PGP 9.5, a new marker for human neuroendocrine tumours

Abstract

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.

Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumours

“…Similar findings have been reported by others (Bergh et al, 1985;Said et al, 1985;Rode et al, 1985;Dhillon et al, 1985;Linnoila et al, 1988b;Graziano et al, 1989). The detection of CK-BB immunoreactivity in 67% of SCLC and 14% of squamous cell tumours compares well with previous radioimmunoassay data (Ruberry et al, 1983).…”

“…These include L-dopa decarboxylase (Baylin et al, 1980;Berger et al, 1981;Gazdar et al, 1988a), peptide hormones including calcitonin (Berger et al, 1981) and gastrin releasing peptide (Yamaguchi et al, 1985) and neurone specific enolase (NSE) (Bergh et al, 1985;Said et al, 1985;Rode et al, 1985;Dhillon et al, 1985;Linnoila et al, 1988b;Graziano et al, 1989). Although elevated levels of neuroendocrine (NE) markers have been detected in NSCLC tumours, the expression of more than one NE marker, though common in small cell lung cancer (SCLC) occurs much less frequently in NSCLC (Berger et al, 1981).…”

Highlights of the biology of endocrine tumours of the gut and pancreas.

“…The positive assessment of endocrine differentiation of tumours requires the identification of general markers of neuroendocrine differentiation by immunohistochemistry (Bishop et al 1988). Widely used are cytosol markers such as neuron-specific enolase (NSE) (Bishop et al 1982) and protein gene product 9.5 (PGP 9.5) (Rode et al 1985), the membrane-bound neural cell adhesion molecules (NCAM) (Al-Khafaji et al 1998, Lantuejoul et al 1998, or granule markers such as chromogranin A and the ATP-dependent vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) (associated with large, dense-core vesicles) (Lloyd & Wilson 1983, Rindi et al 1986, Erickson et al 1996, Kolby et al 1998, Eissele et al 1999, Rindi et al 2000 and synaptophysin (associated with small synaptic-like vesicles) (Jahn et al 1985, Wiedenmann & Franke 1985, Buffa et al 1988. The identification of specific tumour cell types requires hormone immunohistochemistry, searching first for hormones expressed by the DES cells of the anatomical district where the tumour is found and then for 'ectopic' hormones according to specific hyperfunctional syndromes (e.g.…”

Neuronal protein gene product 9.5 (IEF SSP 6104) is expressed in cultured human MRC‐5 fibroblasts of normal origin and is strongly down‐regulated in their SV40 transformed counterparts

“…The identification was confirmed by 2D immunoblof tin~ showin~ tl~at polyclonal antibodies rai~ed against PGP 9,5 react strongly with IEF SSP 6104. The presence of this protein in cultured normal fibroblasts, however, is somewha~ surprising since PGP 9,5 has been reported to be a specific marker for neuronal and neuroendo¢:rine tissue [5,19] and antibodies against the protein have been used in a number of immunochemical studies to stain tumours o)' neuronal and neuroendocrine origin [20][21][22] The function of UCHs is unknown but may involve some of the above-mentioned processes, e,g. regulation of the specificity of the ubiquitin-dependent proteolysis system, control of gene transcription and cell cycle, regulation of the stress response, posttranslational processing of newly synthesized polyubiquitin and ubi.…”