Microscopic Benign and Invasive Malignant Neoplasms and a Cancer-Prone Phenotype in Prophylactic Oophorectomies

Salazar, Hernando; Godwin, Andrew K.; Daly, Mary B.; Laub, Paul B.; Hogan, W. J.; Rosenblum, Norman G.; Boente, Matthew P.; Lynch, Henry T.; Hamilton, Thomas C.

doi:10.1093/jnci/88.24.1810

Cited by 247 publications

(188 citation statements)

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“…Werness et al 15 were unable to identify a difference in the frequency of atypia in prophylactically removed ovaries and controls on light microscopic examination, but demonstrated a statistically significant increase in nuclear enlargement and chromatin heterogeneity in prophylactically removed ovaries morphometrically. Several other groups have failed to demonstrate epithelial atypia in the prophylactic oophorectomy specimens from women with a strong family history of ovarian cancer 16 or with known BRCA1 or 2 mutations. 17,18 Two groups of investigators have noted mild atypia of the surface epithelium in uninvolved ovaries contralateral to ovarian carcinomas or borderline tumors; 4,19 the latter group, however, failed to detect atypia in epithelial inclusion glands.…”

Section: Morphologic Datamentioning

confidence: 99%

Origins and molecular pathology of ovarian cancer

2005

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Epithelial ovarian cancer comprises the majority of malignant ovarian tumors in adult women. These neoplasms are classified into distinct morphologic categories based on the appearance of the epithelium into tumors of serous, mucinous, endometrioid, clear cell, transitional, squamous, mixed and undifferentiated type. Current data indicate that each of these histologic subtypes is associated with distinct morphologic and molecular genetic alterations: high-grade serous and possibly endometrioid carcinomas most probably arise from surface epithelial inclusion glands with TP53 mutations and dysfunction of BRCA1 and/or BRCA2; low-grade serous carcinomas probably arise in a stepwise fashion in an adenoma-borderline tumor-carcinoma sequence from typical to micropapillary borderline tumors to low-grade invasive serous carcinoma via activation of the RAS-RAF signaling pathway secondary to mutations in KRAS and BRAF; mucinous carcinomas arise via an adenoma-borderline tumor-carcinoma sequence with mutations in KRAS; low-grade endometrioid carcinomas arise from endometriosis via mutations in CTNNB1 (the gene encoding b-catenin) and PTEN. Although the morphologic data strongly support an origin of clear cell carcinoma from endometriosis, there is limited data on the genetic alterations in these uncommon tumors. Thus it is likely that most low-grade, relatively indolent ovarian carcinomas of serous, mucinous and endometrioid type arise from pre-existing cystadenomas or endometriosis whereas most high-grade serous carcinomas arise without an easily identifiable precursor lesion. Modern Pathology (2005) 18, S19-S32. doi:10.1038/modpathol.3800306Keywords: ovarian cancer; ovarian borderline tumors; histogenesis; molecular pathology Epithelial ovarian cancer comprises the majority of malignant ovarian tumors in adult women. These neoplasms are classified into distinct morphologic categories based on the appearance of the epithelium into tumors of serous, mucinous, endometrioid, clear cell, transitional, squamous, mixed and undifferentiated type. 1,2 Two types of ovarian surface epithelial lesions have been described as possible precursors of these carcinomas: lesions that appear in situ in surface epithelium or surface epithelial inclusion glands (SEIG); and preexisting benign epithelial ovarian tumors and endometriosis. The morphologic and genetic data implicating each as a precursor lesion of the major histologic subtypes of ovarian carcinoma are discussed. Surface epithelium and surface epithelial inclusion glands as precursor lesions Morphologic DataTwo types of morphologic data are available regarding the malignant potential of ovarian surface epithelium and inclusion glands, alterations in these structures and studies on microscopic ovarian carcinoma.Surface epithelium and surface epithelial inclusion glands Despite the widespread acceptance of the origin of surface epithelial cancers from the ovarian surface epithelium and its inclusion glands, only rarely have putative precursor lesions been described at these sites. Two...

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Section: Morphologic Datamentioning

confidence: 99%

Origins and molecular pathology of ovarian cancer

2005

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“…Besides the above considerations the rationale for this was the recent localization to 6q27, in a region de®ned by markers D6S133 and D6S281, of a locus for SV40-mediated immortalization of human cells (Sandhu et al, 1994;Banga et al, 1997). Assuming that a progression mechanism is at work in the tumorigenesis process leading to frank carcinomas as opposed to a di erentiation/maturation model (although this matter is still unsettled) (Liu and Nuzum, 1995;Zheng et al, 1995;Wolf et al, 1996;Salazar et al, 1997) the region mentioned above is expected to be altered in benign neoplasms.…”

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“…Lastly, although it is still highly controversial whether ovarian carcinomas arise de novo or from preexistent lesions (Liu and Nuzum, 1995; Zheng et al, Wolf et al, 1996;Salazar et al, 1997), the fact that the region where SEN6 has been mapped is deleted in benign ovarian neoplasms suggests that a possible causal link between the loss of such gene and the immortalization of a few ovarian surface epithelial cells is worth of consideration.…”

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confidence: 99%

Physical map of the D6S149-D6S193 region on chromosome 6Q27 and its involement in benign surface epithelial ovarian tumours

et al. 1998

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A detailed long range restriction map of the region de®ned by markers D6S149 and D6S193 on chromosome 6q27 has been constructed. This was achieved by YAC cloning and contig assembling of the same region. Seven YAC clones were found to span the almost 1000 Kb region¯anked by the two markers which on the genetic map resulted to be 1.9 cM apart. With some of the characterized YAC clones we undertook a molecular cytogenetic analysis of 20 benign ovarian tumors. The rationale for this was the recent mapping to a region of chromosome 6q27,¯anked by markers D6281 and D6S133, of a locus for the SV40-mediated immortalization of human cells (SEN6 gene). Noteworthy we found that the the D6S149-D6S193 region (comprised in the larger D6S281-D6S133 physical interval) was altered in all samples analysed adding support to the occurrence of a immortalization step in this type of tumors.

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“…If the patient has had a diploid borderline tumor expectant management may be reasonable [9]. But in patients with invasive ovarian Stage I tumors clinical check ups beyond childbearing age is doubtful because of a risk of contra lateral ovarian pre-neoplastic phenotypes in these high-risk women is high [27,28].…”

Section: Discussionmentioning

confidence: 99%

Fertility-sparing surgery and outcome in fertile women with ovarian borderline tumors and epithelial invasive ovarian cancer

Borgfeldt

Iosif

Måsbäck

2007

European Journal of Obstetrics & Gynecology and Reproductiv

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Results: During the follow-up period of median 92 months, range 11-185 months, no relapse was found in the patients with stage Ia tumors including both the borderline tumors (n=12) and the invasive well (n=9) and moderately (n=1) differentiated ovarian cancers. One patient with poorly differentiated ovarian cancer stage 1c was pregnant at 13 weeks at the primary operation.Although, unilateral oophorectomy was performed she insisted in continuing the pregnancy. At 37 weeks she had a caesarian section and the ovarian cancer was disseminated. Chemotherapy was given but she died less than a year later. No other patient received chemotherapy. In total 30 children was born by 15 patients. Prophylactic removal of the remaining ovary +/-hysterectomy was accepted only in six of the women after completing their desire to have more children. However, several of these patients do not accept the recommendation of prophylactic oophorectomy of the contra lateral ovary and hysterectomy after completion of childbearing age. Conclusions4

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Microscopic Benign and Invasive Malignant Neoplasms and a Cancer-Prone Phenotype in Prophylactic Oophorectomies

Abstract: We suggest that the ovaries removed from ovarian cancer-prone individuals as a preventative measure should be thoroughly examined histologically to identify or rule out microscopic or near-microscopic invasive neoplasms.

Cited by 247 publications

References 0 publications

Origins and molecular pathology of ovarian cancer

Origins and molecular pathology of ovarian cancer

Physical map of the D6S149-D6S193 region on chromosome 6Q27 and its involement in benign surface epithelial ovarian tumours

Fertility-sparing surgery and outcome in fertile women with ovarian borderline tumors and epithelial invasive ovarian cancer

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