Cíl studie: Podat přehled současné literatury zabývající se významem přítomnosti L1cell adhesion molecule (L1CAM) u pacientek s endometriálním karcinomem. Metodika: Vyhledávání relevantních studií zaměřených na endometriální karcinom a L1CAM pomocí databáze MEDLINE pomocí slov: endometrial cancer AND L1CAM v časovém rozmezí od roku 2000 do září 2017. Závěr: L1CAM je nezávislý prognostický faktor pro zhoršené celkové přežití, progresi nemoci a je spojen s pokročilým onemocněním a high-risk histologií karcinomu endometria. Možnost využití L1CAM jako předoperačního stratifikačního faktoru pro provedení systematické lymfadenektomie, nebo pooperačně k adjuvantní léčbě je slibnou metodou, musí však být ještě potvrzena dalšími prospektivními studiemi.
Objective: To summarize the knowledge about the role of L1CAM in endometrial cancer patients. Methods: Searching MEDLINE of the original studies related to L1CAM and endometrial cancer from 2000 to September 2017 byusing a searching terms: endometrial cancer AND L1CAM. Results: L1CAM is an independent predictor for poor survival, progression of disease, and is associated with advanced stage,high–risk endometrial cancer. Preoperave selection of patients to lymphadenectomy or postoperative selection of patients totailor adjuvant treatment depending on L1CAM positivity is promising, but should be confirmed by prospective trials.
- MeSH
- Immunohistochemistry methods utilization MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Neural Cell Adhesion Molecule L1 * analysis MeSH
- Endometrial Neoplasms * diagnosis MeSH
- Surgical Clearance methods MeSH
- Prognosis MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
BACKGROUND: Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. METHODS: The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. RESULTS: In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. CONCLUSIONS: The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied.
- MeSH
- Adult MeSH
- Carcinoma, Endometrioid chemistry mortality pathology MeSH
- Neoplasm Invasiveness MeSH
- Kaplan-Meier Estimate MeSH
- Carcinoma chemistry mortality pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Neural Cell Adhesion Molecule L1 analysis MeSH
- Neoplasm Proteins analysis MeSH
- Endometrial Neoplasms chemistry mortality pathology MeSH
- Prognosis MeSH
- Recurrence MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Neoplasm Grading MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Aging involves tissue accumulation of senescent cells (SC) whose elimination through senolytic approaches may evoke organismal rejuvenation. SC also contribute to aging-associated pathologies including cancer, hence it is imperative to better identify and target SC. Here, we aimed to identify new cell-surface proteins differentially expressed on human SC. Besides previously reported proteins enriched on SC, we identified 78 proteins enriched and 73 proteins underrepresented in replicatively senescent BJ fibroblasts, including L1CAM, whose expression is normally restricted to the neural system and kidneys. L1CAM was: 1) induced in premature forms of cellular senescence triggered chemically and by gamma-radiation, but not in Ras-induced senescence; 2) induced upon inhibition of cyclin-dependent kinases by p16INK4a; 3) induced by TGFbeta and suppressed by RAS/MAPK(Erk) signaling (the latter explaining the lack of L1CAM induction in RAS-induced senescence); and 4) induced upon downregulation of growth-associated gene ANT2, growth in low-glucose medium or inhibition of the mevalonate pathway. These data indicate that L1CAM is controlled by a number of cell growth- and metabolism-related pathways during SC development. Functionally, SC with enhanced surface L1CAM showed increased adhesion to extracellular matrix and migrated faster. Our results provide mechanistic insights into senescence of human cells, with implications for future senolytic strategies.
- MeSH
- Cell Adhesion physiology MeSH
- Cell Cycle MeSH
- Down-Regulation MeSH
- Fibroblasts MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Humans MeSH
- Neural Cell Adhesion Molecule L1 genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Cell Movement physiology MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Gene Expression Regulation drug effects radiation effects MeSH
- RNA Interference MeSH
- Signal Transduction MeSH
- Cellular Senescence MeSH
- Transforming Growth Factor beta metabolism pharmacology MeSH
- Gamma Rays MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
AIMS: In this study, we aimed to investigate how positivity for L1 cell adhesion molecule (L1CAM) was associated with outcome and relapse pattern in patients with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IA-IB endometrial cancer. MATERIALS AND METHODS: This retrospective study included 358 patients who underwent surgical treatment for endometrial carcinoma. Tumor samples from 312 patients (87.2%) were available for L1CAM analysis by immunohistochemistry. RESULTS: Of the 312 tumor samples analyzed, 93 (29.8%) were L1CAM-positive. L1CAM positivity was significantly more common in grade 3 compared to grade 1-2 carcinomas (p=0.02). Patients with L1CAM positivity more commonly experienced disease progression. Distant metastasis was significantly associated with L1CAM positivity (p=0.01). Progression-free interval and overall survival did not significantly differ between L1CAM-positive and L1CAM-negative cases. CONCLUSION: L1CAM is a promising independent prognostic marker associated with aggressive tumor behavior and recurrence risk, but not with overall survival.
- MeSH
- Cell Adhesion MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Carcinoma, Endometrioid epidemiology genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local epidemiology genetics pathology MeSH
- Neural Cell Adhesion Molecule L1 genetics MeSH
- Biomarkers, Tumor genetics MeSH
- Endometrial Neoplasms epidemiology genetics pathology MeSH
- Prognosis MeSH
- Disease Progression MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Cervical cancer (CC) is the fourth most common malignancy. The significant prognostic factors are tumor size and lympho-vascular space invasion. Considering that these are nonspecific factors, research has been aimed at finding a specific molecular marker related to a higher incidence of relapse and mortality in patients with CC. OBJECTIVE: Our study investigated the prognostic value of L1 cell adhesion molecule (L1CAM) expression in rare histological subtypes of cervical cancer (adenocarcinomas and adenosquamous cell carcinomas). METHODS: This is a single-institution retrospective study with 35 patients who underwent radical hysterectomy for early-stage cervical adenocarcinoma or adenosquamous cell carcinoma in 2007 through 2017. Paraffin sections of the tumor were used for L1CAM analysis by immunohistochemistry. RESULTS: L1CAM expression was positive in 15 (42.8%) of the 35 tumors. L1CAM expression did not differ significantly in regard to the stage of disease, tumor size, grading, or lymphovascular space invasion (LVSI) (p = 0.619, p = 0.341, p = 0.445, p = 0.999). Progression-free interval and overall survival did not differ between L1CAM-positive and L1CAM-negative groups (p = 0.704, p = 0.386, respectively). CONCLUSIONS: In our study, L1CAM expression is not a negative prognostic factor associated with aggressive tumor behavior, recurrence risk and overall survival.
- MeSH
- Adenocarcinoma * pathology metabolism virology MeSH
- Carcinoma, Adenosquamous * pathology metabolism virology MeSH
- Adult MeSH
- Papillomavirus Infections complications virology pathology metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Neural Cell Adhesion Molecule L1 * metabolism MeSH
- Biomarkers, Tumor * metabolism MeSH
- Uterine Cervical Neoplasms * pathology virology metabolism mortality MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Discrimination between low- and high-grade endometrial carcinomas (ECs) is clinically relevant but can be challenging for pathologists, with moderate interobserver agreement. Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is an oncofoetal protein that is associated with nonendometrioid endometrial carcinomas but has been limited studied in endometrioid carcinomas. The aim of this study is to investigate the diagnostic and prognostic value of IMP3 in the discrimination between low- and high-grade ECs and its added value to L1CAM. IMP3 and L1CAM expression was assessed in tumors from 378 patients treated for EC at 1 of 9 participating European Network for Individualised Treatment of Endometrial Cancer centers. IMP3 was expressed in 24.6% of the tumors. In general, IMP3 was more homogeneously expressed than L1CAM. IMP3 expression was significantly associated with advanced stage, nonendometrioid histology, grade 3 tumors, deep myometrial invasion, lymphovascular space invasion, distant recurrences, overall mortality, and disease-related mortality. Simultaneous absence of IMP3 and L1CAM expression showed the highest accuracy for identifying low-grade carcinomas (area under the curve 0.766), whereas simultaneous expression of IMP3 and L1CAM was strongly associated with high-grade carcinomas (odds ratio 19.7; 95% confidence interval 9.2-42.2). Even within endometrioid carcinomas, this combination remained superior to IMP3 and L1CAM alone (odds ratio 8.6; 95% confidence interval 3.4-21.9). In conclusion, IMP3 has good diagnostic value and together with L1CAM represents the optimal combination of diagnostic markers for discrimination between low- and high-grade ECs compared to IMP3 and L1CAM alone. Because of the homogenous expression of IMP3, this marker might be valuable in preoperative biopsies when compared to the more patchy L1CAM expression.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Neural Cell Adhesion Molecule L1 analysis biosynthesis MeSH
- Biomarkers, Tumor analysis MeSH
- Endometrial Neoplasms pathology MeSH
- RNA-Binding Proteins analysis biosynthesis MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Neoplasm Grading methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
We report the case of a hydrocephalic fetus in which clinical exome sequencing revealed a recurrent synonymous variant of unknown significance, c.453G>T, in the L1CAM gene. This report presents the second case of X-linked hydrocephalus in a fetus with this variant. Since we reproduced the RNA analysis, we were able to reclassify this variant as likely pathogenic. Our results stress the importance of not excluding synonymous variants during prioritization.
- Publication type
- Journal Article MeSH
AIM: Our study aimed to assess expression of L1 cell adhesion molecule (L1CAM) in early-stage cervical squamous-cell cancer as a prognostic factor. PATIENTS AND METHODS: This retrospective, single-institution study included 154 patients who underwent radical hysterectomy for early-stage squamous cell cervical cancer between 2007 and 2017. Tumor samples from 154 patients were available for L1CAM analysis by immunohistochemistry. Among all patients, radical abdominal hysterectomy was performed in 144 cases. RESULTS: L1CAM expression was positive in 24 tumors (15.6%) of the whole group. In relation to the grade of differentiation and the presence of lymphovascular invasion, L1CAM expression did not show an association (p=0.154 and p=0.306, respectively). The disease-free interval and overall survival also did not significantly differ between L1CAM-positive and L1CAM-negative cases (p=0.427 and p=0.240, respectively). For histopathological characteristics, L1CAM-positive cases had a significantly higher median tumor size (p=0.015). Even in the selected group of 115 cases without nodal infiltration, L1CAM status had no effect on the relapse rate during follow-up. CONCLUSION: Our study did not confirm the results of previous studies showing L1CAM expression to be a negative prognostic factor in cervical cancer. In our study, increased L1CAM expression in early-stage squamous-cell cervical cancer was not associated with adverse prognosis regarding disease recurrence, disease-free survival, nor overall survival. L1CAM expression was correlated only with the size of the tumor.
- Publication type
- Journal Article MeSH
Circulating tumor markers are not routinely used in patients with endometrial cancer (EC). This pilot study evaluated the role of monitoring new biomarkers DJ1 and L1CAM, in correlation with CA125 and HE4, for the effects of anticancer treatment and preoperative management in EC patients. Serial serum levels of DJ1, L1CAM, CA125 and HE4 were collected in 65 enrolled patients. Serum DJ1, L1CAM, CA125 and HE4 levels were significantly higher at the time of diagnosis compared to those measured during follow-up (FU). In patients with recurrent disease, serum DJ1, CA125 and HE4 levels were significantly higher at the time of recurrence compared to levels in disease-free patients. Serum L1CAM levels were also higher in patients with recurrence but without reaching statistical significance. While DJ1 levels were not affected by any of the observed patient-related characteristics, L1CAM levels were significantly higher in patients with age ≥60 years who were overweight. At the time of EC diagnosis, DJ1 and L1CAM serum levels did not correlate with stage, histological type or risk of recurrence. This is a preliminary description of the potential of serial DJ1 and L1CAM serum level measurement for monitoring the effects of treatment in EC patients.
- Publication type
- Journal Article MeSH
OBJECTIVE: Pre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC. METHODS: Retrospective multicenter study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), analyzing pre-operative IHC expression of p53, L1 cell-adhesion molecule (L1CAM), estrogen receptor (ER) and progesterone receptor (PR), and relate to ESMO-ESGO-ESTRO risk groups, LN status and outcome. RESULTS: A total of 763 EC patients were included with a median follow-up of 5.5-years. Abnormal IHC expression was present for p53 in 112 (14.7%), L1CAM in 79 (10.4%), ER- in 76 (10.0%), and PR- in 138 (18.1%) patients. Abnormal expression of p53/L1CAM/ER/PR was significantly related with higher risk classification groups, and combined associated with the worst outcome within the 'high and advanced/metastatic' risk group. In multivariate analysis p53-abn, ER/PR- and ESMO-ESGO-ESTRO 'high and advanced/metastatic' were independently associated with reduced disease-specific survival (DSS). Patients with abnormal IHC expression and lymph node metastasis (LNM) had the worst outcome. Patients with LNM and normal IHC expression had comparable outcome with patients without LNM and abnormal IHC expression. CONCLUSION: The use of pre-operative IHC biomarkers has important prognostic relevance in addition to the ESMO-ESGO-ESTRO risk classification and in addition to LN status. For daily clinical practice, p53/L1CAM/ER/PR expression could serve as indicator for surgical staging and refine selective adjuvant treatment by incorporation into the ESMO-ESGO-ESTRO risk classification.
- MeSH
- Survival Analysis MeSH
- Cohort Studies MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Neural Cell Adhesion Molecule L1 metabolism MeSH
- Biomarkers, Tumor metabolism MeSH
- Endometrial Neoplasms diagnosis mortality pathology MeSH
- Predictive Value of Tests MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
