Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The membrane epithelial mucin MUC1 is expressed at the luminal surface of most simple epithelial cells, but expression is greatly increased in most breast cancers. The aims of present study were to investigate expression of the MUC1 gene and interactive affects in metastases. Whole cell RNA isolation from 50 sentinel lymph nodes (SNLs) of breast cancer patients was performed using reverse transcription and real-time PCR. All patients were diagnosed with breast cancer and without metastasis, confirmed by IHC staining. The evaluation of tumor and normal samples for expression of MUC1 gene, the results were 49.1% non-expressive and 45.3% expression (Student t, p = 0.03). Also in comparison of normal breast tissue and breast cancer SLN for MUC1 gene, MUC1 negative SLNs were 75.0% (18 samples) and MUC1 positive samples were 25.0% (6 samples). Over-expression of MUC1 gene may offer a target for therapy related to progression and metastasis in women with breast cancer.
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PMID:Overexpression of the MUC1 Gene in Iranian Women with Breast Cancer Micrometastasis. 2716 38

Histological regression in primary cutaneous melanoma occurs in 10-35% of cases. Although a large body of literature exists to suggest that histological regression serves very little purpose in predicting biologic behaviour with melanoma, recognizing the presence of regression at clinical and histological ground may still retain some value in grading melanoma aggressiveness. In the current review, a comprehensive overview of the main aspects of regression will be provided. Histologically, many classifications have been reported so far, but all of them only agreed on the presence of an infiltrate of lymphocytes admixed with pigment-laden macrophages underlying an atrophic epidermis with flattened rete ridges. Upon dermoscopy, regression is also named Blue White Scar-like areas and could be variably admixed with granularity or peppering. Almost fully regressed lesions represent a main diagnostic issue in dermoscopy, and thus, confocal microscopy can be of help to identify whether the tumour is melanocytic or not. The clinical utility of regression as a prognostic factor has been challenged recently. Nowadays, evidences showed that it is less likely associated to SLN metastases.
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PMID:Regression in cutaneous melanoma: a comprehensive review from diagnosis to prognosis. 2740 35

Histological regression in primary cutaneous melanoma occurs in 10-35% of cases. Although there is a large body of literature on histological regression and prognosis in melanoma patients, not clear data concerning this feature has been reported. In the current review, a comprehensive overview of the main aspects of regression will be provided. The clinical utility of regression as a prognostic factor has been challenged recently. Nowadays evidences reported that this feature is protective on SLN metastases. Despite its association with poor prognostic factors, it maintained a favourable prognostic role in many different survival studies.
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PMID:Prognostic role of histological regression in cutaneous melanoma. 2784 12

Sentinel lymph node biopsy (SLNB) is an accurate, safe method for determining the axillary lymph node status. However, insufficient evidence exists to support the recommendation of SLNB in patients who have had neoadjuvant chemotherapy (NAC) to downsize tumours and allow for breast conservation surgery. The present study aimed to use molecular approaches to evaluate the feasibility and accuracy of SLNB in patients treated with NAC prior to SLN mapping and surgery. A total of 50 consecutive patients with operable invasive breast carcinomas who had received prior NAC were assessed using the one-step nucleic acid amplification (OSNA) method. The rate of SLN identification was 100%. The OSNA assay showed that 29 patients (58%) were negative for SLN and 21 patients (42%) were positive. In 19 of these 21 patients (90.48%), the SLN was the only positive lymph node. No axillary lymph nodes metastases were observed in patients with isolated tumour cells or with micrometastases. The OSNA assay is a highly sensitive, specific and reproducible diagnostic technique that can be used to analyse SLNs following NAC. The total tumoral load may assist with predicting additional non-SLN metastases.
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PMID:Intraoperative molecular analysis of sentinel lymph nodes following neoadjuvant chemotherapy in patients with clinical node negative breast cancer: An institutional study. 2788 35

Purpose: Sentinel lymph node biopsy (SLNB) has emerged as the preferred standard procedure in patients with breast cancer, melanoma and other types of cancer. Herein, we developed a method to intra-operatively map SLNs and differentiate tumor metastases within SLNs at the same time, with the aim to provide more accurate and real-time intraoperative guidance. Experimental Design: Hyaluronic acid (HA), a ligand of lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, is employed as a SLN mapping agent after being conjugated with a near-infrared fluorophore (Cy5.5). Different sized HAs (5, 10 and 20K) were tested in normal mice and mice with localized inflammation to optimize LN retention time and signal to background ratio. Cetuximab, an antibody against epidermal growth factor receptor (EGFR), and trastuzumab, an antibody against human epidermal growth factor receptor 2 (HER2), were labeled with near-infrared fluorophore (IRDye800) for detecting metastatic tumors. LN metastasis model was developed by hock injection of firefly luciferase engineered human head neck squamous carcinoma cancer UM-SCC-22B cells or human ovarian cancer SKOV-3 cells. The metastases within LNs were confirmed by bioluminescence imaging (BLI). IRDye800-Antibodies were intravenously administered 24 h before local administration of Cy5.5-HA. Optical imaging was then performed to identify nodal metastases. Results: Binding of HA with LYVE-1 was confirmed by ELISA and fluorescence staining. HA with a size of 10K was chosen based on the favorable migration and retention profile. After sequential administration of IRDye800-antibodies intravenously and Cy5.5-HA locally to a mouse model with LN metastases and fluorescence optical imaging, partially metastasized LNs were successfully distinguished from un-metastasized LNs and fully tumor occupied LNs, based on the different signal patterns. Conclusions: Fluorophore conjugated HA is a potential lymphatic mapping agent for SLNB. Dual-tracer imaging with the combination of lymphatic mapping agents and tumor targeting agents can identify tumor metastases within SLNs, thus may provide accurate and real-time intra-operative guidance to spare the time spent waiting for a biopsy result.
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PMID:Mapping Sentinel Lymph Node Metastasis by Dual-probe Optical Imaging. 2804 24

Breast cancer stem cells (CSCs) have been hypothesized to be the driving force behind tumorigenesis and metastasis. In this study, we evaluated the relationships between CSC expressions in primary breast cancers and corresponding metastatic sentinel and nonsentinel lymph nodes (SLNs and NSLNs). The clinical implications of these relationships were also investigated. CSC expressions were evaluated in 167 breast cancer specimens and associated lymph node biopsies (when present). We used double immunohistochemistry of CD44/CD24 and single immunohistochemistry of ALDH-1 on paraffin-embedded breast tissue, SLN, and NSLN specimens. Seven cases had metastatic NSLNs without SLN involvement-so-called "skip metastasis." Fifty cases of SLNs (29.9%) and 33 cases of NSLNs (25.7%) had metastases. In the breast cancers, metastatic SLNs, and NSLNs, the expression rates of CD44+/CD24- were 47.9%, 26.1%, and 34.6 %, respectively, while the expression rates of ALDH-1+ were 42.5%, 36.4%, and 33.3%, respectively. Significant relationships were not observed between CSC expressions in breast cancer and metastatic SLNs or NSLNs. The presence of skip metastasis correlated with negative ALDH-1 in breast cancer ( P = .04), as well as several clinicopathologic factors: age >50 years ( P = .004), negative lymphovascular tumor emboli ( P = .02), and high Ki-67 expression ( P = .04). Axillary lymph node metastasis showed no significant relationship with any CSC marker. However, CD44+/CD24- and ALDH-1 expressions of metastatic SLNs correlated with CSCs of primary breast cancers. In summary, skip metastasis correlated with negative expression of ALDH-1 in primary breast cancers, which could be promising as a means of assessing the risk of skip metastasis.
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PMID:Axillary Skip Metastases and the False-Negative Rate of Sentinel Lymph Node Biopsy in Patients With Breast Cancer Are Related to Negative ALDH-1 Expression and Ki-67 Expression. 2814 49

this is a 10-year retrospective chart review evaluating the potential impact of the most recent American Cancer Society mammography screening guidelines which excludes female patients aged 40 to 44 years from routine annual screening mammography. Instead they recommend screening mammography starting at age 45 with the option to begin screening earlier if the patient desires. The institutional cancer registry was systematically searched to identify all women aged 40 to 44 years treated for breast cancer over a 10-year period. These women were separated into two cohorts: screening mammography detected cancer (SMDC) and nonscreening mammography detected cancer (NSMDC). Statistical analysis of the cohorts was performed for lymph node status (SLN), five-year disease-free survival, and five-year overall survival. Women with SMDC had a significantly lower incidence of SLN positive cancer than the NSMDC group, 9 of 63 (14.3%) versus 36 of 81 (44 %; P < 0.001). The five-year disease-free survival for both groups was 84 per cent for SMDC and 80 per cent for NSMDC; this was not statistically significant. The five-year overall survival was statistically significant at 94 per cent for the SMDC group and 80 per cent for the NSMDC group (P < 0.05). This review demonstrates the significance of mammographic screening for early detection and treatment of breast cancer. Mammographic screening in women aged 40 to 44 detected tumors with fewer nodal metastases, resulting in improved survival and reaffirming the need for annual mammographic screening in this age group.
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PMID:Mammographic Screening at Age 40 or 45? What Difference Does It Make? The Potential Impact of American Cancer Society Mammography Screening Guidelines. 2882 89

According to the current guidelines on treatment of breast cancer patients, identification of metastases in the sentinel lymph node (SLN (+)) is not an absolute indication for necessary axillary lymph node dissection (ALND). In our study, we present long-term outcomes of treatment among SLN(+) patients referred for conservative treatment, for example, no further ALND. A total of 3145 breast cancer patients subjected to sentinel lymph node biopsy (SLNB) between November 2008 and June 2015. SLN metastases were identified in 719 patients (22.9%). Locoregional recurrences and distant metastases as endpoints were distinquished. The mean follow-up time for patients after ALND was 36.2 months (6-74 months); 18.8 months (6-38 months) for patients with SLN macrometastases without ALND; and 34.0 months (6-74 months) for patients with micrometastases. Adjuvant ALND was performed in 626 of SLN(+) patients. Conservative treatment was applied in the remaining 93 cases. Among SLN(+) patients without adjuvant ALND, there was one case of recurrence (1.07%). In the group of patients without SLN, metastases recurrence was noted in 32 patients (1.32%). Among SLN(+) patients diagnosed with macrometastases, recurrence concerned 2.01% of analyzed cases (all subjected to ALND). Lack of radical surgical treatment in SLN(+) breast cancer patients did not lead to worsening long-term outcomes. In the occurrence of macrometastases to the sentinel lymph node, abandoning completion axillary lymph node dissection might be a reasonable option. However, it would require continuation of current research, preferably involving a clinical trial.
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PMID:Does the presence of sentinel lymph node macrometastases in breast cancer patients require axillary lymph node dissection?-Single-center analysis. 2947 70

As a minimally invasive method, sentinel lymph node biopsy (SLNB) in conjunction with guidance methods is the standard method to determine cancer metastasis in breast. The desired guidance methods for SLNB should be capable of precise SLN localization for accurate diagnosis of micro-metastases at an early stage of cancer progression and thus facilitate reducing the number of SLN biopsies for minimal surgical complications. For this, high sensitivity to the administered dyes, high spatial and contrast resolutions, deep imaging depth, and real-time imaging capability are pivotal requirements. Currently, various methods have been used for SLNB guidance, each with their own advantages and disadvantages, but no methods meet the requirements. In this review, we discuss the conventional SLNB guidance methods in this perspective. In addition, we focus on the role of the PA imaging modality on real-time SLN identification and biopsy guidance. In particular, PA-based hybrid imaging methods for precise SLN identification and efficient biopsy guidance are introduced, and their unique features, advantages, and disadvantages are discussed.
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PMID:Multimodal photoacoustic imaging as a tool for sentinel lymph node identification and biopsy guidance. 3060 2

The standard approach in the management of cutaneous malignant melanoma is considered to be a complete excision of the primary lesion with an appropriate margin of the normal tissue according to Breslow thickness. Usually sentinel lymph node biopsy (SLNB) can help to determine the nodal status, and thus improve the accuracy of staging of the disease. However, the role of SLNB in melanoma treatment remains controversial. NCCN guidelines strongly support routine performance of therapeutic lymphadenectomy in all melanoma patients with clinically positive nodes without radiographic evidence of distant metastases. Patients with positive SLNB should have had completion lymph node dissection (CLND) for regional disease control. Between 2012 and 2016, 168 consecutive patients underwent surgery for primary cutaneous malignant melanoma at St. Elisabeth Cancer Institute in Bratislava. The indication for SLNB and the procedure was made according to international guidelines. In this retrospective study, a cohort of 78 patients was analyzed (35 women and 43 men). Inclusion criteria comprised patients with cutaneous melanoma with no evidence of distant metastases or clinical lymphadenopathy. SLNB comprised a dual labelling method (Tc-99m Nanocolloid / blue dye) in a one-day protocol. Median follow-up was 657 days. The primary composite outcome was the time to the first disease-related event (death, reintervention, worsening of symptoms). Primary outcome measures were overall (disease-specific) and disease-free survival. The overall identification rate of SLN in melanoma patients by dual labelling method was 98.5%. All patients with positive SLNB on frozen section underwent complete regional lymphadenectomy. Using multivariable analysis Breslow thickness of the lesion (p=0.00004, HR 4.03 on logarithmic scale) was identified as the strongest independent predictor of the disease-free survival (DFS) and male gender was significant predictor of DFS. An increase in tumor thickness was associated with significantly higher risk of an event. Neither SLN positivity nor initial S-100 level proved to be significant predictors of the event at the 0.05 level of probability. Multidisciplinary approach represents the gold standard of care for melanoma patients and surgery remains the best option for most localized cases. Although the usefulness of SLNB procedure has been questioned, it provides an excellent staging method, moreover, it can identify high-risk patients. The routine use of completion lymphadenectomy after a positive SLNB is still controversial. It is not clear whether CLND following a positive SLN biopsy improves survival but it could provide regional disease control.
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PMID:Recurrence after sentinel lymph node biopsy in cutaneous melanoma: a single-center experience in Slovak patients. 3105 35


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