Factor In Laryngeal Cancer Research Articles

The impact of the tumor immune microenvironment and tumor-infiltrating lymphocyte subgroups on laryngeal cancer prognosis.

The absence of improvement in survival rates across various cancers, including laryngeal cancer, has led to an increasing interest in understanding the immune response to cancer. In head and neck cancers, immune modulatory mechanisms such as immune microenvironment and immune infiltration are important in cancer pathogenesis. This study aims to explore the distribution of tumor-infiltrating lymphocyte (TIL) subgroups in the immune microenvironment and evaluate their impact on tumor histopathological characteristics and prognosis. The study included 50 patients who underwent laryngectomy for laryngeal squamous cell carcinoma, in Istanbul University - Cerrahpaşa, Faculty of Medicine Department of Otorhinolaryngology, between January 2016 and January 2018. Pathology specimens were evaluated using immunohistochemistry to assess the expressions of the CD3, CD20, CD8, CD4, CD25, and FoxP3 markers, identifying subgroups of TILs. The investigation aimed to uncover how these subgroups influence tumor histopathological features and survival outcomes. The high infiltration of CD3, CD20, and CD4 had a positive impact on disease-specific survival, disease-free survival, and recurrence-free survival. In addition, overall survival was positively affected by high CD3 and CD4 infiltrations. However, no significant relationship was observed between the expressions of CD8, FoxP3, and CD25 and any of the survival parameters. The infiltration of CD3, CD20, and CD4 positive cells indicative of a robust antitumoral immune response-emerged as favorable prognostic factors in laryngeal cancer. These findings suggest that enhancing the infiltration of CD3, CD20, and CD4 lymphocytes could be a therapeutic strategy worth exploring in clinical trials.

Synergistic association between underweight and type 2 diabetes on the development of laryngeal cancer: a national population-based retrospective cohort study

BackgroundAlthough cigarette smoking is the most significant risk factor for laryngeal cancer, other risk factors might also be associated with the development of laryngeal cancer. We investigated whether underweight and type 2 diabetes are associated with laryngeal cancer in a Korean population.MethodsA total of 9,957,059 participants (≥20 years) without prior history of cancer who underwent a National Health Insurance Service health checkup in 2009 were followed up until December 31, 2018. Newly diagnosed laryngeal cancer was identified using claim data, and underweight was defined as body mass index (BMI) < 18.5 kg/m2. A Cox proportional-hazards models with multivariable adjustment were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs).ResultsDuring the median follow-up period of 8.3 years, 3504 cases of laryngeal cancer occurred. Underweight was associated with increased risk of laryngeal cancer after adjusting for potential confounders (HR: 1.43, 95% CI: 1.22–1.69) compared to those who were not underweight. Underweight and type 2 diabetes were synergistically associated with higher risk of laryngeal cancer (HR: 2.33, 95% CI: 1.54–3.51), compared to those without either condition. This relationship was stronger in those with an age < 65 years (HR: 3.33, 95% CI: 1.88–5.87) and alcohol consumption (HR: 2.72, 95% CI: 1.64–4.53).ConclusionsThese results suggest that underweight may be a significant risk factor for laryngeal cancer and that underweight and type 2 diabetes might synergistically increase the risk of laryngeal cancer.

IL-17 Affects the Progression, Metastasis, and Recurrence of Laryngeal Cancer via the Inhibition of Apoptosis through Activation of the PI3K/AKT/FAS/FASL Pathways.

Background Cytokines play important roles in the development and prognosis of laryngeal cancer (LC). Interleukin-17 (IL-17) from a distinct subset of CD4+ T cells may significantly induce cancer-elicited inflammation to prevent tumor immune surveillance. Methods The expression levels of IL-17 were examined among 60 patients with LC. Immunofluorescence colocalization experiments were performed to verify the localization of IL-17 and FAS/FASL in Hep-2 and Tu212 cells. The role of IL-17 was determined using siRNA techniques in the LC cell line. Results In the LC patients, cytokines were dysregulated in LC tissues compared with normal tissues. It was found that IL-17 was overexpressed in a cohort of 60 LC tumors paired with nontumor tissues. Moreover, high IL-17 expression was significantly associated with the advanced T category, the late clinical stage, differentiation, lymph node metastasis, and recurrence. In addition, the time course expression of FAS and FASL was observed after stimulation and treatment with the IL-17 stimulator. Finally, in vitro experiments demonstrated that IL-17 functioned as an oncogene by inhibiting the apoptosis of LC cells via the PI3K/AKT/FAS/FASL pathways. Conclusions In summary, these findings demonstrated for the first time the role of IL-17 as a tumor promoter and a prometastatic factor in LC and indicated that IL-17 may have an oncogenic role and serve as a potential prognostic biomarker and therapeutic target in LC.

H.pylori and Pepsin as a Putative Risk Factors in Laryngeal Cancer Patients.

Background: Laryngeal cancer constitutes 26-30% of all head and neck malignant tumors. Chronic stimulation by acid reflux may lead to a malignant change in the laryngopharyngeal mucosa. Pepsin assay could be a rapid, sensitive, and specific diagnostic marker of extra-esophageal reflux (EES). Helicobacter pylori is involved in the pathogenesis of peptic ulcer, and gastric carcinoma with growing interest in the presence of Helicobacter pylori in the upper aerodigestive tract.Aim: The aim of the study is to confirm the role of H.pylori and pepsin as risk factors in laryngeal cancer patients.Patients and Methods: Seventy-five patients were enrolled in this study, and divided into 3 groups; Group (A) 32 patients with suspected laryngeal malignancy. Group (B) 20 patients with benign laryngeal lesions. Group (C) 22 patients free from laryngeal disease, scheduled for non-laryngeal surgery. All patients were subjected to laryngo-pharyngeal lavage (LPL) using sterile water, before starting the surgical procedure and was analyzed for detection of Pepsin an H. Pylori, also culture for H. Pylori was done.Results: Strong positive association exist between H. pylori and Pepsin and occurrence of laryngeal carcinoma, while there was no statistically significant relationship with occurrence of a benign laryngeal lesions.Conclusion: GER is a risk factor or co-carcinogen in the pathogenesis of laryngeal carcinoma and not considered as a risk factor for benign laryngeal lesions. H. pylori culture and Pepsin assay in LPL can be used as non-invasive tool for detection of GER.

Downregulation of miR-29c-3p is associated with a poor prognosis in patients with laryngeal squamous cell carcinoma

BackgroundLaryngeal squamous cell carcinoma (LSCC) is considered to be a common malignancy of the head and neck with poor prognosis for its late diagnosis, metastasis and recurrence. Growing evidence demonstrates that the dysregulation of miR-29c-3p (microRNA-29c-3p) plays an important role in various tumor processes. Our study investigates the expression of miR-29c-3p in LSCC and analyzes the correlation of its dysregulation with clinicopathologic parameters and prognosis.MethodsThe expression of hsa-miR-29c-3p in LSCC tissues and the adjacent normal laryngeal tissues was detected in 96 LSCC formalin-fixed paraffin-embedded tissues by quantitative real-time PCR (qRT-PCR). The SPSS statistical software package (17.0) was used to analyze the associations between miR-29c-3p expressions and various clinicopathological characteristics. The overall survival (OS) was analyzed by the Kaplan-Meier method and log-rank test, and we analyzed the independent factor of prognosis by Cox proportional hazard analysis.ResultsA downregulation of miR-29c-3p expression in LSCC was significantly correlated with smoking index, tumor size, tumor site, differentiation, T classification, TNM stage, and lymph node metastasis (P < 0.05), but there was no correlation with age and alcohol consumption (P > 0.05). In the multivariate survival analysis, low miR-29c-3p expression was associated with shorter overall survival (P < 0.05). Furthermore, miR-29c expression was an independent prognostic factor for laryngeal cancer patients.ConclusionsMiR-29c-3p has different expression levels at different stages of tumor progression, suggesting that miR-29c-3p may be a promising biomarker for evaluating the progression of LSCC and the prognosis of patients with LSCC. MiR-29c-3p can also be a novel molecular target for anti-laryngeal cancer therapy.

Observational study on patients with laryngeal cancer and/or vocal leukoplakia concurrent with laryngopharyngeal reflux

Objective: To observe the incidence and to determine the significance of laryngopharyngeal reflux (LPR) in laryngeal cancer and vocal leukoplakia. Methods: The patients who had been diagnosed as laryngeal cancer or vocal leukoplakia between January 2014 and June 2017 were included in this study. All of them received 24-hour multichannel intraluminal impedance-pH monitoring. The prevalence of LPR and numerous parameters from the 24-hour pH monitoring in laryngeal cancer patient and vocal leukoplakia patient groups were analyzed. The chi-square test was used for counting data, t test and Mann-Whitney U were used for measuring data. Results: In the 91 laryngeal cancer patients, the prevalence of pathologic LPR was 28.6%(26/91), the median number[P(25), P(75), P(95)]of acid reflux events was 0[0, 3, 5], time of acid exposure was 0[0, 14, 234]s, number of weakly acidic reflux events was 3[0, 6, 11]. In the 54 vocal leukoplakia patients, the prevalence of pathologic LPR was 29.6%(16/54), the number of acid reflux events was 0[0, 3, 4], time of acid exposure was 0[0, 13, 118]s, number of weakly acidic reflux events was 1.5[0, 5, 9]. The incidence of LPR did not vary in the laryngeal cancer patient and vocal leukoplakia patient groups, but were both higher than healthy Chinese volunteers according to a report in the other literature. Furthermore, all the three patients with no history of tobacco or alcohol existed acid or weakly acidic reflux episodes. Conclusions: Laryngopharyngeal reflux might play a role as an etiologic factor in laryngeal cancer and vocal leukoplakia.

Survival analysis of surgically treated laryngeal cancer in Hospital Tengku Ampuan Afzan, Kuantan, Pahang from January 2002 to June 2013

Introduction: Laryngeal cancers are one of the most prevalent head and neck cancer in Malaysia. However, little information is available on survival rate for larynx cancer in Malaysia has been reported. The purpose of the present study was to evaluate the survival and the prognostic factors in surgically treated patient with laryngeal cancer in Hospital Tengku Ampuan Afzan, Kuantan, Pahang. Methods: Retrospective analysis of surgically treated patient of laryngeal cancer treated in Hospital Tengku Ampuan Afzan during January 2002 to June 2013 was analyzed. The overall survival rate was measured using the Kaplan Meier method. Prognostic factor was identified by log rank test taking p value &lt;0.05 as statistical significance. Results: A total 36 cases were analyzed. Two-thirds (86.1%) of the cases were at an advanced stage (stage III &amp; IV) at presentation. The 2, 5 and 10 year overall survivals for the laryngeal cancer were 62%, 34% and 22% respectively. The histopathological examination result was the strongest prognostic factors in laryngeal cancer. Conclusions: The results revealed remarkably poor outcomes of the patients in the series, indicating a strong need to increase the proportion of early stage presentations and maximize the treatment efficacy to improving outcomes.

Prognostic Value of Mean Platelet Volume and Platelet to Lymphocyte Ratio in Laryngeal Carcinoma

Objective: In this study, we aimed to investigate whether platelet lymphocyte ratio (PLR) and Mean platelet volume (MPV) values can be used as prognostic and diagnostic markers in laryngeal cancer. Methods: A total of 242 patients with laryngeal pathology were reviewed retrospectively. PLR, MPV and platelet values were compared in patients with benign and malignant pathologies. The correlation of PLR, MPV and platelet values of patients with malignant pathologies with their age, gender, smoking, alcohol use, degree of differentiation, and clinical stage was investigated. Results: The PLR values were significantly higher in smokers (p=0.009), alcohol drinkers (p=0.001), clinical stage IV patients (p=0.001), and patients with poor differentiated laryngeal cancer (p=0.001), compared to nonsmokers, non­alcohol consumers, clinical stage III patients, and patients with well-differentiated laryngeal cancer. MPV values were significantly lower in patients with clinical stage IV (p=0.018), and poor differentiated (p=0.010), laryngeal cancer com­pared to patients with clinical stage III and well-differentiated laryngeal cancer. The PLR value was significantly higher in the malignant group than in the benign group (p<0.001). Conclusion: Our results showed that PLR values can be used as diagnostic and prognostic factors and MPV values can be used as prognostic factors in laryngeal cancer. J Clin Exp Invest 2016; 7 (2): 134-138

Role of perineural invasion as a prognostic factor in laryngeal cancer.

The diffusion of laryngeal cancer cells in the perineural space is a parameter associated with a negative prognosis, high loco-regional recurrence and low disease-free survival rates. The spread of tumor cells on the perineural sheath highlights the histopathological and clinically aggressive behavior of this type of tumor, which may extend proximally or distally in the nerve for >10 cm. Therefore, the surgical resection margin is generally insufficient to treat patients with laryngeal cancer presenting with perineural invasion (PNI) with surgery alone. In PNI, the minor laryngeal nerves are frequently involved, rather than the superior and inferior laryngeal nerves. The aim of the present study was: i) To evaluate the prognostic importance of PNI; ii) to correlate the rate of infiltration with factors associated with the tumor, including histotype, site and tumor-node-metastasis stage, and with the type of surgery (total or partial laryngectomy); and iii) to evaluate the rate of disease-free survival according to the outcome of combined surgery and radiotherapy (RT) treatment, by means of retrospective analysis. The results of the present study highlighted the importance of performing a closer clinical and instrumental follow-up in patients with laryngeal cancer whose histopathological examination is positive for PNI. In such cases, it is important to complement the surgical therapeutic treatment with adjuvant RT.

Computer based correlation of the texture of P63 expressed nuclei with histological tumour grade, in laryngeal carcinomas.

Background. P63 immunostaining has been considered as potential prognostic factor in laryngeal cancer. Considering that P63 is mainly nuclear stain, a possible correlation between the texture of P63-stained nuclei and the tumor's grade could be of value to diagnosis, since this may be related to biologic information imprinted as texture on P63 expressed nuclei. Objective. To investigate the association between P63 stained nuclei and histologic grade in laryngeal tumor lesions. Methods. Biopsy specimens from laryngeal tumour lesions of 55 patients diagnosed with laryngeal squamous cell carcinomas were immunohistochemically (IHC) stained for P63 expression. Four images were digitized from each patient's IHC specimens. P63 positively expressed nuclei were identified, the percentage of P63 expressed nuclei was computed, and 118 textural, morphological, shape, and architectural features were calculated from each one of the 55 laryngeal lesions. Data were split into the low grade (21 grade I lesions) and high grade (34 grade II and grade III lesions) classes for statistical analysis. Results. With advancing grade, P63 expression decreased, P63 stained nuclei appeared of lower image intensity, more inhomogeneous, of higher local contrast, contained smaller randomly distributed dissimilar structures and had irregular shape. Conclusion. P63 expressed nuclei contain important information related to histologic grade.

Protection against laryngeal and pharyngeal carcinoma: Heterozygous vs. homozygous deletions of GSTM1 and GSTT1

Deletions in GSTM1 and GSTT1 genes are considered to be a risk factor for cancer development but the exact location of these deletions in the genome was unknown. Three main objectives of the current study were to: (a) identify the boundaries of these deletions in the human genome, (b) screen homozygous (−/−) and heterozygous (+/−) deleted, as well as homozygous present (+/+) individuals using PCR assays, (c) detect associations of pharyngeal (PC) and laryngeal cancer (LC) with the respective genotypes. In total, 102 PC and 92 LC patients were screened and compared with 150 controls. PCR mapping and sequencing revealed a 6 kbp deletion for GSTM1 and a 9 kbp deletion for the GSTT1 gene. The mean age of PC cases was 48.1 (±16.7) years; for LC cases it was 48.5 (±17.4) years and for controls 46 (±17.7) years. The OR (odds ratio) for the GSTM1 null genotype in PC and LC cases was 10.2 and 1.0 (95% CI 5.04–20.7 and 1.1–1.7) respectively. Similarly, for GSTT1 the OR was 4.02 with a 95% CI of 2.3–7.1 in PC cases. For LC cases the OR was 0.8 with 95% CI of 0.4–1.7. A non-significant number of LC and PC patients had heterozygous deletions of GSTM1 compared to controls (OD 0.5, 95% CI 0.2– 1.6 and OR 0.5, 95% CI 0.2– 1.5 respectively). The GSTT1 gene also showed a non-significant association in PC (OD 0.9, 95% CI 0.4–1.9), as well as in LC patients (OD 0.7, 95% CI 0.3–1.7). The homozygous genotype was significantly associated with PC and LC, whereas the heterozygous was not so. The GSTM1 (−/−) and GSTT1 (−/−) genotypes are a risk factor for LC and PC, whereas the (+/−) genotypes are not.

Helicobacter pylori infection of the larynx may be an emerging risk factor for laryngeal squamous cell carcinoma

Several studies have implicated Helicobacter pylori as a risk factor in laryngeal cancer, but other studies disagree. It is fundamental that the relationship between Helicobacter pylori and laryngeal cancer be verified in order to provide evidence of ways to prevent the initiation and development of this carcinoma. In total, 81 patients with laryngeal squamous cell carcinoma and 75 control subjects were enrolled in a case-control study. Semi-nested polymerase chain reaction techniques were applied to detect Helicobacter pylori in the laryngeal mucosa and enzyme-linked immunosorbent assays were used to detect serum antibodies against Helicobacter pylori. Risk factors associated with laryngeal carcinoma were analyzed using logistic regression models. The presence of Helicobacter pylori in the larynx was higher in patients with laryngeal cancer than in control subjects (71.6 vs. 25.3%, p<0.001). Among patients with laryngeal carcinoma, rates of Helicobacter pylori infection were higher in normal laryngeal tissues than in tumor tissues. After adjusting for confounding factors, regression analysis indicated that the microbe was an independent risk factor for laryngeal cancer (OR=7.15, 95% CI [3.29, 15.53], p<0.001). This study suggests that Helicobacter pylori is present in the mucosa of the larynx. The microorganism may be an independent risk factor for laryngeal squamous cell carcinoma. The laryngeal mucosa thus provides a reservoir for the bacteria possibly, and is a likely staging place for its transmission to other areas.

The relationship between the frequency of cervical metastases and tumor related factors in laryngeal cancer and outcome of surgical treatment in these cases

Objectives: We aimed to assess the associations between localization, size, stage and histopathological differentiation of primary tumor in larynx and neck metastases and the impact of disease stage on survival. Materials and methods: We analyzed the medical records of 333 laryngeal cancer patients who underwent total or partial laryngectomy as primary treatment, combined with neck dissection and/or postoperative radiotheraphy if required, between 2000 and 2010 years at our clinic. Age and gender of patients, tumor localization, size, stage and histopathological differentiation of tumor; presence of preoperative positive lymph nodes, performed operations, operation findings and histopathological results were analysed retrospectively. Results: Tumor localizations were glottic in 172 (51.6%) cases, supraglottic in 108 (32.4%), and transglottic 53 (15.9%) of the the cases. In glottic cancers; cervical metastases were observed in 18.6% of the patients, whereas occult metastases in 11%. In supraglottic cancers; cervical metastasis rate was 45.3% and occult metastases rate was 24%. In transglottic cancers, cervical metastases rate was 49% and occult metastases was 22.6%. Postoperative recurrence was 41 (12.3%). Postoperative radiotherapy was recommended to 111 of 333 patients. The overall survival rate was 75.4% at 50th month and the cumulative survival rate was 68.9%. Conclusion: In conclusion, although there is controversy regarding the optimal treatment in the N0 larynx cancers, in case of a high risk for occult metastases, elective unilateral or bilateral neck dissection should be performed according to the anatomic localization of the tumor. In addition, survival rate decreased significantly with the increasing tumor stage.

Reevaluation of Gastroesophageal Reflux Disease as a Risk Factor for Laryngeal Cancer

Reevaluation of Gastroesophageal Reflux Disease as a Risk Factor for Laryngeal Cancer

The Role of Laryngopharyngeal Reflux as a Risk Factor in Laryngeal Cancer: A Preliminary Report

ObjectivesTo evaluate the significance of laryngopharyngeal reflux (LPR) as a risk factor in laryngeal cancer.MethodsWe performed a case-control study with 29 consecutive laryngeal cancer patients who had undergone 24-hour ambulatory double pH monitoring from 2003 to 2006. The control group included 300 patients who had undergone 24-hour ambulatory double pH monitoring due to LPR-related symptoms. We analyzed the prevalence of LPR and numerous parameters from the 24-hour ambulatory double pH monitoring in the laryngeal cancer patient and control groups. Pathologic LPR is defined when more than three episodes of LPR occur in 24 hours.ResultsThe prevalence of pathologic LPR was significantly higher in the laryngeal cancer group than the control group (P=0.049). The reflux number of the upper probe was significantly higher in the laryngeal cancer group (P<0.001). However the effects of pathologic LPR on laryngeal cancer risk were diluted after adjusting for smoking and alcohol consumption in the multivariable logistic regression.ConclusionThe pathologic LPR might be a possible risk factor in the development of laryngeal cancer. A further study should be necessary to verify the exact role of LPR in laryngeal cancer.

Polymorphisms of CYP1A1 and GSTM1 and laryngeal cancer risk: evidence-based meta-analyses

Previous evidence implicates CYP1A1 and GSTM1 polymorphisms as risk factors for various cancers. A number of studies have been devoted to the association of CYP1A1 or GSTM1 polymorphism with susceptibility to laryngeal carcinoma, with the results inconsistent and inconclusive. The aim of the present study was to assess the possible associations of laryngeal cancer risk with CYP1A1 genetic variation and GSTM1 null genotype respectively. The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications, then the extracted data were further analyzed using systematic meta-analyses. The results showed that the overall odds ratio (OR) was 1.32 (95% CI = 1.08-1.61) for CYP1A1 Mspl polymorphism. Using subgroup analysis, the pooled ORs were 1.38 (95% CI = 0.98-1.95) in Asians and 1.29 (95% CI = 1.01-1.65) in Caucasians. For CYP1A1 exon7 polymorphism, the overall OR was 1.38 (95% CI = 0.98-1.95). The overall OR was 1.24 (95% CI = 1.03-1.49) for GSTM1 polymorphism and the pooled ORs were 1.36 (95% CI = 0.75-2.48) in Asians, 1.16 (95% CI = 0.94-1.44) in Caucasians and 1.52 (95% CI = 1.05-2.19) in Turkey population. The data suggest CPY1A1 MspI polymorphism as a risk factor for laryngeal cancer in Caucasians but not in Asians. However, the results suggest a marked correlation of GSTM1 polymorphism with laryngeal cancer risk in Turkey population but not Caucasians and Asians.

An immunohistochemical study of cyclin D1 protein expression in laryngeal squamous cell carcinoma

Conclusion. Contrary to most reports, our study shows that the expression of cyclin D1 is not an independent prognostic factor in patients with laryngeal cancer (LC). No correlation between cyclin D1 expression and survival rates in LC was found in a multivariate analysis. Objectives. The aim of this study was to determine the possible relevance of the expression of cyclin D1 protein in LC as prognostic criteria and to analyse correlation of the expression with clinicopathological features and survival rates. Materials and methods. Immunohistochemistry staining was used to detect the expression of cyclin D1 in 130 samples of laryngeal cancer and in 22 specimens of laryngeal nodules. Results. Cyclin D1 expression was found in 52 (40%) LC samples and in 3 (13.6%) samples of laryngeal nodules. There was no significant correlation between cyclin D1 expression and clinicopathological features of LC. A multivariate analysis of survival confirmed that cyclin D1 expression was not an independent prognostic factor in LC.

Intratumoral microvessels density and morphometric study of angiogenesis as prognostic factor in laryngeal cancer

Introduction: Angiogenesis is a multistage process which leads to the formation of new vessels. Intratumoral vascularity correlates with growth and metastases in many human solid tumors. The purpose of this paper was to determine the possible prognostic value of neovascularisation measured as intratumoral microvessel density (MVD) and microvessel area (MVA), respectively, in laryngeal cancer. Methods: A total of 151 patients with laryngeal cancer who received initial treatment were analysed. Using monoclonal antibody against von Willebrand factor (FVIII), immunohistochemical staining was performed on surgically obtained biopsy specimens and microvessels counted in the most active areas of tumor vascularisation (hotspots). Moreover, microvessel area was counted using morphometric method. Results: In univariate analysis, TNM (p<0.001), T-stage (p=0.001), N-stage (p<0.001) and MVD (p=0.001) were significantly correlated with overall survival; TNM (p<0.001), T-stage (p<0.001), N-stage (p<0.001) and MVD (p=0.01) were related to disease-free survival. In multivariate analysis, T-stage (p=0.01), N-stage (p<0.001) and MVD (p=0.002) were significantly correlated with overall survival. Only MVD (p=0.02) was significantly correlated with disease-free survival. We did not found significant influence of neovascularisation measured as MVA to the survival in patients with laryngeal cancer, although we observed correlation between MVD and MVA. Conclusions: The present study confirmed that multivariate analysis in accordance with the Cox proportional hazards model revealed that angiogenesis measured as MVD was an independent predictor of overall and disease-free survival.

Prognostic factors in laryngeal carcinoma: the role of apoptosis, p53, proliferation (Ki-67) and angiogenesis.

Even though the roles of different known or suggested prognostic factors in laryngeal cancer have been studied in detail, clinical stage at time of diagnosis and anatomic subsite of the tumour remain the only practical predictors of clinical outcome and offer the only guidelines in the planning of treatment. In this study, the relative roles of known demographic and clinical prognostic factors, in addition to four histopathological factors, were evaluated in a sample of 100 laryngeal carcinoma patients with multivariate analysis using the Cox regression model. In addition to advanced stage (stage III-IV) (relative hazard of death (HR) 8.9, p=0.01) and supraglottic disease (HR 5.6, p=0.02), high apoptotic index (HR 11.1, p=0.05) was significantly associated with poor survival. Cell proliferation, p53 and angiogenesis did not significantly affect the prognosis. In the future, high degree of apoptosis could be used to identify patients with poor prognosis in laryngeal cancer.

Prognostic value of CD44 variant 6 in laryngeal epidermoid carcinomas.

CD44 variant exon 6 (v6) belongs to a family of transmembrane glycoproteins involved in cell adhesion. To determine the prognostic role of CD44v6 in laryngeal cancer and to examine its relation with other clinicopathologic prognostic factors. A retrospective cohort study was designed with 93 laryngeal cancer cases. They were selected randomly from patients treated with laryngectomy between January 1, 1983, and December 31, 1993. Faculty of Medicine, Hacettepe University, Ankara, Turkey. The ages of the patients ranged from 31 to 73 years. Eighty-eight patients were men and 5 were women. Three had stage I, 33 had stage II, 27 had stage III, and 30 had stage IV disease at the time of surgery. Histological sections of tumors and metastatic lymph nodes were reevaluated for several histopathological factors. Sections were stained using anti-CD44v6 monoclonal antibody by immunohistochemical methods. CD44v6 expression was seen only in the lower one third of the normal squamous epithelium but in all layers of dysplasia and in situ carcinoma. Besides a general evaluation of tumor staining, immunostaining was evaluated separately for cell groups located in the center of neoplastic islands (nonbasal cells), at the periphery of the neoplastic islands (basal cells), and at the infiltration zones (marginal cells). Decreased disease-free survival was noted when there was extensive staining in the general evaluation and in cases with extensive staining in marginal and nonbasal cells (P =.03). Using Cox regression analysis, the greatest dimension of the largest metastatic lymph node and extensive expression of CD44v6 in nonbasal tumor cells were independent prognostic factors. Our results suggest that CD44v6 expression is an important prognostic factor in laryngeal cancer.