PGP 9.5 is a soluble protein isolated from brain and is a general marker for neuronal and neuroendocrine tissue. Its function is not known. Until now neurone specific enolase (NSE) has been the only general marker for the paracrine system and tumours derived from it. Seventy-four neuroendocrine tumours, 17 melanocytic naevi, 51 melanomas and four granular tumours were stained immunohistochemically for PGP 9.5 and NSE. A variety of pulmonary and non-neuroendocrine tumours were also stained. Two so-called goblet cell carcinoids of the appendix were included in the series. Using NSE 59/74 neuroendocrine tumours were positive and 58/74 stained for PGP 9.5. In combination 63/74 of these tumours were positive for either NSE or PGP 9.5 or both. Staining for PGP 9.5 was better for demonstration of nerves in routinely processed material than was staining for NSE. Twenty-one out of 43 primary melanomas stained for PGP 9.5 and 36 showed staining for NSE. Only two of eight metastatic melanomas melanocytic stained for PGP 9.5 while seven of these eight stained for NSE. Six of 17 melanocytic naevi stained for PGP 9.5 and five stained for NSE. All four granular cell tumours stained for PGP 9.5 and NSE. Both "goblet cell carcinoids' of the appendix were negative for NSE and PGP 9.5. Fifteen out of 32 pulmonary cancers showed staining for either marker and no non endocrine tumour showed any specific staining. Staining for PGP 9.5 is a valuable additional probe in the exploration of the paracrine system and the diagnosis of tumours arising from it.
Forty-eight neuroendocrine tumours of the larynx were studied, of which 41 were classified as large cell neuroendocrine carcinoma. Most of these tumours occurred in the supraglottic larynx and the patients were predominantly male. Exquisite pain was a presenting feature in one third. These carcinomas metastasized, frequently to skin, giving rise to painful secondary lesions, but long-time survival occurred. Histologically, large cell neuroendocrine carcinoma had a number of features seen in neuroendocrine tumours at other sites, including grouping into 'Zellballen' which mimics paraganglioma. Four tumours were definite paragangliomas. These tumours have behaved benignly. There were three cases of small cell neuroendocrine carcinoma, a tumour which is histologically identical to its counterpart in the bronchus and has a very aggressive course. All three types of tumour expressed general neuroendocrine markers, but only large cell neuroendocrine carcinoma marked for both cytokeratin and calcitonin. In the paraganglioma cases sustentacular cells were identified and marked for S-100 protein and glial fibrillary acidic protein. Histological examination, supplemented with immunohistochemistry, helped distinguish these tumours into those requiring different treatment regimens.
The aetiology of pain in interstitial cystitis is not understood, although it has been reported to be due to release of mediators from mast cell granules. Cystolysis and intravesical instillation of dimethyl sulphoxide have been shown to relieve pain in this condition. We have studied the nerve population within the bladder wall using immunohistochemical stains for protein gene product 9.5. A group of 18 cases of chronic interstitial cystitis and 12 controls; neuropathic bladder (n = 1), chronic bacterial cystitis (n = 3), systemic lupus erythematosus cystitis (n = 2) and normals (n = 6), were investigated. There were significantly more nerve fibres within the sub-urothelial and detrusor muscle layers in chronic interstitial cystitis than there were in normals. Patients with chronic cystitis of other aetiology did not have a significant increase in nerve fibre density within the bladder wall suggesting a specific association between nerve fibre proliferation and interstitial cystitis. Cystolysis is shown to deplete selectively the submucosal nerve plexuses without altering the nerve density within detrusor muscle. This finding explains the desensitisation of the bladder without impairment of detrusor function after this procedure.
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