Calretinin is a calcium-binding protein, 29 kDa, member of the family of so-called EF-hand proteins, to which also the S-100 proteins belong. Calretinin is abundantly expressed in neurons. Outside the nervous system, calretinin is found in mesothelial cells, steroid producing cells (adrenal cortical cells, testicular Leydig cells, ovarian theca interna cells), testicular Sertoli cells, rete testis, ovarian surface epithelium, some neuroendocrine cells, breast glands, eccrine sweat glands, hair follicular cells, thymic epithelial cells, endometrial stromal cells, and fat cells. Convoluted tubules of kidney are calretinin positive when stained with the pAbs from Swant and Zymed, not with the mAbs that we have tested (DAK Calret 1; 5A5). The significance of this is at present not known. In calretinin positive cells, the protein is generally found in both the cytoplasm and nuclei.
Calretinin is detected in most malignant mesothelioma. The proportion reaches 100% in some studies but the results are rather divergent, much depending on the protocol (including the antibody). Sarcomatoid and small cell mesothelioma is stained in considerably less than 100% of the cases. Other tumours usually found positive for calretinin are adenomatoid tumour, sex cord-stromal tumours (mostly Sertoli-stromal tumours), mesonephric cervical adenocarcinoma, Wolffian adnexal tumour, synovial sarcoma and ameloblastoma. Some adenocarcinomas also stain (e.g., adenocarcinomas of colon and pancreas are reported to be positive in 20% of the cases), however, the staining is usually more localized and often limited to the cytoplasm, while the nuclei are unstained. Studies of the occurrence of calretinin in, e.g., neural crest and neuroendocrine tumours have not been published.
Calretinin is a useful marker for differentiating malignant mesothelioma from carcinomas. Calretinin is also applicable for the differential diagnosis of ovarian stromal tumours.
Adrenal gland and appendix are recommendable positive and negative tissue controls for CR.
Adrenal gland will serve as a “low-level expressor” (LE) positive tissue control, in which an at least weak to moderate, distinct cytoplasmic and nuclear staining of the majority of the cortical epithelial cells must be seen. Appendix serves both as negative tissue and “high-level expressor” (HE) positive tissue control. Columnar epithelial cells and smooth muscle cells should be negative, while strong, distinct cytoplasmic and nuclear staining of the peripheral nerves (ganglion cells and axons) and macrophages should be seen. Furthermore, fat cells in the submucosa of the appendix could serve as an additional LE positive tissue control.
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