Chromogranin

Immunohistochemical expression

Chromogranin A and B are members of a family of acidic glycoproteins located in neurosecretory granules.  The most abundant is chromogranin A (molecular weight 68kD⁴).  The two others major members are chromogranin B (or secretogranin I) and chromogranin C (or secretogranin II), with other granins including secretogranins III, IV and V⁵, VGF and NESP-55.   Chromogranins can be detected in nearly all neuroendocrine tumours. Positivity depends on the number of dense core granules; there may be a lack of immunoreactivity in small cell carcinoma and Merkel cell carcinoma, where secretory granules are sparse⁵. Greater sensitivity in small cell carcinomas may be achieved with antigen retrieval².

see comparison of neuroendocrine markers

medullary carcinoma of the thyroid

• parathyroid tumours

• paraganglioma

  carcinoids: rectal carcinoids express predominantly chromogranin B rather than chromogranin A:

foregut 15/171 midgut 12/121 hindgut 6/101

See comparison of chromogranins A and B, secretogranin II and NESP-55.

Chromogranin A undergoes post-translational processing, with cleavage at dibasic amino acid residues. There is very preliminary evidence that different neuroendocrine neoplasms process chromogranin A differently: this may possibly be of diagnostic use³:

			amino acid sequence and name of fragment
tumour		number of cases	17-38	116-130	176-195	238-247	375-384	411-424	250-284 mabCgA
			vasostatin	chromostatin	chromacin		mid-parastatin	C-terminal parastatin	N-terminal pancreastatin
Islet cell tumours (14)	benign insulinoma	5	- to +++	-	+ to +++	-	-	-	++ to +++
	malignant insulinoma	4	+ to +++	+ to +++	++ to +++	+ to +++	+ to +++	-	++ to +++
	malignant glucagonoma	2	- to ++	- to ++	+	- to ++	- to ++	-	+ to ++
	malignant somatostatinoma	1	+	+	++	-	+	+	+++
	malignant vipoma	1	++	++	+++	++	-	-	+++
	malignant non-functional	1	++	+	++	+	++	-	++
duodenal carcinoid		2	+ to ++	- to +	+++	- to +	- to +	- to ++	++ to +++
ileal carcinoid		5	+ to ++	- to +	+++	- to ++	-	NE	+++
appendiceal carcinoid		2	+++	++ to +++	++ to +++	++	+++	NE	+++
bronchial carcinoid		5	- to ++	- to +	- to +++	+ to +++	-	- to +++	+ to +++
benign phaeochromocytoma		5	+ to +++	- to ++	++ to +++	+ to +++	- to +++	+ to +++	+++
malignant phaeochromocytoma		3	- to +	-	++	-	- to +	- to +	++ to +++
medullary thyroid carcinoma		6	- to ++	- to ++	++ to +++	- to ++	- to +++	+ to ++	++ to +++
parathyroid adenoma		2	- to +	- to +	+	- to +	+	NE	- to +

Key: -: negative, +: <10% of cells, ++: 10 to 50% of cells, +++: >50% of cells. NE: not examined.

Malignant islet cell tumours appear to express more fragments than do benign islet cell insulinomas. Appendiceal carcinoids express more fragments than do malignant carcinoids.

Diagnostic utility

with synaptophysin, identification of neuroendocrine differentiation in tumours.

medullary carcinomas of the thyroid are positive while follicular carcinomas are negative

References

¹Al-Khafaji et al. Immunohistologic analysis of gastrointestinal and pulmonary carcinoid tumours. Human Pathol 1998;29:992-9.

²Lyda, M.H. and Weiss, L.M. Immunoreactivity for epithelial and neuroendocrine antibodies are useful in the differential diagnosis of lung carcinomas. Hum Pathol 2000;31:980-7.

³Portel-Gomes, G.M., Grimelius, L., Johansson, H., Wilander, E. and Stridsberg, M. Chromogranin A in human neuroendocrine tumors: an immunohistochemical study with region-specific antibodies. Am J Surg Pathol 2001;25:1261-7.

⁴Shy, S.W., Lee, W.H., Chou, M.C., Lai, Y.S. and Tu, Y.C. Small cell lung carcinoma: clinicopathological, immunohistochemical, and ultrastructural study. J Surg Oncol 1990;45:146-61.

⁵Erickson, L. A. and R. V. Lloyd (2004). "Practical markers used in the diagnosis of endocrine tumors." Adv Anat Pathol 11(4): 175-89.

⁶Kimura, N., M. Pilichowska, et al. (2000). "Immunohistochemical expression of chromogranins A and B, prohormone convertases 2 and 3, and amidating enzyme in carcinoid tumors and pancreatic endocrine tumors." Mod Pathol 13(2): 140-6.

This page last revised 20.7.2004.

©SMUHT/PW Bishop