The immunohistochemical molecular risk classification in endometrial cancer: A pragmatic and high-reproducibility method

Perrone, Emanuele; Felice, Francesca De; Capasso, Ilaria; Distefano, E; Lorusso, Domenica; Nero, Camilla; Arciuolo, Damiano; Zannoni, Gian Franco; Scambia, Giovanni; Fanfani, Francesco

doi:10.1016/j.ygyno.2022.03.009

Cited by 14 publications

(7 citation statements)

References 36 publications

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“…[29][30][31] The lack of strong and uniform ER/PR expression in EC has been previously described, with frequency ranging from 7% to 21% of EC (endometrioid and non-endometrioid histology). [8][9][10][11][32][33][34][35][36][37][38] Frequencies of loss of ER/PR expression vary from 3.8% to 7%, where all grades of EEC were included. 11,13,33 Incidence of loss of ER/PR, specifically in low-grade recurrent EEC, is not known.…”

Section: Discussionmentioning

confidence: 99%

Estrogen/Progesterone Receptor Loss, CTNNB1 and KRAS Mutations Are Associated With Local Recurrence or Distant Metastasis in Low-Grade Endometrial Endometrioid Carcinoma

Chibbar

Foerstner

Suresh

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be associated with loss of expression of ER-alpha (ER-α) as well as with β-Catenin-1 (CTNNB1) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. This study reports on institutional experience with the incidence of recurrence in low-grade EEC and their association with CTNNB1 and KRAS mutations as well as estrogen/progesterone receptor (ER/PR) expression. Forty-eight (8.5%) out of 568 cases of low-grade EEC with biopsy-proven recurrence were identified; and were analyzed by immunohistochemistry for ER, PR, p53, MMR protein, and mutation analysis for exon 3 of the CTNNB1 and exon 2 of KRAS in relation to recurrence type, local or distant metastasis/recurrence. Twenty-three patients (4%) developed local, and 25 patients (4.4%) developed distant metastases/recurrence. Decreased expression or loss of ER/PR was found in 17/44 (38.6%) patients with recurrence. Eighty-four percent of patients with low-grade EEC and local recurrence had CTNNB1 mutations. Seventy-three percent of patients with distant metastasis/recurrence had KRAS mutations. The association of these mutations with the type of recurrence was statistically significant for both. Five cases with the morphology of low-grade EEC were reclassified as mesonephric-like carcinoma and were universally characterized by distant metastasis/recurrence, loss of ER/PR expression, large tumor size, absence of CTNNB1 mutations, and the presence of KRAS mutations. In low-grade EEC, CTNNB1 and KRAS mutations are associated with local recurrence and distant metastasis/recurrence, respectively, suggesting that these 2 different progression types may be conditioned by tumor genotype. ER/PR immunohistochemistry may be helpful in identifying poor performers in low-grade EEC. Furthermore, identification of the decreased expression or loss of ER/PR in tumors with low-grade histology should prompt consideration of mesonephric-like carcinoma, which is a more aggressive tumor than the low-grade EEC. KRAS mutations were associated with distant metastasis/recurrence in tumors with and without mesonephric-like phenotype.

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Section: Discussionmentioning

confidence: 99%

Estrogen/Progesterone Receptor Loss, CTNNB1 and KRAS Mutations Are Associated With Local Recurrence or Distant Metastasis in Low-Grade Endometrial Endometrioid Carcinoma

Chibbar

Foerstner

Suresh

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…According to metabolic parameters, some groups suggested that MTV and TLG might be promising markers for LN involvement [47]; the present work corroborates this hypothesis, as MTV and TLG were the only parameters capable of discriminating and predicting LN metastases. Contrarily, the finding that 18 F-FDG PET might serve as a predictive tool for p53 overexpression is novel and of particular interest, this alteration being recognized as a relevant prognostic factor in EC [48]. In fact.…”

Section: Discussionmentioning

confidence: 99%

Role of Machine Learning (ML)-Based Classification Using Conventional 18F-FDG PET Parameters in Predicting Postsurgical Features of Endometrial Cancer Aggressiveness

Bezzi

Bergamini

Mathoux

et al. 2023

Cancers

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Purpose: to investigate the preoperative role of ML-based classification using conventional 18F-FDG PET parameters and clinical data in predicting features of EC aggressiveness. Methods: retrospective study, including 123 EC patients who underwent 18F-FDG PET (20092021) for preoperative staging. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were computed on the primary tumour. Age and BMI were collected. Histotype, myometrial invasion (MI), risk group, lymph-nodal involvement (LN), and p53 expression were retrieved from histology. The population was split into a train and a validation set (80–20%). The train set was used to select relevant parameters (Mann-Whitney U test; ROC analysis) and implement ML models, while the validation set was used to test prediction abilities. Results: on the validation set, the best accuracies obtained with individual parameters and ML were: 61% (TLG) and 87% (ML) for MI; 71% (SUVmax) and 79% (ML) for risk groups; 72% (TLG) and 83% (ML) for LN; 45% (SUVmax; SUVmean) and 73% (ML) for p53 expression. Conclusions: ML-based classification using conventional 18F-FDG PET parameters and clinical data demonstrated ability to characterize the investigated features of EC aggressiveness, providing a non-invasive way to support preoperative stratification of EC patients.

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“… 22 LVSI is a clinicopathological feature closely related to LNM, progression-free survival and overall survival of EC. 23 At the same time, studies have shown that metabolic disorders can increase the risk of EC and tumor progression. Case–control studies in China showed that EC was positively associated with total serum cholesterol, triglycerides (TGs), low-density lipoprotein cholesterol, and dyslipidemia but negatively associated with HDL.…”

Section: Discussionmentioning

confidence: 99%

Assessing Metabolic Risk Factors for LVSI in Endometrial Cancer: A Cross-Sectional Study

Lin¹,

Lu²,

Lu³

et al. 2022

TCRM

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Objective This study analyzed metabolic factors associated with lymphovascular space invasion (LVSI) and compared the difference between type 1 and type 2 endometrial cancer (EC). Methods Four hundred patients primarily diagnosed with EC who underwent hysterectomy with pathological results at Fujian Medical University Cancer Hospital from January 2019 to January 2021 were included. Demographic variable data were collected as well as pathological results. Laboratory evaluations included fasting blood glucose (FBG), serum cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A (Apo A) and apolipoprotein B (Apo B). Characterization of binary logistic regression models was used to test the odds ratios (ORs) between LVSI and its metabolic parameters with different subtypes of EC. Results The results indicated that CA125, ROMA, Ki67 score, FBG and TC were higher in EC patients with LVSI (all p<0.05). Negative ER and PR expression was positively associated with LVSI (P<0.05). CA125, ROMA, FBG, TC and ER were found to be independent risk factors for LVSI. CA125, ROMA and FBG were significantly elevated in type 1 EC patients with LVSI compared with those without LVSI (all p<0.05). TC and Ki67 scores were much higher in type 2 EC patients with vs without LVSI (all p<0.05). Negative PR expression was positively related to both type 1 and type 2 EC patients with LVSI. Consequently, CA125, ROMA, FBG and Apo B were found to be independent risk factors for LVSI in type 1 EC, and TC was found to be an independent risk factor for LVSI in type 2 EC. Conclusion FBG and TC were both independent risk factors for LVSI in EC. FBG and Apo B were independent risk factors for LVSI in type 1 EC. TC was an independent risk factor for LVSI in type 2 EC.

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The immunohistochemical molecular risk classification in endometrial cancer: A pragmatic and high-reproducibility method

Cited by 14 publications

References 36 publications

Estrogen/Progesterone Receptor Loss, CTNNB1 and KRAS Mutations Are Associated With Local Recurrence or Distant Metastasis in Low-Grade Endometrial Endometrioid Carcinoma

Estrogen/Progesterone Receptor Loss, CTNNB1 and KRAS Mutations Are Associated With Local Recurrence or Distant Metastasis in Low-Grade Endometrial Endometrioid Carcinoma

Role of Machine Learning (ML)-Based Classification Using Conventional 18F-FDG PET Parameters in Predicting Postsurgical Features of Endometrial Cancer Aggressiveness

Assessing Metabolic Risk Factors for LVSI in Endometrial Cancer: A Cross-Sectional Study

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