Increased prevalence of p53 overexpression from typical endometriosis to atypical endometriosis and ovarian cancer associated with endometriosis.
OBJECTIVE
To evaluate the expression of p53, c-erb-B-2, MIB1 and Bcl-2 in normal endometrium, endometriosis, atypical endometriosis and ovarian cancer associated with endometriosis, looking for immunohistochemical markers that may help determine endometriosis with premalignant potential.


METHODS
Between 1948 and 1999, 410 epithelial ovarian cancers and 521 cases of endometriosis were surgically treated at Fundación Jiménez Díaz. Pathology reports and slides were reviewed. Four groups were defined: (1) endometriosis/cancer (n=17); (2) atypical endometriosis (n=6); (3) endometriosis (n=17); (4) endometrium (n=7). Tumors and controls were immunostained and evaluated for expression of p53, c-erb-B-2, MIB1 and Bcl-2. Statistical analysis was performed using Chi-square for linear trends, Fisher exact and Kruskal-Wallis tests.


RESULTS
Of the 410 cancers, 17 (4.1%) had associated endometriosis and of the 521 endometriosis, 6 (1.2 %) had atypical changes. Fourteen of 17 (82.4%) cancers associated with endometriosis and all atypical endometriosis had p53 overexpression. Only 2 of 17 (11.8%) endometriosis and none of the endometriums had mutant p53 (P<0.01). We found a trend towards increased expression of MIB1 (0.073) in the cancer and atypical endometriosis groups, and no differences in expression of Bcl-2 or c-erb-B-2. The sensitivity and specificity of p53 as a marker for the diagnosis of atypical endometriosis and cancer associated with endometriosis were 87%; CI 95% (73.2-100%) and 92% (80.6-100%), respectively. When comparing all groups, the mean positive p53 and MIB1 cell count was statistically significant (P=0.01).


CONCLUSIONS
Overexpression of p53 in atypical endometriosis and cancer associated with endometriosis is a common finding and may be used to identify endometriosis with premalignant potential.
Sáinz de la Cuesta
Ricardo
R
Departments de Obstetricia y Ginecología, Anatomía Patológica y Epidemiología, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Avenida de los Reyes Católicos, 2, 28040 Madrid, Spain.
Izquierdo
Manuel
M
Cañamero
Marta
M
Granizo
Juan José
JJ
Manzarbeitia
Felix
F
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D004715:Endometriosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011237:Predictive Value of Tests; D015995:Prevalence; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012680:Sensitivity and Specificity; D013030:Spain / Q000453:epidemiology
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2