Treatment and recurrence patterns in endometrial stromal sarcomas and the relation to c-kit expression.
BACKGROUND
Endometrial stromal sarcomas (ESS) are a rare gynecologic malignancy. The optimal management of this cancer remains unclear, although previous reports have failed to demonstrate a clear benefit to adjuvant chemotherapy or radiation. With the successful application of directed biological therapy in other sarcomas, a review of the behavior and biology of this disease is warranted.


OBJECTIVE
To review outcomes and patterns of failure in patients with endometrial stromal sarcoma diagnosed over 31 years at our institution and the relationship to protooncogene c-kit expression.


METHODS
Hospital records and pathology were reviewed for 28 patients with endometrial stromal sarcomas [19 low-grade (LGESS) and 9 high-grade (HGESS)] treated between 1972 and 2003. Archival tissue samples from 16 patients were available and stained with CD 117 (c-kit) antibody (1:25 dilution). Staining intensity was graded 1+ to 3+ and distribution of the cellular staining as focal (10-30% of the cells), intermediate (30-60% of the cells), or diffuse (>60% of the cells). Positive tumors had more than 10% of cells comprising the neoplasm display immunoreactivity. RESULTS.: We found a significant difference in 5-year overall survival between LGESS and HGESS (P = 0.001). There was no significant difference in overall survival for patients with local versus advanced disease (P = 0.53) or in overall survival for those who underwent lymphadenectomy and those who did not (P = 0.92). 50% of patients received postoperative radiation with no difference in disease-free or overall survival (P = 0.68 and P = 0.53). Ten patients relapsed (36%, four HGESS and six LGESS). Seven of sixteen (43.8%) tumor samples expressed detectable c-kit. Five of seven (71%) were HGESS, and the other two (22%) were LGESS tumors. The median survival of patients with c-kit-positive versus c-kit-negative tumors was 12 and 47 months, respectively.


CONCLUSIONS
This study confirms the superior overall prognosis of LGESS relative to HGESS, despite the similar rates of relapse. Although hard to assess, due to population heterogeneity and small numbers, adjuvant chemotherapy and radiation appear to be of limited benefit. Expression of c-kit was common, especially in high-grade lesions and may represent a potential therapeutic target.
Geller
Melissa A
MA
Department of Obstetrics and Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Argenta
Peter
P
Bradley
William
W
Dusenbery
Kathryn E
KE
Brooker
Doris
D
Downs
Levi S
LS
Judson
Patricia L
PL
Carson
Linda F
LF
Boente
Matthew P
MP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008197:Lymph Node Excision; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D018203:Sarcoma, Endometrial Stromal / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
D019009:Proto-Oncogene Proteins c-kit