CXCL12和CXCR4在食管鳞癌组织中的表达及其与预后的关系

背景与目的：新近研究显示CXCL12／CXCR4在多种肿瘤组织中有表达,并与肿瘤细胞的增殖、侵袭特性相关;本研究旨在检测CXCL12及其受体CXCR4在食管鳞癌中的表达,研究两者对食管癌预后的影响及其与临床及病理因素之间的关系。方法：收集食管癌术后标本186例及正常食管上皮组织20例（对照组）,应用免疫组化法检测食管癌组织中CXCR4与CXCL12的表达。结果：186例食管癌组织中CXCR4的表达率为67．2％,CXCL12的表达率为63．4％,20例正常食管上皮组织中无CXCR4及CXC112蛋白表达。多因素分析：PTNM分期及CXCR4的表达是影响食管癌根治术后患者预后的独立因素（P〈0．05）：CXCL12阳性组与阴性组5年生存率分别为18．8％和21．0％,差异无统计学意义（P〉0．05）。CXCR4阳性组与阴性组5年生存率分别为2．2％和28．5％。差异有统计学意义（P〈0．05）;有淋巴结转移组及病理分期T3期组CXCR4表达率较无淋巴结转移组及病理分期T1-2组高（P〈0．05）,食管癌组织中CXCR4的表达与CXCL12的表达之间无相关性。结论：CXCL12和CXCR4在食管癌组织中均有较高的表达,CXCR4的表达水平与食管肿瘤的发展及预后有一定的关系。     

前哨淋巴结活检在中国皮肤和肢端恶性黑色素瘤患者诊治中的临床意义

背景与目的：恶性黑色素瘤近年来在中国发病率呈上升趋势。前哨淋巴结活检（sentinel lymph node biopsy,SLNB）在欧美是皮肤恶性黑色素瘤外科诊治规范的重要环节,但在中国却未广泛开展。中国黑色素瘤具有多肢端亚型、浸润深度厚、溃疡率高和预后差等特点。但中国黑色素瘤外科治疗后的预后仍未明确。该研究旨在分析中国黑色素瘤患者的临床数据,评价SLNB的可行性及其对预后的影响。方法：回顾性分析2009—2017年在复旦大学附属肿瘤医院治疗的无临床淋巴转移和远处转移征象的黑色素瘤患者。每例患者在接受原发病灶扩大切除的同时,进行相应区域淋巴结的SLNB。前哨淋巴结（sentinel lymph node,SLN）的定位通过美兰染色和同位素示踪完成。所有患者术后均进行随访。结果：本研究共纳入452例黑色素瘤患者。平均Breslow浸润深度为3.29 mm,66.4%为肢端病灶,溃疡率达59.7%。SLN阳性率为26.8%,假阴性率为4%,淋巴结总转移率为30.8%。本组患者5年总生存率（overall survival,OS）和无病生存率（disease-free survival,DFS）分别为66.6%和55.8%。SLN状态是显著影响患者预后的独立危险因素,而Breslow浸润深度是预测SLN转移状态的独立危险因素。结论：对于无临床大体转移的中国黑色素瘤患者,应常规开展SLNB。SLN状态是影响复发和总体生存的重要因素,SLNB能提高淋巴结微转移患者的生存,提供准确的临床分期。     

CXCL12及受体CXCR4在卵巢上皮性癌中的表达及其临床意义

目的:探讨趋化因子CXCL12及其受体CXCR4在卵巢上皮性癌组织中的表达及与临床病理特征和预后的关系。方法:采用免疫组织化学SP法检测6例正常卵巢表面上皮、44例卵巢上皮性癌原发灶和30例相应大网膜转移灶组织中的CXCL12和CXCR4蛋白表达。结果:正常卵巢表面上皮无CXCL12和CXCR4蛋白表达;卵巢上皮性癌原发灶的CXCL12和CXCR4表达阳性率分别为91%和59%。CXCL12表达强度与术中腹水量有显著相关性(P=0.014)。难治复发组的CXCR4阳性率(81%)显著高于无复发组(28%,P<0.001)。单因素分析显示:CXCR4阳性表达的患者中位数肿瘤无进展生存时间和总生存时间(15个月、27个月)明显短于CXCR4阴性表达者(>21个月、>32个月,分别为P<0.001和P=0.017)。多因素分析显示:CXCR4表达和残余灶大小是影响卵巢上皮性癌患者的肿瘤无进展生存时间和总生存时间的独立预后因素。结论:CXCR4在卵巢上皮性癌中的表达阳性率较高,是影响其预后的独立指标之一。     

Small cell melanoma and ulceration as predictors of positive sentinel lymph node in malignant melanoma patients

Malignant melanoma (MM) early lymph node (LN) metastasis usually appears first in the sentinel LN (SLN). Breslow thickness is the main factor considered in the selection of patients to be submitted to SLN biopsy. The present study aimed to describe other independent prognostic factors useful in SLN candidate selection. During one year, 94 MM patients (90 primary cutaneous MM with Breslow thickness > or = 0.76 mm, and four cutaneous relapses), were submitted to SLN biopsy in the Melanoma Unit at the Hospital Clinic, Barcelona, Spain. The prognostic factors studied were: Breslow thickness, Clark's level of invasion, mitotic rate, cellular type (small, epithelioid, fusocellular, sarcomatoid), vertical growth phase, regression > 50%, severe vascularization, infiltrate (lymphocytic, plasmocytic), ulceration, neurotropism, intravascular/intraneural invasion, protein p16 expression and recurrence. Nineteen SLN (20.2%) were positive and 75 (79.8%) negative. No positive SLN occurred in MM with Breslow thickness < or = 1.0 mm. Breslow thickness > or = 2 mm (P = 0.005), severe vascularization (P = 0.005), small cell (P = 0.000) and ulceration (P = 0.005) were significant prognostic factors by univariate analysis. Small cell (P = 0.008) and ulceration (P = 0.05) were also significant prognostic factors in a multivariate analysis. The probability of finding a positive SLN for small cell was 56.9% [95% confidence interval (CI), 26.8-82.6%]. The probability of positive SLN for ulceration was 35.5% (95% CI, 14.2-64.7%). For small cell and ulceration together the probability increased to 86.3% (95% CI, 54.3-97.1%). The results of this study corroborated ulceration as a prognostic factor for SLN candidate selection and for the first time we have described small cell melanoma morphology as a significant factor associated with positive SLN.     

Can sentinel node biopsy be safely omitted in thin melanoma? Risk factor analysis of 1272 multicenter prospective cases

BackgroundThe indication to sentinel node biopsy (SNB) for thin melanomas (Breslow <1 mm) is still subject to controversies. The aim of this paper is to review all SNB performed for thin melanoma and to analyze factors related to lymphatic metastasis. Moreover, the diagnostic performance of the 5th, 6th, 7th and 8th AJCC classifications for cutaneous melanoma were investigated.MethodsAll sentinel node biopsies performed for thin melanomas were selected from a multicentre prospectively-collected database. For each patient the following was collected: age, sex, date of treatment, site of primary melanoma, histopathologic features (Breslow, Clark, number of mitoses/mm², presence of ulceration) and the results of the sentinel node biopsy.ResultsFrom 1998 to 2017 were performed a total of 1272 SNB for thin melanoma. Mean age was 51years with 48.7% of male patients. Overall, 5.6% positive SNB were found. At univariate and multivariate analyses, Breslow thickness and ulceration were related to the presence of lymphatic metastasis. We compared the four versions of the AJCC classification: among pT1a patients there were respectively 5.32%, 5.63%, 3.72% and 3.49% of positive SNB.Conclusionsin thin melanoma Breslow thickness and ulceration were the only factors related to a positive SNB. Although convincing improvements resulted from the implementation of AJCC classifications with a reduction of positive biopsies among pT1a, a 10.71% rate among all positive nodes remains in the low-risk group. No recommendations can be drawn from this research and adjunctive evidences are needed to better identify patients at risk of nodal metastasis.     

CEACAM1 expression in cutaneous malignant melanoma predicts the development of metastatic disease.

PURPOSE: The cell adhesion molecule CEACAM1 is involved in intercellular adhesion and subsequent signal transduction events in a number of epithelia. CEACAM1 downregulation has been demonstrated in colorectal and prostate carcinomas. This study sought to analyze whether its expression in malignant melanoma is associated with metastasis. PATIENTS AND METHODS: CEACAM1 expression was immunohistochemically evaluated in 100 primary cutaneous malignant melanomas and correlated with metastasis in a 10-year follow-up. Furthermore, CEACAM1 expression was analyzed in metastatic lesions (11 distant metastases and six sentinel lymph node metastases). Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard regression analysis adjusted for standard prognostic indicators were performed to assess the prognostic relevance of CEACAM1 expression. RESULTS: A total of 28 of 40 patients with CEACAM1-positive primary melanomas developed metastatic disease, compared with only six of 60 patients with CEACAM1-negative melanomas. Often, the strongest CEACAM1 expression was observed at the invading front. In addition, CEACAM1 expression was preserved in the metastatic lesions. Kaplan-Meier analysis revealed a highly significant association between CEACAM1 expression and metastasis (P <.0001); multivariate Cox regression analysis, including CEACAM1 expression status adjusted for tumor thickness, presence of ulceration, and mitotic rate, confirmed that CEACAM1 is an independent factor for the risk of metastasis and demonstrated that the predictive value of CEACAM1 expression is superior to that of tumor thickness. CONCLUSION: Expression of the cell adhesion molecule CEACAM1 in the primary tumors in melanoma patients is associated with the subsequent development of metastatic disease. This raises the possibility of a functional role for this cell adhesion molecule in the metastatic spread it indicates.     

Expression of Melan-A/MART-1 antigen as a prognostic factor in primary cutaneous melanoma

In this study we assessed the expression of the Melan-A/MART-1 antigen by immunohistochemistry using monoclonal antibody A103 in 73 primary cutaneous melanomas and its correlation with tumor staging and patient survival. Melan-A/MART-1 was expressed in 90% of primary tumors, with loss of expression increasing with Breslow thickness. Kaplan-Meier analysis demonstrated a significantly reduced disease-free interval and overall survival rate for patients not expressing this antigen. The poor prognosis of such patients was even worse for those presenting with a primary melanoma and a Breslow thickness of > or = 1 mm. Thus, Melan-A/MART-1 is not only a useful and specific additional marker for the diagnosis of primary cutaneous melanoma, but it may also help refine the prognosis of patients with malignant melanoma.     

Reduced pSmad2 immunodetection correlates with increased primary melanoma thickness

Cutaneous melanoma is the most aggressive of cutaneous neoplasms. Identifying patients with an increased risk for the development of metastases is critical. This study investigates phospho-Smad2, a central factor of the transforming growth factor beta pathway, on formalin-fixed, paraffin-embedded tissues from 60 primary cutaneous melanomas (Breslow >1 mm), for its candidacy for being a prognostic marker in primary cutaneous melanoma. Phospho-Smad2 positivity was assessed for correlation with clinical parameters including Breslow index, melanoma type, survival, development of metastases, sentinel lymph node status and age. Phospho-Smad2 positivity was not associated with survival or development of metastases, suggesting that it would not be a useful prognostic marker. Despite this, we found phospho-Smad2 positivity to be correlated with low tumour thickness, indicating that as the primary tumour grows there is an increased inhibition of transforming growth factor beta signalling resulting in suppressed Smad2 phosphorylation. Additionally, phosphorylation of Smad2 in neighbouring melanoma cells and keratinocytes was interrelated, which is a further indication that Smad2 phosphorylation in primary melanoma is affected by local area microenvironmental factors. We hypothesize that the observed decrease in transforming growth factor beta signalling in thicker primary melanomas is due to the increased production of signalling inhibitors.     

Clinical significance of CXCR3 and CXCR4 expression in primary melanoma

Tumor cell migration involved in metastases is a tightly regulated, nonrandom process. Chemokines have been identified as critical molecules guiding cell migration. We performed a prospective study to analyze a possible association between the expression of chemokine receptors CXCR3 and CXCR4 by primary melanoma and clinical outcome. Forty primary melanomas were available for analysis; 57% of the tumors expressed CXCR3 and 35% expressed CXCR4 by melanoma cells. At initial diagnosis, 5 patients had subclinical lymph node involvement and after a median follow-up time of 32 months, 2 additional patients developed regional lymph node metastases and 5 patients developed distant metastases. The expression of CXCR4, but not CXCR3, by melanoma cells in primary lesions was significantly associated with the presence of ulceration, increased tumor thickness, a greater risk of developing regional and distant metastases and a higher mortality rate. Our study underscores the value of CXCR4 expression as a useful marker for predicting outcome in patients with localized melanoma. In addition, our findings support that, among chemokine receptors, CXCR4 might be an appropriate therapeutic target for adjuvant therapy in patients at risk for metastatic disease.     

Objective histopathologic grading of cutaneous malignant melanomas by stereologic estimation of nuclear volume. Prediction of survival and disease-free period

Modern stereologic techniques enable unbiased and shape-independent estimation of the three-dimensional nuclear volume (Vv). This study investigates the prognostic impact of Vv in 47 patients with malignant melanomas (10 years of follow-up) and compares Vv to traditional prognostic parameters and two-dimensional morphometric estimates. The averaged Vv was 226 microns3 and 457 microns3 in Stage I and II melanomas, respectively. The Vv was significantly increased in the case of ulceration, nodular melanoma, and Clark's level greater than III. The Vv showed only poor correlation to two-dimensional morphometric estimates. Cox regression analysis indicated Vv to possess excellent prognostic information, only rivaled by tumor ulceration, the latter being a 100% predictor of metastatic spread. Histologic type, Clark's level of invasion, tumor thickness (according to Breslow), and patient sex were without independent prognostic significance, which may be due to attributes of the small data base. It is concluded that Vv may be a powerful prognostic indicator in cutaneous melanomas, suitable for objective malignancy grading. The clinical and prognostic value of nuclear Vv needs further investigation in a larger and contemporary series of patients with malignant melanomas.     

Immunohistochemical detection of incipient melanoma micrometastases. Relationship with sentinel lymph node involvement

It is acknowledged that tumour thickness, ulceration and lymph node invasion are the most important prognostic factors for cutaneous melanomas. Other histopathological features may also be informative. The aim of this study was to ascertain whether immunohistochemical methods can improve the detection of satellite micrometastases in primary melanoma patients. In addition, the predictive value of cutaneous satellite micrometastases for sentinel lymph node involvement was evaluated. A total of 265 primary cutaneous melanomas and 68 of the respective sentinel nodes were studied using a panel of seven antibodies directed against melanocyte-related antigens. In 12.4% of the 265 cases, small satellite micrometastases were detected by immunohistochemistry. Sentinel lymph node metastases were found in 14% of the 68 cases. Invasion of the sentinel lymph node correlated with the presence of cutaneous satellite micrometastases. It is concluded that the presence of cutaneous satellite micrometastases may be an indication for the performance of sentinel lymph node biopsy, and this finding calls for a closer follow-up of these patients.     

Sentinel node biopsy in cutaneous melanoma: correlations between melanoma prognostic factors and sentinel node status

This study aims to correlate the most important prognostic factors of primary melanoma with sentinel node (SN) positive for metastases. We have enrolled 84 patients subjected to sentinel node biopsies for cutaneous melanomas of Breslow's thickness > or = 0.75 mm by using an intra-operative gamma probe after lymphoscintigraphy, without blue dye support. SN metastases were reported in 27% of cases (14% by histology and 13% by immunohistochemistry). By chi-square test Breslow's thickness > 2mm (p= 0.004), IV and V Clark's level (p= 0.02), ulceration (p= 0.05) and high mitotic rate (p= 0.05) were statistically significant (p < 0.05) with reference to SN positive for metastases, unlike the site of cutaneous melanoma, vertical growth phase, tumour infiltrating lymphocytes, regression and vascular invasion. Breslow's thickness remains the first prognostic factor to be considered for sentinel node biopsy in cutaneous melanoma, but other markers must be carefully estimated.     

The sentinel lymph node status is an important factor for predicting clinical outcome in patients with Stage I or II cutaneous melanoma.

BACKGROUND: In a cohort of patients, the authors investigated whether and to what extent the sentinel lymph node (SLN) status contributes to predicting the probability of remaining disease free for at least 3 years. In addition, several traditional prognostic factors were analyzed: Breslow thickness, Clark invasion level, ulceration, lymphatic invasion, location, type of the melanoma, and age and gender of the patient. METHODS: In 263 consecutive patients with proven American Joint Committee on Cancer Stages I and II cutaneous melanoma, the triple technique SLN procedure was used, i.e., preoperative visualization of the lymph channels from the initial site of the melanoma toward the SLN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and lymph nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabeled lymph nodes. Median follow-up time was 48 months (range, 36-84 months). Multivariate logistic regression analysis was performed to examine the influence of the SLN status and several other prognostic factors on a minimum 3-year disease free survival. RESULTS: In 20% of patients, the SLN proved to be tumor positive. For SLN negative patients, the 5-year disease free survival rate was 91% (+/- 2.4%), and for SLN positive patients it was 49% (+/- 9%). Five variables showed a strong and statistically significant independent prognostic association with outcome, i.e., SLN status (P = 0.0007), thickness of primary melanoma (1.01-2.0 mm; P = 0.04), ulceration (P = 0.05), and lymphatic invasion (P = 0.01) of primary melanoma, and age (40-50 years; P = 0.01). CONCLUSIONS: The SLN status-along with Breslow thickness, ulceration, lymphatic invasion, and age--seems to have strong additional value in predicting a minimum 3-year disease free period after the SLN procedure. Patients with a positive SLN have a poorer prognosis than those with a negative SLN.     

Sentinel node biopsy in malignant melanoma: Swedish experiences 1997-2005

The sentinel node biopsy (SNB) procedure is a multidisciplinary technique, invented to gain prognostic information in different malignant tumors. The aim of the present study was to study the cohort of patients with malignant melanoma, operated with SNB, from the introduction of the technique in Sweden, concerning the prognostic information retrieved and the outcome of the procedures. In Sweden all patients with malignant melanoma are registered at regional Oncological Centers. From these databases ten centers were identified, treating malignant melanoma and performing sentinel node biopsy. Consecutive data concerning tumor characteristics, outcome of the procedure and disease related events during the follow-up time were collected from these ten centers. All cases from the very first in each centre were included. The SNB procedure was performed in 422 patients with a sentinel node (SN) detection rate of 97%, the mean Breslow thickness of the primary tumors was 3.2 mm (median 2.4 mm) and the proportion of ulcerated melanomas 38%. Metastasis in the SN was found in 19% of the patients but there was a wide range in the proportion of SN metastases between the different centers (5-52%). After a follow-up of median 12 months of 361 patients, SN negative patients had better disease-free survival than SN positive (p<0.0001). A false negative rate of 14% was found during the follow-up time. In this study the surgical technique seemed acceptable, but the non-centralized pathology work-up sub-optimal. However, SNB was still found to be a significant prognostic indicator, concerning disease free survival.     

Validation of a clinicopathological and gene expression profile model to identify patients with cutaneous melanoma where sentinel lymph node biopsy is unnecessary

BackgroundIn patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) serves as an important technique to asses disease stage and to guide adjuvant systemic therapy. A model using clinicopathologic and gene expression variables (CP-GEP; Merlin Assay) has recently been introduced to identify patients that may safely forgo SLNB. Herein we present data from an independent validation cohort of the CP-GEP model in Swedish patients.MethodsArchival histological material (primary melanoma tissue) from a prospectively collected cohort of 421 consecutive patients with pT1-T4 melanoma undergoing SLNB between 2006 and 2014 was analyzed using the CP-GEP model. CP-GEP combines Breslow thickness and patient age with the expression levels of eight genes from the primary melanoma. Stratification is based on their risk for nodal metastasis: CP-GEP Low Risk or CP-GEP High Risk.ResultsThe SLNB positivity rate was 13%. Of 421 primary melanomas, the CP-GEP model identified 86 patients as having a low risk for nodal metastasis. In patients with pT1-2 melanomas, the SLNB reduction rate was 35.4% (95% CI: 29.4–41.8) with a negative predictive value (NPV) of 96.5% (95% CI: 90.0–99.3). Among patients with pT1-3 melanomas, CP-GEP suggested a SLNB reduction rate of 24.0% (95% CI: 19.7–28.8) and a NPV of 96.5% (95% CI: 90.1–99.3). Only one of 118 pT3 tumors was classified as CP-GEP Low Risk, and all pT4 tumors were classified as being high risk for nodal metastasis.ConclusionThis study demonstrates that CP-GEP can identify patients with a low risk for nodal metastasis. Patients with pT1-2 melanomas have the highest clinical benefit from using the test, where 35% of the patients could forgo a SLNB procedure.     

Prognostic factors in patients with thick cutaneous melanoma (> 4 mm)

BACKGROUND: The current study was conducted to examine the role of multiple clinical and histologic factors in the prognostic assessment of patients with thick primary melanoma (> 4 mm, classified as T4). METHODS: A retrospective analysis was performed in 329 patients with T4 cutaneous melanomas who were seen at the University of California at San Francisco Melanoma Center between 1978 and 2000. Fourteen histopathologic features were recorded prospectively by a single dermatopathologist. In addition, 9 clinical factors were analyzed. RESULTS: Several histologic factors were found to have a significant impact on the survival of patients with T4 melanoma. On univariate analysis, tumor thickness, ulceration, mitotic rate, microsatellites, vascular involvement, and histogenetic type of the primary tumor all were found to have a significant impact on the overall survival rate. Regional lymph node involvement reduced the overall survival of T4 patients dramatically. The 5-year overall survival of patients with lymph node-negative T4 disease was 61%, compared with 30% for those with lymph node-positive disease. When lymph node status was taken into account, tumor thickness, vascular involvement, and ulceration all remained independent predictors of overall survival on multivariate Cox regression analysis. Neither age, gender, nor anatomic location appeared to affect the recurrence-free or overall survival rates. CONCLUSIONS: Patients with thick primary cutaneous melanomas (> 4 mm) comprise a heterogeneous group. The presence or absence of lymph node involvement, vascular involvement, and ulceration appears to result in significantly divergent overall survival rates in this patient cohort. Consideration of these factors has important implications in the management of patients with T4 melanoma.     

CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in vivo via beta(1) integrin

The chemokine receptor, CXCR4, is expressed by human melanomas, and its ligand, CXCL12, is frequently produced at sites of melanoma metastasis. Herein, we examine CXCR4-enhanced binding of B16 murine melanoma cells to endothelial cells (ECs) and recombinant adhesion molecules in vitro to determine the role of tumor- and EC-derived adhesion molecules in tumor metastasis. By flow cytometry, unstimulated primary lung ECs showed constitutive expression of vascular cellular adhesion molecule 1 (VCAM-1), whereas skin-derived ECs did not. All B16 cell lines tested showed constitutive expression of alpha(4) and beta(1) integrin chains but showed no expression of beta(2) integrins. CXCR4-B16 arrest on VCAM-1/immunoglobulin-coated plates and tumor necrosis factor alpha-stimulated ECs under physiological shear stress conditions (1.5 dynes/cm(2)) was rapid, resistant to shear stress of 10 dynes/cm(2), and showed no evidence of rolling before arrest. In vitro, CXCR4-B16 cell binding to ECs was blocked by anti-beta(1) and anti-CXCL12 monoclonal antibodies. In vivo, metastasis of CXCR4-B16 cells to murine lungs was strongly inhibited by anti-CXCL12 and two different anti-beta(1) monoclonal antibodies. Finally, CXCR4-B16 exposed to CXCL12 rapidly increased binding affinity for soluble VCAM-1/immunoglobulin as detected by a flow cytometric assay. Thus, beta(1) integrins play a critical role in CXCR4-mediated B16 tumor cell metastasis in vivo and may be a potential target for inhibition of tumor metastasis, particularly to the lung.     

Are there factors that predict the result of selective sentinel lymph-node biopsy in melanoma?

Background

Sentinel lymph node biopsy is an appropriate method to assess lymphatic involvement in cutaneous melanoma. We collated clinical and histo-pathological parameters of primary tumours to assess their predictive value of sentinel lymph node involvement.

Patients and methods

Factors such as age, gender, histology subtype, site, Breslow index, lesion size, and the presence of ulceration, signs of regression, lympho-vascular invasion and/or inflammatory infiltration of the primary lesion were collated from 142 patients diagnosed with cutaneous melanoma. During the scheduled surgery, a selective sentinel lymph node biopsy was taken. The procedure was successful in terms of localisation with scintigraphy, detection and surgical removal. Univariate and multivariate statistical analyses were applied to the variables in relation to the sentinel lymph node biopsy results.

Results

There were significant differences with respect to size (p=0.046), the presence of ulceration in the primary lesion (p=0.0146), the Breslow index (p=0.0001) and lympho-vascular invasion in the primary lesion (p=0.00005). Logistic regression showed an independent predictive value for sentinel lymph node involvement.

Conclusions

The data indicate that, apart from Breslow index, the presence of lymphatic invasion in the primary tumour, the size of the melanoma, and the presence of ulceration are independent factors predictive of a positive result of selective sentinel lymph node biopsy in cutaneous melanoma. Although prospective studies are still awaited, these variables need to be taken into account when such biopsies are proposed, even with less thick tumours.     

Evidence and interdisciplinary consense-based German guidelines: diagnosis and surveillance of melanoma

Melanoma is a malignant tumor that arises from melanocytic cells and primarily involves the skin. The most important exogenous etiological factor is exposure to ultraviolet irradiation. Diagnosis of melanoma is based primarily on its clinical features, and the A-B-C-D rule is useful in identifying pigmented lesions, which are suspicious for melanoma (Asymmetry, Border irregular, Color inhomogeneous and Diameter more than 5 mm). Dermoscopy is very helpful in clarifying the differential diagnosis of pigmented lesions. About 90% of melanomas are diagnosed as primary tumors without any evidence for metastasis. The tumor-specific 10-year survival for all such tumors is about 75-85%. The most important prognostic factors for primary melanoma without metastases are vertical tumor thickness (Breslow depth) as measured on the histological specimen, presence of histopathologically recognized ulceration, invasion level (Clark level) and identification of micrometastases in the regional lymph nodes via sentinel lymph node biopsy. The current tumor node metastasis classification for the staging of primary melanoma is based on these factors. Melanomas can metastasize either by the lymphatic or by the hematogenous route. About two-thirds of metastases are originally confined to the drainage area of regional lymph nodes. A regional metastasis can appear as satellite metastases up to 2 cm from the primary tumor, as intransit metastases in the skin between the site of the primary tumor and the first lymph node and as regional lymph node metastases. In the stage of regional metastasis, the differentiation between micrometastasis and macrometastasis and the number of lymph nodes involved are crucial. As soon as distant metastasis develops, prognosis depends on the site of the metastasis and on the lactate dehydrogenase levels in the blood. The frequency and extent of follow-up examinations is based on the initial tumor parameters. In thin primary melanomas up to 1-mm tumor thickness, clinical examinations at 6-month intervals are sufficient and in thicker primary melanomas, at 3-month intervals. Lymph node sonography as well as determination of the tumor marker protein S100beta are recommended. Additionally, in the stage of regional metastasis, whole body imaging should be performed every 6 months; in the stage of distant metastasis, surveillance has to be scheduled individually.