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:

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:

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