Nuclear staining

Nuclear immunomarkers, such as oestrogen and progesterone receptors, TTF-1, microphthalmia transcription factor, Myo-D1, myogenin, cyclins, Rb2/p130, CDX-2, p57, and Fli-1 are generally easier to interpret than are cytoplasmic or membrane markers. Transcription factors usually yield an "all or none" signal, often of in excess of 90% of nuclei. There is much less likelihood of confusion with biotin or other sources of false-positive cytoplasmic staining. Staining is usually largely independent of the degree of differentiation.

However difficulty can arise for the following reasons:

It is helpful to compare the nuclei with appropriate negative and positive internal control nuclei. A red chromogen such as AEC (3-amino-9-ethylcarbazole) may be helpful.

Some nuclear markers such as Fli-1, when positive, stain over 50% of nuclei and circumspection is required if only a few nuclei stain1. One paper set the threshold for positivity for CDX-2 at 25% of nuclei2. A much lower threshold can be safely applied for TTF-1 as a marker of lung tumours. It is important to know the threshold level of nuclear staining for the marker being used.


1Folpe, A. L., Chand, E. M., Goldblum, J. R., Weiss, S. W. Expression of Fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics. Am J Surg Pathol 2001;25:1061-1066.

2Werling, R.W., Yaziji, H., Bacchi, C.E. and Gown, A.M. CDX2, a Highly Sensitive and Specific Marker of Adenocarcinomas of Intestinal Origin: An Immunohistochemical Survey of 476 Primary and Metastatic Carcinomas. Am J Surg Pathol 2003;27:303-10.

This page last revised 29.5.2003.