Prognostic value of p27Kip1 expression in Basaloid Squamous Cell Carcinoma of the larynx.

BACKGROUND: Very few reports have investigated the role of cell cycle regulators as biomarkers in Basaloid Squamous Cell Carcinoma (BSCC) of the larynx, a definite morphologic, uncommon, very aggressive variant of squamous cell carcinoma. Lower expression of Ki67/Mib-1, a proliferation marker highly expressed in the majority of tumours, and p53, a tumour suppressor protein that can induce an arrest of the G1-S transition, was related to a better prognosis in laryngeal BSCC. In the head and neck, p27kip1, a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors, has emerged as an independent prognostic factor, able to identify low-expressing tumours with unfavourable course. Up to date the role of this protein was never studied in BSCC. Aim of our study was to investigate the potential prognostic value of p27kip1 levels and their correlation with Ki67/Mib-1 and p53 expression in BSCC of the larynx. METHODS: The retrospective study group consisted of 15 male and 1 female patients, affected by laryngeal BSCC, ranging in age from 44 to 69 years (mean 58). The tumour originated from the supraglottis in thirtheen cases and from the glottis in the remaining three. Ten patients had metastatic cervical lymph nodes at presentation and were classified as N+. Post surgical stage was IV in four patients, III in nine, II in two cases and I in the remaining one. Follow-up ranged from a minimum of 5 months up to 9 years. Paraffin-embedded tissue sections of each laryngeal tumour were analyzed for p27kip, Ki67/Mib-1 and p53 expression by immunohistochemistry. RESULTS: The immunohistochemical study showed p27kip1 expression in 40% of the patients with no evidence of disease (NED) and in none (0%) of the patients dead of disease (DOD), whilst p53 was expressed in 60% of patients in NED status and in 90% of patients in DOD status. Ki67/Mib-1 was positive in 80% of NED patients and in 100% of DOD patients. At multivariate analysis, performed by means of Discriminant analysis, low levels of p27kip1 expression significantly correlated with poor prognosis (P < 0.05). CONCLUSION: p27kip1 protein has been shown to be a significant independent prognostic factor in laryngeal SCC. In our series of laryngeal BSCC the resulting data seem to confirm the clinical prognostic relevance of p27kip1 low expression, which directly correlated with biological aggressiveness and consequent shortened survival.

Clinical and prognostic aspects of laryngeal clear cell carcinoma.

Clear cell carcinoma (CCC) of the larynx is a rare pathological finding; only eight cases are described in the literature. It occurs in older adults and shows a predilection for men. We report the ninth observation of laryngeal CCC in the literature. We reviewed the literature and correlated the prognosis of the tumour according to its site of onset and treatment. The literature review showed that this neoplasm is highly aggressive, with a high recurrence rate and short mean survival time; the treatment of choice is surgery, and chemo- or radiotherapy are used mainly for the treatment of recurrences.

Overexpression of the cytokine osteopontin identifies aggressive laryngeal squamous cell carcinomas and enhances carcinoma cell proliferation and invasiveness.

PURPOSE: Osteopontin is a secreted cytokine that binds to the cell surface CD44v6 receptor. We studied osteopontin and CD44v6 expression in laryngeal squamous cell carcinomas and correlated osteopontin expression levels with clinicopathologic tumor features. EXPERIMENTAL DESIGN: We used immunohistochemistry, immunoblotting, and reverse transcription-PCR to study osteopontin expression in 58 laryngeal squamous cell carcinomas. Cultured squamous carcinoma cells were treated with exogenous osteopontin or with RNA interference to knockdown osteopontin expression. RESULTS: Osteopontin expression was higher in all the invasive carcinomas than in patient-matched normal mucosa. Its expression levels were significantly correlated with tumor stage and grade and with the presence of lymph node and distant metastases. Osteopontin positivity was negatively correlated with overall survival (P = 0.03). Osteopontin expression was paralleled by intense cell surface reactivity for CD44v6. Treatment of squamous carcinoma cells with recombinant osteopontin sharply increased proliferation and Matrigel invasion in comparison with the untreated cells parallel to activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/mitogen-activated protein kinase signaling cascade. Osteopontin knockdown by RNA interference, anti-CD44 antibodies, and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibition prevented these effects. CONCLUSIONS: These results identify osteopontin as a marker and a potential therapeutic target in cases of aggressive laryngeal squamous cell carcinomas.

Connexin 26 mutations in nonsyndromic autosomal recessive hearing loss: speech and hearing rehabilitation.

OBJECTIVE: Hearing loss is the most common form of sensory impairment, with approximately one infant/1000 born with profound congenital deafness. A pre-lingual bilateral sensorineural hearing impairment poses a substantial problem as it negatively impacts on the subject's ability to conduct a normal social life. The aim of the study was to observe, in a group of children affected by pre-lingual non-syndromic autosomal recessive hearing impairment: (1) the role of the possible mutation of connexin 26 in the pathogenesis of the hearing loss; (2) the audiological and clinical aspects of the hearing impairment; (3) therapy to be adopted for the different patients. METHODS: The study was carried out on 39 patients, 16 males and 23 females, aged between six and 17 years (mean 12 years), affected by non syndromic congenital deafness, presumably hereditary, referred to the out-patients audiology clinic for children of the Department of Otolaryngology of the Federico II University of Naples. RESULTS: Our study conducted on 39 children with pre-lingual bilateral sensorineural autosomal recessive deafness showed as follows: (I) from a molecular perspective: an incidence of 41% in the cases studied of mutations in the encoding of the connexin 26 gene; a prevalence in our case study of the 35delG mutation (69%). (II) The characteristics of the hearing impairments in the children studied were homogeneous, regardless of the presence or absence of a connexin 26 mutation: the hearing impairment was pre-lingual bilateral sensorineural, the impairment often involved mainly the high frequencies, but, especially in the severe forms an involvement of all the frequencies was not rare; the hearing impairments were symmetrical and non progressive in time. (III) The results of the application of prosthesis and thereafter rehabilitative language therapy are generally satisfactory but correlated of course to the severity of the hearing loss. CONCLUSION: In conclusion, we hope that further developments in the research on genetic hearing impairments will promptly result in advances in clinical practice.

Comparison of intranasal and transdermal estradiol on nasal mucosa in postmenopausal women.

OBJECTIVE: To compare nasal symptomatology and function and local concentrations of estradiol (E2), estradiol receptor (ERalpha), vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) in nasal biopsies of 20 postmenopausal women complaining of paradoxical nasal stuffiness before and after treatment with intranasal or transdermal E2. DESIGN: Twenty healthy postmenopausal women willing to start hormone therapy (HT) were allocated to one of two groups, using a computer-generated randomization list. Ten postmenopausal women were treated with transdermal 17beta-estradiol 50 microg daily plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group A). Ten postmenopausal women were treated with intranasal 17beta-estradiol 300 microg/day (one spray delivery of 150 microg per nostril) plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group B). Fourteen fertile women undergoing nasal mucosa biopsy during plastic surgery were used as controls for the immunohistochemical evaluation (Group C). All women in groups A and B underwent evaluation of nasal stuffiness score, mucociliary transport time, rhinoscopy, and active anterior rhinomanometry at the beginning of the study and after, VIP, SP, and 6 months of HT. Nasal biopsies and evaluation of local concentrations of E2, ERalpha NPY were performed in groups A and B before and after 6 months of HT and in group C. RESULTS: Both intranasal and transdermal HT improve nasal symptomatology and nasal mucosa appearance and reduce mean mucociliary transport time. The effectiveness of intranasally administered therapy at improving nasal function is significantly better than transdermal therapy. In comparison with premenopausal controls, untreated postmenopausal women of group A and B showed significantly decreased immunopositivity for E2, ERalpha, and SP. HT induced a significant increase in E2, ERalpha, VIP, and SP and a decrease in NPY immunopositivity. Intranasal therapy was associated with a significantly higher immunopositivity for VIP and SP. CONCLUSIONS: HT improves nasal function and symptomatology in postmenopausal women with paradoxical nasal stuffiness, modulating nasal mucosa function through an action on cholinergic, adrenergic, and sensory peptides. Intranasally administered HT is more effective at improving nasal function than transdermal HT.

The 11th nerve syndrome in functional neck dissection.

OBJECTIVES: Assessment of the incidence of shoulder joint disability and evaluation of the role of a personal postoperative physical rehabilitative protocol therapy in reducing pain and shoulder dysfunction and improving the quality of life (QOL) of patients who have undergone functional neck dissection (FND) associated with total laryngectomy. SETTING, DESIGN, AND OUTCOME MEASURES: Sixty laryngectomees who had undergone FND were divided into two groups (A and B). Group A received physical therapy after surgery. Clinical evaluation was done according to the Constant modified questionnaire, including physical assessment of passive and active shoulder movement and information regarding patients' QOL. Bilateral quantitative electromyography (Q-EMG) of scapulohumeral muscles was carried out on all patients. Results were evaluated by Student t test and multivariate analysis to find out which variables were important in predicting pain and return to work. RESULTS: Six months after surgery, the patients in group A had better results concerning passive forward elevation (P = 0), shoulder active motility (P = 0), pain (P <.001), working and recreational activity (P = 0), and score of Constant (P = 0) compared with the patients in group B. From a multivariate analysis of clinical parameters important in predicting pain, significant predictors (P <.01) were shown to be global shoulder active motility, active forward elevation, abduction, active external rotation, internal rotation hand to back, working and recreational activity, and score of Constant. Regarding return to work, a significant predictor (P <.01) was the score of Constant. Electromyography work-up showed deterioration in early postoperative periods and improvements in late postoperative periods. CONCLUSION: The post-surgical variable clinical picture of shoulder disability is related not only to the accessory nerve injury, but also to the secondary glenohumeral stiffness resulting from the scapulohumeral girdle muscles weakness and postoperative forced immobility. Physical therapy aimed to early recover passive motion and to avoid the occurrence of joint fibrosis has been shown to have a real contributory role in decreasing shoulder complaints and improving the patients' QOL.