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Cluster analysis of immunohistochemical markers in leiomyosarcoma delineates specific anatomic and gender subgroups
Article first published online: 22 JUL 2009
Copyright © 2009 American Cancer Society
Volume 115, Issue 18, pages 4186–4195, 15 September 2009
How to Cite
Carvalho, J. C., Thomas, D. G. and Lucas, D. R. (2009), Cluster analysis of immunohistochemical markers in leiomyosarcoma delineates specific anatomic and gender subgroups. Cancer, 115: 4186–4195. doi: 10.1002/cncr.24486
- Issue published online: 4 SEP 2009
- Article first published online: 22 JUL 2009
- Manuscript Accepted: 9 FEB 2009
- Manuscript Revised: 26 JAN 2009
- Manuscript Received: 3 DEC 2008
- cluster analysis;
- smooth muscle;
- estrogen receptor;
- progesterone receptor;
- Wilms tumor-1 protein (WT1) protein
Leiomyosarcoma (LMS) can be categorized into uterine, retroperitoneal, nonretroperitoneal soft tissue, cutaneous, visceral, and osseous anatomic subtypes. The differential expression of smooth muscle markers, estrogen receptor (ER), progesterone receptor (PR), and Wilms tumor-1 protein (WT1) by anatomic subtype and gender was explored.
A total of 78 LMS comprised of 30 uterine and 48 nonuterine tumors were studied. Nonuterine tumors were comprised of 17 soft tissue, 16 retroperitoneal, 7 cutaneous, 5 visceral, and 3 osseous subtypes. Immunohistochemical staining intensity on tissue microarray slides was scored as 0, 1+, or 2+, and cluster analysis was performed on the data.
Smooth muscle actin was the most sensitive antibody (95%), followed by muscle-specific actin (91%), calponin (88%), desmin (73%), caldesmon (66%), and myosin (64%). Caldesmon and myosin were usually coexpressed, and were highest in retroperitoneal tumors (94%). There was no discernable correlation noted between histologic differentiation and smooth muscle marker expression. ER was much more common in women, with the highest frequencies noted in female retroperitoneal (86%) and uterine (63%) tumors. Nuclear WT1 was expressed in 11% of all tumors, and was limited to ER-positive uterine and female retroperitoneal tumors. Cluster analysis segregated 4 groups, most notably 1 driven by ER and PR, with the vast majority being uterine and female retroperitoneal tumors.
Smooth muscle markers demonstrated variable sensitivities in LMS, with a tendency for anatomic subtypes to segregate based on expression patterns of these markers. ER defined a subgroup of uterine and female retroperitoneal tumors, and WT1 was limited to such tumors, suggesting a common line of differentiation as well as potential therapeutic targets. Cancer 2009. © 2009 American Cancer Society.