Prognosis and Reproducibility of New and Existing Binary Grading Systems for Endometrial Carcinoma Compared to FIGO Grading in Hysterectomy Specimens

Guan, Hui; Semaan, Assaad; Bandyopadhyay, Sudeshna; Arabi, Haitham; Feng, Jining; Fathallah, Lamia; Pansare, Vaishali; Qazi, Aamer; Abdul‐Karim, Fadi W.; Morris, Robert T.; Munkarah, Adnan; Ali-Fehmi, Rouba

doi:10.1097/igc.0b013e31821454f1

Cited by 43 publications

(30 citation statements)

References 19 publications

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“…Levels of reproducibility of these tumour characteristics are similar to our results for LVSI assessment. None of the previous studies specifically focused on LVSI assessment, but there are two studies that report on reproducibility of LVSI in EC . LVSI and other tumour characteristics were reviewed as part of an upfront pathology review before randomisation in the PORTEC‐3 trial .…”

Section: Discussionmentioning

confidence: 99%

“…A high rate of interobserver agreement between the original pathology report and central pathology review was found for LVSI (κ = 0.72). In the study by Guan et al ., LVSI assessment was part of an alternative binary grading system in EC . Here, LVSI was defined as clusters of malignant epithelial cells within vascular spaces located outside the main tumour.…”

Section: Discussionmentioning

confidence: 99%

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Reproducibility of lymphovascular space invasion (LVSI) assessment in endometrial cancer

et al. 2019

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AimsLymphovascular space invasion (LVSI) in endometrial cancer (EC) is an important prognostic variable impacting on a patient's individual recurrence risk and adjuvant treatment recommendations. Recent work has shown that grading the extent of LVSI further improves its prognostic strength in patients with stage I endometrioid EC. Despite this, there is little information on the reproducibility of LVSI assessment in EC. Therefore, we designed a study to evaluate interobserver agreement in discriminating true LVSI from LVSI mimics (Phase I) and reproducibility of grading extent of LVSI (Phase II).Methods and resultsScanned haematoxylin and eosin (H&E) slides of endometrioid EC (EEC) with a predefined possible LVSI focus were hosted on a website and assessed by a panel of six European gynaecological pathologists. In Phase I, 48 H&E slides were included for LVSI assessment and in Phase II, 42 H&E slides for LVSI grading. Each observer was instructed to apply the criteria for LVSI used in daily practice. The degree of agreement was measured using the two‐way absolute agreement average‐measures intraclass correlation coefficient (ICC). Reproducibility of LVSI assessment (ICC = 0.64, P < 0.001) and LVSI grading (ICC = 0.62, P < 0.001) in EEC was substantial among the observers.ConclusionsGiven the good reproducibility of LVSI, this study further supports the important role of LVSI in decision algorithms for adjuvant treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reproducibility of lymphovascular space invasion (LVSI) assessment in endometrial cancer

et al. 2019

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“…In our current system risk stratification is achievable only AFTER surgical staging (myometrial invasion and stage are major components). Although adjuvant therapy can be guided from the post-staging information and risk group assignment, these again are limited by the irremediable irreproducibility of histotype and grade [5-8]. This could change with use of the ProMisE molecular classifier.…”

Section: Discussionmentioning

confidence: 99%

“…Histotype and grade assignment in EC is unreliable, even among expert pathologists [5-8], leading to inconsistent categorization of tumors within and between cancer centers. Current risk stratification systems used to guide adjuvant therapy are based on these irreproducible histomorphologic features.…”

Section: Introductionmentioning

confidence: 99%

Molecular classification of endometrial carcinoma on diagnostic specimens is highly concordant with final hysterectomy: Earlier prognostic information to guide treatment

Talhouk

Hoang

McConechy

et al. 2016

Gynecologic Oncology

159

123

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Objective Categorization and risk stratification of endometrial carcinomas is inadequate; histomorphologic assessment shows considerable interobserver variability, and risk of metastases and recurrence can only be derived after surgical staging. We have developed a Proactive Molecular Risk classification tool for Endometrial cancers (ProMisE) that identifies four distinct prognostic subgroups. Our objective was to assess whether molecular classification could be performed on diagnostic endometrial specimens obtained prior to surgical staging and its concordance with molecular classification performed on the subsequent hysterectomy specimen. Methods Sequencing of tumors for exonuclease domain mutations (EDMs) in POLE and immunohistochemistry for mismatch repair (MMR) proteins and p53 were applied to both pre- and post-staging archival specimens from 60 individuals to identify four molecular subgroups: MMR-D, POLE EDM, p53 wild type, p53 abn(abnormal). Three gynecologic subspecialty pathologists assigned histotype and grade to a subset of samples. Concordance of molecular and clinicopathologic subgroup assignments were determined, comparing biopsy/curetting to hysterectomy specimens. Results Complete molecular and pathologic categorization was achieved in 57 cases. Concordance metrics for pre- vs. post-staging endometrial samples categorized by ProMisE were highly favorable; average per ProMisE class sensitivity(0.9), specificity(0.96), PPV(0.9), NPV(0.96) and kappa statistic 0.86(95%CI, 0.72-0.93), indicating excellent agreement. We observed the highest level of concordance for ‘p53 abn’ tumors, the group associated with the worst prognosis. In contrast, grade and histotype assignment from original pathology reports pre- vs. post-staging showed only moderate levels of agreement (kappa=0.55 and 0.44 respectively); even with subspecialty pathology review only moderate levels of agreement were observed. Conclusion Molecular classification can be achieved on diagnostic endometrial samples and accurately predicts the molecular features in the final hysterectomy specimens, demonstrating concordance superior to grade and histotype . This biologically relevant information, available at initial diagnosis, has the potential to inform management (surgery, adjuvant therapy) from the earliest time point in cancer care.

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“…Prognosis is established based on histological grade, depth of myometrial invasion, cervical involvement, vascular space involvement, pelvic and aortic lymph node metastases, adnexal metastases, and positive peritoneal cytology (Guan et al ., 2011). Apparently, the stage of the tumor is the most important factor in predicting patients' outcome as it determines the mode of treatment and significantly influences survival (Gressel et al ., 2015; Bogani et al ., 2016).…”

Section: Introductionmentioning

confidence: 99%

Fertility-preservation in endometrial cancer: is it safe? Review of the literature

Carneiro

Lamaita

Ferreira

et al. 2016

JBRA Assisted Reproduction

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Almost 5% of women with endometrial cancer are under age 40, and they often have well-differentiated endometrioid estrogen-dependent tumors. Cancer survival rates have improved over the last decades so strategies to avoid or reduce the reproductive damage caused by oncologic treatment are needed. We reviewed the published literature to find evidence to answer the following questions: How should we manage women in reproductive age with endometrial cancer? How safe is fertility preservation in endometrial cancer? Can pregnancy influence endometrial cancer recurrence? What are the fertility sparing options available? Progestins may be prescribed after careful evaluation and counseling. Suitable patients should be selected using imaging methods and endometrial sampling since surgical staging will not be performed. Conservative treatment should only be offered to patients with grade 1 well-differentiated tumors, absence of lymph vascular space invasion, no evidence of myometrial invasion, metastatic disease or suspicious adnexal masses, and expression of progesterone receptors in the endometrium. The presence of co-existing ovarian metastatic of synchronous cancer should be investigated and ruled out before the decision to preserve the ovaries. The availability of Assisted Reproductive Technology (ART) has made it possible for women with endometrial cancer to give birth to a child without compromising their prognoses. Gamete, embryo or ovarian tissue cryopreservation techniques can be employed, although the latter remains experimental. Unfortunately, fertility preservation is rarely considered. Current recommendations for conservative management are based on the overall favorable prognosis of grade 1 minimally invasive tumors. Selected patients with endometrial cancer may be candidates to a safe fertility-preserving management.

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Prognosis and Reproducibility of New and Existing Binary Grading Systems for Endometrial Carcinoma Compared to FIGO Grading in Hysterectomy Specimens

Abstract: The 3-tiered FIGO grading system retained its superior prognostic power. However, available binary grading systems remain an attractive option by being highly reproducible and by eliminating the clinical ambiguity of intermediate grades of disease.

Cited by 43 publications

References 19 publications

Reproducibility of lymphovascular space invasion (LVSI) assessment in endometrial cancer

Reproducibility of lymphovascular space invasion (LVSI) assessment in endometrial cancer

Molecular classification of endometrial carcinoma on diagnostic specimens is highly concordant with final hysterectomy: Earlier prognostic information to guide treatment

Fertility-preservation in endometrial cancer: is it safe? Review of the literature

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