L1CAM: amending the “low-risk” category in endometrial carcinoma

Kommoss, Felix K.F.; Kommoss, Friedrich; Grevenkamp, Friederike; Bunz, Anne-Kathrin; Taran, Florin‐Andrei; Fend, Falko; Brucker, Sara; Wallwiener, D.; Schönfisch, Birgitt; Greif, Karen F.; Lax, Sigurd; Staebler, Annette; Kommoss, Stefan

doi:10.1007/s00432-016-2276-3

Cited by 37 publications

(41 citation statements)

References 27 publications

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“…Together with our finding that L1CAM overexpression is associated with a worse outcome in the important MMR‐D and p53wt groups suggests it may have value within those subtypes, but further validation is required. It should be noted that there are very few tumours with L1CAM overexpression in the MMR‐D and p53wt groups (7 and 6%, respectively), which limits our power to validate previous studies demonstrating the prognostic significance of L1CAM among low‐risk tumours .…”

Section: Discussionmentioning

confidence: 80%

“…Our objective in this study was to re-evaluate select molecular markers of purported prognostic significance: L1-cell adhesion molecule (L1CAM) [14][15][16], progesterone receptor (PR) [17][18][19], estrogen receptor alpha (ER) [18][19][20], stathmin (STMN) [21,22], and phosphatase and tensin homolog (PTEN) [23,24], assessing their value in the framework of modern molecular classification (by ProMisE).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of endometrial carcinoma prognostic immunohistochemistry markers in the context of molecular classification

Karnezis

Leung

Magrill

et al. 2017

The Journal of Pathology CR

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Molecular subclassification of endometrial carcinoma (EC) with Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identifies four subtypes [DNA polymerase epsilon (POLE) mutant, mismatch repair‐deficient, p53 wild‐type (wt), and p53 abnormal]. The aim of this study was to evaluate additional EC biomarkers in the context of these subtypes. Tissue microarrays encompassing 460 previously characterized ECs were assessed for L1‐cell adhesion molecule (L1CAM), progesterone receptor (PR), estrogen receptor (ER) alpha, stathmin, and phosphatase and tensin homolog (PTEN), by immunohistochemistry (IHC). Associations with clinicopathological parameters, molecular subtype, and outcomes were determined. About 413 ECs (75% endometrioid, >15% serous) had complete data. L1CAM overexpression was found in 16%, associated with older age, lower body mass index (BMI), advanced stage, grade 3 (97%), non‐endometrioid histology (84%), deep myometrial invasion, lymphovascular space invasion (LVSI), and ER‐negative, PR‐negative status. Tumours overexpressing L1CAM were associated with poor outcomes {hazard ratio (HR) [95% confidence interval (CI)] 3.35 [2.10–5.23] for disease‐specific survival [DSS], p < 0.0001}. PR positivity was associated with younger women, higher BMI, early stage (77% stage I), low grade (61%), endometrioid histology (90%) without LVSI or nodal disease, ER positivity (90%), p53wt tumours (55%), and favourable outcomes [HR (CI) 0.39 (0.25–0.62) for DSS, p < 0.0001]. ER positive tumours were early stage (73%), low grade, endometrioid histology, with improved DSS. Stathmin and PTEN IHC were not associated with outcomes. There was minimal agreement between IHC and mutation status for PTEN. L1CAM overexpression was significantly associated with the p53 abnormal molecular subtype, which accounted for more than 70% of the tumours overexpressing L1CAM. PR expression also correlated with molecular subtype, with most PR negative tumours being p53 abnormal. Multivariable analysis demonstrated that only ProMisE subtype [overall survival (OS), DSS, and progression‐free survival] and age (OS only) maintained an association with outcomes. The prognostic significance of the single biomarkers tested could be explained based on their being covariable with the ProMisE molecular subtype.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Evaluation of endometrial carcinoma prognostic immunohistochemistry markers in the context of molecular classification

Karnezis

Leung

Magrill

et al. 2017

The Journal of Pathology CR

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“…Among the most frequently used staging systems for estimating the prognosis and risk of recurrence in thyroid carcinomas are those developed by the Union for International Cancer Control (UICC) and American Joint systems consistently include clinicopathological parameters, however, factors such as age, gender, tumor type and size, extracapsular extension, lymph nodes, lymphovascular invasion (LVI), and distant metastasis are not all covered by a single staging system [7][8][9][10][11][12][13]. Although LVI is a poor prognostic factor for numerous cancers, including laryngeal, uterine, endometrial, colorectal, cervical, bile duct, and vulvar cancer, none of the staging systems include LVI in staging of thyroid carcinomas [14][15][16][17][18][19][20]. In a clinical series conducted by Ieni et al [21], 295 PTC patients (8 of them with a newly described entity -micropapillary/hobnail variant [MPHC]) were evaluated and the authors concluded that the prognosis of MPHC-PTC tumors was better compared to the other groups, possibly due to a lower rate of vascular invasion in this group [21].…”

Section: Introductionmentioning

confidence: 99%

Relationship between lymphovascular invasion and clinicopathological features of papillary thyroid carcinoma

Sezer

Çelık

Bulbul

et al. 2017

Bosn J of Basic Med Sci

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Lymphovascular invasion (LVI) is an important prognostic factor in various solid tumors, however, data on the association between LVI and thyroid carcinomas are limited. In this study, we evaluated the relationship between LVI and clinicopathological features of papillary thyroid carcinoma (PTC). Six hundred seventy-eight patients diagnosed with PTC between 2012 and 2015 were included into the study. Patients were classified based on the presence or absence of LVI. Gender, age, ultrasonography (US), tumor size and multifocality, BRAFV600E mutation, perineural and capsular invasion, extrathyroid extension (ETE), nodal metastasis, and recurrences were evaluated, and risk analysis was performed for each parameter. The number of patients with LVI [LVI (+)] was 63, while the number of patients without LVI [LVI (-)] was 615. The female/male ratio was 564/114. LVI was present in 18.4% of male patients and in 7.4 % of female patients. In the age group between 17-25 years LVI was detected in 6/13 patients, and this result was statistically significant compared to other age groups (p = 0.004). Suspicious lymph nodes upon US, perineural or capsular invasion, ETE, tumor size, and nodal metastasis were significantly more frequent in LVI (+) group (p < 0.001). The frequency of BRAFV600E mutation was also significantly higher in LVI (+) group (p < 0.001). Overall, the presence of LVI was associated with gender, tumor size, age, lymph node metastasis, pathological lymph nodes, perineural and capsular invasion, ETE, and BRAFV600E mutation. These results suggest that in PTC patients undergoing thyroidectomy, the presence of LVI should be considered as an indicator of aggressive clinicopathological features and those patients should be followed up carefully for recurrences and metastasis.

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“…A large multicenter evaluation of L1CAM expression in early-stage type I endometrial carcinomaexpected to have excellent prognosis, with more than 80% 10-year OS -showed that despite appropriate treatment, a number of patients exhibited recurrence and poor survival and this trend was associated with L1CAM expression [16,17]. L1CAM has subsequently been proposed to be a strong prognostic factor in endometrial carcinoma and it has been suggested that the classical "low-risk" disease should potentially be further risk strati ed [18].…”

Section: Introductionmentioning

confidence: 99%

L1CAM Expression in Recurrent Estrogen Positive/HER2 Negative Breast Cancer

Moisini

Zhang

D’Aguiar

et al. 2020

Preprint

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Background: We investigate L1CAM expression in ER positive/HER2 negative breast carcinomas. The finding of a potential correlation between high L1CAM expression and recurrent/metastatic disease in luminal A and B breast carcinomas may be helpful for risk stratification and open opportunities for targeted therapies.Methods: 304 cases comprising 152 cases of ER positive, PR positive/negative and HER2 negative recurrent/metastatic breast carcinomas and 152 non-recurrent controls were included. ER, PR, HER-2, Ki-67 status, Nottingham grade, tumor size, tumor stage, number of foci, lymph node status, lymphovascular invasion, phenotype, laterality, age at diagnosis and first distant or local recurrence were recorded. Results: L1CAM positive cases showed increased specificity for recurrence and these patients were significantly younger than L1CAM negative ones. Compared to L1CAM negative recurrent cases, L1CAM positive ones had a noticeably higher Ki-67, tended to be larger and recurred sooner. All L1CAM positive recurrent/metastatic cases were of the luminal B subtype compared to 67.3% of the L1CAM negative cases. Conclusions: L1CAM is highly specific for recurrence in a subset of breast cancer patients and may be associated with more aggressive behavior, particularly in luminal B breast cancers with higher Ki-67 expression. Further investigation about the prognostic value of L1CAM is warranted.

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L1CAM: amending the “low-risk” category in endometrial carcinoma

Abstract: The current definition of "low-risk" in endometrial carcinoma should be amended. "Low-risk carcinomas" should be limited to L1CAM-negative tumours. L1CAM status will play a key role in future algorithms to tailor adjuvant treatment and patient follow-up strategies.

Cited by 37 publications

References 27 publications

Evaluation of endometrial carcinoma prognostic immunohistochemistry markers in the context of molecular classification

Evaluation of endometrial carcinoma prognostic immunohistochemistry markers in the context of molecular classification

Relationship between lymphovascular invasion and clinicopathological features of papillary thyroid carcinoma

L1CAM Expression in Recurrent Estrogen Positive/HER2 Negative Breast Cancer

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