Calretinin in mesothelioma - cytoplasmic or nuclear?

There is some confusion as to whether the significant staining with calretinin in mesotheliomas is nuclear or cytoplasmic, or both.

Doglioni et al1 reported the immunoreactivity in mesothelioma to be both cytoplasmic and nuclear, but did not further comment on which component was most reliable in the differentiation of mesothelioma from carcinoma. Miettinen et al10 and Ordonez12 similarly report staining to be both nuclear and cytoplasmic. Brockstedt et al2 illustrate staining with calretinin in a figure which shows both nuclear and cytoplasmic immunoreactivity, notwithstanding which, their analysis of immunoreactivity is based on cytoplasmic staining. Comin et al7 reported the staining of all 42 mesotheliomas in their study to be both cytoplasmic and nuclear, always strong and diffuse, in contrast to the very weak cytoplasmic staining in 2 of 23 adenocarcinomas. Davidson et al8 illustrate "the characteristic 'Bull's Eye'" staining pattern of both cytoplasm and nuclear distribution" in (reactive) mesothelial cells from effusions. Abutaily et al11 reported staining to be both cytoplasmic and nuclear. Ordonez expressed the opinion that staining is both nuclear and cytoplasmic13. However, there are a number of studies in which the nuclei in mesotheliomas have been generally negative and the immunoreactivity has been purely cytoplasmic3,4,5,6. There is one report of four mesotheliomas, showing both nuclear and cytoplasmic staining in ante mortem specimens, for which the corresponding post mortem specimens from the same patients show loss of nuclear staining in all cases, with reduction (two cases) or loss (two cases) of cytoplasmic staining9. This issue appears to remain unresolved.

A range of carcinomas, when positive for calretinin, show both cytoplasmic and nuclear staining: this is true of acinar-type adenocarcinoma, small cell carcinoma, large cell carcinoma with and without neuroendocrine differentiation, and squamous cell carcinoma10. Abutaily et al11 give conflicting information on two cases of primary pulmonary adenocarcinoma NOS, in the text stating staining to be both cytoplasmic and nuclear but in the legend to a figure recording cytoplasmic staining of occasional cells.


1 Doglioni, C., Tos, A. P., Laurino, L., Iuzzolino, P., Chiarelli, C., Celio, M. R., Viale, G. Calretinin: a novel immunocytochemical marker for mesothelioma. Am J Surg Pathol1996;20:1037-46.

2 Brockstedt U, Gulyas M, Debra K. An optimized batter of eight antibodies that can distinguish most cases of epithelial mesothelioma form adenocarcinoma. Am J Clin Pathol 2000;114:203-9.

3 Carella R et al. Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma. Am J Surg Pathol 2001;25:43-50.

4 Cury, P. M.,et al. Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura. Mod Pathol 2000;13:107-12.

5 Leers, M. P., Aarts, M. M., Theunissen, P. H. E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma. Histopathology 1998;32:209-16.

6 Frisman, D. M., cCarthy, W. F., Schleiff, P., Buckner, S. B., Nocito, J. D., Jr., O'Leary, T. J. Immunocytochemistry in the differential diagnosis of effusions: use of logistic regression to select a panel of antibodies to distinguish adenocarcinomas from mesothelial proliferations. Mod Pathol 1993;6;179-84.

7 Comin, C. E., Novelli, L., Boddi, V., Paglierani, M., Dini, S. Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma. Hum Pathol 2001;32:529-536.

8 Davidson, B., Nielsen, S., Christensen, J., Asschenfeldt, P., Berner, A., Risberg, B., Johansen, P. The role of desmin and N-cadherin in effusion cytology: a comparative study using established markers of mesothelial and epithelial cells. Am J Surg Pathol 2001;25:1405-1412.

9 Roberts, F., McCall, A. E., Burnett, R. A. Malignant mesothelioma: a comparison of biopsy and postmortem material by light microscopy and immunohistochemistry. J Clin Pathol 2001;54:766-70.

10 Miettinen, M. and Sarlomo-Rikala, M. Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura. Am J Surg Pathol 2003;27:150-8.

11 Abutaily, A.S., Addis, B.J. and Roche, W.R. Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. J Clin Pathol 2002;55:662-8.

12 Ordonez NG. The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study. Mod Pathol 2006; 19:34-48

13 Ordonez NG. Immunohistochemical diagnosis of epithelioid mesothelioma: an update. Arch Pathol Lab Med 2005; 129:1407-14 FULL TEXT

This page last revised 27.7.2006.

©SMUHT/PW Bishop