Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer.
BACKGROUND
Several molecular-genetic alterations in endometrial cancers, including aneuploidy and aberrant expression of p53 and HER-2/neu, have been associated with poor prognosis. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathologic prognostic factors, a multivariable analysis was performed.


METHODS
Immunohistochemical staining for p53, HER-2/neu, estrogen receptor, progesterone receptor, and epidermal growth factor receptor was performed on frozen sections from 100 primary endometrial cancers. DNA ploidy was determined using computerized image analysis of Feulgen-stained touch preparations. In addition, information regarding surgical-pathologic features of the cancers was obtained. Univariable analysis was performed followed by multivariable analysis using Cox's proportional hazards model to identify variables predictive of poor prognosis.


RESULTS
With univariable analysis, race, histologic type, stage, grade, myometrial invasion, estrogen receptor, progesterone receptor, ploidy, p53 and HER-2/neu were predictive of the presence of persistent or recurrent disease. In the multivariable analysis, only International Federation of Gynecology and Obstetrics stage (P = 0.005), grade (P = 0.005), myometrial invasion (P = 0.024), and ploidy (P = 0.028) were significant.


CONCLUSIONS
Among molecular-genetic prognostic factors, DNA ploidy was the most strongly predictive of persistent or recurrent disease.
Lukes
A S
AS
Department of Obstetrics and Gynecology/Division of Gynecologic Oncology, Duke Comprehensive Cancer Center, Durham, North Carolina.
Kohler
M F
MF
Pieper
C F
CF
Kerns
B J
BJ
Bentley
R
R
Rodriguez
G C
GC
Soper
J T
JT
Clarke-Pearson
D L
DL
Bast
R C
RC
Berchuck
A
A
D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology / Q000601:surgery; D004247:DNA / Q000032:analysis / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000235:genetics*; D011003:Ploidies; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D004247:DNA; D066246:ErbB Receptors; D009856:Oncogene Proteins, Viral; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53