Calretinin

by Jan Klos

Background

It is a calcium binding protein with unknown function. It is structurally related to S-100 protein and Inhibin. Its is present in the cytoplasm and nucleus of the variety of cell types.

Positivity in normal tissues

Neural cells, mesothelium, steroid producing cells, Sertoli cells in testis, surface epithelium of the ovary, some neuroendocrine cells, breast glands, eccrine sweat glands, hair follicular cells, thymic epithelial cells, endometrial stromal cells, mast cells and fat cells.

Positivity in tumors

Mesothelial proliferations including mesothelioma (approaching 100% in proliferations with epithelioid morphology and around 50% in proliferations with sarcomatoid morphology), close to 100% of sex cord-stromal tumors of the ovary, granular cell tumors, adrenal cortical tumors, Wolffian adnexal tumour, ameloblastoma, solid papillary carcinoma with reverse polarity of the breast. High percentage of certain carcinomas (serous carcinomas of the ovary, mesonephric carcinomas of the cervix, giant cell carcinomas of the lung, carcinomas of thymus, cholangiocarcinoma) are also reported positive. About one in four metastatic breast carcinomas may also show positivity . Mesenchymal tumors like cardiac myxomas, synovial sarcomas, fibrosarcoma are also positive in majority of cases.

Staining pattern

Staining pattern is nuclear and cytoplasmic.

Control tissue

Adrenal gland (weak expression) and neural tissue (preferably appendix with ganglions and axons showing strong expression)

Application

  • Sensitive but not specific marker applicable in a panel for mesothelial proliferations, sex cord-stromal tumors.
  • For differentiation between mesothelial and epithelial proliferations (adenocarcinoma) Calretinin is recommended as a part of the panel together with the wide spectrum anti-epithelial antibody (EP-CAM, MOC31 or E-Cadherin). Positivity, usually focal, in a number of adenocarcinomas may be a potential pitfall.
  • Positive staining is also supportive for neuronal differentiation in tumors.
  • Ameloblastoma including its variants.
  • Be aware of observed variation in sensitivity and specificity of staining  depending on the protocol, clone and staining platforms.

Selected references

  1. Alsadoun N1, MacGrogan G2, Truntzer C  et al. Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases. Mod Pathol 2018 Sep;31(9):1367-1380.  doi: 10.1038/s41379-018-0047-1. Epub 2018 May
  2. https://www.nordiqc.org/downloads/assessments/101_18.pdf
  3. https://app.immunoquery.com/
  4. Movahedi-Lankarani, S; Kurman, R.J. Calretinin, a More Sensitive but Less Specific Marker Than α-Inhibin for Ovarian Sex Cord-Stromal Neoplasms. An Immunohistochemical Study of 215 Cases. The American Journal of Surgical Pathology: Nov 2002, Vol. 26. 11. p 1477-148
  5. Pernick N. Calretinin. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainscalretinin.Html. Accessed February 7th, 2021.