Skip to main content Accessibility help

Neuroendocrine differentiation in head and neck squamous cell carcinoma

  • V H Schartinger (a1), C Falkeis (a2), K Laimer (a3), G M Sprinzl (a1), H Riechelmann (a1), M Rasse (a3), I Virgolini (a4) and J Dudás (a1)...



Tumours with neuroendocrine differentiation frequently express chromogranin A, synaptophysin and somatostatin receptors. The role of neuroendocrine differentiation in head and neck squamous cell carcinoma is not yet clear.


The presence of chromogranin A, synaptophysin and somatostatin receptors was studied immunohistochemically in 78 head and neck squamous cell carcinoma specimens.


Sparse chromogranin A expression was found in 41 per cent, associated with high chromogranin A messenger RNA expression and the presence of dense core granules. Low synaptophysin expression was found in 18 per cent. The highest staining scores were found for somatostatin receptor 5 (82 per cent), followed by somatostatin receptor 1 (69 per cent) and somatostatin receptor 2 (54 per cent), whereas somatostatin receptors 3 and 4 expression was low. Expression was not correlated with tumour stage or survival.


Cells with neuroendocrine differentiation are sparsely scattered in some head and neck squamous cell carcinomas. Their pathophysiological role is elusive. In contrast, somatostatin receptor and particularly somatostatin receptor 5 expression is frequent in head and neck squamous cell carcinoma. Somatostatin receptor expression is not considered to indicate neuroendocrine differentiation in head and neck squamous cell carcinoma.


Corresponding author

Address for correspondence: Volker H Schartinger, Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35,6020 Innsbruck, Austria Fax: +43 512 504 23144 E-mail:


Hide All
1Modlin, IM, Gustafsson, BI, Moss, SF, Pavel, M, Tsolakis, AV, Kidd, M. Chromogranin A – biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol 2010;17:2427–43
2Erickson, LA, Lloyd, RV. Practical markers used in the diagnosis of endocrine tumors. Adv Anat Pathol 2004;11:175–89
3Valtorta, F, Pennuto, M, Bonanomi, D, Benfenati, F. Synaptophysin: leading actor or walk-on role in synaptic vesicle exocytosis? Bioessays 2004;26:445–53
4Brazeau, P, Vale, W, Burgus, R, Ling, N, Butcher, M, Rivier, J et al. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973;179:77–9
5Grozinsky-Glasberg, S, Shimon, I, Korbonits, M, Grossman, AB. Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms. Endocr Relat Cancer 2008;15:701–20
6Rekhtman, N. Neuroendocrine tumors of the lung: an update. Arch Pathol Lab Med 2010;134:1628–38
7Fujita, T, Yamaji, Y, Sato, M, Murao, K, Takahara, J. Gene expression of somatostatin receptor subtypes, SSTR1 and SSTR2, in human lung cancer cell lines. Life Sci 1994;55:1797–806
8Nisman, B, Heching, N, Biran, H, Barak, V, Peretz, T. The prognostic significance of circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide and neuron-specific enolase in patients with advanced non-small-cell lung cancer. Tumour Biol 2006;27:816
9Yuan, A, Liu, J, Liu, Y, Cui, G. Chromogranin A-positive tumor cells in human esophageal squamous cell carcinomas. Pathol Oncol Res 2007;13:321–5
10Stafford, ND, Condon, LT, Rogers, MJ, MacDonald, AW, Atkin, SL. The expression of somatostatin receptors 1 and 2 in benign, pre-malignant and malignant laryngeal lesions. Clin Otolaryngol Allied Sci 2003;28:314–19
11Condon, LT, Stafford, ND, Bedford, KJ, MacDonald, AW, Atkin, SL. The expression of somatostatin receptors 3, 4 and 5 in laryngeal pathology. Eur Arch Otorhinolaryngol 2008;265(suppl 1):S63–7
12Laimer, K, Blassnig, N, Spizzo, G, Kloss, F, Rasse, M, Obrist, P et al. Prognostic significance of 14-3-3 sigma expression in oral squamous cell carcinoma (OSCC). Oral Oncol 2009;45:127–34
13Sagman, U, Mullen, JB, Kovacs, K, Kerbel, R, Ginsberg, R, Reubi, JC. Identification of somatostatin receptors in human small cell lung carcinoma. Cancer 1990;66:2129–33
14Li, M, Li, W, Kim, HJ, Yao, Q, Chen, C, Fisher, WE. Characterization of somatostatin receptor expression in human pancreatic cancer using real-time RT-PCR. J Surg Res 2004;119:130–7
15Glueckert, R, Bitsche, M, Miller, JM, Zhu, Y, Prieskorn, DM, Altschuler, RA et al. Deafferentation-associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain-derived neurotrophic factor and acidic fibroblast growth factor. J Comp Neurol 2008;507:1602–21
16Schmutzhard, J, Glueckert, R, Bitsche, M, Abraham, I, Falkeis, C, Schwentner, I et al. The cochlea in fetuses with neural tube defects. Int J Dev Neurosci 2009;27:669–76
17Howe, MC, Chapman, A, Kerr, K, Dougal, M, Anderson, H, Hasleton, PS. Neuroendocrine differentiation in non-small cell lung cancer and its relation to prognosis and therapy. Histopathology 2005;46:195201
18Banks, ER, Frierson, HF Jr, Mills, SE, George, E, Zarbo, RJ, Swanson, PE. Basaloid squamous cell carcinoma of the head and neck. A clinicopathologic and immunohistochemical study of 40 cases. Am J Surg Pathol 1992;16:939–46
19Wieneke, JA, Thompson, LD, Wenig, BM. Basaloid squamous cell carcinoma of the sinonasal tract. Cancer 1999;85:841–54
20Abbona, G, Papotti, M, Viberti, L, Macri, L, Stella, A, Bussolati, G. Chromogranin A gene expression in non-small cell lung carcinomas. J Pathol 1998;186:151–6
21Kharmate, G, Rajput, PS, Watt, HL, Somvanshi, RK, Chaudhari, N, Qiu, X et al. Dissociation of epidermal growth factor receptor and ErbB2 heterodimers in the presence of somatostatin receptor 5 modulate signaling pathways. Endocrinology 2011;152:931–45
22Miederer, M, Seidl, S, Buck, A, Scheidhauer, K, Wester, HJ, Schwaiger, M et al. Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in 68 Ga-DOTATOC PET/CT. Eur J Nucl Med Mol Imaging 2009;36:4852
23Culler, MD, Oberg, K, Arnold, R, Krenning, EP, Sevilla, I, Diaz, JA. Somatostatin analogs for the treatment of neuroendocrine tumors. Cancer Metastasis Rev 2011;30(suppl 1):917
24Anthony, L, Freda, PU. From somatostatin to octreotide LAR: evolution of a somatostatin analogue. Curr Med Res Opin 2009;25:2989–99
25Kvols, LK, Woltering, EA. Role of somatostatin analogs in the clinical management of non-neuroendocrine solid tumors. Anticancer Drugs 2006;17:601–8



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed