Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.
Identifieur interne : 000353 ( Main/Exploration ); précédent : 000352; suivant : 000354Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.
Auteurs : Lars-Christian Horn [Allemagne] ; Anne K. Höhn ; Jens Einenkel ; Udo SieboltsSource :
- International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists [ 1538-7151 ] ; 2014.
English descriptors
- KwdEn :
- Adult, Aged, Cystadenofibroma (genetics), Cystadenofibroma (pathology), DNA Mutational Analysis, Female, Humans, Lymphatic Metastasis (genetics), Lymphatic Metastasis (pathology), Middle Aged, Ovarian Neoplasms (genetics), Ovarian Neoplasms (pathology), Peritoneal Neoplasms (genetics), Peritoneal Neoplasms (secondary), Polymerase Chain Reaction, Proto-Oncogene Proteins (genetics), Proto-Oncogene Proteins B-raf (genetics), Proto-Oncogene Proteins p21(ras), Young Adult, ras Proteins (genetics).
- MESH :
- chemical , genetics : Proto-Oncogene Proteins, Proto-Oncogene Proteins B-raf, ras Proteins.
- genetics : Cystadenofibroma, Lymphatic Metastasis, Ovarian Neoplasms, Peritoneal Neoplasms.
- pathology : Cystadenofibroma, Lymphatic Metastasis, Ovarian Neoplasms.
- secondary : Peritoneal Neoplasms.
- Adult, Aged, DNA Mutational Analysis, Female, Humans, Middle Aged, Polymerase Chain Reaction, Proto-Oncogene Proteins p21(ras), Young Adult.
Abstract
Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.
DOI: 10.1097/PGP.0000000000000103
PubMed: 25272298
Affiliations:
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Höhn</name></author><author><name sortKey="Einenkel, Jens" sort="Einenkel, Jens" uniqKey="Einenkel J" first="Jens" last="Einenkel">Jens Einenkel</name></author><author><name sortKey="Siebolts, Udo" sort="Siebolts, Udo" uniqKey="Siebolts U" first="Udo" last="Siebolts">Udo Siebolts</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25272298</idno><idno type="pmid">25272298</idno><idno type="doi">10.1097/PGP.0000000000000103</idno><idno type="wicri:Area/PubMed/Corpus">000318</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000318</idno><idno type="wicri:Area/PubMed/Curation">000318</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000318</idno><idno type="wicri:Area/PubMed/Checkpoint">000318</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000318</idno><idno type="wicri:Area/Ncbi/Merge">000725</idno><idno type="wicri:Area/Ncbi/Curation">000725</idno><idno type="wicri:Area/Ncbi/Checkpoint">000725</idno><idno type="wicri:Area/Main/Merge">000354</idno><idno type="wicri:Area/Main/Curation">000353</idno><idno type="wicri:Area/Main/Exploration">000353</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.</title><author><name sortKey="Horn, Lars Christian" sort="Horn, Lars Christian" uniqKey="Horn L" first="Lars-Christian" last="Horn">Lars-Christian Horn</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Pathology (L.-C.H., A.K.H.), Division of Breast, Gynecologic & Perinatal Pathology Department of Obstetrics and Gynecology (J.E.), Institute of Trier Institute of Pathology (U.S.), Division Molecular Pathology, University of Leipzig, Leipzig, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Pathology (L.-C.H., A.K.H.), Division of Breast, Gynecologic & Perinatal Pathology Department of Obstetrics and Gynecology (J.E.), Institute of Trier Institute of Pathology (U.S.), Division Molecular Pathology, University of Leipzig, Leipzig</wicri:regionArea><placeName><region type="land" nuts="1">Saxe (Land)</region><region type="district" nuts="2">District de Leipzig</region><settlement type="city">Leipzig</settlement></placeName></affiliation></author><author><name sortKey="Hohn, Anne K" sort="Hohn, Anne K" uniqKey="Hohn A" first="Anne K" last="Höhn">Anne K. Höhn</name></author><author><name sortKey="Einenkel, Jens" sort="Einenkel, Jens" uniqKey="Einenkel J" first="Jens" last="Einenkel">Jens Einenkel</name></author><author><name sortKey="Siebolts, Udo" sort="Siebolts, Udo" uniqKey="Siebolts U" first="Udo" last="Siebolts">Udo Siebolts</name></author></analytic><series><title level="j">International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists</title><idno type="eISSN">1538-7151</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Cystadenofibroma (genetics)</term><term>Cystadenofibroma (pathology)</term><term>DNA Mutational Analysis</term><term>Female</term><term>Humans</term><term>Lymphatic Metastasis (genetics)</term><term>Lymphatic Metastasis (pathology)</term><term>Middle Aged</term><term>Ovarian Neoplasms (genetics)</term><term>Ovarian Neoplasms (pathology)</term><term>Peritoneal Neoplasms (genetics)</term><term>Peritoneal Neoplasms (secondary)</term><term>Polymerase Chain Reaction</term><term>Proto-Oncogene Proteins (genetics)</term><term>Proto-Oncogene Proteins B-raf (genetics)</term><term>Proto-Oncogene Proteins p21(ras)</term><term>Young Adult</term><term>ras Proteins (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Proto-Oncogene Proteins</term><term>Proto-Oncogene Proteins B-raf</term><term>ras Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cystadenofibroma</term><term>Lymphatic Metastasis</term><term>Ovarian Neoplasms</term><term>Peritoneal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Cystadenofibroma</term><term>Lymphatic Metastasis</term><term>Ovarian Neoplasms</term></keywords><keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Peritoneal Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>DNA Mutational Analysis</term><term>Female</term><term>Humans</term><term>Middle Aged</term><term>Polymerase Chain Reaction</term><term>Proto-Oncogene Proteins p21(ras)</term><term>Young Adult</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>District de Leipzig</li><li>Saxe (Land)</li></region><settlement><li>Leipzig</li></settlement></list><tree><noCountry><name sortKey="Einenkel, Jens" sort="Einenkel, Jens" uniqKey="Einenkel J" first="Jens" last="Einenkel">Jens Einenkel</name><name sortKey="Hohn, Anne K" sort="Hohn, Anne K" uniqKey="Hohn A" first="Anne K" last="Höhn">Anne K. Höhn</name><name sortKey="Siebolts, Udo" sort="Siebolts, Udo" uniqKey="Siebolts U" first="Udo" last="Siebolts">Udo Siebolts</name></noCountry><country name="Allemagne"><region name="Saxe (Land)"><name sortKey="Horn, Lars Christian" sort="Horn, Lars Christian" uniqKey="Horn L" first="Lars-Christian" last="Horn">Lars-Christian Horn</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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