Distinct β-catenin and PIK3CA mutation profiles in endometriosis-associated ovarian endometrioid and clear cell carcinomas.
OBJECTIVE
We focused on the differences in molecular mechanisms in the early stages of endometriosis-associated ovarian endometrioid carcinoma (OEMCa) and ovarian clear cell carcinoma (OCCCa).


METHODS
Alterations in the β-catenin and PIK3CA genes, as well as expression of their associated markers, were investigated.


RESULTS
Mutations in exon 3 of the β-catenin gene were identified in 21 (60%) of 35 OEMCas. The mutations were also detected in the coexisting nonatypical (52.4%) and atypical (73.3%) endometriosis, and the single-nucleotide substitutions were identical in most cases. In contrast, the mutations were not identified in any of the OCCCas and their coexisting endometriosis. PIK3CA mutations were observed in 11 (31.4%) of 35 OEMCas and 10 (35.7%) of 28 OCCCas. Ten of 11 OEMCas had PIK3CA mutations in exon 9, and eight of 10 OCCCas had them in exon 20. The same mutations were also detected in the coexisting nonatypical and/or atypical endometriosis in three OEMCas and four OCCCas. In addition, significant differences in the expression of pAkt, hepatocyte nuclear factor 1β, hypoxia-inducible factor 1α, p65, and inducible nitric oxide synthase were evident between the two types of tumors and their coexisting endometriosis.


CONCLUSIONS
Distinct molecular events may occur in relatively early stages of tumorigenesis of endometriosis-associated OEMCas and OCCCas.
From the Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Toshihide
T
Matsumoto
From the Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Masaaki
M
Yamazaki
From the Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Hiroyuki
H
Takahashi
From the Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Sabine
S
Kajita
From the Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Erina
E
Suzuki
From the Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Tomoko
T
Tsuruta
From the Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan. msaegusa@med.kitasato-u.ac.jp.
Makoto
M
Saegusa
D018262:Adenocarcinoma, Clear Cell / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D004715:Endometriosis / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics*
C495270:CTNNB1 protein, human; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
Endometriosis; Ovarian clear cell carcinoma; Ovarian endometrioid carcinoma; PIK3CA; β-Catenin