Extensive survey of STAT6 expression in a large series of mesenchymal tumors

Abstract

Objectives: Expression of strong nuclear STAT6 is thought to be a specific marker for solitary fibrous tumors (SFTs). Little is known about subtle expression patterns in other mesenchymal lesions.

Methods: We performed immunohistochemical studies against the C-terminus of STAT6 in tissue microarrays and whole sections, comprising 2366 mesenchymal lesions.

Results: Strong nuclear STAT6 was expressed in 285 of 2,021 tumors, including 206 of 240 SFTs, 49 of 408 well-differentiated/dedifferentiated liposarcomas, eight of 65 unclassified sarcomas, and 14 of 184 desmoid tumors, among others. Expression in SFTs was predominately limited to the nucleus. Other positive tumors typically expressed both nuclear and cytoplasmic STAT6. Complete absence of STAT6 was most common in pleomorphic liposarcoma and alveolar soft part sarcoma (60% and 72% cases negative, respectively).

Conclusions: Strong nuclear STAT6 is largely specific for SFTs. Physiologic low-level cytoplasmic/nuclear expression is common in mesenchymal neoplasia and is of uncertain significance.

Keywords: Immunohistochemistry; STAT6; Sarcoma; Solitary fibrous tumor.

Figure 1

Scoring of nuclear STAT6 immunohistochemical staining. A. Score 0, complete absence of nuclear and cytoplasmic expression. B. Score 1+ nuclear, 1+ cytoplasmic weak positivity. C. Score 2+ nuclear stain, D. 3+ nuclear stain. All images at 200×

Figure 2

Variable STAT6 staining was seen in solitary fibrous tumors. A-D. H&E demonstrating histologic features of representative solitary fibrous tumors with E. negative-to-focal-weak nuclear STAT6, F. 2+ nuclear and cytoplasmic expression, G. 2+ nuclear expression, H. 3+ nuclear STAT6. All images at 200×.

Figure 3

Moderate STAT6 nuclear expression may occur in desmoid tumors. A. H&E, B. STAT6, 2+ nuclear, 1+ cytoplasmic staining. Both panels at 200×.

Figure 4

Strong nuclear and cytoplasmic STAT6 expression is rarely seen in unclassified sarcomas. A-D, H&E, E-H corresponding STAT6 stains showing strong nuclear and cytoplasmic expression. All images at 200×.

Figure 5

STAT6 expression was common in scar tissue. A. Representative H&E, B. Representative STAT6 showing 2+ cytoplasmic and nuclear expression. Both panels at 200×.