TY - JOUR
T1 - Concurrent endometrial intraepithelial carcinoma (EIC) and serous ovarian cancer
T2 - can EIC be seen as the precursor lesion?
AU - Roelofsen, Thijs
AU - van Kempen, Léon C L T
AU - van der Laak, Jeroen A W M
AU - van Ham, Maaike A
AU - Bulten, Johan
AU - Massuger, Leon F A G
PY - 2012
Y1 - 2012
N2 - OBJECTIVE: The pathogenesis of serous ovarian carcinoma (SOC) is still unknown. Recently, endometrial intraepithelial carcinoma (EIC) was proposed to be the precursor lesion of SOC. This study examines the model of EIC as precursor for SOC.METHODS: Cases of SOC with a noninvasive or superficially invasive serous lesion, a hyperplastic lesion with/without atypia, or EIC in the endometrium were selected for inclusion in this study. Tissue sections from both ovaries, the fallopian tubes, and the uterus were extensively reviewed by an expert gynecopathologist. For both EIC and SOC, immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor; TP53 mutation analysis; and in situ ploidy analysis were performed.RESULTS: Nine cases of SOC with concurrent EIC in the endometrium were identified. Immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor revealed almost identical expression patterns and similar intensities in each pair of EIC and coincident SOC. Identical TP53 mutations were found in SOC and coinciding EIC in 33% of the cases, suggesting a clonal origin. DNA ploidy analysis, as a marker for neoplastic progression, demonstrated an increased number of aneuploid nuclei in SOC compared to their corresponding EIC (P = 0.039). In addition, the mean amount of DNA per nucleus in SOC was higher (ie, more aneuploid) compared to EIC (P = 0.039).CONCLUSION: This study provides a first indication of EIC as possible precursor lesion for SOC. This finding could have major clinical implications for future ovarian cancer management and underscores EIC as a possible target for early SOC detection and prevention.
AB - OBJECTIVE: The pathogenesis of serous ovarian carcinoma (SOC) is still unknown. Recently, endometrial intraepithelial carcinoma (EIC) was proposed to be the precursor lesion of SOC. This study examines the model of EIC as precursor for SOC.METHODS: Cases of SOC with a noninvasive or superficially invasive serous lesion, a hyperplastic lesion with/without atypia, or EIC in the endometrium were selected for inclusion in this study. Tissue sections from both ovaries, the fallopian tubes, and the uterus were extensively reviewed by an expert gynecopathologist. For both EIC and SOC, immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor; TP53 mutation analysis; and in situ ploidy analysis were performed.RESULTS: Nine cases of SOC with concurrent EIC in the endometrium were identified. Immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor revealed almost identical expression patterns and similar intensities in each pair of EIC and coincident SOC. Identical TP53 mutations were found in SOC and coinciding EIC in 33% of the cases, suggesting a clonal origin. DNA ploidy analysis, as a marker for neoplastic progression, demonstrated an increased number of aneuploid nuclei in SOC compared to their corresponding EIC (P = 0.039). In addition, the mean amount of DNA per nucleus in SOC was higher (ie, more aneuploid) compared to EIC (P = 0.039).CONCLUSION: This study provides a first indication of EIC as possible precursor lesion for SOC. This finding could have major clinical implications for future ovarian cancer management and underscores EIC as a possible target for early SOC detection and prevention.
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma in Situ/diagnosis
KW - Cohort Studies
KW - Cystadenocarcinoma, Serous/diagnosis
KW - DNA Mutational Analysis
KW - Endometrial Neoplasms/diagnosis
KW - Female
KW - Genes, p53
KW - Humans
KW - Immunohistochemistry
KW - Middle Aged
KW - Neoplasms, Multiple Primary/diagnosis
KW - Ovarian Neoplasms/diagnosis
KW - Ploidies
KW - Precancerous Conditions/diagnosis
U2 - 10.1097/IGC.0b013e3182434a81
DO - 10.1097/IGC.0b013e3182434a81
M3 - Article
C2 - 22249577
SN - 1048-891X
VL - 22
SP - 457
EP - 464
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
IS - 3
ER -