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.
References
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
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revised 27.7.2006.
©SMUHT/PW Bishop