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Prognostic value of the expression of chemokines and their receptors in regional lymph nodes of melanoma patients.

ABSTRACT: Chemokines and their receptors have been reported to drive immune cells into tumours or to be directly involved in the promotion or inhibition of the development of tumours. However, their expression in regional lymph node (LN) tissues in melanoma patients remains unknown. The present study investigated the relationship between the expression of mRNA of chemokines and their receptors and clinicopathology of the regional LN tissues of skin cutaneous melanoma (SKCM) patients available in The Cancer Genome Atlas. The relationship between chemokines and their receptors and the composition of immune cells within the tumour was analysed. In SKCM regional LN tissues, the high expression of 32 types of chemokines and receptors, namely CCL2, 4-5, 7-8, 13, 22-25, CCR1-9, CXCL9-13, 16, CXCR3, 5, 6, XCL1-2 and XCR1 in LN was associated with favourable patient prognosis. Conversely, high expression of CXCL17 was an indicator of poor prognosis. The expression of mRNA for CXCL9-11, 13, CXCR3, 6, CCL2, 4, 5, 7, 8, 25, CCR1, 2, 5, and XCL1, 2 in regional LN tissues was positively correlated with the fraction of CD8-positive T cells and M1 macrophages, and was negatively correlated with M0 macrophages. CCR4, 6-9, CCL13, 22, 23 and XCR1 were positively correlated with the fraction of memory B cells and naive T cells, and negatively correlated with M0 macrophages and resting mast cells, suggesting that chemokines and their receptors may affect the prognosis of patients by guiding immune cells into the tumour microenvironment to eliminate tumour cells.

SUBMITTER: Xiong TF

PROVIDER: S-EPMC7131952 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Prognostic value and management of regional lymph nodes in locoregional breast cancer recurrence: a systematic review of the literature.

Project description:PurposeManagement of regional lymph nodes in breast cancer recurrence has been heterogeneous. To facilitate clinical practice, this review aims to give an overview on the prognosis, staging and operative management of (inapparent) regional lymph nodes.MethodsCurrent national and international guidelines are reviewed and a structured search of the literature between Jan 1, 1999 and Feb 1, 2021 on the repeat sentinel node biopsy (re-SNB) procedure was performed.ResultsPositive regional lymph nodes in recurrent breast cancer indicate a poorer outcome with axillary recurrences being the most favorable tumor site among all nodal regions. Most preferred staging method is ultrasound ± guided biopsy. PET-CT, scintimammography, SPECT-CT may improve visualization of affected lymph nodes outside the axilla. Concerning operative management 30 articles on re-SNB were identified with a mean harvesting rate of 66.4%, aberrant drainage and aberrant metastasis in 1/3 of the cases. Total rate of metastasis is 17.9%. After previous axillary dissection (ALND) the re-SNB has a significantly lower harvesting rate and higher aberrant drainage and aberrant metastasis rate. The prognostic outcome after re-SNB has been favorable.ConclusionNodal status in recurrent disease has prognostic value. The choice of operative management of clinically inapparent regional lymph nodes during local recurrence should be based on the previous nodal staging method. Patients with previous ALND should be spared a second systematic ALND. Re-SNB or no axillary surgery at all are possible alternatives. Lymphoscintigraphy may be performed to identify extraaxillary drainage. However, for definite recommendations randomized controlled studies are heavily needed.

| S-EPMC9470629 | biostudies-literature

Prospective cohort study of ultrasound surveillance of regional lymph nodes in patients with intermediate-risk cutaneous melanoma.

Project description:BACKGROUND:For patients with intermediate-thickness melanoma, surveillance of regional lymph node basins by clinical examination alone has been reported to result in a larger number of lymph nodes involved by melanoma than if patients had initial sentinel node biopsy and completion dissection. This may result in worse regional control. A prospective study of both regular clinical examination and ultrasound surveillance was conducted to assess the effectiveness of these modalities. METHODS:Between 2010 and 2014, patients with melanoma of thickness 1·2-3·5 mm who had under-gone wide local excision but not sentinel node biopsy were recruited to a prospective observational study of regular clinical and ultrasound nodal surveillance. The primary endpoint was nodal burden within a dissected regional lymph node basin. Secondary endpoints included locoregional or distant relapse, progression-free and overall survival. RESULTS:Ninety patients were included in the study. After a median follow-up of 52 months, ten patients had developed nodal relapse as first recurrence, four had locoregional disease outside of an anatomical nodal basin as the first site of relapse and six had relapse with distant disease. None of the patients who developed relapse within a nodal basin presented with unresectable nodal disease. The median number of involved lymph nodes in patients undergoing lymphadenectomy for nodal relapse was 1 (range 1-2; mean 1·2). CONCLUSION:This study suggests that ultrasound surveillance of regional lymph node basins is safe for patients with melanoma who undergo a policy of nodal surveillance.

| S-EPMC6593779 | biostudies-literature

Prognostic value of HPV-mRNA in sentinel lymph nodes of cervical cancer patients with pN0-status.

Project description:Up to 15% of patients with cervical cancer and pN0-status develop recurrent-disease. This may be due to occult metastatic spread of tumor cells. We evaluated the use of human-papillomavirus-(HPV)-mRNA as a molecular marker for disseminated tumor cells to predict the risk of recurrence. For this prospective, multi-center prognostic study, 189 patients free of lymphnode metastases by conventional histopathology could be analyzed. All patients underwent complete lymphadenectomy. Of each sentinel node (SLN) a biopsy was taken for the detection of HPV-E6-E7-mRNA. Median follow-up time after surgery was 8.1 years. HPV-mRNA could be detected in SLN of 52 patients (27.5%). Recurrence was observed in 22 patients. Recurrence-free-survival was significantly longer for patients with HPV-negative SLN (log rank p = 0.002). By Cox regression analysis the hazard ratio (95%CI) for disease-recurrence was 3.8 (1.5 - 9.3, p = 0.004) for HPV-mRNA-positive compared to HPV-mRNA-negative patients. After adjustment for tumor size as the most influential covariate the HR was still 2.8 (1.1 - 7.0, p = 0.030). In patients with cervical cancer and tumor-free lymph nodes by conventional histopathology HPV-mRNA-positive SLN were of prognostic value independent of tumor size. Particularly, patients with tumors larger than 20mm diameter could possibly benefit from further risk stratification using HPV-mRNA as a molecular marker.

| S-EPMC4673218 | biostudies-literature

Evolving management of positive regional lymph nodes in melanoma: Past, present and future directions.

Project description:Sentinel lymph node (SLN) biopsy has become the standard of care for lymph node staging in melanoma and the most important predictor of survival in clinically node-negative disease. Previous guidelines recommend completion lymph node dissection (CLND) in cases of positive SLN; however, the lymph nodes recovered during CLND are only positive in a minority of these cases. Recent evidence suggests that conservative management (i.e. observation) has similar outcomes compared to CLND. We sought to review the most current literature regarding the management of SLN in metastatic melanoma and to discuss potential future directions.

| S-EPMC6902307 | biostudies-literature

Prognostic value of Ki-67 in breast cancer patients with positive axillary lymph nodes: a retrospective cohort study.

Project description:IntroductionKi-67 expression is a biomarker for proliferation. Its prognostic value is recognized in breast cancer (BC) patients with negative axillary nodes, but is less clear in BC patients with positive axillary lymph nodes.MethodsWe retrospectively reviewed the medical records of 1131 Chinese BC patients treated from January 2002 to June 2007 and 450 patients met the inclusion criteria: positive nodes, adjuvant therapy, and complete biomarker profile (estrogen receptor (ER), progesterone receptor (PR), HER2, p53, Ki-67). Univariate and multivariate regression analysis were used to correlate biomarkers and tumor characteristics with metastasis free survival (MFS) and overall survival (OS).ResultsMedian follow-up time was 46 months (range 5-76 months). The Ki-67 expression was associated significantly with histological grade, ER, PR, HER2, and P53 status (P<0.05). Tumor stage, nodal stage, and ER status were independent prognostic factors for MFS. Ki-67 status was associated significantly with OS but not MFS. To determine whether the extent of LN involvement in the BC patients influenced the role of Ki-67 in survival rates, we compared these variables in patients with 1-3 positive lymph nodes (N1) to those of patients with ≥ 4 positive lymph nodes. Ki-67 status was an independent prognostic factor for MFS (Hazard Ratio, 3.27, P = 0.026) and overall survival (HR, 10.64, P = 0.007) in patients with 1-3 positive nodes (N1).ConclusionsThe possibility that Ki-67 expression together with clinical factors can improve prediction of the prognosis of BC patients with 1 ∼ 3 positive axillary lymph nodes warrants further studies.

| S-EPMC3911937 | biostudies-literature

The Prognostic Role of Para-Aortic Lymph Nodes in Patients with Colorectal Cancer: Is It Regional or Distant Disease?

Project description:IntroductionVisible para-aortic lymph nodes of ?2 mm in size are common metastatic patterns of colorectal cancer (CRC) seen on imaging. Their prognostic value, however, remains inconclusive. We aimed to assess the prognostic role of visible para-aortic lymph nodes (PALNs).MethodsPatients with confirmed pathologic diagnosis of CRC were enrolled. Correlations among clinicopathologic variables were analyzed using the ?2 test. The Cox proportional hazards model was applied for univariate and multivariate analyses. Survival was estimated using the Kaplan-Meier method and log-rank test. A prognostic model for visible PALNs in CRC patients was established.ResultsIn total, 4527 newly diagnosed CRC patients were enrolled. Patients with visible PALNs had inferior overall survival compared to those without visible PALNs (5-year overall survival, 67% vs. 76%, P = 0.015). Lymphovascular invasion (LVI) (hazard ratio = 1.865, P = 0.015); nodal disease (pN+) status (hazard ratio = 2.099, P = 0.006); elevated preoperative serum carcinoembryonic antigen (CEA) levels (hazard ratio = 2.263, P < 0.001); and visible PALNs ?10 mm (hazard ratio = 1.638, P = 0.031) were independent prognostic factors for patients with visible PALNs. If each prognostic factor scored one point, 5-year overall survival of lower- (prognostic score 0-1), intermediate- (prognostic score 2), and high- (prognostic score 3-4) risk groups were, 78%. 54%, and 25% respectively (P < 0.001).ConclusionsThe prognostic model, which included LVI, pN+ status, preoperative serum CEA level, and the size of visible PALNs, could effectively distinguish the outcome of patients with visible PALNs.

| S-EPMC4482546 | biostudies-literature

Prostanoid induces premetastatic niche in regional lymph nodes.

Project description:The lymphatic system is an important route for cancer dissemination, and lymph node metastasis (LNM) serves as a critical prognostic determinant in cancer patients. We investigated the contribution of COX-2-derived prostaglandin E2 (PGE2) in the formation of a premetastatic niche and LNM. A murine model of Lewis lung carcinoma (LLC) cell metastasis revealed that COX-2 is expressed in DCs from the early stage in the lymph node subcapsular regions, and COX-2 inhibition markedly suppressed mediastinal LNM. Stromal cell-derived factor-1 (SDF-1) was elevated in DCs before LLC cell infiltration to the lymph nodes, and a COX-2 inhibitor, an SDF-1 antagonist, and a CXCR4 neutralizing antibody all reduced LNM. Moreover, LNM was reduced in mice lacking the PGE2 receptor EP3, and stimulation of cultured DCs with an EP3 agonist increased SDF-1 production. Compared with WT CD11c+ DCs, injection of EP3-deficient CD11c+ DCs dramatically reduced accumulation of SDF-1+CD11c+ DCs in regional LNs and LNM in LLC-injected mice. Accumulation of Tregs and lymph node lymphangiogenesis, which may influence the fate of metastasized tumor cells, was also COX-2/EP3-dependent. These results indicate that DCs induce a premetastatic niche during LNM via COX-2/EP3-dependent induction of SDF-1 and suggest that inhibition of this signaling axis may be an effective strategy to suppress premetastatic niche formation and LNM.

| S-EPMC4347225 | biostudies-literature

Sentinel Lymph Node Biopsy for T1b Melanoma: Balancing Prognostic Value and Cost.

Project description:BackgroundThe purpose of this study is to report the additional prognostic information and cost associated with sentinel lymph node biopsy (SLNB) for patients with T1b melanoma.Patients and methodsAn institutional database was queried for patients with T1b melanoma (0.8-1.0 mm or < 0.8 mm with ulceration) with at least 5 years of follow-up. Results of SLNB, completion lymphadenectomy (CLND), recurrence, and melanoma-specific survival (MSS) were assessed. Institutional costs of melanoma care were converted to Medicare proportional dollars. A Markov model was created to estimate long-term costs.ResultsAmong the total 392 patients, 238 underwent SLNB. Median follow-up was 10.5 years. SLNB was positive in 19 patients (8.0%). Patients who underwent SLNB had higher 10-year nodal recurrence-free survival (98.6% vs. 91.2%, p < 0.001) but not MSS (94.4% vs. 93.2%, p = 0.55). Ulceration (HR 4.7, p = 0.022) and positive sentinel node (HR 11.5, p < 0.001) were associated with worse MSS. Estimates for 5-year costs reflect a fourfold increase in total costs of care associated with SLNB. However, a treatment plan that forgoes adjuvant therapy for resected stage IIIA melanoma but offers systemic therapy for a node-basin recurrence would nullify the additional cost of SLNB.ConclusionsSLNB is prognostic for T1b melanoma. Its impact on the overall cost of melanoma care is intimately tied to systemic therapy in the adjuvant and recurrent settings.

| S-EPMC8366311 | biostudies-literature

The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma.

Project description:BackgroundThe current American Joint Committee on Cancer (AJCC) system only considered the importance of the size and laterality of lymph nodes while not the positive lymph node number (PLNN) for hypopharyngeal squamous cell carcinoma (HPSCC).MethodsA total of 973 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004-2015) were identified. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects. We applied six Cox regression models to compare the survival prognostic values of PLNN and AJCC systems.ResultsPositive lymph node number showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in univariate and multivariable analyses. The increased PLNN of HPSCC gave rise to poor OS and CSS. The survival model incorporating a composite of PLNN and TNM classification (C-index for OS:0.682, C-index for CSS:0.702) performed better than other models.ConclusionsA positive lymph node number could serve as a survival predictor for patients with HPSCC and a complement to enhance the prognostic assessment effects of TNM cancer staging systems.

| S-EPMC9291443 | biostudies-literature

Competing-risks model for predicting the prognostic value of lymph nodes in medullary thyroid carcinoma.

Project description:BackgroundMedullary thyroid carcinoma (MTC) is an infrequent form malignant tumor with a poor prognosis. Because of the influence of competitive risk, there may suffer from bias in the analysis of prognostic factors of MTC.MethodsBy extracting the data of patients diagnosed with MTC registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1998 to 2016, we established the Cox proportional-hazards and competing-risks model to retrospectively analyze the impact of related factors on lymph nodes statistically.ResultsA total of 2,435 patients were included in the analysis, of which 198 died of MTC. The results of the multifactor competing-risk model showed that the number of total lymph nodes (19-89), positive lymph nodes (1-10,11-75) and positive lymph node ratio (25%-53%,>54%), age (46-60,>61), chemotherapy, mode of radiotherapy (others), tumor size(2-4cm,>4cm), number of lesions greater than 1 were poor prognostic factors for MTC. For the number of total lymph nodes, unlike the multivariate Cox proportional-hazards model results, we found that it became an independent risk factor after excluding competitive risk factors. Competitive risk factors have little effect on the number of positive lymph nodes. For the proportion of positive lymph nodes, we found that after excluding competitive risk factors, the Cox proportional-hazards model overestimates its impact on prognosis. The competitive risk model is often more accurate in analyzing the effects of prognostic factors.ConclusionsAfter excluding the competitive risk, the number of lymph nodes, the number of positive and the positive proportion are the poor prognostic factors of medullary thyroid cancer, which can help clinicians more accurately evaluate the prognosis of patients with medullary thyroid cancer and provide a reference for treatment decision-making.

| S-EPMC10578593 | biostudies-literature

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