Cases Of Laryngeal Squamous Cell Carcinoma Research Articles

The Prognostic Significance of Tumor Budding and Cell Nest Size in Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a commonly occurring malignancy in the head and neck region. However, due to the heterogeneity of primary tumor sites, tumor behavior, and molecular mechanisms, there is currently no consensus on the accuracy of clinicopathological prognostic factors for individual cases. Tumor histopathologic behavior remains a crucial factor in predicting aggressiveness. Recent studies have shown that peritumoral tumor budding (TB) combined with cell nest size (CNS) is a reliable marker for predicting lymph node metastasis, advanced cancer prognosis, and therapeutic response in SCCs of different origins. This study aims to investigate the relationship between TB and CNS in the context of nodal metastasis and overall prognosis in patients diagnosed with LSCC. Our objective is to establish the significance of TB and CNS status as a cost-effective, easily assessed, and highly reliable prognostic factor among this patient population. In this retrospective cross-sectional study, we analyzed 128 LSCC cases that underwent total laryngectomy at Amir Alam Hospital. We evaluated TB and CNS based on the Boxberg etal. Our study demonstrated a significant correlation between TB, and nodal involvement (p = 0.015), vascular invasion (p = 0.035), and mortality rate (p = 0.001), as well as a significant statistical correlation between high TB and extra-laryngeal extension (p = 0.006), clinical stage (p = 0.011), and mortality rate (p = 0.001). Moreover, small nest size was also associated with the clinical stage (p = 0.047), extra-laryngeal extension (p = 0.015), and mortality rate (p < 0.001). Based on our results, TB, CNS, and clinical stage are independent prognostic factors for mortality rate and are correlated with disease-specific survival. Given the effect of TB and CNS on the overall prognosis and survival of patients with LSCC, evaluating these two factors on routine H&E microscopic examination of LSCC specimens is recommended to facilitate individualized risk assessment and treatment planning.

The Diagnostic Role of α-smooth Muscle Actin in Superficial Invasive Laryngeal Squamous Cell Carcinoma

Abstract Background Diagnosis of superficial invasion of laryngeal squamous cell carcinoma (LSCC) is a major challenge for pathologists as its confirmation is mainly based on histomorphologic features especially in presence of differentials and in absence of reliable diagnostic immunohistochemical markers. Despite focusing on study of tumor cells, the study of tumor microenvironment (TME) and its major component cancer associated fibroblasts (CAFs) will help to understand the participation of the tumor stroma in tumor development, progression and invasion differentiating it from other premalignant and benign lesions whose features may overlap with superficial invasive LSCC causing diagnostic dilemma. CAFs are characterized by the expression of α-smooth muscle actin protein (α-SMA) which represents the major component used to detect mesenchymal cells during process of TME. Objective To assess the diagnostic role of α-smooth muscle actin immunohistochemical expression in superficially invasive laryngeal squamous cell carcinoma. Methods The current study was conducted retrospectively on 108 cases of laryngeal biopsy samples as archived formalin fixed paraffin embedded blocks obtained from the Pathology Department lab of Ain Shams University Hospitals (Jan 2020-Dec 2022). The cases included in the current study were divided into 4 groups; Group 1: included 32 superficial invasive LSCC cases, Group 2: included 20 Laryngeal HGD/SIL cases, Group 3: included 36 PEH cases and Group 4: included 20 invasive LSCC cases. Data concerned with gender, age, lesion laterality, site and smoking history were obtained from the electronically archived reports. The histopathological data were re-examined microscopically by at least two authors. After then, the expression of Alpha SMA was evaluated in different groups, followed by statistical evaluation of the obtained results. Results Immunoreactivity of α-SMA was expressed in 87.5% of superficial invasive LSCC cases and 100% of invasive LSCC cases, while no reactivity was observed in all cases of HGD/SIL group, and rarely in PEH group (5.6%). There was statistically significant correlation between alpha SMA and both stroma changes and percentage of TILs in stroma of superficial invasive LSCC and no statistically significant relationship between alpha SMA expression and age, sex, lesion’s laterality, site, microscopic growth pattern, smoking, koiliocytic changes and hyperkeratosis in superficial invasive LSCC cases. The α-SMA expression pattern in stroma of superficial invasive LSCC was significantly different from that of HGD/SIL and PEH groups. Conclusion Alpha SMA is a potentially valuable marker for labelling CAFs and plays a reliable ancillary role in confirming the invasion for superficial invasive LSCC and differentiating it from HGD/SILs and PEH cases.

Factors associated with total laryngectomy following organ-preserving treatment of laryngeal SCC.

A subset of laryngeal squamous cell carcinoma (LSCC) patients undergoing larynx preserving treatment ultimately require total laryngectomy (TL) for oncologic or functional reasons. This study aims to identify TL risk factors in these patients. Retrospective cohort study using Veterans Affairs (VA) database. T1-T4 LSCC cases treated with primary radiotherapy (XRT) or chemoradiotherapy (CRT) were assessed for TL and recurrence. Binary logistic and Cox regression and Kaplan-Meier analyses were implemented. Of 5390 cases, 863 (16.0%) underwent TL. On multivariable analysis, age (adjusted odds ratio: 0.97 [0.96-0.98]; p < .001) and N3 disease (0.42 [0.18-1.00]; p = .050) were associated with reduced risk of TL, whereas current alcohol use (1.22 [1.04-1.43]; p = .015) and >T1 disease (T2, 1.76 [1.44-2.17]; p < .001; T3, 2.06 [1.58-2.68]; p < .001; T4, 1.79 [1.26-2.53]; p = .001) were associated with increased risk of TL. However, N2 (adjusted hazard ratio: 1.30 [1.10-1.55]; p = .003) and N3 (2.02 [1.25-3.26]; p = .004) disease were associated with an increased risk for local recurrence. Compared to XRT, treatment with CRT was associated with reduced risk for local recurrence after adjusting for other factors (0.84 [0.70-0.99]; p = .044). Those who do not receive TL following local recurrence have poorer disease-specific survival (log-rank, p < .001). In patients without local recurrence, N2 disease was associated with a fourfold increase in risk of TL (4.24 [1.83-9.82]; p < .001). Advanced nodal stage was associated with reduced rates of salvage TL in the setting of local recurrence, and subsequent worse prognosis after recurrence. Conversely, advanced nodal stage may increase the risk for functional salvage TL in patients without recurrence. Level 3.

Single-cell atlas profiling revealed cellular characteristics and dynamic changes after PD-1 blockade therapy of brain metastases from laryngeal squamous cell carcinoma.

Brain metastasis (BM) in laryngeal squamous cell carcinoma (LSCC) is uncommon but prognosis is poor. Anti-PD-1 immunotherapy benefits some advanced LSCC cases, yet its efficiency is limited by tumor complexity. We analyzed paired metastatic tumor samples from before and after immunotherapy using single-cell RNA sequencing (scRNA-seq), along with a primary LSCC dataset and bulk RNA sequencing. This identified changes post-immunotherapy and revealed differences in single-cell transcriptomes among LSCC, primBM, and neoBM. Our findings show that anti-PD-1 treatment suppresses metastasis-promoting pathways like VEGF and EMT in cancer cells, and alters immune cell functions. Notably, it upregulates T cell activation, leading to CD8 T cell exhaustion from excess heat shock proteins, notably HSPA8. However, CD8 T cell cytotoxic functions improve post-treatment. In myeloid cells, anti-PD-1 therapy enhances antigen presentation and promotes a proinflammatory shift post-metastasis. Additionally, NUPR1 is linked to BM in LSCC, and NEAT1 is a potential metastatic cancer cell cycle participant. Our study provides insights into cancer heterogeneity and the impact of PD-1 immunotherapy on metastasis, aiding precise diagnosis and prognosis.

The Follicular Dendritic Cells and HPV 18 Interrelation in Head and Neck Squamous Cell Carcinomas of the Larynx.

Background and Objectives: Even if they are cells of controversial origin (mesenchymal, perivascular, or fibroblastic), follicular dendritic cells (FDC) are present in all organs. The aim of this study was to establish the FDC expression pattern and its interrelation with HPV 18 expression in laryngeal squamous cell carcinoma (LSCC). Materials and Methods: Fifty-six cases of LSCC were evaluated by simple and double immunostaining. The following score was used: 0 (negative or few positive cells), 1 (10-30% of positive cells), 2 (30-50% of cells), and 3 (over 50% of cells). Results: The expression of CD 21-positive cells with dendritic morphology (CDM) was noticed in the intratumoral area of conventional (well and poorly differentiated types and HPV 18 positive cases with a value of 2 for the score) and papillary types (HPV-18 negative cases with a score of 1). The highest value of 2 for the score of CDM in HPV-18 positive cases was found in the peritumoral area of well- and poorly-differentiated conventional LSCCs. A significant correlation was found between scores of CDM from the intratumoral area and those of the peritumoral area (p = 0.001), between CDM and non-dendritic morphology cells (NDM) of the intratumoral area (p = 0.001), and between HPV-18 status and peritumoral NDM cells (p = 0.044). Conclusions: The FDC and NDM cell score values of intratumoral and peritumoral areas may represent important parameters of LSCCs. This may contribute to a better stratification of laryngeal carcinoma cases and the individualized selection of clinical treatment protocols.

Correlation of signal transducer and activator of transcription-3 andβ-catenin expression in laryngeal squamous cell carcinoma

The specific roles of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and β-Catenin in laryngeal squamous cell carcinoma (LSCC) remain unclear. In this study, the correlations between p-STAT3, β-Catenin, and clinicopathological characteristics were investigated using tissues and clinical data from 124 LSCC cases. Immunohistochemistry and immunofluorescence assays were used to examine p-STAT3 and β-Catenin expression and localization in these samples. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognostic significance of these proteins. LSCC cell lines were treated with a STAT3 inhibitor (dihydroartemisinin) or activator (interleukin-6) to explore the mechanism of p-STAT3 and β-Catenin. There was an inverse correlation between p-STAT3 and β-Catenin expression in the LSCC samples. Patients with high p-STAT3 and low β-Catenin expression levels had significantly worse overall survival. Multivariate Cox regression analysis revealed that lymph node metastasis and β-Catenin expression were both independently correlated with unfavorable overall survival. Cell treatment with the p-STAT3 inhibitor inhibited the nuclear accumulation of β-Catenin, while p-STAT3 activator treatment could promote β-Catenin translocation to the nucleus. Overall, our data indicate that p-STAT3 expression is associated with LSCC by promoting β-Catenin degradation.

The Clinical Significance of CD163+ Tumor-Associated Macrophages (TAMs) in Laryngeal Squamous Cell Carcinoma.

Background and objective The tumor's microenvironment is currently considered an important indicator of the tumor's prognosis, treatment failure, and recurrence. CD163+ tumor-associated macrophages (TAMs) are a marker of poor prognosis in many types of human cancers. In the present study, the expression of CD163+ TAMs was analyzed in laryngeal squamous cell carcinomas (LSCCs) using immunohistochemistry, and this expression was correlated with the clinical and pathological characteristics of LSCCpatients. Materials and methods One commercial human larynx microarray with 80 cases of LSCCs, was used for this study.For comparison with normal laryngeal mucosa, a second microarray carrying normal tissues from all human anatomical sites, including normal laryngeal tissues, was used.Immunohistochemical staining was performed, and the primary antibody was a mouse monoclonal against human CD136. The absence of the primary antibody was used as a negative control.The percentage of positive cells was categorized into five scores: 0 (0%); 1, (1%-10%); 2, (11%-50%); 3, (51%-80%); and 4, (>80%). A case was scored as positive for CD163 with a score >= 1. The χ2 test was used to assess the CD163 expression in LSCC cases (N=80).A statistically significant difference was defined as P 0.05. Results The human larynx microarray containing 80 cases of LSCCs was used for this study. The age of the cancer patients in this array was in the range of 39 to 72, with a median of 53. LSCC grades were distributed as follows: 25 patients were designated as grade I, 43 were designated as grade II, and 6 were designated as grade III. Two tumors' (2/80) cores were missing from the microarray. Sixtumors on the microarray did not have a grade designation reported by the manufacturer of the array. The expression of CD163 in normal, benign, unmatched laryngeal tissue was absent. In cancer cases, on the other hand, a significant number of LSCCs had TAMs that were positive for CD163 (87% positive tumors, with an IHC score ranging from 1 to 4, χ2=30.634; p<0.001). The rest of the LSCC cases (10 in total) had negative CD163 expression (score of 0). Conclusion A significant majority of LSCCs were found to have CD163+ TAMs expression using tissue microarrays (TMAs). This expression is positively correlated with the tumor's grade, clinical manifestation, and TNM staging. Morphologic evidence shows that the majority of LSCCs express the highest range of immunohistochemistry (IHC) scores for CD163 protein in the membranes and cytoplasm of their TAMs. This study provides evidence of the clinical significance of CD163+TAMs in LSCCs and proposes further studies to pinpoint the exact role of these cells in LSCC patients.

Survival outcomes in patients with T3-4aN0M0 glottic laryngeal squamous cell carcinoma and evaluation of postoperative radiotherapy.

This study aimed to evaluate the clinical outcomes of patients with T3-4aN0M0 glottic laryngeal squamous cell carcinoma (LSCC) treated with laryngectomy, and to assess the postoperative radiotherapy (PORT) results in terms of the survival of T3-T4aN0M0 patients with negative margins. This was a retrospective review of 369 T3-4aN0M0 glottic LSCC cases. The 5-year cancer-specific survival (CSS) and overall survival (OS) rates were 67.5 and 66.7%, respectively. Patients who received total laryngectomy had worse survival [5-year CSS, 62.5%; disease-free survival (DFS), 56.2%] than those who underwent partial laryngectomy (5-year CSS, 79.3%; DFS, 65.4%). More advanced-stage cancer is a predictor of poor survival. There was no significant difference in CSS or DFS between patients with positive margins following rescue therapy and those with negative margins. Furthermore, no difference in the survival rates was observed between patients with negative margins who received PORT and those who did not (5-year DFS: 59.1 vs. 63.8%, P=0.057 and CSS: 62.5 vs. 69.5%, P=0.074). For T3-4aN0M0 glottic LSCC patients, surgical treatment remained a good option, as it can achieve satisfactory oncological outcomes. However, PORT did not increase survival in surgically managed pT3-4aN0M0 LSCC patients with negative margins.

Expression and clinical significance of FGFR1 and FGFR2 in laryngeal squamous cell carcinoma.

BackgroundFibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor receptor 2 (FGFR2) may be of significance in the development of laryngeal squamous cell carcinoma (SCC) tissues. Examination of the expression results of these factors may offer new insights into treatment of the disease, such as genetic and histological targeted target therapy.MethodsWe selected tissue from 30 cases of laryngeal SCC, 23 cases of adjacent normal mucosa, and 26 cases of benign laryngeal mucosal tissues from patients who received surgery at the Otolaryngology Department of the Affiliated Hospital of Chengde Medical College between September 2020 and January 2022. The laryngeal cancers included nine cases of supraglottic, 20 glottic (vocal cord), and one case of subglottic cancer, while all benign laryngeal mucosal lesions were obtained from vocal cord polyps. The expression of FGFR1 and FGFR2 was detected in 30 laryngeal cancers, 23 adjacent normal mucosa, and 26 vocal cord polyps by immunohistochemical technology [immunohistochemistry (IHC)], and the correlation analysis of their expression in laryngeal cancer was performed. P<0.05 was represented statistically significant.ResultsThe expression of FGFR1 and FGFR2 was significantly different in laryngeal SCC and the normal tissue >0.5 cm from the tumor margin (P<0.05), and between laryngeal SCC and vocal polyps (P<0.05). There was no difference in FGFR1 and FGFR2 expression (P>0.05) between normal mucosal margins and vocal cord polyp tissue, and no correlation between FGFR1 and FGFR2 in laryngeal SCC and sex, age, smoking history, alcohol consumption history, tumor diameter, tumor lymph node metastasis, tumor differentiation degree, and Tumor-Node-Metastasis (TNM) stage (P>0.05), A moderate positive correlation between FGFR1 expression and FGFR2 expression in laryngeal SCC was seen (Rs=0.499, P<0.01).ConclusionsFGFR1 and FGFR2 may participate in the occurrence of SCC of the throat: (I) positive FGFR1 and FGFR2 expressions are not associated with gender, age, smoking history, alcohol consumption history, tumor diameter, lymph node metastasis, degree of differentiation, or TNM stage. (II) FGFR2 increases successively with higher FGFR1 expression and with a positive correlation in laryngeal SCC.

Tumor-Stroma Ratio and Programmed Cell Death Ligand 1 Expression in Preoperative Biopsy and Matched Laryngeal Carcinoma Surgical Specimen.

Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical–pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical–pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS < 1 evaluated on surgical specimens was associated with a low TSR (stroma rich) on both biopsies and surgical specimens (p = 0.0143 and p = 0.0063). Low TSR showed a significant negative prognostic value when evaluated on both biopsies and surgical specimens (HR = 8.808, p = 0.0003 and HR = 11.207, p = 0.0002). CPS ≥ 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols.

Association between pathological differentiation and survival outcomes of patients with laryngeal squamous cell carcinoma.

To investigate the prognostic value of histopathological differentiation for the survival of patients with laryngeal squamous cell carcinoma (LSCC). Retrospective clinical and histopathological differentiation data on consecutive cases of LSCC from a single institution over a 10-years period were collected and analyzed in this study. Oncological outcomes were assessed based on disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) using the Kaplan-Meier method and Cox proportional hazards regression analysis. Propensity score matching (PSM) was performed to reduce or eliminate the bias due to confounding variables. A total of 998 LSCC cases were identified in this study. As compared to well to moderately differentiated LSCC, poorly differentiated tumors had adjusted hazard ratios (aHRs) of 1.78 (95% confidence interval [CI] 1.31-2.43), 2.00 (95% CI 1.51-2.65), and 1.72 (95% CI 1.28-2.31) for DSS, DFS, and OS, respectively. The new patient cohort consisted of 138 patients with well to moderately differentiated LSCC and 138 patients with poorly differentiated LSCC after PSM. The survival outcomes of patients with well to moderately differentiated LSCCs were significantly better than those of patients with poorly differentiated tumors in DSS (aHR 1.91; 95% CI 1.24-2.95), DFS (aHR 2.07; 95% CI 1.37-3.12), and OS (aHR 2.14; 95% CI 1.39-3.28). This study showed that survival outcomes of patients with poorly differentiated LSCC were significantly worse than those of patients with well to moderately differentiated LSCC. In addition, histopathological differentiation is an important prognostic factor for LSCC survival. Therefore, further treatment plans should focus on poorly differentiated LSCC to improve the survival outcomes.

Association between cancer surface area and histopathological parameters of laryngeal squamous cell carcinoma in total laryngectomy specimens

Background/Aim. Numerous histopathological parameters, such as cartilage penetration, perineural and lymphovascular invasion, presence of metastatic tissue in regional lymph nodes (LNs), extranodal extension (ENE) of nodal metastases, as well as the presence of cancer tissue on resection borders, are all important factors influencing survival in patients with laryngeal squamous cell carcinoma (LSCC). The aim of the study was to determine if there is an association between cancer surface area (CSA) and these histopathological characteristics. The presence of ENE of metastatic tissue in regional LNs was also investigated. Methods. In a retrospective study, one hundred and forty cases of LSCC were revised and processed after total laryngectomy. The cases were found in the archives of the Histopathology Laboratory of the Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center of Serbia. Results. A significant difference was found in CSA depending on cancer penetration into the thyroid cartilage, perineural invasion, and positive resection margins. Cancers with larger CSA were more common in the advanced T stage. Metastases were found in 36 out of 72 (50%) neck LN samples submitted for evaluation. The difference in CSA was also found depending on the presence of metastatic tissue in regional LNs. ENE was present in 69.4% of involved LNs, and it was more frequent in LNs 3 cm in size or larger. Conclusion. There is a significant difference in CSA depending on the presence of cartilage penetration, perineural invasion, presence of cancer tissue on resection borders, and presence of metastases in regional LNs. Larger cancers tend to be of a higher T stage. ENE is more common in LNs 3 cm in size or larger.

Prognostic value of the age-adjusted Charlson comorbidity index in patients over 60 years old with laryngeal squamous cell carcinoma

Objective: To evaluate the value of the age-adjusted Charlson comorbidity Index (ACCI) in predicting the prognosis and guiding the clinical treatment of laryngeal squamous cell carcinoma (LSCC) in patients over 60 years old. Methods: Retrospective analysis of 249 cases of LSCC in Shanxi Provincial Cancer Hospital and First Hospital of Shanxi Medical University from 2008 to 2015 was performed. There were 234 males and 15 females, aged from 60 to 88 years. The clinical characteristics, treatment information and follow-up data were collected. ACCI was used to score the comorbidities of the patients. Receiver operating characteristic (ROC) curve was drawn and the patients were divided into high ACCI group and low ACCI group according to the cut-off value of ACCI. Prognostic factors were analyzed. Kaplan-Meier method was used for survival analysis, rank sum test was used for comparison between groups, χ2 test was used for enumeration data. Results: Overall survival (OS) was 54.6%, progression-free survival (PFS) was 59.4%, and cancer-specific survival (CSS) was 58.6%. Both the median survival time and PFS time were 60 months. The best cutoff point of the ACCI group was 5. Cox multivariate analysis showed that ACCI was an independent risk factor for OS, PFS and CSS (OR=1.553, 1.499 and 1.534,respectively, all P<0.05). In the high ACCI group, OS (χ2=4.120 and 4.115,P<0.05) and CSS (χ2=4.510 and 5.009,P<0.05) of patients treated with surgery plus radiotherapy and patients with radiotherapy alone were better than those of patients with surgery alone (P<0.05). But in the low ACCI group, there was no significant difference in prognosis among the three treatment regimens (P>0.05). Conclusion: High ACCI offors important prognostic information for LSCC in patients over 60 years old, and can guide clinical treatment options.

The role of α-smooth muscle actin in confirming the microinvasion of laryngeal squamous cell carcinoma

BackgroundThe diagnosis of microinvasive laryngeal squamous cell carcinoma (LSCC) is not always straightforward and sometimes can be very challenge in daily clinical practice. The focus lies in the confirmation of microinvasion. Cancer-associated fibroblasts (CAFs), as the major element of reactive tumor stroma, are believed to participate actively in the growth and invasion of tumor cells. ObjectivesTo evaluate the diagnostic role of α-smooth muscle actin (α-SMA) labelling CAFs in microinvasive LSCC. MethodsA total of 81 laryngeal biopsy specimens were retrieved, including 41 cases of microinvasive LSCC with depth of invasion no more than 3 mm, 20 laryngeal squamous intraepithelial lesion (SIL), and 20 benign pseudoepitheliomatous hyperplasia (PEH). All cases were stained for immunohistochemistry, using antibody against the α-SMA antigen. The correlation between the presence of CAFs in microinvasive LSCC and tumor histological characteristics was investigated. ResultsImmunoreactivity of α-SMA was detected in twenty-nine microinvasive LSCC (29/41, 71%), while no reactivity was observed in laryngeal SIL (0/20, 0%), and rarely in PEH (2/20, 10%). The α-SMA expression pattern in stroma of microinvasive LSCC was significantly different from that of SIL (χ2 = 26.966, p = 0.000) and PEH (χ2 = 19.838, p = 0.000). In addition, there seemed to be a certain correlation between the histological characteristics of microinvasive LSCC and the presence of interstitial CAFs. ConclusionsThis study highlights the practical role of utilizing α-SMA in the pathological diagnosis of microinvasive LSCC, with emphasis on variable histomorphologic features of microinvasive LSCC.

Gastroesophageal reflux disease: A risk factor for laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma in the NIH-AARP Diet and Health Study cohort.

Prior studies have suggested that gastroesophageal reflux disease (GERD) may be associated with risk of squamous cancers of the larynx and esophagus; however, most of these studies have had methodological limitations or insufficient control for potential confounders. We prospectively examined the association between GERD and esophageal adenocarcinoma (EADC), esophageal squamous cell carcinoma (ESCC), and laryngeal squamous cell carcinoma (LSCC) in 490,605 participants of the NIH-AARP Diet and Health Study cohort who were 50-71 years of age at baseline. Exposure to risk factors were obtained from the baseline questionnaire. GERD diagnosis was extracted among eligible participants via linkage to Medicare diagnoses codes and then multiply imputed for non-Medicare-eligible participants. Hazard ratios (HRs) and 95% CIs of GERD were computed using Cox regression. From 1995 to 2011, we accrued 931 cases of EADC, 876 cases of LSCC, and 301 cases of ESCC in this cohort and estimated multivariable-adjusted HRs of 2.23 (95% CI, 1.72-2.90), 1.91 (95% CI, 1.24-2.94), and 1.99 (95% CI, 1.39-2.84) for EADC, LSCC, and ESCC, respectively. The associations were independent of sex, smoking status, alcohol intake, and follow-up time periods. We estimated that among the general population in the United States, 22.04% of people aged 50-71 years suffered from GERD. Using risk factor distributions for the United States from national survey data, 16.92% of LSCC cases and 17.32% of ESCC cases among individuals aged 50-71 years were estimated to be associated with GERD. GERD is a common gastrointestinal disorder, but future prospective studies are needed to replicate our findings. If replicated, they may inform clinical surveillance of GERD patients and suggest new avenues for prevention of these malignancies.

Overexpression of KIAA1199 is an independent prognostic marker in laryngeal squamous cell carcinoma.

BackgroundKIAA1199 is a recently identified novel gene that is upregulated in various human cancers with poor survival, but its role and the underlying mechanisms in laryngeal squamous cell carcinoma (LSCC) remain unknown. Here, we collected tissues from 105 cases of LSCC to investigate the relationships between KIAA1199 protein expression and clinical factors.MethodsWestern blotting and real-time quantitative PCR (RT-PCR) were used for detect the protein and mRNA expression of KIAA1199 in LSCC tissue. Immunohistochemistry (IHC) staining was used to detect the expression of KIAA1199. Patient clinical information, for instance sex, age, pathological differentiation, clinical region, T stage, N stage, clinical stage, operation type, neck lymph dissection, smoking status, and drinking status were recorded. Kaplan–Meier survival analysis and Cox analysis were applied to identify the relationship between KIAA1199 and LSCC.ResultsWestern blotting results showed KIAA1199 protein was significantly higher in tumor tissues vs. adjacent non-cancerous tissues (0.9385 ± 0.1363 vs. 1.838 ± 0.3209, P = 0.04). The KIAA1199 mRNA expression was considerably higher in tumor tissues (P < 0.001) than in adjacent non-cancerous tissues by RT-PCR. IHC results showed up-regulated KIAA1199 expression was related with some severe clinicopathological parameters: pathologic differentiation (P = 0.002), T stage (P < 0.001), N stage (P < 0.001), clinical stage (P < 0.001), survival time (P = 0.008) and survival status (P < 0.001). Kaplan–Meier survival analysis showed that patients with high KIAA1199 protein expression had poor overall survival (OS) (P < 0.05). Cox analysis suggested that the KIAA1199 protein expression constituted an independent prognostic marker for LSCC patients (P < 0.001).ConclusionOur findings revealed that KIAA1199 protein expression may be used to predict LSCC patient outcome.

CD105- and CD31-assessed microvessel density in laryngeal carcinoma biopsies as a predictor of recurrence after exclusive primary surgery

PurposeSurgery is currently indicated as a unimodal therapeutic approach with curative intent in selected laryngeal squamous cell carcinomas (LSCCs) ranging from stage I to III. The main aim of this study was to evaluate the prognostic role of CD105- and CD31-assessed microvessel density (MVD) in biopsy and in surgical specimens from a cohort of consecutive stage I-III LSCCs who had undergone exclusive primary surgery, according to current guidelines. Materials and methodsCD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 24 consecutive cases of LSCC who underwent exclusive surgery. ResultsOn biopsy specimens, CD105- and CD31-assessed MVD were positively associated with recurrence risk (hazard ratio [HR] 1.266, p = 0.0034 and HR 1.265, p = 0.0081, respectively). In surgical specimens, CD105- and CD31-assessed MVD were significantly associated with disease-free survival (DFS) (HR 1.213, p = 0.0016 and HR 1.237, p = 0.0023 respectively). Considering a stratification based on median value, recurrence risk was higher in patients with a CD105-assessed MVD>0 in both biopsies and surgical specimens (HR 11.005, p = 0.0326 and HR 34.483, p = 0.0311). No significant differences in terms of recurrence risk were found for CD31-assessed on biopsies or on surgical specimens. ConclusionsThis study supports the role of biopsy CD105-MVD as a predictor of recurrence after exclusive surgery for LSCCs. Further prospective studies are mandatory to better characterize the prognostic role of CD105-MVD evaluated on biopsies to develop novel criteria to identify patients at higher risk of recurrence for more aggressive approaches or adjuvant treatment.

Evaluation of the prognostic significance of P53 and Proliferating cell nuclear antigen (PCNA) in laryngeal squamous cell carcinoma

Background: Laryngeal tumors are considered to be the most frequent neoplasm of head and neck cancers, they account for almost 25% of the malignant neoplasms involving this region. Even though it shows better clinical outcome, its prognosis still worse due to its local invasiveness, lymph node and distant metastasis. Thus, a better realization of the molecular pathways developing laryngeal carcinogenesis may help in the identification of new predictive and prognostic biomarkers, and developing novel management strategies for this cancer. Material and methods: This study included 40 cases of laryngeal squamous cell carcinoma (LSCC), 38 cases were received as punch biopsies and only 2 cases were received as excisional biopsies. Immunohistochemical staining of all cases using P53 and PCNA was done. Results: The immunohistochemical expression of p53 was positive in the nuclei of 31 out of 40 (77.5%) LSCC cases. PCNA expression was positive in 28 out of 40 (70%) LSCC cases. P53 expression was significantly correlated with the increase in tumor size, higher tumor stageand lymph node invasion.PCNA expression, as well, was significantly correlated with the increase in tumor size, higher tumor stage, tumor grade, tumor site and lymph node invasion.Conclusions: p53 and PCNA are properly independent predictors of the outcomes in patients with LSCC, and their immunohistochemical expression may aid in predicting the clinical course in patients with LSCC, and selecting patients who should be treated more cautiously.

Prognostic Significance of CD105- and CD31-Assessed Microvessel Density in Paired Biopsies and Surgical Samples of Laryngeal Carcinoma.

Small pretreatment laryngeal biopsies may not fully represent a tumor’s biological profile. This study on laryngeal squamous cell carcinoma (LSCC) aimed to investigate the prognostic role of CD105- and CD31-assessed microvessel density (MVD) in paired biopsies and surgical specimens and the association and discrepancy between CD105- and CD31-assessed MVD in biopsies and surgical specimens. CD105- and CD31-assessed MVD was analyzed in paired biopsies and surgical specimens of 45 consecutive cases of LSCC. In the LSCC biopsies and surgical specimens, median CD105-assessed MVD was significantly higher in N+ than in N0 cases (p = 0.0008, and p = 0.0002, respectively). Disease-free survival (DFS) was associated with CD105- and CD31-assessed MVD in both biopsies and surgical specimens (p < 0.0001 for all specimens). Multivariable Cox’s regression showed that pathological grade (p < 0.0001) and CD105-assessed MVD in LSCC biopsies (p = 0.0209) predicted DFS. Lin’s concordance coefficient showed that CD31 overestimated MVD compared with CD105 in LSCC biopsies and surgical specimens. CD105-assessed MVD should be further investigated in larger LSCC series as a potential prognostic marker for identifying: patients at higher risk of recurrence who might warrant more aggressive therapy; and cN0 patients requiring elective neck dissection for a significant risk of regional metastasis.

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.