Peritumoral lymphangiogenesis induced by vascular endothelial growth factor C and D promotes lymph node metastasis in breast cancer patients

ABSTRACT: BACKGROUND: Mounting clinical and experimental data suggest that the migration of tumor cells into lymph nodes is greatly facilitated by lymphangiogenesis. Vascular endothelial growth factor (VEGF)-C and D have been identified as lymphangiogenic growth factors and play an important role in tumor lymphangiogenesis. The purpose of this study was to investigate the location of lymphangiogenesis driven by tumor-derived VEGF-C/D in breast cancer, and to determine the role of intratumoral and peritumoral lymphatic vessel density (LVD) in lymphangiogenesis in breast cancer. METHODS: The expression levels of VEGF-C/D were determined by immunohistochemistry, and intratumoral LVD and peritumoral LVD were assessed using immunohistochemistry and the D2-40 antibody in 73 patients with primary breast cancer. The associations of intratumoral LVD and peritumoral LVD with VEGF-C/D expression, clinicopathological features and prognosis were assessed. RESULTS: VEGF-C and D expression were significantly higher in breast cancer than benign disease (P < 0.01). VEGF-C (P < 0.001) and VEGF-D (P = 0.005) expression were significantly associated with peritumoral LVD, but not intratumoral LVD. Intratumoral LVD was associated with tumor size (P = 0.01). Peritumoral LVD was significantly associated with lymph node metastasis (LNM; P = 0.005), lymphatic vessel invasion (LVI; P = 0.017) and late tumor,node,metastasis(TNM) stage (P = 0.011). Moreover, peritumoral LVD was an independent risk factor for axillary lymph node metastasis, overall survival and disease-free survival in multivariate analysis. CONCLUSIONS: This study suggests that tumor-derived VEGF-C/D induce peritumoral lymphangiogenesis, which may be one mechanism that leads to lymphatic invasion and metastatic spread. Peritumoral LVD has potential as an independent prognostic factor in breast cancer patients.     

胃癌组织中幽门螺杆菌L型感染与淋巴管形成关系的研究

目的 研究胃癌组织中D2-40、LYVE-1标记的微淋巴管密度(LVD)、血管内皮生长因子受体(VEGFR-3)表达与幽门螺杆菌L型(helicobacter pylori L-form,Hp-L型)感染之间的关系.方法 应用革兰染色和免疫组化SP法检测80例胃癌组织和25例对照组的Hp-L型感染,同时用免疫组化SP法检测上述组织的LVD值和VEGFR-3的表达,分析Hp-L型与LVD以及VEGFR-3表达的关系结果 胃癌组织中革兰染色L型检出阳性率为67.5％;免疫组化Hp-L型抗原表达阳性率为65％,两种方法检测同时阳性的病例50例,占62.5％.胃癌组的Hp-L型阳性率、LVD及VEGFR-3表达阳性率均高于对照组(P＜0.01);胃癌组中Hp-L阳性组的LVD值和VEGFR-3表达阳性率高于Hp-L阴性组.LVD与胃癌淋巴结转移具有一定关系.结论 Hp-L型感染与胃癌的发生、发展密切相关,Hp-L型可能是肿瘤淋巴管生成的重要促进因子,影响胃癌的侵袭和转移.     

VEGF-D的表达与膀胱移行细胞癌LVD及淋巴结转移有关

目的观察血管内皮生长因子D(vascular endothelial growth factor D,VEGF-D)在人膀胱移行细胞癌组织内的表达,探讨VEGF-D在膀胱移行细胞癌组织淋巴管密度(lymphatic vessel density,LVD)及淋巴结转移之间的关系。方法取人膀胱移行细胞癌组织蜡块30例,免疫组化法观察VEGF-D在膀胱移行细胞癌组织内的表达情况。以淋巴管内皮特异性标记物D2-40标记淋巴管,计数癌组织内淋巴管密度。结果VEGF-D蛋白主要表达于癌细胞胞浆内,VEGF-D在淋巴结转移组膀胱移行细胞癌组织内的表达水平明显高于无淋巴结转移组(P0.05);淋巴结转移组膀胱移行细胞癌组织内的淋巴管密度明显高于无淋巴结转移组(P0.05)。VEGF-D表达与膀胱移行细胞癌淋巴管密度及淋巴结转移之间具有显著的相关性。结论VEGF-D表达在膀胱移行细胞癌组织内淋巴管生成及淋巴结转移中起重要作用。     

血管内皮生长因子-C与乳腺癌淋巴管生成和淋巴结转移的关系

目的探讨血管内皮生长因子-C与乳腺癌淋巴管生成和淋巴结转移的关系。方法免疫组化法检测21例乳腺增生组和68例乳腺浸润性导管癌组病灶组织内VEGF-C蛋白的表达,并用淋巴管内皮细胞特异性标志物D2-40标记肿瘤新生淋巴管,计数肿瘤淋巴管的密度（LVD）。结果乳腺浸润性导管癌组VEGF-C的表达和淋巴管的密度（LVD）都明显高于乳腺增生组（P〈0．01）;乳腺浸润性导管癌中VEGF-C阳性组中淋巴管的密度（11．32±5．78）与VEGF-C阴性组中的淋巴管密度（8．75±3．53）,差别有统计学意义（P〈0．01）;乳腺浸润性导管癌中VEGF-C蛋白的表达和淋巴管密度（LVD）都与有无腋窝淋巴结转移及淋巴结转移个数有关（P〈0．05）。结论VEGF-C在乳腺浸润性导管癌淋巴管的生成中起着重要的作用;VEGF-C的高表达和淋巴管密度（LVD）的升高是促进乳腺导管癌淋巴结转移的重要的影响因素。     

Expression of vascular endothelial growth factor C in human pterygium

Vascular endothelial growth factor C (VEGF-C) and its receptor VEGFR-3 mediate lymphangiogenesis. In this study, we analyzed the expression of VEGF-C and VEGFR-3 as well as lymphatic vessels in the pterygium and normal conjunctiva of humans. Fifteen primary nasal pterygia and three normal bulbar conjunctivas, surgically removed, were examined in this study. The lymphatic vessel density (LVD) and blood vessel density were determined by the immunolabeling of D2-40 and CD31, markers for lymphatic and blood vessels, respectively. VEGF-C and VEGFR-3 expression in pterygial and conjunctival tissue proteins was detected by Western blotting and were evaluated using immunohistochemistry. The LVD was significantly higher in the pterygium than normal conjunctiva (p < 0.05). Western blot demonstrated high-level expression of VEGF-C and VEGFR-3 in the pterygium compared with normal conjunctiva. VEGF-C immunoreactivity was detected in the cytoplasm of pterygial and normal conjunctival epithelial cells. The number of VEGF-C-immunopositive cells in pterygial epithelial cells was significantly higher than in normal conjunctival cells (p < 0.05). VEGFR-3 immunoreactivity was localized in the D2-40-positive lymphatic endothelial cells. The present findings suggest the potential role of VEGF-C in the pathogenesis and development of a pterygium through lymphangiogenesis and the VEGF-C/VEGFR-3 pathway as a novel therapeutic target for the human pterygium.     

Lymphangiogenic VEGF-C and VEGFR-3 expression in genetically characterised gastrointestinal stromal tumours

This study aimed to assess the distribution of VEGF-C and VEGFR-3 expression in gastrointestinal stromal tumours (GISTs), and to analyse the value of lymphatic vessel density (LVD) in a tumour that is believed to preferentially metastasize through blood vessel conduits. A panel of immunohistochemical antibodies was used to evaluate 51 cases of genetically characterised GISTs: VEGF-C, VEGFR-3, D2-40 (for LVD assessment) and CD31 (for blood vessel density--BDV--assessment). The results were correlated with the clinical-pathological data. The large majority of cases (86.2%; 44/51) showed a mutation of the KIT gene, most of them (72.5%; 37/51) revealing mutations in exon 11. VEGFR-3 was predominantly expressed in KIT mutated GISTs (p=0.019). High LVD was correlated with the absence of metastasis (p=0.010) and high BVD showed a positive correlation with the occurrence of metastasis (p=0.049). The strong expression of VEGF-C and VEGFR-3 in GIST's cells was not correlated with the clinical parameters of aggressiveness, nor with high LVD.     

Clinical significance of peritumoral lymphatic vessel density and lymphatic vessel invasion detected by D2-40 immunostaining in FIGO Ib1-IIa squamous cell cervical cancer

The clinical significance of lymphangiogenesis in cervical cancer remains controversial. Our aim was to investigate the correlation between lymphangiogenesis, lymphatic vessel invasion (LVI) and tumor metastasis, invasion and prognosis in squamous cell cervical cancer. Paraffin sections of 90 patients with FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) Ib1-IIa squamous cell cervical cancer were stained for immunohistochemistry with a D2-40 monoclonal antibody against the carcinoembryonic antigen M2A. The lymphatic vessel density (LVD) and LVI were measured, and their relationship with the clinicopathological data was analyzed. D2-40-positive lymphatic vessels were found in 75 of the 90 patients (83.3 %). All D2-40-positive vessels were located in peritumoral areas. The mean±SD of the peritumoral LVD was 10.08±4.16. The positive rate of LVI was 32.0 % (24/75). The recurrence rate of patients with LVD >10 (62.1 %, 18/29) was significantly higher than that of patients with LVD ≤10 (34.8 %, 16/46, P = 0.021). The 5-year recurrence-free survival rate of patients with LVD >10 (41.0 %) was significantly lower than that of patients with LVD ≤10 (67.0 %, P = 0.045). Univariate analysis showed that the peritumoral LVD (≤10 vs >10) was correlated with LVI (absent vs present, P = 0.016). The peritumoral LVD and LVI showed no correlation with age, FIGO stage, tumor size, tumor grade, depth of invasion, or pelvic lymph node metastasis (all: P > 0.05). Peritumoral lymphangiogenesis was correlated with the recurrence and recurrence-free survival in patients with squamous cell cervical cancer. Examination of peritumoral LVD in these patients might therefore help to estimate the risk of recurrence.     

TGF-β1和Smad4在膀胱癌中的表达及其与淋巴结转移的关系

目的：观察转化生长因子β1（TGF-β1）和Smad4在膀胱癌组织内的表达情况,并分析其与膀胱癌淋巴管生成及淋巴结转移之间的关系。方法：选择在本院确诊的膀胱癌患者50例,根据淋巴结转移与否分为淋巴结转移组（30例）和无淋巴结转移组（20例1。应用免疫组化法检测膀胱癌组织内TGF-β1和Smad4的表达。以D2—40作为淋巴管内皮特异性标记物,检测膀胱癌组织内淋巴管生成情况并分析其与TGF-β1和Smad4的表达的关系。结果：TGF．B1主要表达于膀胱癌细胞胞浆内,在淋巴结转移组的表达率明显高于无淋巴结转移组（P=0．017）。Smad4表达于膀胱癌细胞胞浆和胞核内,在无淋巴结转移组的表达率明显高于有淋巴结转移组（P=0．005）。Smad4表达阳性组的淋巴管数密度（LVD）明显低于Smad4表达阴性组（P=0．037）。TGF-p1的表达与Smad4的表达呈显著的负相关性（P=0．001）。结论：TGF-β1的表达与膀胱癌淋巴管生成及淋巴结转移呈显著正相关,Smad4的表达与膀胱癌淋巴管生成及淋巴结转移呈显著负相关,TGF-β1／Smad4信号通路可能在膀胱癌淋巴管生成和淋巴结转移过程中起重要作用。     

How useful is the assessment of lymphatic vascular density in oral carcinoma prognosis?

Background

Lymphatic vessels are major routes for metastasis in head and neck squamous cell carcinoma (HNSCC), but lymphatic endothelial cells (LECs) are difficult to recognize in tumor histological sections. D2-40 stains podoplanin, a molecule expressed in LECs, however, the potential prognostic usefulness of this molecule is not completely understood in HNSCC. We aimed to investigate the value of assessing peritumoral and intratumoral lymphatic vessel density (LVD) as prognostic marker for HNSCC.

Methods

Thirty-one cases of HNSCC were stained for D2-40 and CD31. LVD and blood vessel density (BVD) were assessed by counting positive reactions in 10 hotspot areas at ×200 magnification.

Results

D2-40 was specific for lymphatic vessels and did not stain blood vascular endothelial cells. LECs showed more tortuous and disorganized structure in intratumoral lymphatic vessels than in peritumoral ones. No statistical differences were observed between peritumoral-LVD and intratumoral-LVD or between peritumoral-BVD and intratumoral-BVD. Tumor D2-40 staining was positively associated with lymphatic vessel invasion (p = 0.011).

Conclusion

LVD is a powerful marker for HNSCC prognosis. We found significant differences in peritumoral and intratumoral D2-40 immunoreactivity, which could have important implications in future therapeutic strategies and outcome evaluation.

     

肿瘤淋巴管入侵与无淋巴结转移膀胱癌复发及预后的相关性分析

目的:分析肿瘤淋巴管入侵与无淋巴结转移膀胱癌复发和预后之间的关系。方法:选取临床资料完整的膀胱癌病例72例,分为淋巴结转移组(32例)和无淋巴结转移组(40例)。采用Spearman相关分析探讨淋巴管入侵与膀胱癌复发和预后的相关性,应用Kaplan-Meier法描绘生存曲线,Cox比例危险度模型筛选影响膀胱癌患者预后的因素。结果:在72例膀胱癌组织中,淋巴管入侵的阳性率是48.6%(35/72),淋巴管入侵的阳性率随肿瘤分期和分级增加而显著升高(P0.05);淋巴结转移组的淋巴管入侵阳性率为68.8%(22/32),显著高于无淋巴结转移的32.5%(13/40)。淋巴管入侵与膀胱癌的临床分期、分级、淋巴结转移以及无淋巴结转移膀胱癌复发均显著相关(P0.05)。淋巴管入侵阴性的患者的五年总体生存率显著高于淋巴管入侵阳性者,淋巴管入侵是无淋巴结转移膀胱癌复发和预后不良的危险因素。结论:肿瘤淋巴管入侵与膀胱癌临床分期和淋巴结转移密切相关,并影响膀胱癌患者的总体生存率,可作为无淋巴结转移膀胱癌复发和预后的预测因素。     

胃癌前哨淋巴结检测的临床研究

目的:探讨胃癌术中前哨淋巴结(sentinel lymph node,SLN)定位检测的可行性及其临床意义。方法:使用亚甲蓝对40例胃癌患者行前哨淋巴结术中标识活检,随后行D2或D2以上手术。结果:40例胃癌患者中,38例找到前哨淋巴结,检出率为38/40(95%),有32例存在SLN转移,8例SLN为唯一转移部位,且均为T1、T2期。由SLN的病理学状态来预测胃周围淋巴结转移情况的敏感性为32/34(94.12%),特异性为4/4(100%),假阴性率为2/34(5.88%),准确率为34/38(89.47%),其中假阴性的2例,肿瘤都处于T4期。结论:胃癌SLN定位及活检技术能较准确反映早期胃癌的淋巴结转移状况,但对进展期胃癌而言假阴性率较高,对胃癌整个区域淋巴结状态预测的可靠性和可行性尚需进一步验证。     

测定胰腺癌组织微血管密度及淋巴管密度的临床意义

目的:研究胰腺癌组织中微血管密度(Microvessel density,MVD)和淋巴管密度(Lymphatic vessel density,LVD)的变化、与胰腺癌临床病理的联系。方法:采用免疫组织化学SABC法应用CD34及D2-40分别检测41例胰腺导管腺癌患者配对癌组织内、癌旁及正常胰腺组织中MVD及LVD的表达情况,分析其与肿瘤分化程度、分期和淋巴转移间的相关性;以及癌组织MVD与癌旁组织LVD表达之间的关系。结果:在41例胰腺癌组织配对癌组织及正常胰腺组织平均MVD值分别为46.585±16.935,11.100±4.036,两组之间差别有统计学意义(P=0.000<0.01)。配对癌组织内、癌旁及正常胰腺组织中平均LVD值分别为11.244±4.800,15.829±7.470和13.512±5.139;其中癌旁组织与正常胰腺组织LVD值差别无统计学意义(P=0.060>0.05),癌旁组织与胰腺癌组织的LVD值有显著性差异(P=0.000<0.01)。癌组织内MVD值与癌旁组织LVD值之间有相关性(P=0.025<0.05)。结论:胰腺导管腺癌组织中MVD及LVD与肿瘤分化程度、病理分期及淋巴转移存在关联。胰腺癌组织内MVD值与癌旁组织LVD之间存在相关性。     

Identification of Biological Properties of Intralymphatic Tumor Related to the Development of Lymph Node Metastasis in Lung Adenocarcinoma

Background

Intralymphatic tumors in the extratumoral area are considered to represent the preceding phase of lymph node metastasis. The aim of this study was to clarify the biological properties of intralymphatic tumors susceptible to the development of lymph node metastasis, with special reference to the expression of cancer initiating/stem cell (CIC/CSC) related markers in cancer cells and the number of infiltrating stromal cells.

Material and Methods

Primary lung adenocarcinomas with lymphatic permeation in the extratumoral area were retrospectively examined (n = 107). We examined the expression levels of CIC/CSC related markers including ALDH1, OCT4, NANOG, SOX2 and Caveolin-1 in the intralymphatic cancer cells to evaluate their relationship to lymph node metastasis. Moreover, the number of infiltrating stromal cells expressing CD34, α-smooth muscle actin, and CD204 were also evaluated.

Results

Among the intralymphatic tissues, low ALDH1 expression in cancer cells, high SOX2 expression in cancer cells, and a high number of CD204(+) macrophages were independent predictive factors for lymph node metastasis (P = 0.004, P = 0.008, and P = 0.028, respectively). Among these factors, only low ALDH1 expression in cancer cells was significantly correlated with the farther spreading of lymph node metastasis (mediastinal lymph node, pathological N2) (P = 0.046) and the metastatic lymph node ratio (metastatic/resected) (P = 0.028). On the other hand, in the primary tumors, ALDH1 expression in the cancer cells was not associated with lymph node metastasis. Intralymphatic cancer cells expressing low ALDH1 levels exhibited lower E-cadherin expression levels than cancer cells with high levels of ALDH1 expression (P = 0.015).

Conclusions

Intralymphatic cancer cells expressing low levels of ALDH1 and infiltrating macrophages expressing CD204 have a critical impact on lymph node metastasis. Our study also highlighted the significance of evaluating the biological properties of intralymphatic tumors for tumor metastasis.     

MMP2和MMP9在粘膜内胃癌中表达及其临床病理意义

目的:观察基质金属蛋白酶(MMP)家族成员MMP2和MMP9在粘膜内胃癌中的表达及其与淋巴结转移的相关性。方法:研究病例为病理诊断为粘膜内胃癌的档案病例,应用免疫组织化学技术检测MMP2和MMP9在粘膜内胃癌中表达的临床病理意义,特别是与淋巴结转移的相关性。结果:临床病理分析结果显示有淋巴结转移的IMGC病例肿块直径要显著大于无淋巴结转移的IMGC。有淋巴结转移IMGC中低分化腺癌发生率要显著高于无淋巴结转移组。有淋巴结转移IMGC中淋巴管侵犯发生率要显著高于无淋巴结转移组。免疫组化结果显示,MMP2在正常胃粘膜上皮和粘膜内胃癌中的阳性表达率分别是7%和43.93%,有显著性差异(P0.01),MMP9在正常胃粘膜上皮和粘膜内胃癌中的阳性表达率分别为和23%和48.48%,无显著性差异(P0.05)。MMP9在淋巴结转移组中的阳性率(87.5%)显著高于无淋巴结转移组(36%),在有淋巴管侵犯病例中的表达率(83.3%)显著高于无淋巴管侵犯的病例(30%),差异均有统计意义(P0.05);而MMP2的表达与有无淋巴结转移及淋巴管侵犯均无显著相关性(P0.05)。结论:MMP9可能作为预测粘膜内胃癌是否有淋巴结转移的标志物,但需要结合组织分化、肿块大小和淋巴管侵犯等临床病理特点综合判断。MMP2可能与粘膜内胃癌的发生有关而作为早期诊断的指标。     

Lymphangiogenic Markers and Their Impact on Nodal Metastasis and Survival in Non-Small Cell Lung Cancer - A Structured Review with Meta-Analysis

Background

In non-small cell lung cancer (NSCLC), nodal metastasis is an adverse prognostic factor. Several mediating factors have been implied in the development of nodal metastases and investigated for predictive and prognostic properties in NSCLC. However, study results differ. In this structured review and meta-analysis we explore the published literature on commonly recognized pathways for molecular regulation of lymphatic metastasis in NSCLC.

Methods

A structured PubMed search was conducted for papers reporting on the expression of known markers of lymhangiogenesis in NSCLC patients. Papers of sufficient quality, presenting survival and/or correlation data were included.

Results

High levels of vascular endothelial growth factor C (VEGF-C, HR 1.57 95% CI 1.34–1.84) and high lymphatic vascular density (LVD, HR 1.84 95% CI 1.18–2.87) were significant prognostic markers of poor survival and high expression of VEGF-C, vascular endothelial growth factor receptor 3 (VEGFR3) and LVD was associated with lymph node metastasis in NSCLC.

Conclusion

Lymphangiogenic markers are prognosticators of survival and correlate with lymph node metastasis in NSCLC. Their exact role and clinical implications should be further elucidated.     

胃癌前哨淋巴结检测的临床研究

目的：探讨胃癌术中前哨淋巴结（sentinel lymph node,SLN）定位检测的可行性及其临床意义。方法：44t用亚甲蓝对40例胃癌患者行前哨淋巴结术中标识活检,随后行D2或D2以上手术。结果：40例胃癌患者中,38例找到前哨淋巴结,检出率为38／40（95％）,有32例存在SLN转移,8例SLN为唯一转移部位,且均为T1、T2期。由SLN的病理学状态来预测胃周围淋巴结转移情况的敏感性为32／34（94．12％）,特异性为4／4（100％）,假阴性率为2／34（5．88％）,准确率为34／38（89．47％）,其中假阴性的2例,肿瘤都处于T4期。结论：胃癌SLN定位及活检技术能较准确反映早期胃癌的淋巴结转移状况,但对进展期胃癌而言假阴性率较高,对胃癌整个区域淋巴结状态预测的可靠性和可行性尚需进一步验证。     

VEGF-C 和VEGFR-3 在胃癌组织中的表达及临床意义

目的:探讨胃癌患者血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C及血管内皮生长因子受体-3(vascular endothelial growth factor receptor-3,VEGFR-3)在胃癌组织中的表达,从而确定胃癌预后的分子标志物。方法:搜集整理临床资料,采用Real-time PCR及ELISA法检测43例胃癌组织VEGF-C和VEGFR-3的表达。结果:43例胃癌组织中均有不同程度的VEGF-C和VEGFR-3的表达,Real-time PCR结果显示胃癌组织淋巴结转移组和非转移组VEGF-C和VEGFR-3的表达分别为0.07±0.01和0.12±0.01,0.03±0.01和0.06±0.02,与正常对照组相比,差异有显著性(p<0.05)。ELISA检测显示,与正常胃组织中VEGF-C和VEGFR-3的蛋白表达相比,胃癌无淋巴结转移组及胃癌并发淋巴结转移组中VEGF-C和VEGFR-3均明显增加。结论:VEGF-C和VEGFR-3的表达与胃癌淋巴结转移密切相关,提示胃癌标本VEGF-C和VEGFR-3的检测可作为胃癌预后的分子标志物。     

Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI) detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69). Positive LVI was significantly correlated with lymph node metastasis (p < 0.001), tumor size (p < 0.001), histological grading (p = 0.017), tumor depth (p = 0.001), and stage (p < 0.001). Multivariate logistic analysis identified LVI (p = 0.036) as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04) and overall survival (p = 0.032) in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer.     

Clinical Implications of TβRII Expression in Breast Cancer

Objective

To explore the relationship between TβRII [type II TGFβ (transforming growth factor β) receptor] expression and clinicopathological characteristics, and to evaluate the prognostic significance of TβRII expression in breast cancer.

Methods

Clinicopathological data and prognostic information of 108 patients with histologically confirmed breast cancer who were surgically treated at China Medical University between January 2007 and September 2008 were reviewed and the association between the clinicopathological characteristics and TβRII expression was analyzed by chi-square test and multivariate analysis. The expression of TβRII was assessed by immunohistochemistry.

Results

Of the 108 patients, 60 cases were TβRII positive and 48 cases were negative. There was no significant association between TβRII expression of the patients older than 40 years and that of the younger than 40 years (56.0% vs 50.0%; P = 0.742). The TβRII expression rate was significantly increased in patients with lymph node metastasis compared to those without lymph node metastasis (67.40% vs 46.8%; P = 0.033). Statistically significant relationships were found between increasing tumor clinical stage and high TβRII expression (P = 0.011). TβRII expression was not associated with the expression of ER(estrogen receptor)、PR, (progesterone receptor)、Her-2 (human epidermal growth factor receptor 2) (P = 0.925,P = 0.861, and P = 0.840, respectively). Patients with high TβRII expression showed poorer 5-year disease-free survival (DFS) compared to those with low expression (66.7% vs 45.6%; P = 0.028) by univariate analysis. Survival analysis demonstrated that TβRII was associated with poor DFS (P = 0.011). Subgroup analysis revealed that TβRII expression was associated with shorter DFS in patients with lymph node metastasis, ER-positive, PR-positive or Her-2-negative tumors (P = 0.006, P = 0.016, P = 0.022, and P = 0.033, respectively). Cox regression analysis revealed that high TβRII expression was related to poor 5-year DFS, and it was an independent factor for predicting the poor outcome for breast cancer patients (P = 0.016).

Conclusions

High levels of TβRII expression were associated with lymph node metastasis, increasing tumor clinical stage, and poorer 5-year DFS in patients with breast cancer. TβRII may be a potential prognostic marker for breast cancer.