Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non-small cell lung cancer

The monoclonal antibody D2-40 is a new selective marker for lymphatic endothelium. The lymphatic microvessel density (LMVD) using D2-40 has not yet been evaluated in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate LMVD using D2-40 in NSCLC. We investigated LMVD in 77 patients with NSCLC who underwent curative tumor resection. We also determined the relation between LMVD and clinicopathologic factors, VEGF-C and Ang-2 and microvessel density (MVD) using factor VIII-related antigen. The median number of D2-40-positive vessels in the highest LMVD was 25 (range, 5-71). LMVD was significantly associated with tumor status, lymph node metastasis, stage, lymphatic invasion, VEGF-C protein and MVD (p=0.0149 for tumor status; p<0.0001 for nodal status; p<0.0001 for stage; p=0.0153 for lymphatic invasion; p=0.0030 for VEGF-C, and p=0.0029 for MVD). Furthermore, LMVD using D2-40 expression was shown to be an independent predictor of lymph node metastasis by multivariate analysis (p=0.0070). These data indicate that a high LMVD by D2-40 may be an indicator of lymph node metastasis in NSCLC.     

Chalkley Microvessel but not Lymphatic Vessel DensityCorrelates with Axillary Lymph Node Metastasis in PrimaryBreast Cancers

This study aimed to investigate tumor microvessel density (MVD) and lymphatic vessel density (LVD) usingthe Chalkley method as predictive markers for the risk of axillary lymph node metastasis and their relationshipto other clinicopathological parameters in primary breast cancer cases. Forty two node-positive and eightynode-negative breast cancers were immunostained for CD34 and D2-40. MVD and LVD were counted by theChalkley method at x400 magnification. There was a positive significant correlation of the MVD with the tumorsize, coexisting ductal carcinoma in situ (DCIS) and lymph node metastases (P<0.05). In multivariate analysis,the MVD (2.86-4: OR 5.87 95%CI 1.05-32; >4: OR 20.03 95%CI 3.47-115.55), lymphovascular invasion (OR3.46, 95% CI 1.13-10.58), and associated DCIS (OR 3.1, 95%CI 1.04-9.23) independently predicted axillarylymph node metastasis. There was no significant relationship between LVD and axillary lymph node metastasis.However, D2-40 was a good lymphatic vessel marker to enhance the detection of lymphatic invasion compared toH and E staining. In conclusion, MVD by the Chalkley method, lymphovascular invasion and associated DCIScan be additional predictive factors for axillary lymph node metastases in breast cancer. No relationship wasidentified between LVD and clinicopathological variables, including axillary lymph node metastasis.     

Lymphatic vessel density as prognostic factor in breast carcinoma: relation to clinicopathologic parameters

Angiogenesis and lymphangiogenesis are essential for breast cancer growth and progression. This study aimed at investigating lymphatic microvessel density (LVD) and microvessel density (MVD) as prognostic markers in breast carcinoma. Forty breast carcinomas were immunostained for D2-40, CD31 and VEGF. Median lymphatic and blood microvessel densities, as well as VEGF expression, were related to each other and to clinicopathologic parameters including lymph node (LN) status. The efficacy of haematoxylin and eosin (H&E) in detecting lymphatic vessel invasion (LVI) compared to D2-40 immunostaining was also investigated. D2-40 stained normal lymphatic endothelium and myoepithelial cells, but with different staining patterns. D2-40 LVD related significantly to CD31 counts (r=0.470; p=0.002), and LN metastasis (Mann-Whitney U=101.500; p=0.043); however, it did not relate to age, tumor grade, tumor size or LVI. D2-40 identified LVI in 3 more cases (7.5%) than those detected by H&E. VEGF was expressed in 85%of cases, and was significantly related to CD31 and D2-40 counts (p=0.033 and 0.007, respectively). In conclusion, D2-40 LVD showed a significant association with LN metastasis, and can be considered to segregate patients with positive from those with negative LNs. D2-40 enhances the detection of LVI relative to H&E staining reflecting a potential for lymphatic metastatic spread and possible poor prognosis.     

男性乳腺癌125例患者的临床病理特征与生存分析

目的:探讨男性乳腺癌患者的临床病理特征以及治疗和生存情况,并进行预后相关因素的分析.方法:回顾性分析1961年1月-2011年12月共125例男性乳腺癌患者的病历资料和随访资料.采用log-rank检验和COX回归模型分析与男性乳腺癌患者预后相关的因素.结果:125例男性乳腺癌患者的5年总生存率为60.5％,5年无病生存率为54.8％.单因素分析结果显示,是否有恶性肿瘤家族史(P=0.041)、肿瘤大小(P＝0.005)、临床TNM分期(P=0.005)、腋窝淋巴结是否转移(P=0.013)和是否行乳腺癌根治术(P=0.016)是与男性乳腺癌患者总生存率相关的预后因素,而是否有恶性肿瘤家族史(P=0.015)、肿瘤大小(P=0.000)、临床TNM分期(P=0.002)和腋窝淋巴结是否转移(P=0.010)是与男性乳腺癌患者无病生存率相关的预后因素.COX回归模型分析结果显示,肿瘤大小(P=0.045)、腋窝淋巴结是否转移(P=0.026)和是否行乳腺癌根治术(P=0.000)是与总生存率相关的独立预后因素,而肿瘤大小(P=0.010)和是否行乳腺癌根治术(P=0.001)是与无病生存率相关的独立预后因素.结论:肿瘤大小、腋窝淋巴结是否转移和是否行乳腺癌根治术是影响男性乳腺癌患者预后的独立危险因素,早期诊断以及以乳腺癌根治术为主的综合治疗措施是提高男性乳腺癌患者生存率的关键.     

Angiogenesis and p53 protein expression in breast cancer: prognostic roles and interrelationships

The authors have analyzed, on the one hand, the prognostic impact of microvessel density (MVD) and p53 protein expression in patients with breast cancer, and on the other hand, the correlation between the microvascular pattern and the p53 protein expression. Tumors from 120 patients whose paraffin-embedded tissue blocks were available were analyzed using the immunohistochemical method. MVD and p53 protein expression were correlated with histologic grade and tumor size, respectively. The patients with highly vascularized tumor (high MVD) had decreased overall survival (p = 0.04), whereas overexpressed p53 patients did not. In multivariate analysis, axillary lymph node status (p = 0.007), tumor size (p = 0.01), and MVD (p = 0.02) showed important prognostic influence on overall survival. When the simultaneous influence of MVD and p53 protein expression on survival were analyzed, no interrelationship was detected. The results demonstrate the prognostic impact of MVD on overall survival in breast cancer and no association between MVD and p53 protein expression.     

Flt-4-positive vessel density correlates with vascular endothelial growth factor-d expression, nodal status, and prognosis in breast cancer.

PURPOSE: Metastasis to the regional lymph nodes through the lymphatic vessels is a common step in the progression of cancer and an important prognostic factor in many types of cancer. Recent evidence suggests that tumor lymphangiogenesis promotes lymphatic metastasis, and that the presence of Flt-4 on tumor blood and lymphatic vessels may play a important role in mediating lymphangiogenic factor-induced neovascularization. We assessed flt-4-positive vessel density (FVD) in breast cancer, and examined whether FVD associates with lymph node metastasis, VEGF-D expression, or prognosis. EXPERIMENTAL DESIGN: One hundred three invasive breast carcinomas with long-term follow-up were included in our study. Flt-4 was assessed using immunohistochemistry, then we analyzed the relationship between FVD and lymph node status, as well as VEGF-D expression and other established clinicopathological parameters. The relationship between FVD and prognosis was also investigated. RESULTS: Mean FVD of "hot spot" was 29.3 +/- 22.5 for each case. FVD was correlated significantly with lymph node metastasis (P < 0.0001), VEGF-D expression (P = 0.0019), tumor size (P = 0.0015), estrogen receptor (P = 0.0211), progesterone receptor (P = 0.0462), and c-erbB-2 (P = 0.0326). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that high FVD was associated with both worse disease-free survival (P = 0.0035) and overall survival (P = 0.0336). CONCLUSIONS: Increased FVD was correlated with lymph node metastasis and VEGF-D expression. High FVD may be a significant unfavorable prognostic factor for long-term survival in breast cancer. It is possible that Flt-4 becomes a target for antiangiogenic therapy to breast cancer.     

Factors influencing axillary node metastasis in breast cancer

AIMS AND BACKGROUND: The status of the axillary lymph nodes at the time of diagnosis has been accepted as one of the most important prognostic factors for the overall and disease-free survival of patients with breast cancer. The aim of our study was to determine which factors influence axillary node involvement in invasive breast cancer. METHODS: The data presented here were obtained from 344 patients who were treated for invasive breast cancer at the Department of Radiation Oncology, Uluda? University Medical College, Bursa, Turkey. Possible prognostic factors were categorized as patient related and tumor related. The Mann-Whitney U test was used for univariate analysis and logistic regression was used for multivariate analysis. RESULTS: In univariate analysis, a familial cancer history (P = 0.0042), age < 40 years (P = 0.0276), higher T stage (P < 0.0000), nipple involvement (P = 0.0345), skin involvement (P = 0.0270), perineural invasion (P = 0.0231), and lymphatic vessel invasion (P < 0.0000) were correlated with increased axillary node involvement. A higher incidence of > or = 4 involved lymph nodes was associated with higher T stage (P = 0.0004), nipple involvement (P = 0.0292), presence of an extensive intraductal component (P = 0.0023), skin involvement (P = 0.0008), perineural invasion (P = 0.0523), and lymphatic vessel invasion (P < 0.0000) in univariate analysis. In multivariate analysis, age < 40 years (P = 0.0454), cancer history within the family (P = 0.0024), higher T stage (P = 0.0339), lymphatic vessel invasion (P = 0.0003), and perineural invasion (P = 0.0408) were found to be independent factors for axillary lymph node positivity. Age < 40 years (P = 0.0221), perineural invasion (P = 0.0408), and an extensive intraductal component (P = 0.0132) were associated with an increased incidence of > or = 4 involved nodes in the logistic regression analysis. In patients with breast cancer, the incidence of axillary lymph node involvement was independently influenced by age < 40 years, presence of cancer history within the family, higher T stage, lymphatic vessel invasion, and perineural invasion. CONCLUSIONS: In conclusion, absence of familial cancer history, presence of lymphatic vessel invasion, higher T stage, and age below 40 years independently increased the risk of axillary node involvement. Presence of perineural invasion and lymphatic vessel invasion, age below 40, and an extensive intraductal component of more than 25% independently affected the risk of having > or = 4 nodes involved. Patients characterized by these factors may be classified into a higher risk group for nodal involvement, but more data are needed to define factors that can help in the decision-making regarding the omission of axillary treatment.     

Association between mammographic breast density and breast cancer tumor characteristics.

OBJECTIVE: Few studies have examined the association between breast density and breast cancer tumor characteristics. We examined the association between hormonal, proliferative, and histologic tumor characteristics and mammographic breast density in women with breast cancer. METHODS: We conducted a cross-sectional analysis in 546 women diagnosed with invasive breast cancer to evaluate the associations between breast density and tumor size, lymph node status, lymphatic or vascular invasion, histologic grade, nuclear grade, tumor differentiation, mitotic index, tumor necrosis, Ki-67 proliferation, estrogen receptor, progesterone receptor, p53, p27, cyclin E, Bcl-2, and C-erb-B2 invasion. Breast density was classified as fatty (Breast Imaging Reporting and Data System code 1 or 2; n = 373) or dense (Breast Imaging Reporting and Data System code 3 or 4; n = 173) for the cancer-free breast. A single pathologist measured all tumor markers. We examined whether the relationships were modified by interval cancer or screen-detected cancer. RESULTS: Women with a tumor size >1.0 cm were more likely to have dense breasts compared with women with a tumor size < or =1.0 cm after adjusting for confounders (odds ratio, 2.0; 95% confidence interval, 1.2-3.4 for tumor sizes 1.1-2.0 cm; odds ratio, 2.3; 95% confidence interval, 1.3-4.4 for tumor sizes 2.1-10 cm). Tumor size, lymph node status, and lymphatic or vascular invasion were positively associated with breast density among screen-detected cancers. Histologic grade and mitotic index were negatively associated with breast density in women diagnosed with an interval cancer. CONCLUSIONS: These results suggest that breast density is related to tumor size, lymph node status, and lymphatic or vascular invasion in screen-detected cancers. Additional studies are needed to address whether these associations are due to density masking the detection of some tumors, a biological relationship, or both.     

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01).This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.     

血管形成和纤维蛋白降解作用与乳腺癌侵袭转移的关系

目的研究血管形成和纤维蛋白降解作用与乳腺癌侵袭转移的关系。方法应用免疫组化方法,检测110例原发性乳腺癌患者中尿激酶型纤溶酶原激活物(uPA)和微血管密度(MVD)的表达,并结合临床、病理及随访资料进行分析。结果110例患者中,uPA高表达者59例,占53．6％;低表达者51例,占46．4％。MVD计数高者53例,占48．2％;计数低者57例,占51．8％。uPA表达与肿瘤大小、淋巴转移和TNM分期有显著相关性,MVD与肿瘤大小、TNM分期有显著相关性,二者表达与患者年龄、月经状况和激素受体状况无关。uPA和MVD高表达者的无复发生存期均低于低表达者的生存期,特别是uPA和MVD均为高表达者更易复发转移。多因素分析显示,uPA和MVD是影响无复发生存期的主要因素。结论血管形成和纤维蛋白降解作用与乳腺癌的侵袭转移行为密切相关,uPA和MVD可能是预测乳腺癌患者复发转移的独立预后因素。     

Clinical significance of lymphatic and blood vessel invasion in oral tongue squamous cell carcinomas

Although vascular invasion (VI) is recognized as an important predictor of lymph node metastasis and a significant prognostic factor in head and neck squamous cell carcinoma (HNSCC), there is currently no common definition for the pathological evaluation of VI status. We reviewed the medical records of 63 consecutive resected primary oral tongue SCCs (OTSCCs) without preoperative treatment between June 1999 and April 2008, and evaluated VI status by investigating lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) by using immunohistochemistry (IHC) with monoclonal antibody D2-40 (D2-40) and Elastica van Gieson (EVG) staining, respectively. Subsequently, we analyzed their correlations with cervical lymph node metastasis and prognosis. LVI was found in 16 of the 63 tumors (25.4%) and BVI was in 32 tumors (50.8%). Univariate analysis revealed that the presence of LVI is statistically correlated with lymph node metastasis. Moreover, multivariate logistic regression analysis revealed that LVI is an independent risk factor of nodal metastasis (odds ratio=4.262, 95% confidence interval=1.262-14.397, p=0.020). In contrast, Kaplan-Meier survival analysis revealed that patients with BVI had a significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those without BVI (68.6% versus 90.3%, p=0.028 and 68.6% versus 93.5%, p=0.013, respectively). The present study clearly demonstrated that LVI at primary OTSCC had significant correlation with lymph node metastasis, and that BVI was significantly associated with recurrence and poor prognosis. Evaluation of VI status, as LVI and BVI status separately, using IHC with D2-40 and EVG staining may be useful in predicting lymph node metastasis and poor prognosis in OTSCCs.     

Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long-term follow-up.

PURPOSE: Expression of angiogenic and lymphangiogenic factors by tumors may influence the route of metastatic spread. The angiogenic factor vascular endothelial growth D (VEGF-D) is implicated in the development of lymphatic vessels and promotion of lymphatic metastases. The purpose of this study is to determine whether VEGF-D correlates with lymph node metastasis or prognosis. EXPERIMENTAL DESIGN: We assessed VEGF-D expression using immunohistochemistry in 105 invasive breast carcinomas with long-term follow-up. The relationship among VEGF-D expression, lymph node status, and other established clinicopathological parameters was assessed. Whether VEGF-D expression plays prognostic role in breast cancer was also investigated. RESULTS: VEGF-D expression was identified in 86 cases (81.9%). Positive VEGF-D was significantly correlated with lymph node metastasis (P = 0.0238) and high c-erbB-2 expression (P = 0.0211). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that positive VEGF-D was associated with both disease-free survival (P = 0.0023) and overall survival (P = 0.0222). In multivariate analysis using the Cox regression model, positive emerged as an independent indicator for disease-free survival (P = 0.0452). CONCLUSIONS: VEGF-D expression is associated with lymph node metastasis and may be a novel prognostic factor in breast cancer. VEGF-D may be useful in the treatment of breast cancer as a decision-making biomarker for aggressive treatment after operation.     

Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma

BACKGROUND: Cyclooxygenases regulate the production of prostaglandins and play a role in tumor development and progression. The authors investigated the prognostic impact of expression of the cyclooxygenase (COX) isoforms, COX-1 and COX-2, on disease-free survival and progression-free survival in patients with primary breast carcinoma as well as the association between COX expression and other clinicopathologic parameters. METHODS: In this study COX isoform expression was determined by immunohistochemistry in a cohort of 221 patients with primary breast carcinoma. RESULTS: Expression of COX-2 was detected in 36% of breast carcinoma samples and was associated significantly with several clinicopathologic parameters, including positive lymph node status (P < 0.0005), larger tumor size (P < 0.0005), poor differentiation (P < 0.0005), vascular invasion (P = 0.03), and negative estrogen receptor status (P = 0.04). In contrast, COX-1 was expressed in 45% of tumors and was associated with smaller tumor size (P = 0.02) and with negative lymph node status (P = 0.01). In a univariate survival analysis, a significant association was observed between elevated COX-2 expression and decreases in disease-free survival (P = 0.0007) and overall survival (P = 0.02). In a multivariate analysis, expression of COX-2 was of borderline significance for disease-free survival (relative risk, 1.90; 95% confidence interval, 1.00-3.59), adjusting for tumor size, histologic grade, number of positive lymph nodes, and patient age. Elevated expression of COX-1 in tumor tissue had no statistically significant influence on patient prognosis. CONCLUSIONS: The current data suggest that increased expression of COX-2 may play a role in the progression of primary breast carcinoma. It remains to be investigated whether treatment with selective inhibitors of COX-2 may be an additional therapeutic option for patients with breast carcinoma.     

The correlation between immunohistochemically-detected markers of angiogenesis and serum vascular endothelial growth factor in patients with breast cancer

BACKGROUND: As angiogenesis is known to be a crucial factor in breast cancer growth, numerous studies have examined angiogenic markers in breast cancer. Their definite role, however, has not been fully elucidated. MATERIALS AND METHODS: We investigated intratumoral microvessel density (MVD), Vascular Endothelial Growth Factor (VEGF) and its receptor flk-1, and serum VEGF in 46 patients with breast cancer prior to surgery. RESULTS: Median serum VEGF in patients with breast cancer was 257.5 pg/mL (range, 21.9 to 899.6). Serum VEGF showed a significant correlation with tumor stage, but not with lymph node involvement, histological grade, estrogen and progesterone receptor status. Increased MVD was associated with advanced tumor stage (p=0.05) and high tumor grade (p<0.001). A linear significant correlation between elevated serum VEGF and increased MVD was ascertained (p=0.02). CONCLUSION: Our results suggested that angiogenesis as reflected by immunohistochemically-detected MVD and serum VEGF, is involved in breast cancer growth and lymphatic spread.     

Clinical significance of intra-tumoral sinusoidal structures showing lympho-endothelial immunoreactivity in breast cancer

The lymphatic system is known as one of the most important pathways in the disease progression of breast cancer. In this study, we investigated lymphatic systems intra-tumorally, and found a unique structure displaying lymphoendothelial immunoreactivity. These incomplete vessel-like structures that formed sinusoids and specifically reacted with the D2-40 antibody, were found in the tumor stroma and were often infiltrated by cancer cells. To show the clinical significance of these intra-tumoral sinusoidal structures (ISS), we examined 113 specimens of surgically resected breast cancer. In multivariate logistic regression analysis, lymph node status (p=0.024) and disease recurrence (p=0.008) were the independent factors that correlated with the existence of ISS. Positive ISS detection in the tumor correlated more strongly with lymph node metastases than positive lymphovascular invasion by cancer cells. Furthermore, a significant correlation with frequent recurrence and poorer survival were recognized in patients with ISS (p<0.001, log-rank test). The evaluation of ISS by needle-biopsied specimens was as accurate as that with surgical specimens, and a significant correlation between the positive ISS evaluated by biopsy and positive lymph node status (p=0.020) was found. In conclusion, ISS are unique structures which play a crucial role in disease progression through lymphatic systems in breast cancer. In a clinical setting, the detection of ISS by biopsy specimen should be considered as a method for determining prognosis instead of a whole tumor examination.     

Lymphatic invasion is a prognostic factor for bladder cancer treated with radical cystectomy

Background We aimed to elucidate the significance of pathological prognostic factors in patients with bladder cancer treated with radical cystectomy and pelvic lymphadenectomy focusing on the association between lymphatic invasion and disease recurrence. Methods Ninety-one patients with ladder cancer who had undergone radical cystectomy were examined retrospectively. Clinicopathological findings and clinical outcomes were analyzed. Patients who received palliative cystectomy or neoadjuvant chemotherapy and patients who did not receive lymphadenectomy owing to a poor general condition or far advanced local disease status were excluded. Results Lymphatic invasion and lymph node involvement were present in 45.1% and 23.1% of patients, respectively. Multivariate analyses, using the Cox proportional hazards model, indicated that lymphatic invasion (hazard ratio [HR], 5.30; P = 0.007) and lymph node involvement (HR = 3.05; P = 0.016) were independent prognostic factors for disease-specific survival. Of the 91 patients, 29 (31.9%) had recurrent disease during the follow-up period. The rate of recurrence in patients with lymphatic invasion and without lymph node involvement was 50% (11/22), which was not significantly different from that in patients with both lymphatic invasion and lymph node involvement (73.7%; 14/19; P = 0.121), indicating a high risk of disease recurrence in patients with bladder cancer with lymphatic invasion even in the absence of the lymph node involvement. Conclusion In patients with bladder cancer treated with radical cystectomy, lymphatic invasion is an independent prognostic factor for disease-specific and disease-free survival. Patients with lymphatic invasion have a high risk of disease recurrence after radical cystectomy even in the absence of lymph node involvement.     

Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density

Stromal cells, within and around the tumor, as well as tumor cells are both involved in angiogenesis which is an important step in tumor growth and metastasis. Among such stromal cells, macrophages are known to play various roles in tumor angiogenesis and have thus been called tumor-associated macrophages (TAMs). The TAM density, vascular endothelial growth factor (VEGF) expression and the microvessel density (MVD) were immunohistochemically evaluated in 249 paraffin-embedded sections of invasive ductal carcinoma of the breast. The TAM density and MVD were assessed as the average density of three hot spots at a magnification of x400 and x200, respectively. The TAM density showed a significant correlation with both the VEGF expression and MVD, while a significant correlation was also found between the VEGF expression and MVD. The TAM density was also associated with the nuclear grade, estrogen receptor status and MIB-1 count. Patients with a high TAM density had a significantly (p=0.0025) worse disease-free survival (DFS) prognosis than those with a low TAM density, while univariate analyses also indicated both the MVD (p<0.0001) and VEGF expression (p=0.0152) to be prognostic factors for DFS. A multivariate analysis indicated MVD (p=0.0057), as well as lymph node metastasis and the MIB-1 count, to be independently significant prognostic factors for DFS. In conclusion, the present study demonstrated a close association between TAM infiltration and both the VEGF expression and MVD. The prognostic significance of MVD was the strongest among these three factors in breast cancer. These findings suggested that the prognostic implications of TAM infiltration are due to the involvement of TAMs in tumor angiogenesis.     

Can Lymphatic Vascular Density Be Used in Determining Metastatic Spreading Potential of Tumor in Invasive Ductal Carcinomas?

Regional lymph node status is the primary parameter determining treatment strategies and prognoses in breast cancer. Lymphatic vessels in primary tumor tissue play a significant role in lymphatic metastasis. The aim of this study was to investigate the correlation of intra- and peritumoral lymphatic microvessel densities (LVD) with prognostic parameters in breast cancer, including lymphatic invasion (LI). Lymphangiogenesis was investigated using D2-40 monoclonal antibody in 69 invasive ductal carcinoma cases who underwent mastectomy and axillary lymph node dissection. Positively stained microvessels were counted at 400× in dense lymphatic vascular foci (hotspots). Tumor LI was established when at least one neoplastic cell cluster was clearly visible inside a D2-40-positive lymph vessel. Relationships were sought between clinicopathological parameters and mean LVD and LI in primary tumor tissue. Peritumoral LVD was markedly higher than intratumoral LVD (p < 0.001). No significant relationship was found between intratumoral LVD and clinicopathological parameters (p > 0.05). However, significant relationships were detected between peritumoral LVD and LVI [H&E] (p = 0.04), number of lymphatic invasion [n/mm2, D2-40] (p = 0.001), tumor size (p = 0.01), lymph node status (p = 0.03), and tumor stage (p = 0.04). The immunohistochemical determination of LI and LVD can contribute to the prediction of a tumor’s biological behavior in invasive ductal carcinomas. Peritumoral LVD in primary tumor tissue is closely related to parameters influencing the prognosis of a tumor.