To the Editor.—In their recent article, Ozcan et al1 describe PAX-2 as a useful marker for diagnosing metastatic renal cell carcinoma (RCC). The study provides excellent support for the utility of PAX-2 in RCC in lymph nodes, which potentially can be used as a panel in determining the primary tumor when working up cases of nodal metastasis of unknown primary tumor.

We wish to point out a very important limitation of PAX-2 that is not highlighted in the published article. PAX-2, belonging to the paired box–containing gene family, is evolutionarily conserved and shares sequence homologies with PAX-5 (BSAP). While PAX-5 is known to be essential for early B-cell differentiation and is hence expressed in lymphocytes, the expression and role of PAX-2 in lymphocytes is not well documented. We wish to express caution since positive staining for PAX-2 is seen within lymphocytes, thus limiting the utility of lymph nodal metastasis workup. PAX-2 expression may be transient within B lymphocytes. Alternatively, because of sequence homology between PAX-2 and PAX-5, the commercial antibody used in this study may have cross-reactivity with PAX-5 and hence show positive staining within B cells. The authors use PAX-2 from Invitrogen, Carlsbad, California (clone or catalog information not provided in the article). Many of Invitrogen's polyclonal PAX-2 antibodies are derived against murine PAX-2 (peptide sequences 204–373). While Invitrogen's technical data sheet mentions that there is no cross-reactivity with other PAX family of proteins, published data2 suggest that peptide sequences 329 through 416 of mPAX-2 are homologous to hPAX-5.

To illustrate this, we present a recent case reviewed in our consultation service. We recently performed PAX-2 in a lymph node to exclude metastatic RCC. While there was no carcinoma present, the lymphocytes and the confounding vascular lesion (Figures 1 and 2) showed PAX-2 staining. PAX-2 expression profile was described by the same authors in a previous publication,3 and is also seen in their Figure 4, A,1 in which PAX-2 expression is seen in metastatic breast carcinoma and within benign lymphocytes.

Figure 1.

Vascular lesion and benign lymphocytes (hematoxylin-eosin, original magnification ×100).

Figure 2. PAX-2 staining in benign lymphocytes (original magnification ×200).

Figure 1.

Vascular lesion and benign lymphocytes (hematoxylin-eosin, original magnification ×100).

Figure 2. PAX-2 staining in benign lymphocytes (original magnification ×200).

Close modal

Given that PAX-2 staining is seen in lymphocytes, it is very important to recognize this limitation when evaluating lymph nodes for metastatic lesions, especially in the workup of unknown primary tumors.

1.
Ozcan
A
,
Zhai
QJ
,
Javed
R
,
et al
.
PAX-2 is a helpful marker for diagnosing metastatic renal cell carcinoma: comparison with the renal cell carcinoma marker antigen and kidney-specific cadherin
.
Arch Pathol Lab Med
.
2010
;
134
(
8
):
1121
1129
.
2.
Dorfler
P
,
Busslinger
M
.
C-terminal activating and inhibitory domains determine the transactivation potential of BSAP (Pax-5), Pax-2 and Pax-8
.
EMBO J
.
1996
;
15
(
8
):
1971
1982
.
3.
Zhai
QJ
,
Ozcan
A
,
Hamilton
C
,
et al
.
PAX-2 expression in non-neoplastic, primary neoplastic, and metastatic neoplastic tissue: a comprehensive immunohistochemical study
.
Appl Immunohistochem Mol Morphol
.
2010
;
18
(
4
):
323
332
.

The authors have no relevant financial interest in the products or companies described in this article.