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Objectives: In this retrospective study, we evaluated the effectiveness of the tumor volume, grade invasion depth in the prediction of cervical lymph node metastasis. Identification of diagnostic parameters reliably predicting cervical lymph node involvement can be useful in improving the management of laryngeal cancer. Methods: One hundred and seven patients with squamous cell carcinoma of larynx and who underwent surgery were assessed retrospectively. Age, sex, Tumor-Node-Metastasis (TNM) stage, grade, invasion depth and computerised tomography (CT) volume of the tumors were analysed. The association between these parameters and cervical lymph node metastasis was determined. Results: Thirty two patients (29.91%) had positive cervical lymph nodes. Lymph node metastasis is detected in 13 (46.43%) poorly differentiated tumors, and in 19 (24.05%) moderate-well differentiated tumors. Mean volume was 2.15±0.14 cc in lymph node negative patients and 2.97±1.05 cc in lymph node positive patients. Mean invasion depth was 10.1±0.87 mm in lymph node negative patients and in 11.3±1.05 mm lymph node positive patients. The tumor grade and volume predicted successfully lymph node metastasis in patients with squamous cell carcinoma of the larynx, however invasion depth was not associated with nodal metastasis (p=0.047, p=0.0022, p=0.916, respectively). Conclusion: The tumor grade and volume could predict cervical lymph node metastasis in patients with squamous cell carcinoma of the larynx, whereas the depth of invasion did not. Calculation of the tumor volume radiologically can help predict lymph node metastasis by minimizing the variability in measurements such as the depth of invasion. [ABSTRACT FROM AUTHOR]

Background/Aim: Comparison of the expression of Ki-67, MCM3, 5, 7 and MTI/II proteins using immunohistochemistry (IHC) on whole section (WS) and tissue microarray (TMA) of laryngeal squamous cell carcinoma (LSCC) samples. Materials and Methods: A total of 51 archival paraffin blocks of LSCC were used. TMAs were prepared from 1.5 mm core punches. IHC reactions were performed using antibodies against Ki-67, minichromosome maintenance proteins (MCM3, 5, 7) and metallothionein (MTI/II). Results: Spearman rank correlation test revealed moderate positive correlation in the case of Ki-67: WS vs. TMA (r=0.38, p=0.07) and strong positive correlation in regard to the rest of tested markers: MCM3, WS vs. TMA (r=0.49, p=0.0004); MCM5, WS vs. TMA (r=0.61, p<0.0001); MCM7, WS vs. TMA (r=0.59, p<0.0001); MTI/II, WS vs. TMA (r=0.66, p<0.0001). Mann Whitney U-test showed no significant differences in the case of Ki-67 and MCM5. Moreover, Bland-Altman test showed a low level of bias in regard to Ki-67, WS vs. TMA and MCM5, WS vs. TMA. Conclusion: TMA may be an effective and reliable method of assessment of Ki-67 and MCM5 expression in LSCC. [ABSTRACT FROM AUTHOR]

Human laryngeal squamous cell carcinoma (LSCC) is a malignant cancer type. Epithelial‑mesenchymal transition marker Snail family transcriptional repressor 1 (SNAI1) is associated with the occurrence, development, invasion and metastasis of numerous tumor types, such as lung, liver and ovarian cancer. Previous studies have indicated that microRNA‑153 (miR‑153) may serve as a novel tumor suppressor, which is involved in tumor metastasis; however, the role and clinical significance of miR‑153 in LSCC are not fully understood. The aim of the present study was to determine the role of miR‑153 in the growth and aggressiveness of LSCC cells. Bioinformatics prediction method, western blot analysis, Matrigel invasion assay and immunofluorescence were used to analyze whether SNAI1 can be regulated and controlled by miR‑153 in LSCC cells. An inverse association between miR‑153 and SNAI1 was observed in LSCC tissues. It was demonstrated that SNAI1 is a direct target of miR‑153 in LSCC. In addition, the results indicated that miR‑153 knockdown inhibited PCI‑13 cell migration and invasion by targeting SNAI1, which may be a potential marker that can reflect the degree of malignancy in patients with LSCC. Furthermore, miR‑153 knockdown decreased Twist family BHLH transcription factor 1 and metastasis‑associated 1 family member 3 expression in LSCC cells. In conclusion, these data indicated that miR‑153 regulates LSCC migration via the targeting of SNAI1 gene, which may be a potential predictor for patients with LSCC. [ABSTRACT FROM AUTHOR]

Early detection and follow up of the laryngeal malignancies is usually done using the fiber optic exam. The tumors below 1 mm are difficult to be identified using normal white light. Narrow Band Imaging (NBI) is a new technology that uses an optical filter in order to obtain a light with fixed wave length of 415 nm and 540 nm. The special NBI allows the surgeon to visualize the vascular network at the site of the tumor. The mucosal capillaries are displayed in brown and the veins from the submucosa are displayed in cyan. Observing the abnormal vessel patterns will guide the surgeon in performing targeted biopsies that will be used in early detection and follow up of patients with laryngeal malignancies. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the photothermal effects of gold nanorods (GNRs) modified with antiepidermal growth factor receptor (EGFR) monoclonal antibody (mAb) on laryngeal cancer cells. EGFR protein expressions in HEP-2 cells, and normal laryngeal epithelial and laryngeal cancer tissues were detected by western blot. The cytotoxicity against HEP-2 and BEAS-2B cells was tested by MTT assay, and the photothermal effects were assessed by near-infrared (NIR) irradiation. The apoptosis of HEP-2 cells was detected by flow cytometry. EGFR expression in laryngeal cancer tissues was significantly higher than that in normal tissues (P < 0.05). The inhibitory effects of GNRs and anti-EGFR mAb/GNRs on the apoptosis of HEP-2 and BEAS-2B cells were enhanced with increasing dose. Anti- EGFR mAb/GNRs were more cytotoxic to HEP-2 cells and less cytotoxic to BEAS-2B cells than GNRs. NIR irradiation inhibited cell proliferation, which was enhanced with rising power, accompanied by continuously dropping survival rate. The apoptosis rate of the anti-EGFR mAb/GNRs group was significantly higher than that of the GNRs group, and the apoptosis rate of the irradiation + anti- EGFR mAb/GNRs group also significantly exceeded that of the irradiation + GNRs group (P < 0.05). Anti-EGFR mAb/GNRs promoted HEP-2 cell apoptosis more evidently than GNRs did. Functional modification of GNRs augmented the targeted specificity to cancer cells, biocompatibility, and stability. Anti-EGFR mAb/GNRs have great potential in biomedical fields. [ABSTRACT FROM AUTHOR]

Purpose: Preventive detection of premalignant lesions of vocal fold can play an important role for earlier detection of larynx cancer. In this paper, an automatic detection of premalignant lesions based on human voice production theory is designed. More specifically, premalignant lesions such as leukoplakia, Erythroplakia, Keratosis, etc are directly related to the vocal fold, features extracted from glottal fold waveform can be pertinent and critical. The proposed method performs as non-intrusive technique based on the extraction of vocal fold waveform from the recorded utterances. Method: The basic idea is to extract pertinent features from the source signal (glottal waveform). However, such signal is not directly accessible. Hence, we perform a first treatment of recorded speech using Iterative Adaptive Inverse Filtering (IAIF) to extract the glottal waveform. IAIF is applied on two databases: Massachusetts Eye and Ear Inrmary (MEEI) database and Saarbrucken Voice Database (SVD) with sustained vowel samples. From the glottal flow impulses, pertinent instances are used to build pertinent features. A deep exploration of extracted features, using statistical tools such as boxplot and Principal Component Analysis (PCA), leads to select the most critical and pertinent features. By using Support Vector Machine Technique as classification technique, a discrimination between normal and premalignant tumor is achieved. Results: Preliminary results show that some features are not discriminant. Those features are discarded and only pertinent ones are used in learning and testing processing using SVM. The performances are assessed using four criteria, sensitivity, specificity, precision and accuracy. When selected features are combined according to PCA analysis, an accuracy of about 92% is accomplished. Conclusion: It is shown in this study that is possible to detect the premalignant lesions with acceptable and fairly sensitivity, specificity, precision and accuracy. Such algorithm can help detect at earlier stage laryngeal cancer. [ABSTRACT FROM AUTHOR]

Due to the lack of a definite diagnosis, a frequent recurrence rate and resistance to chemotherapy or radiotherapy, the clinical outcome for patients with advanced laryngeal cancer has not improved over the last decade. Annexin A2 is associated with the invasion and metastasis of cancer cells. In the present study, it was demonstrated using differential proteomics analysis that Annexin A2 is highly expressed in laryngeal carcinoma tissues and this was confirmed using immunohistochemistry, which demonstrated that the expression of Annexin A2 in laryngeal carcinoma tissues was significantly higher than in healthy adjacent tissue. In addition, its potential predictive value in the prognosis of patients with laryngeal carcinoma was evaluated. The results demonstrated that Annexin A2 expression was significantly associated with tumor size, lymph node metastasis, distant metastasis and clinical stage. In addition, higher Annexin A2 expression was associated with a poor prognosis of patients with laryngeal cancer. Thus, the results of the present study indicate that Annexin A2 expression is an independent prognostic biomarker for evaluating the malignant progression of laryngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Lymphoepithelial carcinoma is a tumor mostly diagnosed in the nasopharynx, but it has also been described in a variety of nonnasopharyngeal sites. It is extremely rare in the larynx and should be distinguished from squamous cell carcinoma. Therefore, it must be known by clinicians, pathologists and oncologists. In this case report, we discuss its etiopathogeny, its epidemiological, clinical, pathological and therapeutic aspects, and its outcome. Case presentation: An 81-year-old Morrocan man, smoker for 40 years, presented with a 1 year history of dysphonia, dyspnea and dysphagia. Laryngoscopy showed a mass occupying supraglottic, glottic and subglottic levels of the larynx. Cervico-thoracic computed tomography scan showed a laryngeal wall thickening with cervical lymphadenopathy. Laryngeal biopsy was performed. Microscopic analysis and immunohistochemistry confirmed the diagnosis of laryngeal lymphoepithelial carcinoma. Immunostaining for LMP1 was negative. Conclusion: Laryngeal lymphoepithelial carcinoma is an extremely rare and an aggressive tumor. It is rarely associated with the EBV. It must be regarded as a distinct entity. Radiotherapy is advisable as the unique therapy for local tumor. A correct diagnosis and a close collaboration between the pathologist and clinicians is mandatory for an optimal treatment strategy. [ABSTRACT FROM AUTHOR]

Background: Laryngeal cancer is the second most common cancer of the head and neck after cancer of the oral cavity. The primary causes of death in cases of laryngeal cancer are the recurrence of locoregional disease and distant metastasis. Anatomic and tissue alterations resulting from surgery and/or radiotherapy of primary laryngeal tumors can make it difficult to determine a locoregional recurrence or residual disease by physical examination or computed tomography (CT)/magnetic resonance imaging (MRI). The majority of studies have shown a high accuracy in the detection of local and regional recurrence of head and neck cancer after different treatment modalities, using fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. Aim: To determine the diagnostic accuracy of PET/CT in patients with suspicion of locoregional recurrence from laryngeal carcinoma after surgery with or without adjuvant radiotherapy. Materials and methods: This was a retrospective study. Forty-five patients who previously underwent surgical treatment with or without adjuvant radiotherapy for primary laryngeal squamous cell carcinoma and who underwent examination using FDG-PET/CT imaging after clinical and instrumental (CT/MRI) suspicion of locoregional recurrence (T or N) were recruited. Results: Overall specificity, sensitivity, and accuracy of PET/CT were found to be 88%, 100%, and 93.3%, respectively. With respect to the suspected cases of recurrence in the primary site, sensitivity, specificity, and accuracy of PET/CT were found to be 100%, 87.5%, and 91.6%, respectively. In patients with suspected metastatic neck disease, PET/CT revealed a sensitivity, specificity, and accuracy of 100%, 90%, and 95.4%, respectively. Conclusion: According to the results of this study, PET/CT imaging in laryngeal tumors is a useful tool in case of suspected locoregional recurrence where conventional imaging (CT and MRI) is unable to resolve the diagnostic doubt. [ABSTRACT FROM AUTHOR]

Interleukin-35 (IL-35) has been proposed as a novel immune-suppressing cytokine. However, the function of IL-35 in malignant diseases is yet to be elucidated. The present study investigated IL-35 expression levels in laryngeal squamous cell carcinoma (LSCC) tissues and the peripheral blood of patients to explore the potential involvement of IL-35 in LSCC progression. In the present study, IL-35 expression levels in tissues and peripheral blood were analyzed by reverse transcription-quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The association between IL-35 expression levels and clinical characteristics was also evaluated. The present results demonstrated that IL-35 expression in tumor tissues was significantly higher than in adjacent normal tissues, and a significant association between IL-35 expression levels in tissues and the tumor site was detected. Furthermore, the expression of IL-35 in the peripheral blood of patients was significantly decreased subsequent to tumor resection. No correlation between peripheral blood IL-35 expression and clinical characteristics was detected. In conclusion, the present study demonstrated that IL-35 is highly expressed in LSCC tissues and in the peripheral blood of patients with LSCC. There was a notable, significant reduction of peripheral blood IL-35 expression following surgical resection of tumors. These results may be useful for diagnostic or therapeutic purposes in patients with LSCC. [ABSTRACT FROM AUTHOR]

A novel and effective pharynx and larynx cancer segmentation framework (PLCSF) is presented for automatic base of tongue and larynx cancer segmentation from gadolinium-enhanced T1-weighted magnetic resonance images (MRI). The aim of the proposed PLCSF is to assist clinicians in radiotherapy treatment planning. The initial processing of MRI data in PLCSF includes cropping of region of interest; reduction of artefacts and detection of the throat region for the location prior. Further, modified fuzzy c-means clustering is developed to robustly separate candidate cancer pixels from other tissue types. In addition, region-based level set method is evolved to ensure spatial smoothness for the final segmentation boundary after noise removal using non-linear and morphological filtering. Validation study of PLCSF on 102 axial MRI slices demonstrate mean dice similarity coefficient of 0.79 and mean modified Hausdorff distance of 2.2 mm when compared with manual segmentations. Comparison of PLCSF with other algorithms validates the robustness of the PLCSF. Inter- and intra-variability calculations from manual segmentations suggest that PLCSF can help to reduce the human subjectivity. [ABSTRACT FROM AUTHOR]

A cohort study was undertaken to analyze the risk of recurrence among 1616 patients with primary squamous cell carcinoma of the larynx from 1983 to 2010 at a single, tertiary academic center in Oslo, Norway. The cohort was followed from the date of diagnosis to September 2011. Competing risk regression analysis assessed the association between various risk factors and the risk of recurrence, where death was considered a competing event. Recurrence was observed in 368 patients (23%) during the study period. The majority (71%) of recurrences involved the location of the primary tumor. The overall risk of recurrence during the first three years after initiating treatment was 20.5%. Increased risk of recurrence was observed in patients with supraglottic cancer, younger patients, those with T2–T3 tumors and in patients treated in the earlier part of the study period. Significant factors for recurrence in glottic carcinomas were age, treatment in the earlier part of the study and T-status, whereas age was a significant factor in supraglottic cancer. N-status appeared less significant. In conclusion, follow-up of laryngeal squamous cell carcinoma should place particular emphasis on the site of the primary tumor, younger patients, cases of supraglottic cancer and T2-T4 primary tumors, especially during the first three years after treatment. More studies are needed to assess the impact of surgical versus non-surgical treatment, and eventually the significance of recurrence, for disease-specific and overall survival in cases of advanced laryngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Relapse and metastasis are the main causes of unfavorable outcome in head and neck cancers. Whereas, understanding of the molecular background of these processes is far from being complete. Therefore, in this study we aimed to identify potential biomarker candidates of relapse and metastasis in laryngeal squamous cell carcinoma (LSCC) by combining the 2D electrophoresis based protein screen and immunohistochemical analysis of candidate proteins. We screened three groups of LSCC cell lines derived from primary tumors, recurrent tumors and metastases and identified seven proteins that differed significantly in relative abundance between the analyzed groups. Among the identified proteins were the heat shock proteins HSP60 and HSP70 that were significantly downregulated both in recurrences- and metastases-derived cell lines but not in primary tumor-derived cell lines. Moreover, we identified significant upregulation of the annexin V, calreticulin and the inorganic pyrophosphatase (PPA1) exclusively in the metastases-derived cell lines. As these upregulated proteins could potentially become novel biomarkers of metastasis, we have compared their abundance in primary tumor LSCC N(0) cases, primary tumor LSCC N(+) cases as well as in LSCC metastases N(+). Our results show an intense increase of cytoplasmic PPA1 abundance in the N(+) ( p = 0.000042) compared to the N(0) group. In summary, we show a group of proteins deregulated in recurrences and metastases of LSCC. Moreover, we suggest the PPA1 protein as a potential new biomarker for metastasis in this cancer. [ABSTRACT FROM AUTHOR]

We report the utilization of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for enhanced computed tomography (CT) imaging of human laryngeal squamous carcinoma and indirect CT lymphography imaging in New Zealand rabbits. In this work, PEG-modified amine-terminated poly(amidoamine) dendrimers of generation 5 (G5·NH 2 ) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines to generate PEGylated Au DENPs. The formed PEGylated Au DENPs was used for both enhanced CT imaging of human laryngeal squamous carcinoma cells (Hep-2 cells) and the xenograft tumor mode, and indirect CT lymphography imaging in New Zealand rabbits. In vitro cytotoxicity assay, flow cytometry analysis, and cell morphology observation revealed that the formed PEGylated Au DENPs were non-cytotoxic at a Au concentration up to 400 μM for 24 h and indicated their good biocompatibility. Transmission electron microscopy data confirmed that the PEGylated Au DENPs was uptaken dominantly by the lysosomes of the cells. The PEGylated Au DENPs enabled not only enhance CT imaging of a xenograft tumor model in nude mice after intravenous injection of the particles, but also effective indirect CT lymphography imaging in rabbits. These findings suggest that the designed PEGylated Au DENPs can be used as a potentially effective contrast agent for CT imaging of various biological systems and different kinds of carcinoma, especially lymphatic mapping and human laryngeal squamous carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Both induction chemotherapy (ICT) followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx/hypopharynx cancer.Materials and Methods: Of the 60 enrolled patients, randomly assigned into two groups (30 in each group) previously untreated patients with stages III to IV larynx/hypopharynx squamous cell carcinoma were assigned to received two cycles of ICT with interval of 3 weeks (a) Group A paclitaxel 175 mg/m 2 on day 1 and carboplatin 450 mg on day 2 (PC), (b) Group B docetaxel and cisplatin 75 mg/m 2 each on day 1 and ifosfamide 2 g/m 2 on day 1-3 along with mesna (docetaxel-ifosfamide-cisplatin). Both groups were followed by conventional radiotherapy (60-70 Gy/5#/week). Primary end point was a response after ICT. Secondary endpoints included acute toxicities and overall response.Results: Baseline patient and tumor characteristics were well balanced between both groups, the response after ICT seen was 80% in Group A complete response (CR) 36.6% and partial response (PR) 43.3% and in Group B 79% response, CR 33% and PR 46%; whereas toxicities in Group B grade 3/4 neutropenia and grade 2/3 vomiting more severe than Group A. Radiation therapy was well tolerable to both groups with mild side effects.Conclusions: Definite role of neoadjuvant chemotherapy in locally advanced larynx/laryngopharyngeal cancer as organ preservation therapy. The efficacy found was quite similar and improved response in both groups except toxicity profile of Group B more severe, requiring the use of colony stimulating factors and supportive care along with. [ABSTRACT FROM AUTHOR]

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the otolaryngeal region and accounts for 1–2% of all malignancies diagnosed worldwide. miR-340 down-regulation and EZH2 up-regulation have been frequently identified in multiple cancers, but the role of miR-340 and EZH2 in LSCC has not been explored. In this study, we investigated the regulative role of miR-340 in EZH2 expression and LSCC progression. The results showed that EZH2 was up-regulated and miR-340 was down-regulated in both Hep-2 cells and LSCC tissues. Molecularly, our results confirmed that miR-340 directly targeted EZH2 gene and inhibited EZH2 expression. MTT assay and BrdU assay showed that miR-340 transfection reduced the cell proliferation ability of Hep-2 cells. The transwell assay indicated that the invasion and migration ability of Hep-2 cells was dramatically inhibited by miR-340 transfection. In addition, miR-340 transfection induced cell apoptosis with concomitant enhancement of Bax, increase of Caspase-3 expression and activity, and reduction of Bcl-2 expression in Hep-2 cells. Both miR-340 transfection and EZH2 knockdown induced p27 expression and suppressed PI3K/Akt activation in Hep-2 cells. Strikingly, EZH2 knockdown reduced cell proliferation, and EZH2 overexpression significantly rescued the miR-340-mediated suppressive effect on cell proliferation. Moreover, miR-340 could obviously induce the inhibition of Hep-2 cell-derived tumor growth and EZH2/p27 expression ratio in vivo . Taken together, these data suggest that miR-340 impedes LSCC progression by targeting EZH2 with the possible mechanism to enhance the expression of anti-oncogene p27 and suppress PI3K/Akt activation, providing a novel target and a potential therapeutic pathway against LSCC. [ABSTRACT FROM AUTHOR]

Laryngeal lipoma is a rare cause of upper airway obstruction in the pediatric population. We present a case of a 6-year-old boy with a laryngeal lipoma. Diagnosis was subject to doctors-delay, but open neck surgical resection was successful. [ABSTRACT FROM AUTHOR]

Laryngeal spindle cell carcinoma (SpCC) is an uncommon subtype of squamous cell carcinoma which represents 0.5% of all laryngeal squamous cell carcinomas. It is a biphasic tumor consisting of the combination of a malignant mesenchymal spindle cell component and a squamous cell component that includes dysplasia, carcinoma in situ, or invasive carcinoma. Although it has aggressive biological features, the probability of making a diagnosis in the early stages is high as it often leads to obstructive symptoms in the early period. Due to its low incidence, there is no clear consensus on prognostic factors and optimal treatment strategies yet. In this paper, a 60-year-old laryngeal SpCC case that was effectively treated with wide local excision followed by adjuvant radiotherapy was presented with the literature. [ABSTRACT FROM AUTHOR]

Multiple paragangliomas of the head and neck are rare conditions. Carotid paragangliomas are most common multiple paragangliomas. Laryngeal paragangliomas are very rare neuroendocrine tumors and usually are seen as symptomatic solitary lesions. We present multimodality imaging findings of incidentally detected laryngeal paraganglioma in a woman with synchronous carotid body paraganglioma and positive family history. To the best of our knowledge, this is the first case of laryngeal and carotid body paragangliomas in a patient with positive family history. Radiologists should keep in mind that paragangliomas may occur in various locations as multiple tumors. [ABSTRACT FROM AUTHOR]

Primary laryngeal non-Hodgkin's lymphomas are very rare constituting 1% of all laryngeal tumors. Of these, the peripheral T-cell lymphomas are extremely rare with <10 case reports in English literature. Laryngeal lymphomas are clinically confused with the more common laryngeal malignancies like squamous cell carcinoma, thus, histopathological examination is mandatory for diagnosing, sub-typing and guiding therapy for these lymphomas. We report a case of rare primary laryngeal peripheral T-cell lymphoma with autopsy findings. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the expression of EphA7 in human laryngeal squamous cell carcinoma (LSCC) tissues and disclose the potential roles and molecular mechanisms of EphA7 in LSCC. Methods: In the present study, we examined EphA7 expression and its function and mechanism in LSCC. EphA7 expression levels were investigated by quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry in a panel of 35 LSCC patient cases. To investigate the potential mechanism of EphA7 in human laryngeal cancer, we employed EphA7 siRNA to knockdown EphA7 expression in LSCC cell line Hep-2 and AMCHN- 8. Subsequently, MTT, TUNEL, qRT-PCR, and western blotting were performed to disclose the roles of EphA7 on proliferation, invasion and migration, and apoptosis in LSCC cell line Hep-2 and AMC-HN-8. Results: Depletion of EphA7 remarkably inhibited the proliferation and invasion of Hep-2 and AMC-HN-8 cells in comparison to control and EphA7 siRNA negative control (NC)-transfected cells. TUNEL staining assay demonstrated that, compared with the control group, the rate of apoptosis in the EphA7 siRNA group was significantly increased. In addition, knockdown of EphA7 in Hep-2 or AMC-HN-8 cells markedly decreased the expression of EphA7 and PTEN, which could contribute to apoptosis. However, the bpV(phen), a PTEN inhibitor, could attenuate anti-proliferation and pro-apoptotic effects of EphA7 siRNA in Hep-2 and AMC-HN-8 cells. Conclusion: Up-regulation of EphA7 was observed in human LSCC samples and down-regulation of EphA7 effectively suppressed laryngeal carcinoma cell growth and promoted its apoptosis. Thus, EphA7 has a critical role in modulating cell growth and apoptosis, which serves as a potential therapeutic target in human LSCC. [ABSTRACT FROM AUTHOR]

Anti-nuclear antibody ( ANA) testing assists in the diagnosis of several immune-mediated disorders. The gold standard method for detection of these antibodies is by indirect immunofluorescence testing on human epidermoid laryngeal carcinoma ( HEp-2) cells. However, many laboratories test for these antibodies using solid-phase assays such as enzyme-linked immunosorbent assay ( ELISA), which allows for higher throughput testing at reduced cost. In this study, we have audited the performance of a previously established ELISA assay to screen for ANA, making comparison with the gold standard HEp-2 immunofluorescence test. A prospective and unselected sample of 89 consecutive ANA test requests by consultant rheumatologists were evaluated in parallel over a period of 10 months using both tests. ELISA and HEp-2 screening assays yielded 40 (45%) and 72 (81%) positive test results, respectively, demonstrating lack of concordance between test methods. Using standard and clinical samples, it was demonstrated that the ELISA method did not detect several ANA with nucleolar, homogeneous and speckled immunofluorescence patterns. None of these ELISANEG HEp-2POS ANA were reactive with a panel of six extractable nuclear antigens or with double-stranded DNA. Nonetheless, 13 of these samples (15%) originated from patients with recognized ANA-associated disease ( n = 7) or Raynaud's phenomenon ( n = 6). We conclude that ELISA screening may fail to detect clinically relevant ANA that lack defined specificity for antigen. [ABSTRACT FROM AUTHOR]

Purpose: Human papillomavirus (HPV) is a major risk factor for specific cancers of the head and neck, particularly malignancies of the tonsil and base of the tongue. However, the role of HPV in the development of laryngeal cancer has not been definitively established. We conducted a population-based, cancer registry study to evaluate and characterize the genotype-specific prevalence of HPV in invasive laryngeal cancer cases diagnosed in the U.S. Methods: The presence of genotype-specific HPV DNA was evaluated using the Linear Array HPV Genotyping Test and the INNO-LiPA HPV Genotyping Assay in formalin-fixed paraffin embedded tissue from 148 invasive laryngeal cancer cases diagnosed in 1993–2004 within the catchment area of three U.S. SEER cancer registries. Results: HPV DNA was detected in 31 of 148 (21%) invasive laryngeal cancers. Thirteen different genotypes were detected. Overall, HPV 16 and HPV 33 were the most commonly detected types. HPV was detected in 33% (9/27) of women compared with 18% (22/121) of men (p = 0.08). After adjustment for age and year of diagnosis, female patients were more likely to have HPV-positive laryngeal tumors compared to males (adjusted OR 2.84, 95% CI 1.07–7.51). Viral genotype differences were also observed between the sexes. While HPV 16 and 18 constituted half of HPV-positive cases occurring in men, among women, only 1 was HPV 16 positive and none were positive for HPV 18. Overall 5-year survival did not vary by HPV status. Conclusions: HPV may be involved in the development of a subset of laryngeal cancers and its role may be more predominant in women compared to men. [ABSTRACT FROM AUTHOR]

A 67-year-old male presented with a metastatic carcinoma in the right side of the neck from an unknown primary site. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed increased 18F-FDG uptake in the right larynx and right neck lymph nodes. A smooth lesion was identified in the submucosa of the right supraglottic region via a suspension laryngoscopy under general anaesthesia. A biopsy was performed and a frozen section revealed a small-cell (SC) carcinoma. A total laryngectomy and bilateral neck dissection were performed simultaneously, and the pathological results demonstrated a SC neuroendocrine carcinoma. The patient received chemo-radiotherapy postoperatively, however, succumbed due to distant metastasis one year following surgery. [ABSTRACT FROM AUTHOR]

This study addresses the classification problem of the HEp-2 cell using indirect immunofluorescent (IIF) image analysis, which can indicate the presence of autoimmune diseases by finding antibodies in the patient serum. Generally, the method used for IIF analysis remains subjective, and depends too heavily on the experience and expertise of the physician. Recently, studies have shown that it is possible to identify the cell patterns using IIF image analysis and machine learning techniques. However, it still has large gap in recognition rates to the physical experts’ one. This paper explores an approach in which the discriminative features of HEp-2 cell images in IIF are extracted and then, the patterns of the HEp-2 cell are identified using machine learning techniques. Motivated by the progress in the research field of computer vision, as a result of which small local pixel pattern distributions can now be highly discriminative, the proposed strategy employs a parametric probability process to model local image patches (textons: microstructures in the cell image) and extract the higher-order statistics of the model parameters for the image description. The proposed strategy can adaptively characterize the microtexton space of HEp-2 cell images as a generative probability model, and discover the parameters that yield a better fitting of the training space, which would lead to a more discriminant representation for the cell image. The simple linear support vector machine is used for cell pattern identification because of its low computational cost, in particular for large-scale datasets. Experiments using the open HEp-2 cell dataset used in the ICIP2013 contest validate that the proposed strategy can achieve a much better performance than the widely used local binary pattern (LBP) histogram and its extensions, rotation invariant co-occurrence LBP, and pairwise rotation invariant co-occurrence LBP, and that the achieved recognition error rate is even very significantly below the observed intralaboratory variability. [ABSTRACT FROM PUBLISHER]

This is case where a middle aged gentleman presented with history of progressively worsening hoarseness for 1 year. On further history taking and examination including imaging noted patient had supraglottic mass arising from left ventricle, measuring 2x2cm with smooth surface mimicking a benign lesion. Histopatological examination revealed as adenoid cystic carcinoma of left ventricle with perineural invasion. [ABSTRACT FROM AUTHOR]

Background/aim: To investigate the expression of epidermal growth factor receptor--HER1 (EGFR), cerbB2 (HER2), p16, and p53, as well as the relationship of the expression of these genes with conventional parameters in squamous cell carcinoma (SCC) of the larynx. Materials and methods: Samples from 92 cases of diagnosed laryngeal SCC between 2001 and 2011 from the Pathology Department of Ministry of Health Ankara Dışkapı Yıldırım Beyazıt Teaching & Research Hospital were studied by immunohistochemistry using EGFR, cerbB2, p16, andp53 antibodies. Results: An increase in the TNM stage and pathological tumor size status correlated with an increase in EGFR and cerbB2 expression. In the cases with lymphovascular invasion, the expression was detected at a higher ratio. Cases in which high levels of p16 and p53 expression were observed did not show any lymphovascular invasions. Conclusion: Expressions of p53 and p16 were considered to be most effective in early carcinogenesis stages of laryngeal SCC. In comparison with p53 and p16 expression levels, EGFR and cerbB2 expression levels were observed to be associated with poor prognostic parameters and were higher at later stages of laryngeal carcinogenesis development. [ABSTRACT FROM AUTHOR]

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

Over 2,200 cases of carcinoma of the larynx are diagnosed in the UK annually, with an overall 5-year survival rate of 67%. Angiogenesis is vital for the growth and metastasis of solid tumours and the expression of key angiogenesis-related proteins has been shown to be of prognostic significance. In this study we reported the expression of key angiogenesis-related factors, selected from a pilot array study, in a cohort of laryngeal tumours and associated meta-static lymph nodes. Forty patients diagnosed with squamous cell carcinoma of the larynx were recruited. Tissue specimens were obtained intra-operatively, prior to chemo- and/or radiotherapy, from the tumours and secondary lymph nodes. The patient group comprised 32 men and 8 women with a mean age of 68 years (range, 51-89 years). The relative expression of the angiogenesis-related proteins angiogenin, interleukin (IL)-8, tissue inhibitor of metalloproteinases-1 (TIMP-1), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-basic and insulin-like growth factor binding protein 3 (IGFBP3) was determined in the tissue lysates by ELISA. The expression of angiogenin was higher in early-stage compared with late-stage tumours (P=0.034) and the expression of IGFBP3 was higher in tumours compared with the metastatic lymph nodes (P=0.016). No statistically significant differences were recorded for VEGF, FGF, TIMP-1 or IL-8 between tumour stages or primary tumours and lymph nodes. To the best of our knowledge, this study was the first to investigate multiple angiogenic factors in the lysates of laryngeal carcinomas and metastatic nodes and identified angiogenin and IGFBP3 as factors possibly involved in tumour progression. A greater understanding of their function may offer novel prognostic and/or therapeutic options. [ABSTRACT FROM AUTHOR]

Background: MicroRNA (miRNA) is an emerging subclass of small non-coding RNAs that regulates gene expression and has a pivotal role for many physiological processes including cancer development. Recent reports revealed the role of miRNAs as ideal biomarkers and therapeutic targets due to their tissue- or disease-specific nature. Head and neck cancer (HNC) is a major cause of cancer-related mortality and morbidity, and laryngeal cancer has the highest incidence in it. However, the molecular mechanisms involved in laryngeal cancer development remain to be known and highly sensitive biomarkers and novel promising therapy is necessary. Methodology/Principal Findings: To explore laryngeal cancer-specific miRNAs, RNA from 5 laryngeal surgical specimens including cancer and non-cancer tissues were hybridized to microarray carrying 723 human miRNAs. The resultant differentially expressed miRNAs were further tested by using quantitative real time PCR (qRT-PCR) on 43 laryngeal tissue samples including cancers, noncancerous counterparts, benign diseases and precancerous dysplasias. Significant expressional differences between matched pairs were reproduced in miR-133b, miR-455-5p, and miR-196a, among which miR-196a being the most promising cancer biomarker as validated by qRT-PCR analyses on additional 84 tissue samples. Deep sequencing analysis revealed both quantitative and qualitative deviation of miR-196a isomiR expression in laryngeal cancer. In situ hybridization confirmed laryngeal cancer-specific expression of miR-196a in both cancer and cancer stroma cells. Finally, inhibition of miR-196a counteracted cancer cell proliferation in both laryngeal cancer-derived cells and mouse xenograft model. Conclusions/Significance: Our study provided the possibilities that miR-196a might be very useful in diagnosing and treating laryngeal cancer. [ABSTRACT FROM AUTHOR]

Abstract: We report the implementation of the transnasal image-guided high wavenumber (HW) Raman spectroscopy to differentiate tumor from normal laryngeal tissue at endoscopy. A rapid-acquisition Raman spectroscopy system coupled with a miniaturized fiber-optic Raman probe was utilized to realize real-time HW Raman (2800–3020cm−1) measurements in the larynx. A total of 94 HW Raman spectra (22 normal sites, 72 tumor sites) were acquired from 39 patients who underwent laryngoscopic screening. Significant differences in Raman intensities of prominent Raman bands at 2845, 2880 and 2920cm−1 (CH2 stretching of lipids), and 2940cm−1 (CH3 stretching of proteins) were observed between normal and cancer laryngeal tissue. The diagnostic algorithms based on principal components analysis (PCA) and linear discriminant analysis (LDA) together with the leave-one subject-out, cross-validation method on HW Raman spectra yielded a diagnostic sensitivity of 90.3% (65/72) and specificity of 90.9% (20/22) for laryngeal cancer identification. This study demonstrates that HW Raman spectroscopy has the potential for the noninvasive, real-time diagnosis and detection of laryngeal cancer at the molecular level. [Copyright &y& Elsevier]

The article offers information on the study conducted by the authors related to human telomerase RNA component (hTERC) gene amplification detected by fluorescent in situ hybridization (FISH) in precancerous lesions and larynx cancer. It states that the study concluded that hTERC amplification is important in the development of laryngeal squamous cell carcinoma (LSCC).

The aim of this study was to investigate Fragile Histidine Triad Gene (FHIT) expression in laryngeal squamous cell carcinoma. The paraffin embedded tissue blocks of 64 laryngeal squamous cell carcinoma specimens were enrolled in the study. FHIT expression was detected by an immunohistochemical method. Rabbit polyclonal antibody was used for immunohistochemical study. FHIT expression was low in 40.6% of patients and high in 59.6% of patients. Results were compared with clinicopathological variables. There was a significant correlation between high FHIT expression and lymph node metastasis (p<0.05). There was no significant correlation between FHIT expression and age, histological grade, perineural invasion and vascular invasion. In conclusion, FHIT may be accepted to play a role in laryngeal squamous cell carcinoma tumorigenesis as a tumor suppressor gene. [ABSTRACT FROM AUTHOR]

Spindle cell (sarcomatoid) carcinoma is a rare variant of squamous cell carcinoma (SCC). It compromises of 2-3% of laryngeal cancers. Tumor arises from the oral cavity, tonsil larynx, and pharynx. Tumor is majority times misdiagnosed as reactive lesions or mesenchymal malignancies. It is considered to be a biphasic tumor that is composed of an SCC (in situ or invasive) and spindle cell carcinoma (SpCC) with sarcomatous appearance. In this case report, 61-year-male with minimal throat pain and acute onset dysphonia misdiagnosed and treated as a case of bronchial asthma with gastroesophageal reflux confirmed to have exophytic laryngeal growth is the cause for clinical presentation. We performed fiberoptic laryngoscopy and diagnosed to have SpCC of larynx. High index of suspicion is a must in geriatric cases with documented history of smoking and fiberoptic laryngoscopy/bronchoscopy found to be crucial in the evaluation. Histopathology expertise in surgical oncology is essential while planning treatment. [ABSTRACT FROM AUTHOR]

The larynx and thyroid gland are the most common sites for head and neck malignancies. The existence of two primary cancers are rare and especially if they are in the same region, and both are very invasive. Subglotic laryngeal cancer is the rarest, with only 1% frequency of all laryngeal cancers. We are reporting on a case of a forty seven-year-old female urgently admitted to the Ear, Nose and Throat (ENT) Clinic in Tuzla, with severe respiratory insufficiency. The patient underwent total laryngectomy, total thyreoidectomy, radical and functional neck dissection. Histological examination showed laryngeal squamous cell carcinoma and papillary thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Introduction. Each year around 2,200 people in the UK are diagnosed with laryngeal SCC (Office of National Statistics 2009). Compared to pharyngeal carcinoma, it is a highly curable disease with a survival rate of around 60% for all stages and all forms of treatment. Case Presentation. We present the case of a 60-year-old man with a previously treated T4 N2c transglottic squamous cell carcinoma (SCC), who developed an isolated swelling in the extensor compartment of his right forearm at 6 months after radical laryngectomy with bilateral neck dissection. Fine needle aspiration of the forearm lesion revealed SCC consistent with a metastasis from the laryngeal primary. MRI revealed that the lesion was confined to the muscle. Initial staging CT showed no distant metastases or signs of advanced disease, including no evidence of axillary nodal involvement. Conclusion. This case is therefore unusual, as one of only 2 cases reported in the scientific literature of isolated distant muscular metastasis from a laryngeal squamous cell carcinoma. We conclude that any muscular swelling, in the setting of previous head and neck malignancy, should be treated with a high degree of suspicion for metastasis and investigated promptly. [ABSTRACT FROM AUTHOR]

Schwannomas are rare neurogenic tumors derived from the schwann cells. Their laryngeal location is uncommon and the diagnosis is difficult. We report a case of a 17-year-old female who presented with symptoms of intermittent breathlessness mimicking acute attacks of bronchial asthma and resulted in delayed diagnosis, which lead to upper airway obstruction and an emergency tracheostomy. Computed tomography (CT) of neck revealed a soft-tissue mass within the subglottic region. Surgical excision of the growth was done by laryngofissure technique. Histopathological examination of the tumor revealed it to be a schawanoma. The subglottic occurrence of schwannoma is very rare. Case history and detailed clinical examination are important and will guide for relevant investigations and help to reach at a definitive diagnosis. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Choline phosphate-based delivery systems can target the acidic tumor microenvironment. In this study, we set out to evaluate the diagnostic value of Choline phosphate cytidylyltransferase-α (CCTα) in laryngeal squamous cell cancer (LSCC). The expression of CCTα was detected using immunohistochemistry in 50 LSCC patients' tissues and 16 vocal polyps as control group. Then, clinical data was collected and we used receiver operating characteristic curve (ROC) to estimate the potential of CCTα as diagnostic biomarker. We found CCTα levels to be significantly high in the tissues derived from LSCC patients, (p < 0.001). Further, we observed a positive correlation of CCTα with tumor size (p < 0.001), TNM stage (p < 0.001), lymph node metastasis (p < 0.001) as well as the grade of LSCC malignancy (p < 0.001). Furthermore, AUC was determined to be 0.939 by ROC, and the optimal cutoff value 3.100, with 76.0% sensitivity and 100% specificity. We also found an epigenetic basis of CCTα over-expression in LSCC tissues with significantly reduced methylation of CCTα in LSCC tissues, compared to vocal polyps (p < 0.001). These results support epigenetically-induced over-expression of CCTα as a potential diagnostic marker for LSCC. [ABSTRACT FROM AUTHOR]

Background: LZTS2 (leucine zipper tumor suppressor 2), a candidate tumor suppressor gene, suppresses cell growth and plays a vital role in the carcinogenesis and development of tumors. No studies to date have described methylation of the LZTS2 promoter in human cancers, including LSCC (laryngeal squamous cell carcinoma). Therefore, the aim of this study was to explore the relationship between LZTS2 promoter methylation and risk of LSCC. Methods: In our study, LZTS2 promoter methylation levels in LSCC tumor and adjacent normal tissues from 96 patients were measured using quantitative methylation-specific polymerase chain reaction (qMSP) assays. Results: The qMSP analyses revealed that LZTS2 promoter methylation levels in the LSCC tumor samples were significantly higher than those in paired adjacent healthy tissue samples. Furthermore, LZTS2 methylation levels were elevated in smokers, advanced T classified, and clinically staged patients, as well as in patients with lymph node metastases. In addition, Kaplan-Meier survival curves results showed that overall survival of LSCC patients with hypomethylated LZTS2 promoters was significantly higher than that in patients with hyper-methylated LZTS2 promoters (log-rank test P = 0.028). Meanwhile, the area under the receiver operating characteristic curve was 0.920. The diagnostic threshold value for LZTS2 methylation was 11.63% (94.7% sensitivity and 80.4% specificity). Conclusions: LZTS2 promoter hypermethylation is associated with risk, progression, and prognosis of LSCC in a cohort of 96 human subjects; LZTS2 promoter hypermethylation is a candidate diagnostic and prognostic biomarker for LSCC. [ABSTRACT FROM AUTHOR]

Lymphangiomas are congenital lesions of the lymphatic system which are most commonly found in the head and neck, with over 90 % of lesions manifesting in children who are less than 2 years of age. Haemolymphangiomas are rare variant of lymphangioma, with the presence of red blood cells within the lymphatic channels. Laryngeal sites are usually in continuity with foci of disease in the neck. In general, symptoms are non-specific and they vary with the site and size of the mass. Usually, they occur before 2 years of age. Isolated cases of lymphangiomas with involvement of epiglottis are rare and only a few cases have been reported so far. We are reporting the case of a six-year-old girl who presented with a mass in the epiglottis. [ABSTRACT FROM AUTHOR]

A letter to the editor related to a case study of a 64-year-old gentleman was diagnose with fluorodeoxyglucose positron emission tomography/computed tomography (FDG) PET/CT for radiotherapy treated laryngeal cancer.

Cancer neovascularization plays an essential role in the metastasis of larynx carcinoma (LC). However, the underlying molecular mechanisms are not completely understood. Recently, we reported that placental growth factor (PLGF) regulates expression of matrix metalloproteinase 3 (MMP3) through ERK/MAPK signaling pathway in LC. Here, we show that MMP9 upregulated in LC, and appeared to be mainly produced by M2 macrophages (tumor-associated macrophages (TAM)). In a transwell co-culture system, PLGF secreted by LC cells triggered macrophage polarization to a TAM subtype that releases MMP9. Moreover, MMP9 was found to be activated in the PLGF-polarized TAM via transforming growth factor β (TGFβ) receptor signaling activation. Furthermore, PLGF in LC cells induced macrophage polarization in vivo, and significantly promoted the growth of LC. Thus, together with our previous work, our study highlights a pivotal role of cross-talk between TAM and LC in regulating the metastasis of LC. [ABSTRACT FROM AUTHOR]