clude pancreatic islet cell and carcinoid tumors. These tumors comprise a function-Colin F. Johnston, Ph.D. ally and biologically heterogeneous group of neoplasms that rarely show reliable Keith D. Buchanan, M.D., Ph.D. histopathologic signs of malignancy. No etiologic factors are proven to be associated with them, and their exact ontogeny and carcinogenesis remain unknown.

The tumorigenesis of neuroendocrine tumours remains poorly understood, although a minority, the familial multiple endocrine neoplasia (MEN 1 and MEN 2), are known to be of uncommon genetic origin. Mutation of the tumour suppressor gene, p53, is now known to be a common genetic alteration in about half of all types of non-endocrine cancers. In the present study, immunocytochemistry using the monoclonal anti-p53 antibody, DO-7, has been employed to investigate the accumulation of p53 immunoreactivity in a wide range of primary neuroendocrine tumours. Tumours (n = 109) were fixed and processed to paraffin wax according to a constant protocol. Sections were subjected to microwave antigen retrieval prior to immunostaining for p53. Positive nuclear immunostaining was observed in one medullary carcinoma of the thyroid (MCT), one lung carcinoid, and five small cell carcinomas of the lung (SCCL). All other tumour samples were consistently negative. As the neoplasia investigated in this study comprised a wide spectrum of neuroendocrine tumour types and ranged from minute, relatively benign lesions to malignant metastasizing disease and as there was no relationship between the presence of p53 overexpression and clinico-pathological features, the present study suggests that p53 gene mutation may be relatively unimportant in the genesis of neuroendocrine tumours.

histopathologic signs of malignancy. No etiologic factors are proven to be associated with them, and their exact ontogeny and carcinogenesis remain unknown.

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pS2 protein expression has been demonstrated in a range of malignant tissues in an oestrogen-independent pathway. Recently, it has been demonstrated that pS2, in prostate cancer, is closely associated with neuro-endocrine differentiation. In the present study, we have analyzed, by immunohistochemistry along with microwave antigen retrieval, the expression of pS2 protein in a retrospective series of 236 human primary neuro-endocrine tumours and attempted to correlate this with the clinicopathologic features of patients and the presence of oestrogen receptor (ER). pS2 immunoreactivity was detected in 42% of small-cell lung carcinomas, 36% of lung carcinoids, 33% of phaeochromocytomas, 38% of carotidbody tumours, 31% of pancreatic neuro-endocrine tumours, 60% of stomach carcinoids, 55% of ileal carcinoids, 23% of appendiceal carcinoids and 86% of rectal carcinoids respectively in more than 10% tumour cells. No pituitary tumours displayed pS2 immunoreactivity. pS2 transcript was also detected in lung carcinoid and carotid-body tumours by Northern-blot analysis. There was a statistically higher incidence of pS2 expression in carcinoid tumours of the ileum and rectum than in those of the appendix. No association was observed between pS2 expression and the occurrence of the carcinoid syndrome; nor was any correlation observed between the occurrence of pS2 immunoreactivity and that of ER. Our results suggest that the expression of the pS2 protein in a wide spectrum of neuro-endocrine tumours may be implicated in the pathogenesis and progression of some neuro-endocrine tumours in an oestrogen-independent pathway. Int.

The oncogenes c-myc, bcl-2 and c-jun, are abnormally expressed in some carotid body tumors. Their expression may contribute to the genesis of carotid body tumors.

Several genetic aberrations have been implicated in the carcinogenesis of small cell lung carcinomas (SCLCs), including tumour suppressor gene p53 deletion and mutation and amplification of the myc family proto‐oncogenes. However, their exact ontogeny and carcinogenesis remain unknown. There are no proven aetiological factors for lung carcinoid tumours. Recent evidence suggests that the genetic regulation of apoptosis is of critical importance during tumourigenesis and that oncogene and tumour suppressor genes can regulate the rate, or susceptibility, of cells to undergo apoptosis. In this study, the expression of Bcl‐2 protein has been investigated in 77 primary lung neuroendocrine tumours, including 55 SCLCs and 22 carcinoid tumours, and compared with p53 expression. Of the 77 tumours studied, Bcl‐2 immunoreactivity was present in 80 per cent of SCLCs, 43 per cent of typical, and 67 per cent of atypical carcinoid tumours with more than 10 per cent tumour cell positivity. Western and Northern blot analysis revealed that carcinoid tumours expressed the 26 kD protein and bcl‐2 transcripts. Whereas 42 per cent of the SCLCs studied displayed p53 protein immunoreactivity in more than 10 per cent of tumour cells, p53 positivity was not found in lung carcinoid tumours. There are statistical differences in Bcl‐2 and p53 expression between SCLCs and lung carcinoid tumours. These results suggest that disregulation of the genetic mechanisms controlling apoptosis is a critical step in the progression of SCLC, and that the expression of Bcl‐2 is involved in the pathogenesis of SCLC and lung carcinoid tumours. The genetic complementation of simultaneously deregulated Bcl‐2 and p53 may be implicated in the multistep tumourigenesis of small cell lung cancer. © 1998 John Wiley & Sons, Ltd.

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