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High frequency of β‐catenin mutations in borderline endometrioid tumours of the ovary
Author(s) -
Oliva E,
Sarrió D,
Brachtel EF,
SánchezEstévez C,
Soslow RA,
MorenoBueno G,
Palacios J
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1923
Subject(s) - microsatellite instability , pten , kras , malignancy , carcinogenesis , cancer research , biology , catenin , mutation , pathology , immunohistochemistry , carcinoma , cancer , microsatellite , medicine , gene , wnt signaling pathway , pi3k/akt/mtor pathway , genetics , allele , apoptosis
Some low‐grade endometrioid carcinomas arise from a background of endometrioid tumours of borderline malignancy. To determine the molecular mechanisms involved in the initiation of endometrioid carcinoma, the present study investigated whether the genetic alterations reported in these tumours (mutations in PTEN, KRAS , and β‐catenin genes, and microsatellite instability) are already present in endometrioid tumours of borderline malignancy. Eight endometrioid tumours of borderline malignancy were studied. By immunohistochemistry, β‐catenin was expressed in the nuclei of all tumours, suggesting the presence of stabilizing β‐catenin mutations. By mutational analysis, five different β‐catenin mutations were found in seven of eight cases (90%), affecting codons 32, 33, and 37. In contrast, only one tumour harboured a PTEN mutation, which affected codon 130. Neither KRAS mutations nor microsatellite instability was detected. A review of the literature indicated that β‐catenin mutations are characteristic of well‐differentiated endometrioid carcinomas, since they were present in nearly 60% of grade I but in less of 3% of grade III tumours. In conclusion, the present study identifies β‐catenin mutation as a nearly constant molecular alteration in borderline endometrioid tumours, whereas PTEN and KRAS mutations and microsatellite instability are very infrequent. The findings in the present study, and previously reported data, strongly suggest that β‐catenin mutation is an early event in endometrioid ovarian carcinogenesis, and that it is involved in the development of low‐grade endometrioid tumours. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.