Non-Endometrioid Adenocarcinoma of the Uterine Corpus: A Review of Selected Histological Subtypes

Mendivil, Alberto A.; Schuler, Kevin; Gehrig, Paola A.

doi:10.1177/107327480901600107

Cited by 125 publications

(100 citation statements)

References 50 publications

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“…Our data confirm that even in a selected cohort of high-risk patients serous and clear cell histology portends poor prognosis when compared with endometrioid tumors. 28 However, even after exclusion of the non-endometrioid tumors, molecular analysis can discriminate patients with a good and poor prognosis. Importantly, our analyses further support previous studies that showed an association of POLE proofreading mutations with younger age and favorable prognosis.…”

Section: Discussionmentioning

confidence: 99%

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

et al. 2015

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This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P = 0.014) and distant metastasis rates 23%, 64%, and 50% (P = 0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n = 14) and group 2 (microsatellite instable; n = 19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n = 36) and 39% in group 4 (NSMP; Po 0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; Po 0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment. Modern Pathology (2015) 28, 836-844; doi:10.1038/modpathol.2015 published online 27 February 2015 Risk classification of endometrial carcinomas is based upon a combination of clinical and histopathological factors and is used in guiding adjuvant therapy. High-risk factors are (combinations of) advanced age, high-grade, non-endometrioid histology, extensive lymphovascular space invasion, and

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Section: Discussionmentioning

confidence: 99%

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

et al. 2015

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“…Topographic and morphologic data were coded according to the International Classification of Diseases for Oncology (ICD-O), 2nd [26] or 3rd [27] edition. Using these codes, we classified endometrial cancer into type I or type II (Table 1), based on prior literature [16][17][18][19][20] and systematic review of the ICD-O codes by the authors (SU and AM).…”

Section: Methods Study Population and Dietary Assessmentmentioning

confidence: 99%

“…From a molecular point of view, type II endometrial cancer is often associated with p53 mutations, which commonly lead to DNA derangement, chromosomal instability and a more aggressive clinical behavior [17]. Women affected by type II cancers have a higher incidence of advanced-stage disease at diagnosis, a marked tendency to recurrence, and consequently a worse prognosis [18]. Further, uterine carcinosarcoma and type II endometrial cancers share similar molecular characteristics [19] and have similar clinical outcomes [20].…”

Section: Introductionmentioning

confidence: 99%

Dietary and supplemental intake of one-carbon nutrients and the risk of type I and type II endometrial cancer: a prospective cohort study

Uccella¹,

Mariani²,

Wang³

et al. 2011

Annals of Oncology

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Background: Type I and II endometrial cancer are biologically and clinically distinct, with type II cancers having a high frequency of p53 mutations and an association with chromosomal instability. This raises the hypothesis that onecarbon nutrients (folate, methionine, and the enzymic cofactors vitamins B2, B6, and B12), which mediate chromosomal stability and DNA methylation, may be protective for type II but not type I endometrial cancer.Methods: Using a prospective cohort of 23 356 postmenopausal women followed 20 years, we estimated the relative risks (RRs) of type I (N = 471) and II (N = 71) endometrial cancers according to intake of one-carbon nutrients, adjusting for confounders.Results: No associations were observed between dietary or supplemental intake of any one-carbon nutrient and risk of type I cancer. For type II cancer, positive associations were due to supplemental, rather than dietary, intake of these nutrients: supplemental folate (RR = 1.80 for >228.6 versus 0 lg/day; P trend = 0.027) and vitamins B2 (RR = 1.94 for >1.70 versus 0 mg/day; P trend = 0.011), B6 (RR = 2.08 for >2.00 versus 0 mg/day; P trend = 0.012), and B12 (RR = 2.10 for >3.43 versus 0 lg/day; P trend = 0.0060).Conclusion: Contrary to our hypothesis, use of supplements containing folate and vitamins B2, B6, and B12 was associated with an increased risk of type II endometrial cancer.

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“…In support of extensive prior clinical and incidence surveys, we also found that Type II tumors are diagnosed more often among older and non-white women [8,[15][16][17][18][19][20]. These differences in risk factor relationships, in combination with the more frequent occurrence of Type II cancers after menopause, provide some of the strongest epidemiologic support that endometrial cancers are etiologically heterogeneous.…”

Section: Discussionmentioning

confidence: 55%

Etiologic heterogeneity in endometrial cancer: Evidence from a Gyneco- logic Oncology Group trial

Brinton

Felix

Sherman

et al. 2013

Gynecologic Oncology

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Objective-Although the epidemiology of typical endometrial carcinomas (grades 1-2 endometrioid or Type I) is well established, less is known regarding higher grade endometrioid or non-endometrioid carcinomas (Type II). Within a large Gynecologic Oncology Group trial (GOG-210), which included central pathology review, we investigated the etiologic heterogeneity of endometrial cancers by comparing risk factors for different histologic categories.Methods-Based on epidemiologic questionnaire data, risk factor associations, expressed as odds ratios (OR) with 95% confidence intervals (CI), were estimated comparing grade 3 endometrioid and Type II cancers (including histologic subtypes) to grades 1-2 endometrioid cancers. Results-Compared NIH Public Access

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Non-Endometrioid Adenocarcinoma of the Uterine Corpus: A Review of Selected Histological Subtypes

Cited by 125 publications

References 50 publications

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

Dietary and supplemental intake of one-carbon nutrients and the risk of type I and type II endometrial cancer: a prospective cohort study

Etiologic heterogeneity in endometrial cancer: Evidence from a Gyneco- logic Oncology Group trial

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