In-depth proteomics analysis of sentinel lymph nodes from individuals with endometrial cancer.
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ABSTRACT:
SUBMITTER: Aboulouard S
PROVIDER: S-EPMC8233695 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Sentinel lymph node (SLN) mapping is becoming an acceptable alternative to full lymphadenectomy for evaluating lymphatic spread in clinical stage I endometrial cancer (EC). While the assessment of pelvic and para-aortic lymph nodes is part of the surgical staging of EC, there is a long-standing debate over the therapeutic value of full lymphadenectomy in this setting. Although lymphadenectomy offers critical information on lymphatic spread and prognosis, most patients will not derive oncologic benefit from this procedure as the majority of patients do not have lymph node involvement. SLN mapping offers prognostic information while simultaneously avoiding the morbidity associated with an extensive and often unnecessary lymphadenectomy. A key factor in the decision making when planning for EC surgery is the histologic subtype. Since the risk of lymphatic spread is less than 5% in low-grade EC, these patients might not benefit from lymph node assessment. Nonetheless, in high-grade EC, the risk for lymph node metastases is much higher (20-30%); therefore, it is crucial to determine the spread of disease both for determining prognosis and for tailoring the appropriate adjuvant treatment. Studies on the accuracy of SLN mapping in high-grade EC have shown a detection rate of over 90%. The available evidence supports adopting the SLN approach as an accurate method for surgical staging. However, there is a paucity of prospective data on the long-term oncologic outcome for patients undergoing SLN mapping in high-grade EC, and more trials are warranted to answer this question.
| S-EPMC8870608 | biostudies-literature
Project description:Patients with early breast cancer are affected by metastasis to axillary lymph nodes. Metastasis to these nodes is crucial for staging and quality of surgery. Sentinel Lymph Node Biopsy that is currently used to assess lymph node metastasis is not effective. This necessitates identification of biomarkers that can flag metastasis. Early stage breast cancer patients were recruited. Surgical resection of breast was followed by identification of sentinel lymph nodes. Fresh frozen section biopsy was used to assign metastatic and non-metastatic sentinel lymph nodes. Discovery phase included iTRAQ proteomics coupled with mass spectrometric analysis to identify differentially expressed proteins. Data is available via ProteomeXchange with identifier PXD027668. Validation was done by bioinformatic analysis and ELISA. There were 2398 unique protein groups and 109 differentially expressed proteins comparing metastatic and non-metastatic lymph nodes. Forty nine proteins were up-regulated, and sixty proteins that were down regulated in metastatic group. Bioinformatic analysis showed ECM-receptor interaction pathways to be implicated in lymph node metastasis. ELISA confirmed up-regulation of ECM proteins in metastatic lymph nodes. ECM proteins have requisite parameters to be developed as a diagnostic tool to assess status of sentinel lymph nodes to guide surgical intervention in early breast cancer.
| S-EPMC9124668 | biostudies-literature
Project description:Endometrial cancer is the most frequent tumor in the female reproductive system, while the sentinel lymph node (SLN) mapping for diagnostic efficacy of endometrial cancer is still controversial. This meta-analysis was conducted to evaluate the diagnostic value of SLN in the assessment of lymph nodal involvement in endometrial cancer. Forty-four studies including 2,236 cases were identified. The pooled overall detection rate was 83% (95% CI: 80-86%). The pooled sensitivity was 91% (95% CI: 87-95%). The bilateral pelvic node detection rate was 56% (95% CI: 48-64%). Use of indocyanine green (ICG) increased the overall detection rate to 93% (95% CI: 89-96%) and robotic-assisted surgery also increased the overall detection rate to 86% (95% CI: 79-93%). In summary, our meta-analysis provides strong evidence that sentinel node mapping is an accurate and feasible method that performs well diagnostically for the assessment of lymph nodal involvement in endometrial cancer. Cervical injection, robot-assisted surgery, as well as using ICG, optimized the sensitivity and detection rate of the technique. Sentinel lymph mapping may potentially leading to a greater utilization by gynecologic surgeons in the future.
| S-EPMC5542296 | biostudies-literature
Project description:Sentinel lymph nodes are widely accepted in the treatment of endometrial carcinoma. Whereas surgical aspects are well studied, the pathological work-up in terms of grossing, frozen section, and the so-called ultra-staging is still a matter of debate. This results in conflicting national or center-based recommendations. In a series of consecutive 833 sentinel lymph nodes from 206 patients in endometrial carcinomas, we compared three different grossing techniques and the use of frozen section in terms of anatomy, detection rates, and survival. In total, 42 macro-metastases, 6 micro-metastases, and 25 nodes with isolated tumor cells were found. Lymph nodes affected at least with micro-metastasis were about 0.5cm enlarged. Detection rates in lamellation technique increased with a step of 5.9% to 8.3% in comparison to bi-valved or complete embedding. The lamellation technique presented with a slight beneficial prognosis in pN0 subgroup (OS, p=0.05), which besides size effects might be attributed to trimming loss. In frozen section, this effect was less pronounced than expected (OS, p=0.56). Ultra-staging only revealed additional micro-metastases and isolated tumor cells. Exclusively, macro-metastases showed poor survival (p<0.001). In multivariate analysis, T-stage, subtype, and lympho-vascular invasion status outperformed this staging parameter significantly. Grossing of sentinel lymph nodes is the most essential step with evidence to prefer lamellation in 2 mm steps. Step sectioning should consider widely spaced protocols to exclude macro-metastases. Frozen sections might add value to the intra-operative assessment of endometrial carcinoma in selected cases. The excellent biological behavior of cases with isolated tumor cells might question the routine application of pan-cytokeratin as ultra-staging method.
| S-EPMC9485184 | biostudies-literature
Project description:We have previously reported that a quantitative reverse transcription (QRT)-PCR assay accurately analyzes sentinel lymph nodes (SLNs) from breast cancer patients. The aim of this study was to assess a completely automated, cartridge-based version of the assay for accuracy, predictive value, and reproducibility. The triplex (two markers + control) QRT-PCR assay was incorporated into a single-use cartridge for point-of-care use on the GeneXpert system. Three academic centers participated equally. Twenty-nine positive lymph nodes and 30 negative lymph nodes were analyzed to establish classification rules. SLNs from 120 patients were subsequently analyzed by QRT-PCR and histology (including immunohistochemistry), and the predetermined decision rules were used to classify the SLNs; 112 SLN specimens produced an informative result by both QRT-PCR and histology. By histological analysis, 21 SLNs were positive and 91 SLNs were negative for metastasis. QRT-PCR characterization produced a classification with 100% sensitivity, 97.8% specificity, and 98.2% accuracy compared with histology (91.3% positive predictive value and 100% negative predictive value). Interlaboratory reproducibility analyses demonstrated that a 95% prediction interval for a new measurement (DeltaCt) ranged between 0.403 and 0.956. This fully automated QRT-PCR assay accurately characterizes breast cancer SLNs for the presence of metastasis. Furthermore, the assay is not dependent on subjective interpretation, is reproducible across three clinical environments, and is rapid enough to allow intraoperative decision making.
| S-EPMC2765757 | biostudies-literature
Project description:Endometrial cancer (EC) is the most common gynecological neoplasm in developed countries. In literature, there are discordant data regarding the therapeutic value of systematic lymphadenectomy whereas the importance of lymph node status for determining prognosis and the need for adjuvant treatment is undoubted. Given the low risk of lymph-node metastases in the apparent early-stage disease and the significant surgical and postoperative risks when performing a complete pelvic lymphadenectomy, the surgical approach in these patients is controversial, ranging from no nodal evaluation to comprehensive pelvic and aortic lymphadenectomy. The recent introduction of sentinel node mapping represents the mid-way between the execution and omission of node dissection in EC patients. Indeed, the sentinel node mapping has rapidly emerged as an alternative to complete lymphadenectomy to reduce morbidity. In the present review, we discuss the role of sentinel node mapping in the surgical management of EC evaluating all aspects of this procedure.
| S-EPMC8797296 | biostudies-literature
Project description:Endometrial cancer is the most common gynecological cancer worldwide. In women from developed countries, endometrial cancer is usually detected after the age of 60 years. Nearly 90% of the diagnosed cases are sporadic, while 10% are attributed to genetic factors. Thus, it is necessary to develop a diagnostic platform. Currently, the lymph node status is a major prognostic factor in assessing endometrial cancer. However, despite its high sensitivity, it is still in debate. In order to increase its selectivity and specificity, in-depth proteomic study has been performed on patients sentinel lymph node (SNL) samples and on grade I to grade III endometrial carcinoma (EC) samples. We identified specific markers of bad diagnosis that clearly correlate SNL to EC i.e. PRSS3, PTX3, ASS1, YBX2, RBM25, MUC5B. These markers have also been detected in TCGA. By contrast, we also detected good prognosis markers for the overall survival such as CD74, GOLM1, SLC9A3R2, SP100 proteins. Markers for EC and SNL cancer-grading have also been identified. Taken together, it is now possible to propose a novel approach for molecular diagnosis, prognosis and patient’s stratification in EC which will be of excellent utility in therapeutic decision.
2021-09-09 | PXD020410 | Pride
Project description:BACKGROUND: The majority of sentinel node (SN) positive breast cancer patients do not have additional non-SN involvement and may not benefit from axillary lymph node dissection (ALND). Previous studies in melanoma have suggested that microanatomic localization of SN metastases may predict non-SN involvement. The present study was designed to assess whether these criteria might also be used to be more restrictive in selecting breast cancer patients who would benefit from an ALND. METHODS: A consecutive series of 357 patients with invasive breast cancer and a tumor-positive axillary SN, followed by an ALND, was reviewed. Microanatomic SN tumor features (subcapsular, combined subcapsular and parenchymal, parenchymal, extensive localization, multifocality, and the penetrative depth from the SN capsule) were evaluated for their predictive value for non-SN involvement. RESULTS: Non-SN metastases were found in 136/357 cases (38%). Microanatomic location and penetrative depth of SN metastases were significant predictors for non-SN involvement (<0.001); limited penetrative depth was associated with a low frequency of non-SN involvement with a minimal of 10%. CONCLUSIONS: Microanatomic location and penetrative depth of breast cancer SN metastases predict non-SN involvement. However, based on these features no subgroup of patients could be selected with less than 10% non-SN involvement.
| S-EPMC2277442 | biostudies-other
Project description:BackgroundThe sentinel lymph node biopsy (SLNB) takes on a critical significance in breast cancer surgery since it is the gold standard for assessing axillary lymph node (ALN) metastasis and determining whether to perform axillary lymph node dissection (ALND). A bibliometric analysis is beneficial to visualize characteristics and hotspots in the field of sentinel lymph nodes (SLNs), and it is conducive to summarizing the important themes in the field to provide more insights into SLNs and facilitate the management of SLNs.Materials and methodsSearch terms relating to SLNs were aggregated and searched in the Web of Science core collection database to identify the top 100 most cited articles. Bibliometric tools were employed to identify and analyze publications for annual article volume, authors, countries, institutions, keywords, as well as hotspot topics.ResultsThe period was from 1998 to 2018. The total number of citations ranged from 160 to 1925. LANCET ONCOLOGY and JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION were the top two journals in which the above articles were published. Giuliano, AE was the author with the highest number of articles in this field with 15. EUROPEAN INST ONCOL is the institution with the highest number of publications, with 35 articles. Hotspots include the following 4 topics, false-negative SLNs after neoadjuvant chemotherapy; prediction of metastatic SLNs; quality of life and postoperative complications; and lymphography of SLNs.ConclusionThis study applies bibliometric tools to analyze the most influential literature, the top 100 cited articles in the field of SLNB, to provide researchers and physicians with research priorities and hotspots.
| S-EPMC10600391 | biostudies-literature
Project description:PurposePromoter methylation of tumor suppressor genes in histologically negative sentinel lymph nodes (HNSN) of early stage breast cancer patients has not been extensively studied. This study evaluates the methylation frequency and pattern in HNSN to determine if detection of hypermethylation of one or more genes is associated with an increased recurrence risk in node negative breast cancer.Experimental designIn 1998, a prospective study of patients with early stage breast cancer and HNSN was initiated in order to correlate sentinel node analysis with clinical outcome. Nodal tissue was selected from 120 HNSN patients for methylation analysis in at least one and up to six sentinel nodes using a panel of nine genes. Corresponding primary breast tumors from 79 patients were also evaluated for hypermethylation. Methylation analysis was performed using nested Methylation Sensitive PCR (n-MSP). Logistical regression was used to evaluate the relationship between clinical recurrence and methylation status.ResultsOver a median follow-up of 79 months, 13 of the 120 patients had clinical recurrence. Hypermethylation of genes was frequently observed in HNSN, but there was no correlation of methylation pattern and clinical recurrence. However, increased frequency of gene methylation of the primary tumor correlated with clinical recurrence.ConclusionsAlthough hypermethylation of multiple genes occurs frequently in HNSN of breast cancer patients, it is not associated with breast cancer recurrence in the first 7 years of clinical follow-up.
| S-EPMC3422075 | biostudies-literature