Characteristics of metastasis as a prognostic factor for immunotherapy in metastatic renal cell carcinoma

AIMS AND BACKGROUND: This study aimed to evaluate the significance of characteristics of metastasis as prognostic factors in metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: A total of 148 patients who had received immunotherapy were included in the study. Patients were categorized in various ways according to the characteristics of metastasis, including a synchronous metastasis group (n = 77) vs a metachronous metastasis group (n = 71), and a solitary metastasis group (n = 93) vs a multiple metastases group (n = 55). RESULTS: In the synchronous and metachronous metastasis groups, median progression-free survival was 4.3 months (95% confidence interval [CI] 2.9-5.7) and 11.1 months (95% CI 6.7-15.5), respectively (P = 0.004). Median overall survival was 17.1 months (95% CI 9.5-24.7) and 54.8 months (95% Cl 38.371.3) in the two groups (P = 0.019). In the solitary and multiple metastasis groups, median progression-free survival was 11.0 months (95% CI 6.6-15.5) and 3.9 months (95% CI 2.6-5.2), respectively (P <0.001). Median overall survival was 55.2 months (95% CI 50.7-59.7) and 15.6 months (95% CI 10.9-20.3) in the two groups (P <0.001). Multivariate Cox proportional hazards model analysis using the clinical variables showed that T stage (P = 0.026), number of metastatic sites (P = 0.009) and time to metastasis (P = 0.019) were independent predictors of progression-free survival. Using the same variables, only the number of metastatic sites was an independent prognostic predictor of overall survival (P = 0.014). CONCLUSIONS: Our findings suggest that the time to metastasis and the number of metastases are important prognostic factors in metastatic RCC.     

Liver resection for metastatic gastric cancer: experience with 42 patients including eight long-term survivors

BACKGROUND: The indication for liver resection for gastric metastases remains controversial and few previous studies have reported the outcome of surgery in the treatment of liver metastases of gastric cancer. The aim of this study is to clarify the effectiveness of surgical resection for liver metastases arising from gastric cancer. METHODS: A retrospective analysis was performed on the outcome of 42 consecutive patients with synchronous (n = 20) or metachronous (n = 22) gastric liver metastases that were curatively resected. RESULTS: The overall 1, 3 and 5 year survival rates after hepatic resection were 76, 48 and 42%, respectively, and the median survival was 34 months. Univariate analysis revealed that survival significantly differed between cases of solitary and multiple metastases (P = 0.03). Multivariate analysis revealed that solitary liver metastasis and the absence of serosal invasion by primary gastric cancer were favorable independent prognostic factors (P = 0.005 and P = 0.02, respectively). All eight patients who survived for more than 5 years after initial hepatectomy had a solitary metastasis, and six of these had no serosal invasion by the primary gastric cancer. No patient with multiple metastatic diseases survived beyond 3 years. CONCLUSIONS: Patients with a solitary liver metastasis are good candidates for surgical resection, whereas those with multiple gastric liver metastases should be treated by multimodal approaches.     

放射性核素全身骨显象诊断骨转移的临床价值

Of 628 patients with extra-osseous malignancies diagnosed by surgery and/or pathology, 207 (33.0%) were identified as having skeletal metastasis by bone imaging. There was statistical significant difference in the incidence of metastasis in in different malignancies (P less than 0.02). The metastatic rates of nasopharyngeal, lung, prostate and breast cancers were higher than gastrointestinal, kidney, and other malignancies. There was significant differences in the different sites of skeletal metastasis (P less than 0.01). They were thorax, spine, pelvis, limbs and skull in order of incidence. Solitary metastatic rate was 15.9%. Biopsy is advised for patients suspected to have metastatic disease but with only one single "hot spot" in skeletal imaging, particularly in the rib.     

85例颅外转移性乳腺癌放疗疗效观察及预后分析

目的:观察颅外转移性乳腺癌的放疗疗效,探讨全病变放疗意义及预后相关因素。方法:回顾性分析2014—2019年间接受放疗的85例颅外转移性乳腺癌患者的临床资料,其中全病变放疗36例,非全病变放疗49例。采用 Kaplan- Meier法计算生存率并 log- rank检验和...     

The results and prognosis of different treatment modalities for solitary metastatic lung tumor from nasopharyngeal carcinoma:a retrospective study of 105 cases

Background and Objective:Nasopharyngeal carcinoma (NPC) is known for its propensity for distant metastases.Lung metastasis is one of the most important causes of death for patients with NPC.Solitary metastatic lung tumor from NPC is a distinctive group associated with a better survival.This study was to find a more effective treatment modality and prognostic factors for the group.Methods:Clinical data of 105 cases of solitary metastatic lung tumor from NPC were retrospectively analyzed.Survival rate was cal...     

118例小肿块多腋窝淋巴结转移乳腺癌患者的临床特征和预后分析

目的分析小肿块多腋窝淋巴结转移(肿块直径≤2 cm、腋窝淋巴结转移≥4个)乳腺癌患者的临床特征和预后。方法1993年1月至2003年12月我院共收治小肿块多腋窝淋巴结转移乳腺癌患者118例,对其临床病理特征、辅助治疗进行分析,以发现相关的预后因素。结果全组患者的5年总生存率为75.0%。腋窝淋巴结转移4～9个及≥10个者的5年生存率分别为89.5%和59.8%(P=0.009),术后化疗患者与未化疗患者的5年生存率分别为82.1%和53.3%(P=0.001),术后内分泌治疗者与未行内分泌治疗者的5年生存率分别为89.2%和61.9%(P=0.001)。单因素Kaplan-Merier生存分析显示,肿瘤分期、术后化疗和内分泌治疗是影响患者预后的重要因素。Cox多因素预后分析显示,肿瘤分期、术后化疗和内分泌治疗是影响患者预后的独立因素。结论小肿块多腋窝淋巴结转移的乳腺癌患者具有易于转移的趋势,患者预后较差,尤其是腋窝淋巴结转移≥10个的患者;肿瘤分期、辅助化疗和内分泌治疗是影响患者预后的独立因素;合理的综合治疗有可能改善小肿块多腋窝淋巴结转移乳腺癌患者的预后。     

74例乳腺癌骨转移的临床预后因素分析

目的:探讨乳腺癌骨转移的临床特征并分析其预后因素。方法:回顾74例乳腺癌骨转移好发部位、病灶特点、发生时间、激素受体分布情况等并用COX比例风险模型进行乳腺癌骨转移预后因素分析。结果:乳腺癌骨转移好发部位在胸部与脊柱,尤其是肋骨和腰椎,几乎均为溶骨性病灶。骨转移平均发生时间为术后33.4个月。骨转移患者中激素受体阳性率比例较高。COX比例风险模型分析显示雌激素受体状况、病理类型和初发单/多发骨转移情况是影响乳腺癌骨转移预后的独立因素。结论:雌激素受体状况、病理类型和初发单/多发骨转移情况是影响乳腺癌骨转移预后的独立因素。对乳腺癌骨转移规律的认识有助于临床诊断和治疗。     

Involvement of three or more lymph nodes predicts poor prognosis in submucosal gastric carcinoma

BACKGROUND: Multivariate analyses has shown that the status of lymph node metastasis and the depth of tumor penetration through the gastric wall are the most important prognostic factors in patients with advanced gastric carcinoma after curative operation. A clinicopathological study was carried out to clarify a simple and optimal prognostic indicator for early gastric cancer. METHODS: Retrospective analyses of 982 patients with early gastric cancer (562 with mucosal [M] and 420 with submucosal [SM] tumor) treated by gastrectomy with D2 lymph node dissection were performed. RESULTS: The incidence of lymph node metastasis from M and SM tumors was 2.5% (14/562) and 20.2% (85/420), respectively. There were no apparent prognostic indicators in patients with M tumors. In patients with SM tumors, the cancer-specific 5-year survival of those with lymph node metastasis was significantly lower than that of those without such metastasis (77.6% vs 98.2%; P < 0.001). An sharp decrease in survival was seen between patients with two positive nodes and those with three positive nodes, and the cancer-specific 5-year survival rate of patients with three or more metastatic lymph nodes was significantly lower than that of those with one or two nodes (P < 0.001; univariate analysis). Multivariate analysis revealed that the involvement of three or more lymph nodes was the sole independent prognostic determinant (P = 0.016); the level of nodal metastasis was not an independent prognostic factor (P = 0.384). All patients with N2 lymph node echelons (according to the Japanese Research Society for Gastric Cancer classification of the draining lymph nodes of the stomach) in the group with one or two positive nodes survived for more than 5 years. CONCLUSION: The sole independent prognostic factor in SM gastric cancer is the involvement of three or more metastatic lymph nodes. We suggest that this simple prognostic indicator for the follow-up of early gastric cancer, and this could lead to potentially effective adjuvant chemotherapy.     

Comparison of Two Inflammation-Based Prognostic Scores in Patients with Unresectable Advanced Gastric Cancer

Objectives: The objective of this study was to compare the usefulness of two inflammation-based prognostic scores, neutrophil to lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS), assessed at diagnosis in stage IV advanced gastric cancer (AGC). Methods: We retrospectively reviewed the medical records of 104 patients with newly diagnosed metastatic AGC treated with palliative chemotherapy. Results: In the univariate analysis, the following variables were associated with shorter overall survival (OS): poor or undifferentiated histology (p = 0.013), more than 1 metastasis (p = 0.004), the presence of lymph node metastasis (p = 0.003), the presence of bone metastasis (p = 0.019), a lower albumin level (p < 0.001), elevated C-reactive protein (p < 0.001), a high absolute neutrophil count (p = 0.016), NLR ≥3 (p < 0.001) and higher mGPS (p < 0.001 and p = 0.007, respectively). In the multivariate analysis, high NLR and mGPS were independent prognostic factors for shorter OS (p = 0.037, p < 0.001 and p = 0.010, respectively), along with lymph node metastasis (p = 0.005) and histological subtype (p = 0.048). Conclusion: This study suggests that the inflammatory markers, NLR and mGPS, are independent prognostic factors for OS in patients with unresectable AGC treated with palliative chemotherapy.     

Factors affecting survival in breast cancer patients following bone metastasis

AIMS AND BACKGROUND: The purpose of the study was to identify prognostic factors that affect survival following bone metastasis in breast cancer patients with first metastases in the skeletal system. METHODS AND STUDY DESIGN: We analyzed retrospectively the data of 248 metastatic breast cancer patients whose first distant metastasis was in the skeleton. RESULTS: The median age of the patients at diagnosis was 46 years (range, 23-76). Nearly half of the patients were premenopausal (52.4%). The median disease-free survival was 24 months. For most of the patients (221), bone was the sole first metastatic site, and the disease remained confined to the bone in 99 of them. The remaining patients (n = 27) had both bone and visceral metastasis at the time of first relapse. One hundred and fourteen of the patients (46%) had died by the time of analysis. With the median follow-up of 50.5 months from diagnosis, median survival after bone metastasis was 32 months. In univariate analyses, statistically significant predictors for survival after bone metastasis were axillary lymph node status, T stage of disease, hormone receptor status of the primary tumor, the presence of lymphovascular invasion, involvement of skin, the presence of additional nonosseous metastatic sites at the time of bone relapse, and disease-free interval. In multivariate analyses, the presence of additional non-osseous metastatic sites at the time of bone relapse, T stage of disease, hormone receptor status of the primary tumor, and the presence of lymphovascular invasion were found to be significant independent prognostic factors. CONCLUSIONS: In the result of study, for patients with breast cancer, survival following bone metastasis is affected by secondary prognostic factors such as disease-free interval and extent of metastasis besides primary prognostic factors related to the primary tumor.     

伽马刀治疗多发脑转移瘤预后的影响因素分析

目的:了解伽马刀治疗多发脑转移瘤预后的影响因素,从而提高多发脑转移瘤患者的生存率.方法:选择使用伽马刀治疗的多发脑转移瘤患者238例并回顾性分析各种因素对于患者生存率的影响.结果:多发脑转移瘤的中位生存时间为206天,单因素分析伽马刀治疗多发脑转移瘤与KPS、放射剂量、中枢外转移以及原发病灶控制等4个单因素有关;多因素回归分析最后得出,KPS(P=0.003,Wald=9.100)、中枢外转移(P=0.019,Wald=6.542)以及原发病灶控制(P=0.002,Wald=11.492)是影响伽马刀治疗多发脑转移瘤预后的因素.结论:影响多发脑转移瘤患者预后的主要因素包括KPS、中枢外转移以及原发病灶控制.     

Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases.

PURPOSE: We examined whether RNA expression of CD133, a surface molecule expressed on progenitors from hematopoietic and endothelial lineages, and CD146, a pan-endothelial marker, are increased in the blood of cancer patients and whether these factors correlate with patient characteristics and are predictive factors of survival. EXPERIMENTAL DESIGN: We developed a real-time quantification method (nuclear acid sequence-based amplification) to determine expression of CD146 and CD133 mRNA in the peripheral blood mononuclear cells of 131 progressive cancer patients, 37 healthy volunteers, and 5 patients who received granulocyte colony-stimulating factor. Overall survival and other clinicopathologic variables were obtained. Cox proportional hazards studies were done. RESULTS: We show that patients with metastatic disease have a significant increase in CD133 mRNA (P = 0.03), specifically patients with bone metastasis (P < 0.001). Cancer patients with high CD133 mRNA expression, using a defined cutoff value, show a decreased survival compared with patients with low or undetectable CD133 expression (21% versus 45% cumulative survival, respectively, after 20 months; P = 0.01). Among patients with metastasis to the bone, cumulative survival was 22%, compared with 61% for patients with high or low CD133 levels (P = 0.004). Multivariate analysis showed that CD133 expression is an independent predictor for overall survival in patients with bone metastases. CD146 mRNA was not increased in patients with cancer, nor did it correlate with clinical variables or survival. CONCLUSION: CD133, but not CD146, mRNA expression is increased in cancer patients with metastatic disease, specifically with bone metastasis. In addition, CD133 mRNA expression seems to be an independent prognostic factor for overall survival.     

Pattern of distant metastases and predictive nomograms in colorectal mucinous adenocarcinoma: a SEER analysis

BackgroundWe evaluated the metastatic patterns and explored the prognostic value of distant metastasis pattern in patients with metastatic colorectal mucinous adenocarcinoma (MC) using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsBetween 2010 and 2015, newly diagnosed colorectal MC patients were selected using the SEER database. Patient prognosis was compared based on the clinicopathological parameters, treatment method, and the site and number of metastatic organs. Cox analyses were used to identify factors associated with overall survival (OS). A nomogram was built to predict the patient’s survival. Harrell’s concordance index (c-index) and calibration curves were used to analyze the discriminative ability of the prognostic factors.ResultsOf 3,088 patients diagnosed with colorectal MC, the liver was the only metastatic organ in 78.4% (997/1,271) of all liver metastasis cases, the lung was the only metastatic organ in 41.0% (164/400) of all lung metastasis cases, bone was the only metastatic organ in 26.6% (29/109) of all bone metastasis cases, and the brain was the only metastatic organ in 23.5% (4/17) of all brain metastasis cases. Compared with the untreated cases, those treated with chemotherapy, surgery, and radiotherapy had better OS (P<0.001). There were marked OS differences (P<0.001) between patients with and without liver and bone metastases. Patients with bone metastasis had the best survival, while those with brain metastasis had the worst survival (P<0.001). Patients with one metastatic site had better prognosis compared to those with two or three (P<0.001). Patients with liver metastasis had the best survival, while those with bone and brain metastasis had the worst survival (P<0.001). Multivariate analysis showed that age <65 years, non-black race, grade I, N0 stage, chemotherapy, radiation, surgery, liver metastasis, and bone metastasis were independent prognostic factors. A nomogram was constructed to predict survival probability. The c-index value was up to 0.745. The calibration plot showed that the nomogram was clinically useful.ConclusionsMetastatic MC (mMC) patients had a characteristic distant metastasis pattern. This study constructed a new and sufficiently accurate prognostic model of mMC based on population-based data. These findings can be utilized to predict prognosis and guide mMC patient management.     

Outcome of surgical treatment for bone metastases caused by colorectal cancer

BackgroundCancer of the lower intestinal tract, although relatively common, rarely metastasizes to the skeleton. The treatment of metastatic bone disease due to colorectal cancer has thus been poorly described and treatment decisions are therefore difficult. The aim of this study was to describe the outcome of orthopedic surgery in patients with pathological fractures from colorectal cancer and investigate factors that correlate with patient survival, since it influences treatment decisions.MethodsRetrospective review of data collected in a prospectively collected database. 36 patients (38 fractures) who underwent surgery between 2000 and 2019 for metastatic bone disease caused by colorectal cancer were included.ResultsMost metastases were localized in the axial skeleton and 33/36 patients already had visceral metastases. Patients with pathological fractures from colorectal cancer had poor prognosis, with only 5/36 surviving more than 1 year, median survival being 3 months. Patients presenting with a single skeletal metastasis had a superior overall survival (P≤0.001). Post-operative complications were common, noted in 11 patients, and the surgical failure rate was considerable.ConclusionsAlthough relatively rare, bone metastases should be suspected in patients with colorectal cancer presenting with signs and symptoms of spinal cord compression or skeletal pain. In this case, the presence of a solitary skeletal lesion is a favorable prognostic sign. Awareness for local complications after surgery should be high.     

Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells.

BACKGROUND: At metastatic relapse, detection of circulating tumor cells (CTC) in peripheral blood is predictive of poor survival of breast cancer patients. Detection of disseminated tumor cells (DTC) in bone marrow (BM) is an independent prognostic factor in early breast cancer. We evaluated the prognostic value of DTC detection in the BM of metastatic breast cancer patients. MATERIALS AND METHODS: BM aspirates from 138 patients were screened for DTC with the pancytokeratin mAb A45-B/B3, according to the ISHAGE classification. One hundred and ten patients (80%) were enrolled before first-line treatment. Thirty-seven patients were simultaneously screened for CTC in the blood. RESULTS: DTC detection rate in the BM was 59%. DTC were associated with bone metastasis (P = 0.0001), but not with a poorer overall survival. Adverse significant prognostic factors were hormone receptor negativity (P = 0.0004) and more than one line of chemotherapy (P = 0.002). CTC detection in the subgroup of 37 metastatic patients was associated with shorter survival (P = 0.01). CONCLUSIONS: Detection of CTC but not BM DTC had a prognostic significance in stage IV breast cancer patients. CTC in blood are a more reliable and a less invasive tool to evaluate prognostic and monitor tumor response in this metastatic setting.     

Bone Metastases in Follicular Carcinoma of Thyroid

Though the association between follicular carcinoma and bone metastasis is well established, the site-wise distribution is not known. One hundred seventy-three patients of follicular carcinoma presenting between 2003 and 2011 were selected from 1093 patients of follicular lesions presenting at a single institution. Of these, 59 (34%) with bone metastasis were included in the study. Fifty of the 59 patients (84.7%) had metastasis at presentation, while 9 developed bone metastasis during follow-up. Sixty-one percent had solitary metastasis, 15 (25.4%) had multiple bone involvement, while 8 patients (13.6%) had synchronous lung metastasis. Overall, the spine was the commonest site of bone metastases, seen in 20 patients (33.9%), followed by the pelvis, skull, long bones and sternum. Bone metastasis is a known phenomenon in follicular carcinoma. The spine is the commonest site followed by the pelvis.     

99Tcm-MDP全身骨显像对原发性肺癌骨转移的影像学特征的评价分析

Objective: The aim of our study was to explore the eikonic characteristic of skeletal metastasis of primary pulmonary carcinoma. Methods: Whole-body bone scans with 99Tcm methylene diphosphonate were performed in 258 patients with pathologically proven pulmonary carcinoma. The rate of skeletal metastasis, distribution of the metastatic lesions and their characteristics were analyzed. Results: Among the total 258 patients, 142 cases developed skeletal metastasis. The overall rate of skeletal metastasis was 55.0%. The metastases located in axial skeleton were 49.6%, appendicular skeleton 36.0%, trunk bones of the axial skeleton 48.4%, and appendicular girdle skeleton 31.4%. Ribs, thoracic vertebrae, ilium and lumbar vertebrae had a higher rate of skeletal metastasis, which were 38.4%, 24.0%, 21.7%, 20.2%, respectively. 1252 lesions were detected including 406 at the left side of the body, 387 lesions at the middle position and 459 at the right side of the body. There was no significant difference in terms of number of lesions between left side and right side (X2=3.3, P=0.072). 1224 skeletal metastatic foci (97.8%) were presented as strong radioactive, 26 (2.1%) as mixed lesions, and 2 (0.2%) as low radioactive. According to the shape of lesions, there were 810 punctate lesions (71.5%), 159(14.0%)lump form, 108(9.5%) strip form and 56 (4.9%) lamellar form. The accumulative skeletal metastasis rate was 28.7% for the patients with one to three lesions. The metastasis rate decreased gradually as the number of metastatic lesions increased. Conclusion: Skeletal metastasis is very common in patients with pulmonary carcinoma. Most skeletal metastases are characterized by strong radioactive and earlier punctate form; they often occur in the trunk bones of axial skeleton or appendicular girdles. The distribution of earlier metastases has not obvious regularity, and advanced skeletal metastases are widely and randomly distributed in the body, which are characterized by often concurrently multiple and polymorphous lesions.     

Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma.

PURPOSE: To validate the Motzer et al prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma (RCC) and to identify additional independent prognostic factors. PATIENTS AND METHODS: Data were collected on 353 previously untreated metastatic RCC patients enrolled onto clinical trials between 1987 and 2002. RESULTS: Four of the five prognostic factors identified by Motzer were independent predictors of survival. In addition, prior radiotherapy and presence of hepatic, lung, and retroperitoneal nodal metastases were found to be independent prognostic factors. Using the number of metastatic sites as surrogate for individual sites (none or one v two or three sites), Motzer's definitions of risk groups were expanded to accommodate these two additional prognostic factors. Using this expanded criteria, favorable risk is defined as zero or one poor prognostic factor, intermediate risk is two poor prognostic factors, and poor risk is more than two poor prognostic factors. According to Motzer's definitions, 19% of patients were favorable risk, 70% were intermediate risk, and 11% were poor risk; median overall survival times for these groups were 28.6, 14.6, and 4.5 months, respectively (P < .0001). Using the expanded criteria, 37% of patients were favorable risk, 35% were intermediate risk, and 28% were poor risk; median overall survival times of these groups were 26.0, 14.4, and 7.3 months, respectively (P < .0001). CONCLUSION: These data validate the model described by Motzer et al. Additional independent prognostic factors identified were prior radiotherapy and sites of metastasis. Incorporation of these additional prognostic factors into the Motzer et al model can help better define favorable risk, intermediate risk, and poor risk patients.     

Prognostic variables in oligodendroglial tumors: a single-institution study of 95 cases

We analyzed the relationships among clinical variables, histology, 1p/19q status, and outcome in 95 patients with oligodendroglial tumors. The study enrolled adult patients who underwent first-time surgery for a supratentorial oligodendroglial tumor at Oslo University Hospital, Rikshospitalet. Tumors were: 27 oligodendrogliomas, WHO grade II; 32 oligoastrocytomas, WHO grade II; 16 anaplastic oligodendrogliomas, WHO grade III; 14 anaplastic oligoastrocytomas, WHO grade III; and 6 glioblastomas with a major oligodendroglial component, WHO grade IV. The clinical files were reviewed. Three neuropathologists evaluated the histological slides independently. Loss-of-heterozygosity analysis for 1p and 19q was performed by PCR. Favorable prognostic factors from univariate analyses included seizures as presenting symptom, female sex, location in the frontal lobe, low WHO grade, classic histology, absence of gemistocytic cells, and combined 1p/19q loss. Solitary 19q loss was a negative prognostic marker. 1p/19q status was of prognostic significance in both tumors with classic and nonclassic oligodendroglial histology. In the multivariate analysis, WHO grade II (P< .001), frontal tumor location (P= .002), and combined 1p/19q loss (P< .001) remained favorable prognostic variables. Our results suggest that tumor location, WHO grade, and 1p/19q status are important independent variables associated with survival in oligodendroglial tumors. The study suggests that solitary 19q loss is a negative prognostic variable and that 1p/19q loss is associated with prolonged survival also in oligodendroglial tumors without classic histology.     

Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma

BACKGROUND: To identify organ-specific, metastasis-related factors that can be used to predict the development and location of metastasis of clear cell renal cell carcinoma (CRCC), the authors assessed the angiogenesis and the expression of angiogenesis-related genes in primary and metastatic tumors. METHODS: They evaluated intratumoral microvessel density (MVD) by immunohistochemical staining, assessed the expression of angiogenesis-related genes by mRNA in situ hybridization, and determined the clinicopathologic characteristics of 92 archival specimens of primary and metastatic CRCCs from 54 patients. All 38 metastatic tumor specimens were resected from 24 patients. RESULTS: The pathologic stage (P=0.026) of the primary tumor specimen was an important predictor for metastasis, as were MVD (P=0.000025) and the ratio of matrix metalloproteinases (MMPs) to E-cadherin (M/E ratio; P=0.000041). In addition, primary tumor specimens resected from patients with metastatic CRCCs had high MVD, high levels of MMP-2 expression, and a high M/E ratio (P <0.05). Relative to the primary tumors, the metastatic tumors also had high MVD, overexpression of basic fibroblast growth factor, vascular endothelial growth factor, interleukin-8, MMPs, and a high M/E ratio (P <0.05). Multivariate analysis revealed that MVD and the M/E ratio in the primary tumor were independent prognostic factors for metastasis (P=0.049 and P=0.001, respectively). Furthermore, the M/E ratio in metastatic tumor specimens resected from the lung and lymph node was an independent prognostic factor for metastasis (P=0.01823 and P=0.03950, respectively). CONCLUSIONS: The current study indicated that angiogenesis and M/E ratio were specific predictors for metastases of RCC, especially to the lung or lymph node. Therefore, MMPs and E-cadherin could be relevant targets for novel therapeutic strategies to control or prevent the metastasis of RCC.