A clinical and biological comparison between malignant mixed müllerian tumors and grade 3 endometrioid endometrial carcinomas.
OBJECTIVE
To examine the clinicopathologic features, progression-free interval, and survival of patients with grade 3 endometrioid endometrial cancer (G3 EEC) and malignant mixed müllerian tumors (MMMTs). Akt, epidermal growth factor receptor (EGFR), and HER-2/neu expression in these histologic subtypes was also investigated. Associations between phosphorylated Akt and clinicopathologic features were tested.


METHODS
One hundred nineteen women whose conditions were diagnosed with MMMT or G3 EEC from January 1, 1990, to December 31, 2003, met inclusion criteria. Retrospective data review was performed. In addition, Akt and EGFR protein expression was measured in tissue samples using Western blotting and immunohistochemistry. Fluorescence in situ hybridization was used to assay HER-2/neu gene amplification.


RESULTS
Fifty-nine patients with MMMT and 60 patients with G3 EEC were identified. Patients with MMMT were older (P = 0.055), more likely to be African American (P = 0.049), have a family history of breast cancer (P = 0.039), have disease involving the uterine cervix (P = 0.007), and experience postoperative complications (P = 0.012). Patients with MMMT had a significantly shorter progression-free interval (23 vs 57 months, P = 0.001) and survival (55 vs 92 months, P = 0.001) than patients with G3 EEC.Grade 3 EEC and MMMT have significantly higher phospho-Akt levels than grade 1 EEC and normal controls. Phospho-Akt was associated with depth of myometrial invasion (r = 0.46, P = 0.05), but not with stage, lymph-vascular space invasion, or tumor size. The mesenchymal component of MMMT preferentially demonstrated EGFR expression relative to the epithelial component (45% vs 13%, P = 0.06). HER-2/neu amplification was observed in 1 of 37 samples.


CONCLUSIONS
Improved therapy is warranted for both poorly differentiated EEC and MMMT. Recognition of similarities and differences between MMMT and other high-grade histologic types of uterine cancer may provide rationale for new treatment approaches possibly incorporating targeted biological therapies.
Bland
Amy E
AE
Department of Obstetrics and Gynecology, University of Virginia Health System, Charlottesville, VA, USA.
Stone
Rebecca
R
Heuser
Cara
C
Shu
Jianfen
J
Jazaeri
Amir
A
Shutter
Jamie
J
Atkins
Kristin
K
Rice
Laurel
L
D000368:Aged; D018269:Carcinoma, Endometrioid / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000601:surgery; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D051058:Oncogene Protein v-akt / Q000096:biosynthesis; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014594:Uterine Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery
D066246:ErbB Receptors; D051058:Oncogene Protein v-akt