The expression of somatostatin receptors 3, 4 and 5 in laryngeal pathology.

Conventional chemotherapy has no role to play in the curative treatment of laryngeal carcinoma, yet the mortality rate from advanced disease has improved little over the last 20 years. Somatostatin is a naturally occurring peptide, which exerts anti-proliferative and anti-angiogenic effects via 5 membrane-bound receptor subtypes (SSTRs 1-5). We have previously studied the expression of SSTRs 1 and 2 and demonstrated loss of SSTR2 in laryngeal carcinoma. This study was therefore undertaken to study the expression of the remaining SSTR subtypes in laryngeal pathology. The expression of SSTRs 3, 4 and 5 was studied in benign (Reinke's oedema), pre-malignant and malignant laryngeal specimens using immunohistochemistry. There was very little expression of SSTR3, with low to moderate levels detected in just 1/6 (17%) benign and pre-malignant specimens and 3/12 (25%) malignant laryngeal tumours. A variable degree of SSTR4 expression was detected across the three groups, with low to moderate levels in 3/6 (50%) benign specimens, compared to only 1/6 (17%) pre-malignant specimens but 8/12 (67%) malignant laryngeal tumours. The majority of all specimens, however, demonstrated moderate to high levels of expression of SSTR5. This receptor was detected in 4/6 (67%) benign, all pre-malignant (100%) and 10/12 (83%) malignant cases. All the laryngeal carcinomas studied expressed either SSTR4 or SSTR5, with 60% expressing both, but very few expressing SSTR3. Somatostatin receptors warrant further investigation to determine whether they have a therapeutic role in carcinoma of the larynx.

Type-2 submucosal posterior laryngeal cleft diagnosed on CT scan.

Posterior laryngeal cleft (PLC) is a rare developmental abnormality, which requires early diagnostic laryngoscopy and management if considerable morbidity and mortality are to be avoided. We report the case of a 25-year-old man with a life-long history of a weak, breathy voice, in whom the diagnosis of PLC was made by CT scanning. This is the first reported case of a PLC being diagnosed by CT scanning. Whilst direct laryngoscopy should remain the investigation of choice in congenital stridor, CT scanning may occasionally be useful.

Overexpression of Bcl-2 in squamous cell carcinoma of the larynx: a marker of radioresistance.

Squamous cell carcinoma of the larynx can be treated using radiotherapy or surgery, either alone or in combination. Radiotherapy is preferred for early-stage tumours, as it spares the larynx and therefore preserves speech and swallowing. Unfortunately, approximately 15% of tumours treated this way will prove to be radioresistant, as manifest by tumour recurrence within the original radiotherapy field over the ensuing 12 months. By causing extensive DNA damage, radiotherapy aims to induce apoptosis and tumour regression. Our hypothesis was that defects in the mechanisms that recognise DNA damage, induce cell cycle arrest or control apoptosis, either alone or in combination, may be responsible for radioresistance. We therefore undertook an immunohistochemic analysis of pretreatment biopsies of radioresistant (n = 8) and radiosensitive (n = 13) laryngeal tumours. To minimise the impact of confounding factors, strict inclusion criteria were observed; all tumours were of the glottic subsite and all recurrences developed within 12 months of radiotherapy at the site of the original tumour. The expression of key proteins involved in DNA damage recognition (p53), cell cycle arrest (ATM, p16 and p21/WAF1) and apoptosis (Bcl-2 and BAX) were studied. Ki-67 was also assessed as a marker of cell proliferation to exclude low mitotic rate as a cause of radioresistance. A statistically significant correlation was observed between overexpression of Bcl-2 and radioresistance (p = 0.003, Fisher's exact test). We hypothesise that overexpression of the anti-apoptotic protein Bcl-2 allows tumour cells with extensive radiation-induced DNA damage to continue proliferating; the absence of an appropriate apoptotic response manifests clinically as radioresistance.