Chromogranin as a Marker of Neuroendocrine Cells in Cytologic Material—An Immunocytochemical Study

Ae, Walts; Jw, Said; Ip, Shintaku; Rv, Lloyd

doi:10.1093/ajcp/84.3.273

Cited by 49 publications

(21 citation statements)

References 23 publications

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“…Our results with conventional immunohistochemical markers of neuroendocrine neoplasms are similar to previous studies (11,18,28). Said et al examined 9 carcinoid tumors and 12 small cell carcinomas, demonstrating positive staining for chromogranin in all 9 carcinoid tumors and negative staining in all 12 small cell carcinomas (11).…”

Section: Discussionsupporting

confidence: 90%

“…Dardick also failed to demonstrate positive staining of chromogranin in 15 cases of small cell carcinomas by using a very sensitive immunohistochemical approach called immunogold electron microscopy (18). Walts et al also showed absence of staining for chromogranin in 20 cases of small cell carcinomas in cytology specimens (28). However, a few studies have demonstrated that a small proportion of small cell carcinomas are immunohistochemically positive for chromogranin (8).…”

Section: Discussionmentioning

confidence: 99%

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Microtubule-Associated Protein-2: A New Sensitive and Specific Marker for Pulmonary Carcinoid Tumor and Small Cell Carcinoma

et al. 2001

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Microtubule-associated proteins (MAPs) are a major component of cytoskeleton family proteins associated with microtubule assembly. MAP-2 has been shown to be specifically expressed in neuronally differentiated cells. Pulmonary neuroendocrine carcinomas such as carcinoid tumors and small cell carcinomas are derived from neuroendocrine cells. We hypothesize that neuroendocrine cells may also express MAP-2, and therefore, MAP-2 may be used as a marker for pulmonary carcinomas of neuroendocrine differentiation. To investigate the utility of using MAP-2 expression to separate pulmonary neuroendocrine from nonneuroendocrine tumors, we examined the expression of MAP-2 immunohistochemically in 100 cases of pulmonary carcinomas. The immunoperoxidase method with antigen retrieval was used to characterize the expression of MAP-2, chromogranin, synaptophysin, and neuron-specific enolase in 25 small cell carcinomas, 25 carcinoid tumors, 25 adenocarcinomas, and 25 squamous cell carcinomas. All tumors were lung primaries. All 25 cases of carcinoid tumors (100%) as well as 23 of 25 cases (92%) of small cell carcinomas were positive for MAP-2. Four of 25 cases (16%) of adenocarcinomas were positive for MAP-2 and synaptophysin. Among the 25 squamous carcinomas, 4 cases (16%) were positive for MAP-2, 2 cases (8%) were positive for synaptophysin, 11 cases (44%) were positive for neuron-specific enolase, and none was positive for chromogranin. In conclusion, MAP-2 is a new sensitive and specific marker for the pulmonary tumors of neuroendocrine differentiation. We recommend that MAP-2 be added to immunohistochemical panels to separate non-neuroendocrine from neuroendocrine lung tumors.KEY WORDS: Microtubule-associated protein, Neuroendocrine carcinoma, Lung.Mod Pathol 2001;14(9):880 -885

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Microtubule-Associated Protein-2: A New Sensitive and Specific Marker for Pulmonary Carcinoid Tumor and Small Cell Carcinoma

et al. 2001

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“…For example, chromogranin A is a matrix protein associated with neurosecretory granules and therefore is absolutely specific for neuroendocrine differentiation (1,2). However, because detectability is directly related to the number of neurosecretory granules, infrequent staining or absence of staining for chromogranin A has been reported in cases of small cell lung carcinoma (3)(4)(5). On the other hand, anti-neuron-specific enolase (NSE) antibody is highly reactive for neuroendocrine tumors, but its specificity is poor because of cross-reactivity (6).…”

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confidence: 99%

Histidine Decarboxylase Expression as a New Sensitive and Specific Marker for Small Cell Lung Carcinoma

et al. 2003

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Histidine decarboxylase is one of the enzymes of the amine precursor uptake and decarboxylation system and is known to be distributed in mast cells and enterochromaffin-like cells. With the hypothesis that histidine decarboxylase expression is a marker for neuroendocrine differentiation, we studied the immunoreactivity of histidine decarboxylase in neuroendocrine cells and tumors of the thyroid gland, adrenal medulla, lung, and gastrointestinal tract. Formalin-fixed paraffin sections were subjected to immunohistochemistry using antihistidine decarboxylase antibody, and the sensitivity and specificity were compared with those of conventional neuroendocrine markers (CD56, chromogranin A, synaptophysin, and neuron-specific enolase). Enterochromaffin or enterochromaffinlike cells, adrenal chromaffin cells, and thyroid C-cells were positive for histidine decarboxylase, and related tumors (carcinoid tumor, pheochromocytoma, medullary carcinoma) showed a high percentage of positive staining. Furthermore, we used the antibody to distinguish small cell lung carcinoma from non-neuroendocrine lung carcinoma and also to detect neuroendocrine differentiation in large-cell neuroendocrine carcinoma and gastrointestinal small-cell carcinoma. The anti-histidine decarboxylase antibody stained most small cell lung carcinoma (18 of 23, sensitivity 0.78), and was rarely reactive with non-neuroendocrine lung tumors (2 of 44; specificity, 0.95). These values were close to those obtained from CD56 staining (sensitivity/ specificity, 0.87/0.98). Histidine decarboxylase was also positive for 6 of 12 large cell neuroendocrine carcinomas and 4 of 7 gastrointestinal small cell carcinomas. In conclusion, we demonstrated that histidine decarboxylase is useful to distinguish between small cell lung carcinoma and nonneuroendocrine carcinoma and to demonstrate neuroendocrine differentiation.

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“…1). The family of proteins called chromogranins, originally found in chromaffin cells (4), are now thought to be universal markers for neuroendocrine tissues and tumors (5)(6)(7)(8)(9)(10)(11)(12)(13). Recently the amino acid sequences of human chromogranin A (CgA) and B (CgB) have been reported and shown to be very different from each other, particularly in the central section (3,14).…”

Section: Introductionmentioning

confidence: 99%

“…However, the concentrations ofCgB or the CgB fragment peptide (GAWK) in endocrine tumors and plasma have not previously been reported. We developed two RIA systems using antibodies to GAWK (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) and GAWK (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) to measure GAWK-like immunoreactivities (GAWK [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]…”

Section: Introductionmentioning

confidence: 99%

Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value.

Sekiya

Ghatei²,

Salahuddin³

et al. 1989

J. Clin. Invest.

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The highest tissue concentrations of GAWK-LI were found in pheochromocytoma 18,173±3,915;17,852±2,763 [mean±SEMJ pmol/g wet wt tissue; n = 9), which were at least ten times higher than any other tumors producing GAWK-LI. High concentrations of GAWK-LI were also found in other types of endocrine tumors including carcinoid, medullary carcinoma of thyroid, pancreatic, and ACrH-producing lung tumors. On the other hand, low concentrations of GAWK-LI were found in nonendocrine tumors.Plasma concentrations of GAWK-LI were found to be elevated in patients with endocrine tumor, but more so in those with pancreatic tumors than with pheochromocytomas. Plasma concentrations returned to normal after successful tumor removal. Chromatographic profiles of GAWK-LI in extracts of pheochromocytomas and normal adrenals showed high molecular weight peaks that were absent in the extracts of other endocrine tumors and normal pancreas, suggesting differential tissue-specific processing. Thus GAWK-LI is produced by a variety of endocrine tumors and may serve as a plasma tumor marker, especially in patients with pancreatic endocrine tumors.

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Chromogranin as a Marker of Neuroendocrine Cells in Cytologic Material—An Immunocytochemical Study

Cited by 49 publications

References 23 publications

Microtubule-Associated Protein-2: A New Sensitive and Specific Marker for Pulmonary Carcinoid Tumor and Small Cell Carcinoma

Microtubule-Associated Protein-2: A New Sensitive and Specific Marker for Pulmonary Carcinoid Tumor and Small Cell Carcinoma

Histidine Decarboxylase Expression as a New Sensitive and Specific Marker for Small Cell Lung Carcinoma

Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value.

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