Cluster analysis of immunohistochemical markers in leiomyosarcoma delineates specific anatomic and gender subgroups.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Carvalho
Jason C
JC
Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0054, USA.
Thomas
Dafydd G
DG
Lucas
David R
DR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007890:Leiomyosarcoma / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D046888:Tissue Array Analysis; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000401:mortality; D025721:WT1 Proteins / Q000032:analysis
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D025721:WT1 Proteins