Letter to the editor regarding ‘Roh MH, Lassin Y, Miron A et al. High-grade fimbrial-ovarian carcinomas are unified by p53, PTEN and PAX2 expression‘

Gilks, C. Blake; Clarke, Blaise A.; Han, Guangming; Köbel, Martin; Longacre, Teri A.; McCluggage, W. Glenn; Seidman, Jeff D; Shaw, Patricia; Soslow, Robert A.

doi:10.1038/modpathol.2011.94

Cited by 6 publications

(4 citation statements)

References 13 publications

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“…Reclassification of EC to HGSC is an expected result, which has been shown previously in a morphological review of a large population-based series in Canada (21). The differential diagnosis of HGSC and EC, particularly in higher grade cases, is still a matter of controversy among pathologists (22). But many now advocate that the vast majority of cases that show high-grade nuclear atypia regardless of architectural features should be diagnosed as HGSC (2, 36–39).…”

Section: Discussionmentioning

confidence: 99%

“…However, without specific training, which better reflects current pathology practice, the inter-observer agreement is only moderate with Cohen’s κ varying between 0.54 and 0.67 (20). A major diagnostic shift has occurred in recent years affecting the classification of carcinomas with glandular architecture and high-grade nuclear features that were formerly classified as high-grade EC to now be diagnosed as HGSC (Figure S1) (21, 22). This shift is justified by the fact that those carcinomas are molecularly indistinguishable from the morphologically typical HGSC (23).…”

Section: Introductionmentioning

confidence: 99%

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Biomarker-Based Ovarian Carcinoma Typing: A Histologic Investigation in the Ovarian Tumor Tissue Analysis Consortium

Köbel

Kalloger

Lee

et al. 2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Ovarian carcinoma is composed of five major histological types which associate with outcome and predict therapeutic response. Our aim was to evaluate histological type assessments across centres participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model. Methods Tissue microarrays (TMAs) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was performed for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histological type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review. Results The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma (EC) by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of EC compared to HGSC became significant (RR 0.60, 95% CI 0.37–0.93, p=0.021), consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2. Conclusions Research cohorts, particularly those across different centres within consortia, show significant variability in original histological type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type. Impact Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biomarker-Based Ovarian Carcinoma Typing: A Histologic Investigation in the Ovarian Tumor Tissue Analysis Consortium

Köbel

Kalloger

Lee

et al. 2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Using a cutoff of greater than 70% expression and 0% expression (representing a nonsense mutation of p53), an abnormal pattern of p53 expression will be seen in approximately 80% to 90% cases of serous carcinoma. 12,[16][17][18] An important caveat to overreliance on this single antibody is that an abnormal pattern of p53 expression can be seen in a few endometrioid adenocarcinomas (~10%), predominantly in FIGO 3 cases. 19,20 Of note, in cases with ambiguous morphology, where a definitive histologic subtype cannot be established, aberrant p53 expression has been correlated with adverse clinical outcomes.…”

Section: A Useful Panel Of Markers In Ambiguous Casesmentioning

confidence: 99%

Histologic and Immunohistochemical Analyses of Endometrial Carcinomas: Experiences From Endometrial Biopsies in 358 Consultation Cases

Wei

Paintal

Keh³

2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Uterine serous carcinoma is biologically more aggressive than the endometrioid carcinoma. Because uterine serous carcinoma has a high propensity for lymphovascular invasion and intraperitoneal and extraabdominal spread, accurate diagnosis of this tumor type in endometrial biopsies/curettings is critical for appropriate clinical management.Objective.-To share our experience in the evaluation of endometrial biopsy specimens in type I and type II endometrial adenocarcinoma.Design.-We retrospectively reviewed 358 biopsies containing endometrial carcinoma during a recent 3 year period of our consultation records. In cases in which our interpretation differed from the submitting diagnosis, a panel of immunostains was performed. The performance characteristics of each antibody in our panel was calculated in this group of challenging cases.Results. 2,3 For example, the most common genetic alterations in EMC include microsatellite instability, mutations of PTEN, b-catenin, PIK3CA, and K-ras. 4 In contrast, in the case of ESC, p53 mutations are common 3 and ERBB2 (formerly HER2) overexpression or amplification is also frequently seen. 2Clinically, ESC has a higher propensity for lymphovascular invasion and intraperitoneal as well as extra-abdominal spread than EMC.5 During presentation, approximately 40% to 70% of women with ESC will have disease beyond the uterus.6 Furthermore, although tumor grade and depth of myometrial invasion are not predictive of extrauterine spread for ESC, the incidence of extrauterine spread in endometrioid cancers correlates with both tumor grade and depth of myometrial invasion. Based on data from the Surveillance, Epidemiology and End Results database (National Cancer Institute, Bethesda, Maryland), among all cases of endometrial carcinoma, ESC represents 50% of stage III or IV disease and nearly 40% of all deaths 7 although comprising only 10% of cases by incidence. Because of the high propensity for lymphovascular invasion, intraperitone-

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“…29 The concept of splitting vs lumping high-grade Müllerian carcinomas has been contentious in the past, with the argument that the clinical outcome and treatment was the same regardless of the subclassification. 30 Since that time, Soslow et al 23 validated the significance of different histologic patterns by describing variant morphologies (SET) in tumors with BRCA germline mutations that are associated with a better prognosis and a better response to chemotherapy. 3,4,[12][13][14][15][16][17][18][19] We previously reported on a separate cohort of high-grade serous carcinomas, showing an association between BRCA-positivity and variant histology (SET-like), younger age, a lower frequency of serous tubal intraepithelial carcinoma, and trends toward improved survival.…”

Section: Discussionmentioning

confidence: 99%

Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas

et al. 2016

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Extrauterine high-grade serous carcinomas can exhibit various histologic patterns including (1) classic architecture that is papillary, micropapillary and infiltrative and (2) solid, endometrioid, and transitional (ie, SET) patterns. Although the SET pattern has been associated with germline BRCA mutations, potential molecular underpinnings have not been fully investigated. DNA was isolated from 174 carcinomas of the fallopian tube, ovary, or peritoneum. Targeted next-generation sequencing was performed and single-nucleotide and copy number variants were correlated with morphologic subtype. Overall, 79% of tumors were classified as high-grade serous carcinoma (n = 138), and the most common mutations in high-grade serous carcinomas were TP53 (94%), BRCA1 (25%), BRCA2 (11%), and ATM (7%). Among chemotherapy-naive high-grade serous carcinomas, 40 cases exhibited classic morphology and 40 cases had non-classic morphology (SET or ambiguous features). Mutations in homologous recombination pathways were seen across all tumor histotypes. High-grade serous carcinomas with homologous recombination mutations were six times more likely to be associated with nonclassic histology (P = 0.002) and were significantly more likely to be platinum sensitive and have improved progression-free survival (PFS) (P = 0.007 and P = 0.004, respectively). In a multivariate analysis adjusted for age, homologous recombination mutation status and increased copy number variants were independently associated with improved PFS (P = 0.008 and P = 0.005, respectively). These findings underscore the potential significance of variant morphologic patterns and comprehensive genomic analysis in high-grade serous carcinomas with potential implications for pathogenesis, as well as response to targeted therapies. Extrauterine Müllerian carcinomas (ovarian, fallopian tube, and peritoneal) are the eighth most common malignancy in women and the fifth most common cause of death from cancer among women in the United States. 1 The 5-year survival for highgrade serous carcinoma, the most common and most lethal of all pelvic Müllerian carcinomas, is approximately 40%. 2 These tumors are difficult to detect in early stage and thus frequently present with metastatic disease. Although most high-grade serous carcinomas are associated with a poor prognosis, some patients with the disease have significantly better outcomes. [3][4][5] Germline mutations in BRCA1 and BRCA2 account for the majority of inherited cases of high-grade serous carcinomas, and the recognition of these germline mutations has led to the widespread use of prophylactic bilateral salpingo-oophorectomies to

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Letter to the editor regarding ‘Roh MH, Lassin Y, Miron A et al. High-grade fimbrial-ovarian carcinomas are unified by p53, PTEN and PAX2 expression‘

Abstract: Letter to the editor regarding 'Roh MH, Lassin Y, Miron A et al. High-grade fimbrial-ovarian carcinomas are unified by p53, PTEN and PAX2 expression'

Cited by 6 publications

References 13 publications

Biomarker-Based Ovarian Carcinoma Typing: A Histologic Investigation in the Ovarian Tumor Tissue Analysis Consortium

Biomarker-Based Ovarian Carcinoma Typing: A Histologic Investigation in the Ovarian Tumor Tissue Analysis Consortium

Histologic and Immunohistochemical Analyses of Endometrial Carcinomas: Experiences From Endometrial Biopsies in 358 Consultation Cases

Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas

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