Cam 5.2

Immunohistochemical expression

Surprisingly, there is some controversy as to the cytokeratins recognised by Cam 5.2. It is commonly cited as reacting with cytokeratins 8 and 18. This is, for example, the information in Leong, Cooper and Leong, Manual of Diagnostic Antibodies for Immunohistology, second edition. This view appears to be based on an initial paper by Makin et al3, which identified the reactive keratins as having molecular weights of 39, 43 and 50 kDaltons, corresponding to keratins 19, 18 and 8 respectively. This was the information in a previous version of the Becton Dickinson data sheet. However, the latest Becton Dickinson data sheet for Cam 5.2.gives the primary reactivity, demonstrated by gel electrophoresis, as cytokeratin 8. There is no reference for this, so perhaps this is Becton Dickinson's in-house result. But I think all agreed on this point . Looking at the references that they do give, Smedts et al4 subsequently claimed that Cam 5.2 is specific for cytokeratin 8 and to a lesser extent for the closely related cytokeratin 7, but shows no reactivity with 18 or 19. The previous results by Makin et al are attributed to breakdown products of cytokeratin 8, giving smaller molecular weight fractions on immunoblots. They also cite unpublished observations on bacterially synthesised individual recombinant keratins.

Although Becton Dickinson’s data sheet cites Lab Invest 1985;52:243-256, I can see no reference there to anything that I recognise as Cam 5.2. There is only a difference of 2kD between the molecular weights of cytokeratins 7 and 8 and, as far as I know, 7 is always found in the company of 8, so initial studies may plausibly have missed reactivity with keratin 7.

Reacts with normal secretory epithelia but not stratified squamous epithelium.

Diagnostic utility

It is expressed by :

• Adenocarcinoma

• Squamous cell carcinoma including spindle cell carcinoma. May be negative in squamous cell carcinomas of the cervix, vagina and oesophagus

• Renal cell carcinoma

• Hepatocellular carcinoma

• Cholangiocarcinoma

• Neuroendocrine carcinoma, including small cell carcinoma (where there may be dot-like positivity) and Merkel cell carcinoma

• Mesotheliomas generally stain more intensely than do adenocarcinomas2. Expression by fibrous cells is more common in mesotheliomas that in adenocarcinoma1.

• Germ cell tumours, except seminoma

• Synovial sarcoma

• Epithelioid sarcoma

• Epithelial cells of thymoma

• Smooth muscle and smooth muscle tumours

• Some breast sarcomas

• Meningioma

• Neuroblastoma

• Anaplastic B cell lymphoma

There is focal staining in up to 10% of melanomas

References

1Dejmek, A., Brockstedt, U., Hjerpe, A. Optimization of a battery using nine immunocytochemical variables for distinguishing between epithelial mesothelioma and adenocarcinoma. Apmis 1997;105:889-94.

2Comin, 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.

3Makin, C. A., L. G. Bobrow, et al. (1984). "Monoclonal antibody to cytokeratin for use in routine histopathology." J Clin Pathol 37(9): 975-83.

4Smedts, F., F. Ramaekers, et al. (1990). "Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia." Am J Pathol 136(3): 657-68.

©SMUHT/PW Bishop