ2, 5.161; P=0.023). Patients with high c-Met expression had a longer DFS than those with low c-Met expression (log-rank χ2, 6.441; P=0.011). Moreover, patients with high pRb expression and low c-Met expression had the shortest DFS (log-rank χ2, 11.827; P=0.008). Differentiated histological factors had an impact on the risk of recurrence (Cox regression test; crude HR, 9.53; 95% confidence interval, 1.214-74.819; P=0.032). The present study demonstrated that the grading of differentiated squamous cell carcinoma, pRb and c-Met expression are the most useful prognostic factors for the prediction of recurrent LSCC. These might be further applied as potential markers for clinical use.

A Prospective Observational Study on the Role of Immunohistochemical Expression of Orphanin in Laryngeal Squamous Cell Carcinoma Recurrence.

To date, histological biomarkers expressed by laryngeal cancer are poorly known. The identification of biomarkers associated with laryngeal squamous cell carcinoma (SCC), would help explain the tumorogenesis and prevent the possible recurrence of the lesion after treatment. For this reason, the aim of this study is to investigate, for the first time, the Orphanin expression in 48 human specimens of laryngeal SCC and evaluate its possible correlation with patients prognosis. We analyzed pathological specimens from 48 patients with laryngeal SCC to detect the presence of Orphanin by using an immunohistochemistry test. We compared the findings with healthy tissue acquired from patients who underwent surgery for mesenchymal benign tumours of the larynx. The specimens were stained with anti-Orphanin monoclonal antibodies. Results were processed through a computerised image analysis system to determine a scale of staining intensity. All the tumoural specimens examined showed a significant immunoreaction for Orphanin when compared with healthy tissues (p < 0.05) but with a different immune reactivity related to clinical-pathological features. A high Orphanin expression was not significantly related to Histological Grading (HG), TNM, and stage (p > 0.05). In the multivariate analysis, the Orphanin expression was significantly related only to the malignant recurrence (p < 0.05). Our study suggests that Orphanin could have a role in tumorigenesis by increasing the recurrence of cancer; therefore, it should be further explored as a possible biomarker for laryngeal cancer.

Prognostic value of CD103+ tumor-infiltrating lymphocytes and programmed death ligand-1 (PD-L1) combined positive score in recurrent laryngeal squamous cell carcinoma

ObjectivesIn an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery. Materials and MethodsThis was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson’s correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests. ResultsOnly CD103+ TILs showed a statistically significant, weakly-positive correlation with PD-L1 CPS (r2 = 0.264, p < 0.015). No other TIL subsets correlated with PD-L1 CPS in our cohort. The most favorable survival outcomes were seen in patients with pathologic N0 tumors showing high CD103+ TILs and/or high PD-L1 CPS staining. ConclusionAmong patients with persistent or recurrent LSCC, CD103+ TILs only modestly correlated with PD-L1 CPS. A combined biomarker score incorporating CD103+ TILs and PD-L1 CPS greatly enhanced survival discrimination. This model may have additional utility in predicting the clinical benefit of immunotherapies in persistent or recurrent LSCC in the future.

Development and validation of a model to predict the risk of recurrence in patients with laryngeal squamous cell carcinoma after total laryngectomy.

Recurrence is still the main obstacle to the survival of laryngeal squamous cell carcinoma (LSCC) patients who have undergone a total laryngectomy. Previous models for recurrence prediction in patients with LSCC were based on pathological information, while the role of easily accessible inflammatory markers in the prognosis of LSCC patients has rarely been reported. This study sought to develop and validate a model to predict the risk of recurrence in LSCC patients who underwent total laryngectomy. A total of 204 LSCC patients who underwent a total laryngectomy were included in this retrospective cohort study. Demographics, pathology, and inflammatory markers of patients were collected. All the patients were randomly divided into a training set and a test set at a ratio of 4:1. Patients were followed up for 3 years after surgery or until death occurred during this period. The random-forest method was used to develop a predictive model. The performance of the model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC) with the 95% confidence interval (CI), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Of the 204 LSCC patients, 56 (27.45%) patients had a recurrence. The random-forest prediction model was an all-factor model, and the most important predictors of the model were the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR), with proportions of 0.121, 0.100, and 0.092, respectively. The AUCs of the model in predicting the recurrence of LSCC in the training set and the test set were 0.960 (95% CI, 0.931-0.989) and 0.721 (95% CI, 0.716-0.726), respectively. The sensitivity, specificity, accuracy, PPV, and NPV of the model in the test set were 0.750 (95% CI, 0.505-0.995), 0.690 (95% CI, 0.521-0.858), 0.707 (95% CI, 0.568-0.847), 0.500 (95% CI, 0.269-0.921), and 0.870 (95% CI, 0.732-1.000), respectively. A model to predict the risk of recurrence in LSCC patients who have undergone a total laryngectomy was established, and inflammatory markers AGR, NLR, and PLR play an important role in the predictive model.

Association Between Alcohol Dehydrogenase Polymorphisms and the Recurrence of Laryngeal Carcinoma.

Alcohol consumption is closely associated with prognosis for laryngeal squamous cell carcinoma (LSCC) patients. As key enzymes in ethanol metabolism, proteins in the alcohol dehydrogenase (ADH) family make for valuable targets to establish a novel predictive nomogram model. This study attempts to do so by focusing on the single nucleotide polymorphisms (SNPs) of ADH1B and ADH1C in LSCC. Sixty eight LSCC patients that were followed up for more than 10 years were retrospectively analyzed. Endpoints of the current study included disease-free survival and overall survival. Survival analyses were performed using the Kaplan-Meier method and evaluated by log-rank test. The prognostic value of eight ADH1B SNPs and three ADH1C SNPs were evaluated using univariate and multivariate Cox regression analyses. A nomogram model for disease-free survival was established and evaluated using the receiver operating characteristic curve, the C-index, and a calibration plot. Significant association was exhibited between rs17033 (p < 0.001) and rs1229984 (p=0.002) with an increase in LSCC recurrence rate on Kaplan-Meier curves. Multivariate logistic regression analysis revealed that the rs17033 polymorphism of ADH1B was independently associated with an increased risk of LSCC recurrence (HR=3.325, 95% CI=1.684-6.566, p=0.001). Based on these findings, a prognostic nomogram of LSCC patients involving ADH1B rs17033 was constructed. This study has demonstrated an independent association between ADH1B gene variants and the recurrence of LSCC. A nomogram model based on rs17033 of ADH1B, age, T, and N stages were successfully developed for the first time to predict the probability of recurrence in LSCC patients. 3 Retrospective cohort study Laryngoscope, 132:2169-2176, 2022.

Hub Genes of Recurrent Laryngeal Cancer Identified by Weighted Gene Co-Expression Network Analysis

Objective in order to discover correlated gene modules and hub genes for recurrent laryngeal squamous cell carcinoma through weighted gene co-expression network analysis method. The microarray dataset of recurrent laryngeal cancer, namely GSE27020, were obtained from the gene expression Omnibus database. Weighted gene co-expression network analysis was introduced to establish a gene co-expression network, mining key clinical trait correlated hub genes. Gene ontology enrichment analyses were performed for the genes in modules related to recurrent laryngeal squamous cell carcinoma. Then, we build up a proteinprotein interaction network with the genes in interest gene module and identified hub genes through analyze such protein-protein interaction network. The hub genes were mined using cytohubba plus-in. Finally, we analyzed these hub genes overall survival using gene expression profiling interactive analysis database. Forty four gene co-expression gene modules were achieved via weighted gene co-expression network analysis analysis. We found that the orangered4 module was the most correlated module with recurrence in laryngeal squamous cell carcinoma patients. Genes in the orangered4 module were related to organelle organization, response to chemical, regulation of catalytic activity and regulation of cell differentiation. Two genes were discovered as hub genes which were related to poor prognosis, namely annexin A2 and S100 calcium binding protein A10. Here, we found several hub genes that played important roles in recurrent laryngeal squamous cell carcinoma, which may improve our understanding of the mechanisms underlying recurrence laryngeal squamous cell carcinoma.

899P Gene expression analysis of primary and recurrent laryngeal tumors reveals disruption in key regulatory pathways

Laryngeal squamous cell carcinoma (LSCC) is associated with 20-50% recurrence rate after definitive chemoradiation. The primary purpose of this study is to explore transcriptomic changes that occur in primary and recurrent laryngeal tumors in order to determine new genetic targets underpinning the development and recurrence of LSCC.

Salvage carbon dioxide transoral laser microsurgery for laryngeal cancer after (chemo)radiotherapy: a European Laryngological Society consensus statement

PurposeTo provide expert opinion and consensus on salvage carbon dioxide transoral laser microsurgery (CO2 TOLMS) for recurrent laryngeal squamous cell carcinoma (LSCC) after (chemo)radiotherapy [(C)RT].MethodsExpert members of the European Laryngological Society (ELS) Cancer and Dysplasia Committee were selected to create a dedicated panel on salvage CO2 TOLMS for LSCC. A series of statements regarding the critical aspects of decision-making were drafted, circulated, and modified or excluded in accordance with the Delphi process.ResultsThe expert panel reached full consensus on 19 statements through a total of three sequential evaluation rounds. These statements were focused on different aspects of salvage CO2 TOLMS, with particular attention on preoperative diagnostic work-up, treatment indications, postoperative management, complications, functional outcomes, and follow-up.ConclusionManagement of recurrent LSCC after (C)RT is challenging and is based on the need to find a balance between oncologic and functional outcomes. Salvage CO2 TOLMS is a minimally invasive approach that can be applied to selected patients with strict and careful indications. Herein, a series of statements based on an ELS expert consensus aimed at guiding the main aspects of CO2 TOLMS for LSCC in the salvage setting is presented.

Biological tumor markers (maspin, CD105, nm23-H1) and disease relapse in laryngeal cancer: cluster analysis.

The aim of this investigation was to see if a panel of biomarkers (maspin, CD105, and nm23-H1) could be used to stratify patients with laryngeal squamous cell carcinoma (LSCC) in homogeneous disease recurrence risk clusters. Cluster analysis was used to classify 89 patients based on their immunohistochemical expression of nm23-H1, CD105, and maspin. Our analysis identified seven homogeneous clusters: the LSCC recurrence rate was lowest in cluster 6 (non-nuclear maspin pattern, nuclear nm23-H1 expression ≥10%, endothelial CD105 expression <6%; P = .009), and highest in cluster 3 (non-nuclear maspin pattern, nuclear nm23-H1 expression <10%, endothelial CD105 expression ≥6%; P <.001). Similar panels of biological variables identified by cluster analysis should be tested in prospective clinical trials to establish whether treating patients identified as being at higher risk of LSCC recurrence more aggressively could significantly improve their recurrence rate and/or disease-specific survival.

EGFR cut-off point for prognostic impact in laryngeal squamous cell carcinoma

Background: Various molecular biomarkers, including epidermal growth factor receptor (EGFR), have gained importance as predictors of head and neck cancer disease progression.Aims: This study aimed to investigate the ability of EGFR expression as a prognostic marker for laryngeal squamous cell carcinoma (LSCC).Materials and methods: A total of 31 patients with LSCC with immunohistochemistry (IHC) staining for EGFR were examined. Digital image processing was applied to analyze EGFR staining intensity and percent distribution, which were calculated as the H-score. We used a receiver operating characteristic (ROC) curve to identify the best cut-off point of EGFR expression, with H-score separated into high- and low-grade for cancer recurrence prediction.Results: The cut-off point of EGFR expression for high- and low-grades was an H-score of 170 with a sensitivity of 75% and a specificity of 66.7%. Using this cut-off, 14 (45.16%) and 17 (54.84%) patients were categorized as having high- and low-grades EGFR, respectively. The analysis showed a significant reverse correlation between the EGFR grade and LSCC recurrence (RR, 0.4; 95% CI, 0.17–0.98; p = .02).Conclusions: Our study demonstrated that EGFR grading using H-score with the generated cut-off point by the ROC curve might be further applied as a potential marker for LSCC prognostic prediction.

Prognostic Significance of Cell Differentiation and Immune Pathway Mutations in Recurrent Laryngeal Squamous Cell Carcinoma

Organ preservation protocols are commonly used as first line therapy for advanced laryngeal squamous cell carcinoma (SCC). Disease free survival after radiation or chemoradiation ranges from 30-60% and recurrent tumors often display an aggressive phenotype resulting in poor patient outcomes. The aim of this study is to identify genetic alterations associated with overall and disease specific survival in patients with recurrent laryngeal SCC undergoing salvage laryngectomy.

Salvage radiotherapy for recurrent hypopharyngeal and laryngeal squamous cell carcinoma (SCC) after first-line treatment with surgery alone: a 10-year single-centre experience

PurposeSalvage surgery of recurrent hypopharyngeal and laryngeal squamous cell carcinoma (SCC) results in limited local control and survival rates. As a result of recent technological progress, radiotherapy (RT) has become a valuable, potentially curative therapeutic option. Thus, we aimed to determine prognostic factors for survival outcome in order to optimize patient selection for salvage radiotherapy after failure of first-line treatment with surgery alone in this special patient cohort.MethodsSeventy-five patients (85% male, median age of 64 years) underwent salvage RT in a secondary setting for recurrent hypopharyngeal or laryngeal SCC after prior surgery alone between 2007 and 2017. On average, patients were treated with one prior surgery (range 1–4 surgeries). Median time between surgery and salvage RT was 7 months (range 1–47 months) for initially advanced tumors (T3/4, N+, extracapsular spread) and 18 months (range 5–333 months) for initially early stage tumors. The majority of patients received concomitant chemotherapy (n = 48; 64%) or other kind of systemic treatment concurrent to radiotherapy (n = 10; 13%).ResultsMedian follow-up was 41 months (range 3–120 months). Overall, fifteen patients were diagnosed with local failure (all were in-field) at last follow-up (20%). Median time to recurrence was 35 months (range 3–120 months) and 3-year local progression-free survival (LPFS) was 75%, respectively. Dose-escalated RT with 70.4 Gy applied in 2.1 Gy or 2.2 Gy fractions corresponding an EQD2 > 70 Gy (p = 0.032) and the use of concomitant cisplatin weekly chemotherapy (p = 0.006) had a significant positive impact on LPFS. 3-year OS and DPFS were 76 and 85%, respectively. No toxicity-related deaths occurred. Reported grade > 3 side effects were rare (n = 4/70, 6%).ConclusionSalvage radiotherapy resulted in excellent local control rates while radiation dose and the use of cisplatin weekly chemotherapy were identified as prognostic factors for LPFS. Nevertheless, patient selection for curative salvage treatment remains challenging.

Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma.

Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4+, CD8+ and/or CD103+ TIL status in patients with advanced LSCC. Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4+, CD8+, and CD103+ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4+, CD8+, and CD103+ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC. High tumor CD103+ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8+ or CD4+ TIL content. On multivariate analysis, an "immune-rich" phenotype, in which tumors were enriched for both CD103+ and CD4+ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC. An immune profile driven by CD103+ TIL content, alone and in combination with CD4+ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.

Hypothyroidism and Wound Healing After Salvage Laryngectomy

Patients undergoing salvage laryngectomy are predisposed to radiation-induced hypothyroidism and impaired wound healing secondary to the tissue effects of prior treatment. The impact of hypothyroidism on postoperative wound healing is not established. A single-institution retrospective case series was performed. The inclusion criteria specified preoperatively euthyroid adults who underwent salvage laryngectomy with concurrent neck dissection between 1997 and 2015 for persistent or recurrent laryngeal squamous cell carcinoma after radiation or chemoradiation therapy (n = 182). The principal explanatory variable was postoperative hypothyroidism, defined as thyroid-stimulating hormone (TSH) higher than 5.5 mIU/L. The primary end points of the study were pharyngocutaneous fistulas and wounds requiring reoperation. Multivariate analysis was performed. The fistula rate was 47% among hypothyroid patients versus 23% among euthyroid patients. In the multivariate analysis, the patients who experienced hypothyroidism in the postoperative period had a 3.6-fold greater risk of fistula [95% confidence interval (CI) 1.8–7.1; p = 0.0002]. The hypothyroid patients had an 11.4-fold greater risk for a required reoperation (24.4 vs 5.4%) than the euthyroid patients (95% CI 2.6–49.9; p = 0.001). The risk for fistula (p = 0.003) and reoperation (p = 0.001) increased with increasing TSH. This corresponds to an approximate 12.5% incremental increase in the absolute risk for fistula and a 10% increase in the absolute risk for reoperation with each doubling of the TSH. Postoperative hypothyroidism independently predicts postoperative wound-healing complications. The association of hypothyroidism with fistula formation may yield opportunities to modulate wound healing with thyroid supplementation or to provide a biomarker of wound progression.

Leser-Trélat syndrome associated with cancer larynx : A case report

Leser-Trelat syndrome (LTS) is a rare cutaneous paraneoplastic syndrome that barely affects patients with head and neck cancer. Here we present a case of 58-years old male presented with skin manifestation consistent with a sign of Leser-Trelat. A close investigation of the patient revealed that he had a recurrent laryngeal squamous cell carcinoma. The described case is the fifth case of a Leser-Trelat syndrome with squamous cell carcinoma of the larynx and the sixth to be reported in the head and neck squamous cell carcinoma. Thus sudden development of paraneoplastic dermatoses is recurrently a forewarning progression of the malignancy.

Laryngeal recurrence sites in patients previously treated with transoral laser microsurgery for squamous cell carcinoma

BackgroundThe laryngeal framework provides a natural barrier preventing tumour spread to extralaryngeal structures. Transoral laser microsurgery (TLM) for laryngeal squamous cell carcinoma (SCC) may violate these boundaries, altering the pathways of tumor spread for potential recurrences. Our project objective is to describe laryngeal SCC recurrence patterns and overall survival in patients requiring total laryngectomy (TL) after TLM.MethodsPatients undergoing TLM for laryngeal SCC requiring salvage TL were identified from a prospective CO2 laser database containing all patients undergoing TLM for head and neck malignancies at the QEII Health Sciences Center in Halifax, Nova Scotia between March 2002 – May 2014. Surgical pathology reports were analyzed for tumor characteristics, extent of recurrence and invasion of local structures. Kaplan-Meier analyses were performed to evaluate overall survival, disease specific survival (DSS) and locoregional control.ResultsFifteen patients were identified from the database as receiving salvage TL for recurrent disease after initial TLM resection for laryngeal SCC. Final pathology reports demonstrated that 67% (10/15) of patients had thyroid cartilage involvement while 53% (9/15) of patients had cricoid cartilage involvement on salvage TL pathology. 33% (5/15) of patients had perineural invasion and 27% (4/15) had lymphovascular invasion. Mean and median follow-up times were 36.7 months and 26.8 months respectively (range 3.9–112.6). The Kaplan-Meier estimate for overall survival at 36 months was 40% post TL with a standard error (SE) of 13.6%. DSS was 47% (SE 14.2%), and locoregional control was 55% (SE 14.5%) post TL.ConclusionsLaryngeal recurrence sites following TLM seem to be consistent with historical data at known laryngeal sites of vulnerability. Treatment with TLM does not predispose patients to a lower rate of locoregional control and overall survival after total laryngectomy and salvage outcomes are consistent with literature values.

Hypothyroidism and Wound Healing After Salvage Laryngectomy.

Patients undergoing salvage laryngectomy are predisposed to radiation-induced hypothyroidism and impaired wound healing secondary to the tissue effects of prior treatment. The impact of hypothyroidism on postoperative wound healing is not established. A single-institution retrospective case series was performed. The inclusion criteria specified preoperatively euthyroid adults who underwent salvage laryngectomy with concurrent neck dissection between 1997 and 2015 for persistent or recurrent laryngeal squamous cell carcinoma after radiation or chemoradiation therapy (n=182). The principal explanatory variable was postoperative hypothyroidism, defined as thyroid-stimulating hormone (TSH) higher than 5.5mIU/L. The primary end points of the study were pharyngocutaneous fistulas and wounds requiring reoperation. Multivariate analysis was performed. The fistula rate was 47% among hypothyroid patients versus 23% among euthyroid patients. In the multivariate analysis, the patients who experienced hypothyroidism in the postoperative period had a 3.6-fold greater risk of fistula [95% confidence interval (CI) 1.8-7.1; p=0.0002]. The hypothyroid patients had an 11.4-fold greater risk for a required reoperation (24.4 vs 5.4%) than the euthyroid patients (95% CI 2.6-49.9; p=0.001). The risk for fistula (p=0.003) and reoperation (p=0.001) increased with increasing TSH. This corresponds to an approximate 12.5% incremental increase in the absolute risk for fistula and a 10% increase in the absolute risk for reoperation with each doubling of the TSH. Postoperative hypothyroidism independently predicts postoperative wound-healing complications. The association of hypothyroidism with fistula formation may yield opportunities to modulate wound healing with thyroid supplementation or to provide a biomarker of wound progression.

SLC7A11, a component of cysteine/glutamate transporter, is a novel biomarker for the diagnosis and prognosis in laryngeal squamous cell carcinoma.

Solute carrier family 7, membrane11 (SLC7A11) or (xCT) is a component of the cysteine-glutamate transporter, which plays a critical role in glutathione homeostasis which is important to protect cells from oxidative stress. SLC7A11 is distributed in various tissues and participates in the occurrence of a number of diseases, particularly in the pathogenesis of malignant tumors, but its role in laryngeal cancer development has not yet been clearly defined. The objective of the present study was to investigate the role of SLC7A11 in laryngeal squamous cell carcinoma (LSCC). We conducted immunohistochemistry and RT-PCR to evaluate the protein and mRNA levels of SLC7A11 in LSCC and in control tissues, respectively. The knockdown experiments were conducted with SLC7A11 short hairpin RNA (shRNA) lentivirus, and the protein and mRNA levels of SLC7A11 were assessed by RT-PCR and western blotting. The functional study of SLC7A11 invitro was conducted by MTT assay, and the effects on the cell cycle were detected using flow cytometry. Immunohistochemical results revealed that the expression levels of SLC7A11, Ki-67 and p53 in LSCC tissues were higher than those in laryngeal dysplasia tissues. The Spearman rank correlation analysis revealed that the expression of SLC7A11 was positively correlated with the expression of p53 and Ki-67. Cox regression analysis and Kaplan-Meier plots confirmed that the expression levels of SLC7A11 were a prognostic factor for overall survival (OS) rates and postoperative recurrence of LSCC. Moreover, the functional study of SLC7A11 invitro revealed that knockdown of SLC7A11 using shRNA inhibited cell proliferation by inducing cell cycle arrest at the G1phase. Immunohistochemical and RT-PCR results and knockdown experiments of SLC7A11 revealed that SLC7A11 was involved in the progression of LSCC, and may provide clinical information for the evaluation of OS rates and postoperative recurrence of LSCC. Collectively, these observations suggest that SLC7A11 may be a vital biomarker for the diagnosis and prognosis in human LSCC, and targeting SLC7A11 appears to be a potentially significant method for LSCC treatment.

Nuclear survivin expression correlates with endoglin-assessed microvascularisation in laryngeal carcinoma

AimsSurvivin—a member of the family of inhibitor of apoptosis proteins that control cell division, apoptosis and metastasis—is overexpressed in virtually all human cancers, including laryngeal squamous cell carcinoma (LSCC). Recent...

Occult Nodal Disease Prevalence and Distribution in Recurrent Laryngeal Cancer Requiring Salvage Laryngectomy.

The indications for neck dissection concurrent with salvage laryngectomy in the clinically N0 setting remain unclear. Our goals were to determine the prevalence of occult nodal disease, analyze nodal disease distribution patterns, and identify predictors of occult nodal disease in a salvage laryngectomy cohort. Case series with planned data collection. Tertiary academic center. Patients with persistent or recurrent laryngeal squamous cell carcinoma (LSCC) after radiation/chemoradiation failure undergoing salvage laryngectomy with neck dissection. We analyzed a single-institution retrospective case series of patients between 1997 and 2014 and identified those who had clinically N0 (cN0) necks (n = 203). Clinical and pathologic data, including nodal prevalence and distribution, were collected and statistical analyses performed. Overall, cN0 necks had histologically positive occult nodes in 17% (n = 35) of cases. Univariate predictors of occult nodal positivity included recurrent T4 stage (34% T4 vs 12% non-T4; P = .0003) and supraglottic subsite (28% supraglottic vs 10% nonsupraglottic; P = .0006). Histologically positive nodes associated with supraglottic primaries were most frequently positive in ipsilateral levels II and III (17% and 16%). Positive nodes for glottic LSCC were most frequently positive in the ipsilateral and contralateral paratracheal nodes (11% and 9%). Histologically positive occult nodes are identified in 17% of cN0 patients undergoing salvage laryngectomy with neck dissection. Occult nodal disease varies in frequency and distribution based on tumor subsite. Predictors of high (>20%) occult nodal positivity include T4 tumors and supraglottic subsite. In glottic LSCC, the most frequent sites of occult nodal disease are the paratracheal nodal basins.