Posterior Semicircular Canal Plugging Relieves Tumarkin's Crisis in Ménière's Disease Patients.

(1) Background: Patients affected by Ménière's disease can experience Tumarkin's syndrome, which is characterized by postural instability, gait abnormalities, and, occasionally, an abrupt loss of balance known as vestibular drop attack or Tumarkin's crisis. In this study, semicircular canal plugging is proposed as the definitive treatment for this condition. The outcomes of this type of surgery are discussed. (2) Methods: A total of 9 patients with a confirmed diagnosis of Ménière disease suffering from Tumarkin crisis underwent posterior semicircular canal plugging. These patients were assessed with Video Head Impulse Tests, vestibular evoked myogenic potentials, and Pure Tone Audiometry preoperatively and postoperatively. (3) Results: VHIT showed a postoperative decrease in PSC gain median (Preop. 0.86 and postop. 0.52; p < 0.009). No statistically significant differences were described for the anterior semicircular canal and the lateral semicircular canal. No patient experienced new Tumarkin crisis after the surgical treatment. (4) Conclusions: Our ten years of experience with posterior semicircular canal plugging in Ménière disease patients with Tumarkin's syndrome has shown that this type of surgical procedure is successful in controlling Tumarkin's crisis, with high patient satisfaction and little worsening in hearing level.

Role of SAMITAL in the Prevention and Treatment of Chemo-Radiotherapy-Induced Oral Mucositis in Head and Neck Carcinoma: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Trial (ROSAM).

BACKGROUND: In patients affected by head and neck squamous cell carcinoma, the onset of severe oral mucositis is a decisive factor in completing concurrent chemo-radiotherapy, and few interventions have demonstrated a modest benefit. The primary aim of this clinical study was to evaluate the role of SAMITAL in reducing the incidence of severe mucositis induced by concurrent chemo-radiotherapy; the secondary aims were the tolerability and patient-reported quality of life measures. METHODS: Patients were randomized to receive SAMITAL granules for oral suspension of 20 mL, four-time daily or matching placebo in a 1:1 fashion using a stratified-block randomization scheme by disease site and type of chemotherapy. The SAMITAL/placebo was dispensed at the baseline visit and at each weekly visit following radiotherapy initiation. Patients were subjected to weekly endoscopic evaluations to assess the presence of mucositis. In addition, patient-reported outcomes were measured. RESULTS: Among the 116 patients treated with a median total dose of 66 Gy, 59 were randomized to SAMITAL and 57 to placebo. Overall, the incidence of severe mucositis was 51.7%, with 45.8% in the SAMITAL and 57.9% in the placebo arm (OR = 0.6; 95% CI: 0.3-1.3). After chemo-radiotherapy, patients randomized to SAMITAL reported significantly lower xerostomia, coughing and swallowing scores and a better quality of life. CONCLUSION: SAMITAL did not significantly reduce the incidence of severe mucositis in all studied populations. However, the lower rate of mucositis, together with a significantly better quality of life, suggested that a clinical benefit existed. This trial is registered with the EU Clinical Trials Register database, number 2012-002046-20, and with ClinicalTrials.gov, NCT01941992.

Prognostic impact of neutrophils-to-lymphocytes ratio (NLR), PD-L1 expression, and tumor immune microenvironment in laryngeal cancer.

PURPOSE: In laryngeal carcinoma (LSCC), tumor immune microenvironment is attracting increasing interest, given the recent progresses in immunotherapy. Immune cells migrate to tumors as a result of a tumor antigen-induced immune reaction and cancer cells recruit immune regulatory cells to induce an immunosuppressive network, resulting in the escape from host immunity. This interaction reflects both on tumor microenvironment and systemic inflammatory status. Blood neutrophil-to-lymphocyte ratio (NLR), reflecting a highly pro-inflammatory status, has been related to worse oncological survival outcomes. The aim of this study was to analyze in LSCC the relationship between circulating inflammatory cells (also in terms of NLR) and tumor immune microenvironment histopathological features (programmed cell death ligand 1 [PD-L1] expression, and tumor-infiltrating lymphocytes [TILs]), also investigating their clinical-pathological and prognostic significance. METHODS: Blood pre-operative NLR, and, at pathology, PD-L1 (in terms of combined positive score [CPS]) and TILs were assessed on 60 consecutive cases of LSCC. RESULTS: Blood NLR, neutrophils, and lymphocytes counts showed a significant value in predicting DFS and recurrence risk. Moreover, PD-L1 CPS ≥ 1 and TILs count rate ≥30% were associated with higher disease-free survival (DFS) and reduced recurrence risk. A logistic regression model found a significant positive association between increasing NLR values, and PD-L1 CPS < 1 and TILs count rate <30%. CONCLUSIONS: Further studies are needed to better characterize the role of pre-operative blood NLR in association with PD-L1 expression and tumor immune microenvironment features as prognostic factors and markers of anti-tumor immune response in LSCCs, also with regard to the effectiveness of immunotherapeutic protocols.

Postoperative radiotherapy for laryngeal cancer. The prognostic role of programmed death-ligand 1: An immune microenvironment-based cluster analysis.

BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) expression and the tumor's immune microenvironment has yet to be investigated in the specific setting of adjuvant postoperative radiotherapy (PORT) for laryngeal carcinoma (LSCC). The main aim of this exploratory study was to investigate, also by cluster analysis, whether PD-L1 expression (in terms of combined positive score [CPS]), tumor-infiltrating lymphocytes (TIL), and tertiary lymphoid structures (TLS) correlated prognostically with response to PORT in a cohort of consecutive LSCC patients. METHODS: PD-L1, TIL and TLS were assessed in 24 consecutive patients with LSCC who underwent PORT. Cluster analysis was used to classify cases on the strength of these parameters. RESULTS: A CPS ≥ 1 was associated with a significantly lower recurrence rate (p = 0.033), and longer disease-free survival (DFS) (p = 0.012) than a CPS < 1. Two clusters of prognostic relevance emerged from our analysis. Cluster 1 was characterized by a mean CPS of 23.0 ± 37.9, a mean TIL count of 68.0 ± 16.4, and the presence of TLS in all cases. Cluster 2 featured a mean CPS of 3.1 ± 7.3, a mean TIL count of 23.9 ± 16.5, and no cases with TLS. Cluster 1 showed a trend towards a lower recurrence rate (p = 0.071) and longer DFS (p = 0.054) than cluster 2. CONCLUSIONS: Judging from this preliminary investigation, assessing PD-L1 and immune microenvironment markers seems a promising approach for identifying patients at higher risk of LSCC recurrence after PORT, who might reasonably benefit from adjuvant postoperative chemo-RT, or immunotherapy.

Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features.

Introduction: Adverse effects of radiotherapy (RT) significantly affect patient's quality of life (QOL). The possibility to identify patient-related factors that are associated with individual radiosensitivity would optimize adjuvant RT treatment, limiting the severity of normal tissue reactions, and improving patient's QOL. In this study, we analyzed the relationships between genetic features and toxicity grading manifested by RT patients looking for possible biomarkers of individual radiosensitivity. Methods: Early radiation toxicity was evaluated on 143 oncological patients according to the Common Terminology Criteria for Adverse Events (CTCAE). An individual radiosensitivity (IRS) index defining four classes of radiosensitivity (highly radiosensitive, radiosensitive, normal, and radioresistant) was determined by a G2-chromosomal assay on ex vivo irradiated, patient-derived blood samples. The expression level of 15 radioresponsive genes has been measured by quantitative real-time PCR at 24 h after the first RT fraction, in blood samples of a subset of 57 patients, representing the four IRS classes. Results: By applying univariate and multivariate statistical analyses, we found that fatigue was significantly associated with IRS index. Interestingly, associations were detected between clinical radiation toxicity and gene expression (ATM, CDKN1A, FDXR, SESN1, XPC, ZMAT3, and BCL2/BAX ratio) and between IRS index and gene expression (BBC3, FDXR, GADD45A, and BCL2/BAX). Conclusions: In this prospective cohort study we found that associations exist between normal tissue reactions and genetic features in RT-treated patients. Overall, our findings can contribute to the identification of biological markers to predict RT toxicity in normal tissues.

ß-Arrestin-1 expression and epithelial-to-mesenchymal transition in laryngeal carcinoma.

AIM: The novel primary end-point of the present study was to ascertain ß-arrestin-1 expression in a cohort of consecutive patients with laryngeal squamous cell carcinoma (LSCC) with information available on their cigarette-smoking habits. A secondary end-point was to conduct a preliminary clinical and pathological investigation into the possible role of ß-arrestin-1 in the epithelial-to-mesenchymal transition (EMT), identified by testing for E-cadherin, Zeb1, and Zeb2 expression, in the setting of LSCC. METHODS: The expression of ß-arrestin-1, E-cadherin, zeb1, and zeb2 was ascertained in 20 consecutive LSCCs. RESULTS: Statistical analysis showed no significant associations between ß-arrestin-1 and EMT (based on the expression of E-cadherin, Zeb1, and Zeb2). The combined effect of nicotine and ß-arrestin-1 was significantly associated with a shorter disease-free survival ( P=0.01) in our series of LSCC. This latter result was also confirmed in an independent, publicly available LSCC cohort ( P=0.047). CONCLUSIONS: Further investigations on larger series (ideally in prospective settings) are needed before we can consider closer follow-up protocols and/or more aggressive treatments for patients with LSCC and a combination of nicotine exposure and ß-arrestin-1 positivity in tumor cells at the time of their diagnosis. Further studies on how ß-arrestin functions in cancer via different signaling pathways might reveal potential targets for the treatment of even advanced laryngeal malignancies.

Nuclear expression of onco-suppressors nm23-H1 and maspin are associated with lower recurrence rate in laryngeal carcinoma.

PURPOSE: The main aim of the study was to preliminarily investigate the possibly related role of nuclear onco-suppressors maspin and nm23-H1, a metastasis suppressor, in laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: Maspin expression pattern and nuclear nm23-H1 expression were ascertained in 62 consecutive LSCCs. RESULTS: Recurrence rate was significantly lower in patients with a nuclear maspin pattern of expression; nuclear nm23-H1 expression was significantly lower in patients who experienced disease recurrence. Disease free survival (DFS) was significantly longer in patients with maspin nuclear pattern or with nuclear nm23-H1 expression ≥10%. A significant association was found between nuclear nm23-H1 expression and maspin pattern of expression in LSCC. KNN discriminant analysis considered N status, maspin sub-cellular localization and nuclear nm23-H1 expression. The selected variables' accuracy in terms of relapse was 82%. Positive predictive accuracy was 100%, and negative predictive accuracy 79%. CONCLUSIONS: Nuclear nm23-H1 expression and maspin pattern, also in association, show promise as recurrence indicators in LSCC. Further studies are needed to shed more light on the nm23-H1 mechanism of action in LSCC and thus find ways to restore nm23-H1 loss. These preliminary findings suggest that re-activating maspin functions might represent an important goal in the treatment of advanced LSCC.

Nuclear nonmetastatic protein 23-H1 expression and epithelial-mesenchymal transition in laryngeal carcinoma: A pilot investigation.

BACKGROUND: In epithelial-to-mesenchymal transition, epithelial cells lose their features, acquiring a mesenchymal-like phenotype. Nm23-H1 protein relates to tumor cells' metastatic potential, its low expression in carcinomas often meaning a poor prognosis. This study newly investigated the role of nuclear nm23-H1 in laryngeal squamous cell carcinoma epithelial-to-mesenchymal transition. METHODS: Immunohistochemical analyses of nuclear nm23-H1, E-cadherin, N-cadherin, Snail, Zinc finger E-box binding homeobox (ZEB)1, and ZEB2 were performed in 33 consecutive patients with laryngeal SCC. RESULTS: Mean nuclear nm23-H1 expression was lower in patients whose disease recurred (P = .0046). Disease-free survival (DFS) was longer for patients whose nuclear nm23-H1 expression was ≥10% (P = .0083). Nuclear nm23-H1 and E-cadherin expressions correlated directly (P = .018). Mean E-cadherin expression was lower in patients whose disease recurred (P = .03). The DFS was shorter in patients with ZEB2 expression ≥5% (P = .006). CONCLUSIONS: Nuclear nm23-H1 expression warrants further investigation in laryngeal SCC as a prognostic marker identifying patients at higher risk of recurrence. nm23-H1 targeted treatments may be capable of regulating epithelial-to-mesenchymal transition.

Cortactin and phosphorylated cortactin tyr421 and tyr466 expression in supraglottic laryngeal carcinomas and lymph node metastases.

BACKGROUND: The most important adverse prognostic factor for laryngeal squamous cell carcinoma (LSCC) is the presence of cervical lymph node metastases. The supraglottic area of the larynx is richly supplied with lymphatics, and 25%-75% of supraglottic carcinomas metastasize in neck lymph nodes. Cortactin is a multidomain protein related to actin cytoskeleton regulation, podosome and lamellipodia formation, integrin signaling, axon guidance and extracellular matrix degradation. Cortactin is involved in metastasis formation because of its role in cell mobility. The present study focused mainly on the role of cortactin and phosphorylated cortactin (residues tyr421 and tyr466) expression and subcellular localization in primary supraglottic LSCCs and their cervical lymph node metastases. METHODS: The immunohistochemical expression of cortactin, p-Y466-cortactin and p-Y421-cortactin was assessed in 38 primary supraglottic LSCCs and 10 lymph node metastases. The statistical approach included bootstrapping analysis. RESULTS: Despite a significantly higher expression of cortactin in carcinoma cells than in adjacent normal laryngeal mucosa, no associations emerged between prognosis and the expression of cortactin or its isoforms in supraglottic LSCC. Statistical analysis found cortactin expression higher in less-differentiated LSCCs (p = 0.03). A significant direct correlation was found between cortactin and p-Y466-cortactin levels (p = 0.031), and between p-Y466-cortactin and p-Y421-cortactin levels (p = 0.001). CONCLUSIONS: Cortactin expression in carcinoma cells and its known involvement in the EGFR pathway suggest a role for this protein as a target for LSCC therapy. Further prospective studies are needed to investigate the potential of cortactin, p-Y466-cortactin and p-Y421-cortactin expression as markers of response to treatment (particularly EGFR-directed agents) in LSCC.

YAP, TAZ and AREG expression in eighth cranial nerve schwannoma.

BACKGROUND: Although the diagnosis and treatment of eighth cranial nerve (VIII CN) schwannoma (acoustic neuroma) has improved over the years, no factors capable of predicting tumor growth have been identified as yet. This study is a preliminary investigation of the expression in sporadic VIII CN schwannomas of Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), and amphiregulin (AREG), a direct target gene of YAP and TAZ. The expression of YAP, TAZ and AREG was correlated with the volumetric dimensions of tumors on contrast-enhanced magnetic resonance imaging (ceMRI). METHODS: YAP, TAZ and AREG expression was assessed immunohistochemically in surgical specimens of 36 consecutive sporadic VIII CN schwannomas. 3D reconstructions of the tumors and their corresponding volumes in cm3 were obtained from measurements on ceMRI images using the OsiriX® software. RESULTS: We found a significant direct correlation between TAZ expression and VIII CN schwannoma volumes on latest preoperative ceMRI (p<0.0003). Mean TAZ expression was also significantly higher in VIII CN schwannomas with a volume ≥2.1 cm3 than in those with a volume <2.1 cm3(p<0.0018). No significant correlations emerged for YAP or AREG expression and VIII CN schwannoma volume. CONCLUSIONS: The immunohistochemical expression of TAZ (but not YAP or AREG) correlated significantly with schwannoma volume measured on ceMRI. Further investigations are needed to identify the biological factors influencing tumor proliferation (ideally secreted proteins like AREG) that might be detected using non-invasive approaches (i.e., blood samples).

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

AIMS: Survivin-a member of the family of inhibitor of apoptosis proteins that control cell division, apoptosis and metastasis-is overexpressed in virtually all human cancers, including laryngeal squamous cell carcinoma (LSCC). Recent findings also correlate survivin expression with the regulation of angiogenesis. The novel main aim of this study was a preliminary investigation into the potential role of survivin expression in LSCC neoangiogenesis, as determined by endoglin-assessed microvascular density (MVD). METHODS: Immunohistochemical expression of nuclear survivin and endoglin-assessed MVD were ascertained by image analysis in 75 consecutive LSCCs. RESULTS: Statistical analysis disclosed a strong direct correlation between nuclear survivin expression and MVD. Patients whose nuclear survivin expression was ≥6.0% had a significantly higher LSCC recurrence rate, and a significantly shorter disease-free survival (DFS) than those with a nuclear survivin expression <6.0%. The LSCC recurrence rate was also higher and the DFS shorter in patients with endoglin-assessed MVD ≥6.89%. The OR for recurrence was 2.79 in patients with LSCC with a nuclear survivin expression ≥6.0%, and 12.31 in those with an MVD≥6.89%. CONCLUSIONS: Survivin-targeting strategies to enhance tumour cell response to apoptosis and inhibit tumour growth should receive more attention with a view to developing agents for use in multimodality advanced LSCC treatment, or combined with conventional chemotherapy. Given the present preliminary evidence in LSCC, survivin targeting should also be further investigated for anti-angiogenic purposes, to reduce tumour blood flow and induce cancer necrosis.

Prognostic Significance of Serine-Phosphorylated STAT3 Expression in pT1-T2 Oral Tongue Carcinoma.

OBJECTIVES: Phosphorylated (activated) STAT3 (pSTAT3) is a regulator of numerous genes that play an essential part in the onset, development and progression of cancer; it is involved in cell proliferation and preventing apoptosis, and in invasion, angiogenesis, and the evasion of immune surveillance. This study aimed mainly to investigate the potential prognostic role of pSTAT3 expression in oral tongue squamous cell carcinoma (SCC). METHODS: Phospho-ser727 STAT3 immunolabeling was correlated with prognostic parameters in 34 consecutive cases of pT1-T2 tongue SCCs undergoing primary surgery. Computer-based image analysis was used for the immunohistochemical reactions analysis. RESULTS: Statistical analysis showed a difference in disease-free survival (DFS) when patients were stratified by pN status (P=0.031). Most tumors had variable degrees (mean±SD, 80.7%±23.8%) of intense nuclear immunoreaction to pSTAT3. Our findings rule out any significant association of serine-phosphorylated nuclear STAT3 expression with tumor stage, grade, lymph node metastasis, recurrence rate, or DFS. CONCLUSION: In spite of these results, it is worth further investigating the role of pSTAT3 (serine- and tyrosine-pSTAT3) in oral tongue SCC in larger series because preclinical models are increasingly showing that several anticancer strategies would benefit from STAT3 phosphorylation inhibition.

Silver sucrose octasulfate nasal applications and wound healing after endoscopic sinus surgery: a prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVES: The aim of the present prospective, randomized, double-blind, and placebo-controlled investigation (approved by the Ethical Committee of Padova University Hospital [Italy]) was to assess the effect of a nasal gel containing a combination of silver sucrose octasulfate and potassium sucrose octasulfate (Silsos gel® [SG]) in wound healing after endoscopic sinus surgery (ESS) for chronic rhinosinusitis in terms of: nasal symptoms (SNOT22), endoscopic appearance of the sinonasal mucosa (Lund-Kennedy score), nasal air flow (anterior active rhinomanometry), evidence of mucosal inflammatory processes (nasal cytology and histology), and microbiological growth. METHODS: Thirty-four patients with chronic rhinosinusitis were randomized on a 1:1 ratio to receive after ESS either SG or placebo (contained only the excipients [carbopol and propylene glycol] in the same concentrations as in SG). RESULTS/CONCLUSIONS: Judging from the present prospective investigation on patients who underwent ESS for chronic rhinosinusitis, treatment with SG seems to enable a significantly faster improvement in specific symptoms (assessed on the validated SNOT22 scale) than placebo. Patients treated with SG also had a quicker improvement in the endoscopic appearance of their nasal mucosa after ESS than patients treated with placebo. These endoscopic improvements in the SG group were also confirmed at the long-term follow-up, while the same did not apply to the placebo-treated group.

Burkholderia cepacia complex isolation in non-polypoid chronic rhinosinusitis.

PURPOSE: Burkholderia cepacia complex (Bcc) infections of the head and neck have been infrequently reported in immunocompetent patients, while their association with cystic fibrosis is quite well known. One of the main problems associated with Bcc is their intrinsic resistance to most clinically-available antimicrobials. Bcc has already been isolated in sinonasal polyposis, while here we report for the first time on its isolation in patients with chronic rhinosinusitis (CRS) but no nasal polyposis. MATERIALS AND METHODS: Thirty-four consecutive surgically-treated CRS patients without cystic fibrosis were recruited. RESULTS: Bcc was isolated in 4 cases of CRS without polyposis, and in another case in sinonasal polyposis. All tested Bcc strains isolated in non-polypotic CRS were resistant to ciprofloxacin, amikacin, ertapenem, amoxicillin/clavulanate, cefotaxime, and gentamicin. CONCLUSIONS: The novel finding of Bcc species in CRS without polyposis as well suggests that the mechanism by which these bacteria adhere to the epithelium of the upper respiratory tract may be important in the host's colonization.

A panel of biomarkers for predicting response to postoperative RT for laryngeal cancer?

OBJECTIVES: Postoperative radiotherapy (PORT) improves locoregional control and survival rates for patients with advanced laryngeal carcinoma (LSCC), but reported outcomes after PORT for LSCC vary considerably. Predictive markers (including biomarkers) are needed for LSCC to orient the choice of the most appropriate adjuvant therapy for individual patients. The aim of this study was to identify a panel of LSCC tissue markers (considering EGFR, mTOR, survivin, Bcl-2, angiogenin, endoglin [CD105], nm23-H1) capable of pinpointing patients at higher risk of recurrence among 33 LSCC cases treated with PORT. METHODS/RESULTS: Univariate analysis found 4 biomarkers (mTOR, nuclear survivin, CD105, non-nuclear nm23-H1) significantly associated with LSCC recurrence. A collinearity emerged between mTOR and CD105 expressions. The predictive role of two different panels (panel 1: mTOR, nuclear survivin, non-nuclear nm23-H1; panel 2: CD105, nuclear survivin, non-nuclear nm23-H1) was considered. According to the Hosmer and Lemeshow scale, panel 1 demonstrated an outstanding discriminatory power (AUC 0.903) in predicting LSCC recurrence after PORT. Panel 2 had an excellent discriminatory power too (AUC 0.899). CONCLUSIONS: Both panels of biomarkers showed an important discriminatory power in pinpointing patients at higher risk of recurrence after PORT for LSCC who could reasonably benefit from adjuvant postoperative chemo-RT.

Multivariate approach to investigating prognostic factors in deep neck infections.

Deep neck infections (DNI) spread along fascial planes and involve neck spaces. Very few studies have investigated potentially prognostic factors using multivariate statistical models. Our aim was to analyze 282 consecutive cases of DNI using multivariate (logistic) statistical models to identify independent significant factors influencing prognosis in terms of complications and long-term hospitalization (>6 days). In our series, only involvement of more than one neck space was independently significant in prognosticating complications of DNI (odds ratio [OR] 2.46). The presence of comorbidities (OR 2.13), non-odontogenic sites of origin (OR 1.88), leukocyte counts above 11.0 cells × 10(9)/L at presentation (OR 3.57), and the need for both medical and surgical treatments (OR 4.66) was significantly and independently prognostic of long hospital stays. Multivariate analysis can distinguish between risk factors and their relative contribution to outcome. The few published studies using multivariate models to analyze DNI prognosis considered quite large cohorts, but no clinical variables persistently revealed an independent significant prognostic role. This evidence seems to underscore the complex interdependence of several clinical variables in contributing to DNI prognosis, and the heterogeneity of the diagnostic/therapeutic approaches adopted.

The role of angiogenin in pT1-T2 tongue carcinoma neo-angiogenesis and cell proliferation: an exploratory study.

BACKGROUND: Angiogenin (ANG) is a member of the ribonuclease superfamily and of medical interest largely because it supports the growth of primary and metastatic malignancies. This study is the first to investigate the potential role of ANG in tongue carcinoma neo-angiogenesis and cancer cell proliferation. METHODS: Angiogenin expression (in carcinoma cells and endothelial intratumor vessel cells), CD105-assessed micro-vessel density (MVD), and MIB-1 expression were correlated with prognostic parameters in 28 primarily consecutively operated pT1-T2 tongue carcinomas (squamous cell carcinoma [SCC]). Whenever feasible, a computer-based image analysis system was used for the immunohistochemical reaction analysis. RESULTS: No significant correlations emerged between ANG expression in the tongue carcinoma cells or endothelial intratumor vessel cells and tongue SCC recurrence rate or disease-free survival (DFS). ANG expression was also unrelated to CD105-assessed MVD or MIB-1 expression. Conversely, CD105-assessed MVD correlated directly with recurrence rate (P = 0.02) and DFS was significantly shorter in cases with CD105-assessed MVD >167 micro-vessels/mm(2) than in those with CD105-assessed MVD ≤167 micro-vessels/mm(2) (P = 0.042). CONCLUSIONS: Our results support the hypothesis that CD105-assessed MVD would be a valuable parameter for predicting which patients with tongue SCC are at greatest risk of disease recurrence. Despite our study results, the role of ANG in tongue carcinoma warrants further investigation in larger series.

Laryngeal carcinoma prognosis after postoperative radiotherapy correlates with CD105 expression, but not with angiogenin or EGFR expression.

Patients with head and neck squamous cell carcinoma (SCC) respond very differently to radiotherapy (RT). Since clinical factors cannot accurately predict its effects, biological parameters have been investigated, including tumor hypoxia. CD105 is a hypoxia-inducible glycoprotein emerging as a potential prognostic indicator for several solid malignancies. Angiogenin is upregulated under hypoxic conditions and supports primary and metastatic tumor growth. Epidermal growth factor receptor (EGFR) activation stimulates tumor proliferation and angiogenesis. The aim of the present study was to ascertain the prognostic importance of hypoxia-inducible factors (CD105, angiogenin) and EGFR in a series of patients who underwent primary surgery followed by RT for laryngeal SCC. 25 consecutive patients with laryngeal SCC given postoperative RT have been investigated. CD105, angiogenin, and EGFR immunohistochemical expressions in primary laryngeal SCCs have been evaluated also with image analysis. The recurrence rate was significantly higher in SCC patients with a CD105 expression >10.0% (P = 0.012) and their disease-free survival (DFS) was shorter (P = 0.044). Neither angiogenin (in the carcinoma cells or endothelial cells) nor EGFR expression were associated with the prognosis in our patients after primary surgery followed by RT for laryngeal SCC. CD105 should be studied as a potentially predictive biomarker for identifying laryngeal SCCs at higher risk of early recurrence after postoperative RT. Targeted anti-CD105 therapy associated with RT should also be investigated in patients with laryngeal SCCs characterized by high CD105 expression.

Nuclear MASPIN expression relates to a better prognosis in elderly patients with laryngeal carcinoma.

CONCLUSION: MASPIN subcellular location can be considered a prognostic marker that is potentially useful for identifying elderly patients with laryngeal carcinoma at higher risk of early loco-regional recurrence, who may benefit from more aggressive therapy. In a targeted treatment setting, re-activated nuclear MASPIN in combination with anti-angiogenic and/or cytotoxic drugs may be effective in treating laryngeal carcinoma in elderly patients. OBJECTIVES: Aging is associated with molecular, cellular, and physiological changes that influence carcinogenesis and cancer growth. MASPIN has multifaceted anti-tumor effects and available evidence supports the hypothesis that its subcellular location influences its functions. The aim of the present study was to firstly assess the potential prognostic role of subcellular MASPIN location in elderly patients (>65 years old) with laryngeal carcinoma. METHODS: MASPIN expression and location were immunohistochemically determined in 68 consecutive elderly patients with laryngeal carcinoma. RESULTS: Nodal involvement and pathological stage correlated strongly with the prognosis for laryngeal carcinomas in elderly patients, in terms of disease recurrence rate and disease-free survival. The loco-regional recurrence rate was significantly lower (p = 0.041) and the disease-free survival after treatment was significantly longer (p = 0.045) in cases with a nuclear pattern of MASPIN subcellular expression.