Elena Fasanaro

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

Abstract 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.

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.

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.

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.

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).

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 hosts colonization.

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.

Deep neck infections originating from the major salivary glands

OBJECTIVES Before the widespread use of antibiotics, most deep neck infections (DNIs) stemmed from complicated pharyngeal infections. Nowadays, they seem to be due mainly to dental infections. In 2010, our group reported that DNIs originated from a major salivary gland in 14% of cases. The main endpoint of the present investigation was to review our experience of the diagnosis and treatment of DNIs of salivary gland origin. We also compared the characteristics of DNIs originating from salivary glands with those originating elsewhere. METHODS Between 2000 and 2011, 44 patients were treated for DNIs of salivary origin at our institution. These patients were compared with 191 cases of DNI diagnosed as having other sites of origin. RESULTS/CONCLUSIONS In the present series, DNIs originating from a major salivary gland accounted for 19% of all cases of DNI of known origin. Patients with DNI of salivary gland origin were more likely to be elderly than those whose DNI originated from elsewhere (p=0.000). Our multivariate statistical model showed that comorbidities (p=0.051, statistical trend) and the need for surgical treatment (p=0.028) independently predicted long-term hospitalization for DNIs originating from a major salivary gland.

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.