34βE12 expression along the whole spectrum of neuroendocrine proliferations of the lung, from neuroendocrine cell hyperplasia to small cell carcinoma
Article first published online: 31 JAN 2003
Volume 42, Issue 2, pages 156–166, February 2003
How to Cite
Sturm, N., Rossi, G., Lantuéjoul, S., Laverrière, M.-H., Papotti, M., Brichon, P.-Y., Brambilla, C. and Brambilla, E. (2003), 34βE12 expression along the whole spectrum of neuroendocrine proliferations of the lung, from neuroendocrine cell hyperplasia to small cell carcinoma. Histopathology, 42: 156–166. doi: 10.1046/j.1365-2559.2003.01541.x
- Issue published online: 31 JAN 2003
- Article first published online: 31 JAN 2003
- Date of submission 8 July 2002 Accepted for publication 12 September 2002
- lung cancer;
- neuroendocrine tumours;
Aims: Monoclonal antibody 34βE12 (Ck34βE12) recognizes a set of cytokeratins (1, 5, 10, 14) expressed in normal stratified squamous epithelium. We have recently reported its expression in squamous cell carcinoma and basaloid carcinoma, in contrast to large cell neuroendocrine carcinoma, an entity with overlapping morphological features with basaloid carcinoma. We have now examined the role of Ck34βE12 in discriminating between neuroendocrine and non-neuroendocrine proliferations.
Methods and results: We performed an immunohistochemical study of 228 cases, comprising the whole spectrum of lung neuroendocrine proliferations and tumours. All cases of neuroendocrine cell hyperplasia (n = 15), tumorlet (n = 23), typical carcinoid (n = 27) and atypical carcinoid (n = 23) were completely negative for Ck34βE12. Although the neuroendocrine cells of small cell lung carcinoma and large cell neuroendocrine carcinoma were consistently negative, a strong and diffuse positive staining was found in the non-neuroendocrine components of combined small cell carcinoma (three of eight cases) and combined large cell neuroendocrine carcinoma (11 of 12 cases). In addition, scattered Ck34βE12+ cells were noted in 11 of 64 (17%) large cell neuroendocrine carcinoma and in seven of 56 (12.5%) small cell carcinoma, which were not obviously histologically combined. This heterogeneity of high-grade neuroendocrine tumours was not observed in carcinoids which lack Ck34βE12 clusters of reactive cells. There was mutual exclusion between expression of neuroendocrine markers and that of Ck34βE12.
Conclusion: We conclude that 34βE12 expression excludes the neuroendocrine nature of tumour cells and uncovers the real frequency of combined forms in high-grade neuroendocrine tumours.