A Case of Brachial Lymph Node Recurrences after the Resection of Locally Advanced Breast Cancer.

We present a case of two recurrences in the brachial lymph nodes after initial resection, which was performed for radical cure. A 66-year-old woman was diagnosed with left breast cancer T4bN3cM0 Stage IIIC and an immunohistochemistry assay showed estrogen receptor (ER) positivity (5%), progesterone-receptor (PgR) positivity (1%), human epidermal growth factor receptor-2 (HER2) positivity (3+), and low Ki-67 (15%). After four courses of adriamycin and cyclophosphamide, followed by four courses of trastuzumab plus docetaxel, the patient underwent left mastectomy and axillary dissection. Postoperatively, she was diagnosed with breast cancer ypT1cN0M0, and trastuzumab and anastrozole were started. Postoperative irradiation was performed. Three years and 5 months after the initial breast cancer surgery, she had left brachial lymph node recurrence. It was resected, and tamoxifen was administered postoperatively. One year and 9 months after, she had another left brachial lymph node recurrence, and it was resected. She received radiation therapy to her upper limb and started taking exemestane. After 1 year and 3 months since the second recurrence surgery, there has been no recurrence. Our case suggests that the replacement of regional lymph nodes with tumor cells may result in the reconstruction of lymph flow to the upper arm and the development of brachial lymph node metastasis. There are no reports of resection of the recurrent tumor in the brachial lymph node for curative treatment. Therefore, careful follow-up is important in the future.

Pathologic method for extracting good prognosis group in triple-negative breast cancer after neoadjuvant chemotherapy.

The area of residual tumor (ART) is a prognostic factor in patients treated with neoadjuvant chemotherapy (NAC) for lung, pancreatic, and rectal cancers. This study aimed to evaluate the usefulness of ART as a method for predicting the prognosis of triple-negative breast cancer (TNBC) patients after NAC. We included 143 patients with TNBC treated with NAC. The ART at the maximum cut surface of the residual tumor was measured. We divided the patients into three groups: ART-0 (ART = 0 mm2 ), ART-low (0 mm2  < ART ≤ 136mm2 ), and ART-high (ART > 136 mm2 ), and compared their clinicopathologic factors and prognosis. There were no significant differences in either recurrence-free survival (RFS) or overall survival (OS) between ART-0 and ART-low; however, the ART-high group had significantly shorter RFS and OS than the ART-0 and ART-low groups. Multivariate analysis showed that ART-0 and -low and ypN(-) were independent favorable prognostic factors for RFS. Groups with both ART-low and ypN(-) as well as those with ART-0 and ypN(-) showed significantly longer OS and RFS than the other groups (P < .05). Moreover, there was no significant difference in the RFS and OS between the ART-0 and ypN(-) groups and the ART-low and ypN(-) groups (P = .249 and P = .554, respectively). We concluded that ART is a candidate histopathological evaluation method for predicting the prognosis of TNBC patients treated with NAC. Furthermore, postoperative chemotherapy could be omitted in patients with ART-0 and ypN(-) (pathological complete response) and those with ART-low and ypN(-).

Assessment of Upper Limb Physiological Features in Patients with Lymphedema After Breast Surgery Using Multiple Instruments.

Background: Objective assessment of upper limb physiological features may allow for early detection and proper intervention for lymphedema after breast surgery. However, the development of diagnostic instruments and standard measurement procedures are required. Methods and Results: Four instruments (Venustron, Softmeasure, Myoton Pro, and iBDent), tape measurement, and water volumetry were investigated in this study. Inter-limb differences in physiological data were obtained from 40 patients with lymphedema after breast surgery and 38 control subjects. Four instruments and tape measurements were performed at four points. Inter-limb differences between patients with lymphedema and control subjects were determined. All measurements took <20 minutes with minimal pain reported. Inter-limb differences in water volumetry and tape measurements, especially when measured at 5 cm distal to the cubital fossa, were increased in International Society of Lymphology (ISL) stage II cases. All four instruments showed high reproducibility in standard silicon sample measurement. On the other hand, data from human samples were varied, and the utility for assessment of lymphedema was not determined. Conclusion: Water volumetry and tape measurement at 5 cm distal to the cubital fossa were useful to assess lymphedema in ISL stage II cases. Four instruments used in this study were feasible in clinical practice. In addition, inconsistent data from human tissue were not due to sensor limitations, rather, acquisition of accurate data from human tissue seemed to be difficult due to anatomical factors. In addition to high-quality sensor, development of system that produce accurate and reproducible results from human tissue is required.

Taxane-based combinations as adjuvant chemotherapy for node-positive ER-positive breast cancer based on 2004-2009 data from the Breast Cancer Registry of the Japanese Breast Cancer Society.

BACKGROUND: Adding taxane to an anthracycline-based regimen improves survival in node-positive breast cancer patients, as shown by clinical trials and meta-analyses. However, no studies have analyzed the number of metastatic lymph nodes in patients with estrogen receptor (ER)-positive cancer. This study investigated whether adding a taxane to an anthracycline-based regimen improved prognosis in node-positive, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients in a real-world setting. METHODS: Using Japanese Breast Cancer Society registry data, we compared disease-free survival (DFS) of patients with ER-positive, HER2-negative breast cancer, excluding those receiving neoadjuvant chemotherapy, between those who received an anthracycline-based regimen followed by a taxane-based regimen (A + T) and those who received only an anthracycline-based regimen (A w/o T), stratified by lymph node status. A Cox proportional hazards model was used to evaluate DFS in both groups. RESULTS: There were 4566 eligible patients with ER-positive, HER2-negative breast cancer. During the median follow-up period of 60 months, there were 481 recurrences and 149 deaths. There was no significant difference in DFS between the A + T and A w/o T groups among patients with 1-3 positive nodes, while there was a significant difference among patients with ≥ 4 positive nodes. CONCLUSIONS: In patients with ER-positive, HER2-negative breast cancer, adding taxane to an anthracycline regimen did not improve DFS in patients with metastasis in 1-3 lymph nodes. We considered that the group without the addition of taxane might be present in patients with ER-positive, HER2-negative lymph node metastases.

Interstitial growth as an aggressive growth pattern in primary lung cancer.

PURPOSE: Interstitial growth (IG), which is defined as tumor cells continuously growing into the alveolar septa at the tumor periphery, was originally reported as a growth pattern of metastatic sarcoma of the lung. On the other hand, IG in the primary lung cancers has not been well described. This study aimed to examine clinicopathological features of primary lung cancer that harbors IG. METHODS: A total of 2558 primary lung cancers which were resected from 2003 to 2012 in our hospital were examined for IG. We compared clinicopathological data and prognoses between patients with IG(+) and IG(-) specimens. RESULTS: Thirty-three cases out of 2558 (1.3 %) had IG components. IG was significantly more associated with positive smoking history, advanced pathological stage, presence of vascular invasion and pleural invasion. Thirty-three IG(+) cases include nine pleomorphic carcinoma, nine squamous cell carcinoma and eight adenocarcinoma. Interestingly, nine (24 %) out of 38 pleomorphic carcinoma specimens had IG components, which was a higher rate than any other histological subtypes. The IG(+) cancers had significantly shorter overall and recurrence-free survival than did the IG(-) cancers. CONCLUSIONS: We firstly reported on IG in various types of primary lung cancer. IG appears to be a sign of an aggressive lung cancer phenotype, mainly found in pleomorphic carcinoma.

Ezrin-expressing lung adenocarcinoma cells and podoplanin-positive fibroblasts form a malignant microenvironment.

PURPOSE: Cancer cells and cancer-associated fibroblasts (CAFs) together create the tumor microenvironment, which affects malignant behavior. Lung adenocarcinomas with CAFs expressing podoplanin (PDPN) are clinically aggressive, but the molecular mechanism underlying this phenomenon has not been established. So we identified the characteristic immunophenotype of lung adenocarcinoma cells coexisting with PDPN-expressing CAFs (PDPN-CAFs) and examined how it relates to an aggressive clinicopathological outcome. METHODS: We analyzed the clinicopathological characteristics of 119 adenocarcinomas with a uniform size (2-3 cm). The expression levels of ten invasiveness-related proteins which related to cell adhesion and invasiveness, such as Ezrin, were examined in cancer cells from PDPN-CAFs (+) cases and from PDPN-CAFs (-) cases (n = 20 each). To examine the functional importance of the identified protein on the invasion phenotype, we performed wound healing and a Matrigel invasion assay using shRNA-knockdown lung adenocarcinoma cells (PC-9). RESULTS: The PDPN-CAFs (+) cases had significantly higher rates of node metastasis (p < 0.01) and vascular invasion (p < 0.01). The cancer cells from the PDPN-CAFs (+) cases also had a significantly higher staining score for Ezrin (p < 0.01) than those from the PDPN-CAFs (-) cases. The migration and invasion activities of the shEzrin-induced PC-9 cells were significantly lower than those of the control cells. CONCLUSIONS: Our results indicated that within a tumor microenvironment composed of PDPN-CAFs, increased Ezrin expression in cancer cells might play a key role in the invasiveness of lung adenocarcinoma.

High Mobility Group Box1 (HMGB1) released from cancer cells induces the expression of pro-inflammatory cytokines in peritoneal fibroblasts.

High Mobility Group Box1 protein (HMGB1), one of the mediators of inflammation, is associated with tumorigenesis. The HMGB1-Receptor for advanced glycation end-products (RAGE) in gastric adenocarcinoma tissues promoted gastric cancer growth, however, there are no reports concerning the relationship between the expression of HMGB1 in gastric cancer and cancer-related inflammation. Fibroblasts exist most abundantly on cancer tissue where inflammation occurs. So, we studied the effects of HMGB1 released from cancer cells on the fibroblasts. The expression of HMGB1 in cancer cells and nuclear factor-kappa B (NF-kB) in fibroblasts were evaluated immunohistochemically in human gastric cancer specimens. Cytoplasmic HMGB1 expression in the cancer cells and nuclear translocation of NF-kB in fibroblasts were detected at deeper invasion. To determine whether HMGB1 released from cancer cells induces the expression of pro-inflammatory cytokines in fibroblasts, we analyzed the activation of Toll-like receptor (TLR) signaling. Fibroblasts stimulated by recombinant HMGB1 and the HSC44PE-conditioned medium showed the phosphorylation of Interleukin-1 receptor associated-kinase 4 (IRAK4), nuclear translocation of NF-kB, and enhanced pro-inflammatory cytokine expression. Treatment with HSC44PE-conditioned-medium transfected with siRNA-HMGB1 reduced the expressions of pro-inflammatory cytokines in the fibroblasts. We propose that HMGB1 released from cancer cells induces the expression of pro-inflammatory cytokines in peritoneal fibroblasts through the HMGB1-TLR2/4 pathway.

Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination: an autopsy case.

We recently reported the safety, immunological and clinical responses to a GPC3-derived peptide vaccine in a phase I clinical trial of patients with advanced hepatocellular carcinoma (HCC). We conducted a subsequent trial in advanced HCC to assess the histopathological findings before and after vaccination with the GPC3 peptide. Here, we present the clinical course and the pathological study including the autopsy of a patient with advanced HCC in the ongoing clinical trial. A 62-year old patient suffering from HCC refractory to sorafenib therapy received the GPC3 peptide vaccine. The patient had fever and remarkably impaired liver function twice after vaccination. Contrast-enhanced CT after the second vaccination showed multiple low-density areas in the liver tumor, indicating tumor necrosis. In contrast, the tumor thrombus in the right atrium increased. The patient discontinued protocol treatment due to disease progression and died 30 days after the second vaccination. An autopsy was performed to determine the main cause of death and to evaluate the antitumor effect of the vaccination. A histological examination showed central necrosis in most of the intrahepatic tumor. The main cause of death was circulatory failure due to tumor thrombus, which occupied most of the right atrium. An immunohistochemical analysis revealed infiltration of CD8-positive T cells in the residual carcinoma, but not within the cirrhotic area. Ex vivo IFN-γ enzyme-linked immunospot analysis revealed vaccine-induced immune-reactivity against the GPC3 peptide. A histopathological examination at the estimated time of a strong immunological response demonstrated a GPC3 peptide vaccination-induced cytotoxic T-lymphocyte response with an anti-tumor effect.

Forkhead box P3 regulatory T cells coexisting with cancer associated fibroblasts are correlated with a poor outcome in lung adenocarcinoma.

Recently, an association between tumor infiltrating Forkhead box P3 regulatory T cells (Treg ) and an unfavorable prognosis has been clinically shown in some cancers, but the mechanism of Treg induction in the tumor microenvironment remains uncertain. The aims of the present study were to examine the relationship between Treg and patient outcome and to investigate whether Treg induction is influenced by the characteristics of cancer-associated fibroblasts (CAF) in lung adenocarcinoma. The numbers of Treg in both the tumor stroma and the tumor nest were counted in 200 consecutive pathological stage I lung invasive adenocarcinoma specimens. To examine whether the characteristics of CAF influence Treg induction, we selected and cultured CAF from low Treg and high Treg adenocarcinoma. The number of Treg was much higher in the stroma than in the nest (P < 0.01). Patients with high Treg had a significantly poorer prognosis than those with low Treg (overall survival: P = 0.03; recurrence-free survival: P = 0.02; 5-year overall survival: 85.4% vs 93.0%). Compared with the CAF from low Treg adenocarcinoma, culture supernatant of the CAF from high Treg adenocarcinoma induced more Treg (P = 0.01). Also, CAF from high Treg adenocarcinoma expressed significantly higher mRNA levels of transforming growth factor-ß (P = 0.01) and vascular endothelial growth factor (P = 0.01), both of which are involved in Treg induction. Our studies suggest the possibility that CAF expressing immunoregulatory cytokines may induce Treg in the stroma, creating a tumor-promoting microenvironment in lung adenocarcinoma that leads to a poor outcome.

Prognostic impact of CD204-positive macrophages in lung squamous cell carcinoma: possible contribution of Cd204-positive macrophages to the tumor-promoting microenvironment.

INTRODUCTION: Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 (+) TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 (+) TAMs and the clinicopathological features of lung squamous cell carcinoma. METHODS: We investigated the relationships between the numbers of CD204 (+) TAMs and clinicopathological factors, microvessel density, and the numbers of Foxp3 (+) lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 (+) TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 (+) TAMs. RESULTS: A high number of CD204 (+) TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 (+) TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 (+) TAMs were correlated with the microvessel density and the numbers of Foxp3 (+) lymphocytes. A high number of CD204 (+) TAMs was strongly correlated with the tissue expression level of monocyte chemoattractant protein-1. CD204 (+) TAMs were shown to be significant independent prognostic factors in a multivariate analysis. CONCLUSIONS: CD204 (+) TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 (+) TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments.

E-cadherin expression on human carcinoma cell affects trastuzumab-mediated antibody-dependent cellular cytotoxicity through killer cell lectin-like receptor G1 on natural killer cells.

Trastuzumab is a recombinant antibody drug that is widely used for the treatment of HER2-overexpressing breast carcinoma. Despite encouraging clinical results, many HER2-overexpressing carcinomas are primarily resistant to trastuzumab. We attempted to explain trastuzumab resistance and search for solutions. Since the killer cell lectin-like receptor G1 (KLRG1), an inhibitory receptor expressed on subsets of natural killer (NK) cells recognizes E-cadherin as ligands and may inhibit immune responses by regulating the effector function of NK cells, we used HER2-overexpressing carcinoma cells which were expressing E-cadherin to investigate the role of antibody-dependent cellular cytotoxicity (ADCC) through KLRG1 on NK cells in vitro and vivo. The results indicated that HER2-overexpressing carcinoma cells were killed by trastuzumab-mediated ADCC and the ADCC activity was reflected the degree of E-cadherin expression on carcinoma cells. We found that expression of E-cadherin was shown to be a predictor of response to trastuzumab-based treatment for HER2-overexpressing carcinomas, furthermore, trastuzumab-mediated ADCC was markedly enhanced by KLRG1-negative peripheral blood mononuclear cells (PBMCs(KLRG1(-))).

Tumor cells of non-hematopoietic and hematopoietic origins express activation-induced C-type lectin, the ligand for killer cell lectin-like receptor F1.

Killer cell lectin-like receptor F1 (KLRF1) is an activating C-type lectin-like receptor expressed on human NK cells and subsets of T cells. In this study, we show that activation-induced C-type lectin (AICL) is a unique KLRF1 ligand expressed on tumor cell lines of hematopoietic and non-hematopoietic origins. We screened a panel of human tumor cell lines using the KLRF1 reporter cells and found that several tumor lines expressed KLRF1 ligands. We characterized a putative KLRF1 ligand expressed on the U937 cell line. The molecular mass for the deglycosylated ligand was 28 kDa under non-reducing condition and 17 kDa under reducing condition, suggesting that the KLRF1 ligand is a homodimer. By expression cloning from a U937 cDNA library, we identified AICL as a KLRF1 ligand. We generated mAbs against AICL to identify the KLRF1 ligands on non-hematopoietic tumor lines. The anti-AICL mAbs stained the tumor lines that express the KLRF1 ligands and importantly the interaction of KLRF1 with the KLRF1 ligand on non-hematopoietic tumors was completely blocked by the two anti-AICL mAbs. Moreover, NK cell degranulation triggered by AICL-expressing targets was partially inhibited by the anti-AICL mAb. Finally, we demonstrate that AICL is expressed in human primary liver cancers. These results suggest that AICL is expressed on tumor cells of non-hematopoietic origins and raise the possibility that AICL may contribute to NK cell surveillance of tumor cells.

Targeting of bone-derived insulin-like growth factor-II by a human neutralizing antibody suppresses the growth of prostate cancer cells in a human bone environment.

PURPOSE: Advanced prostate cancer frequently involves the bone, where the insulin-like growth factor (IGF)-II is abundant. However, the importance of IGF-II in bone metastasis from prostate cancer is uncertain. The present study was aimed at examining the therapeutic importance of targeting IGF-II in bone metastases from prostate cancer. EXPERIMENTAL DESIGN: We investigated whether inhibiting IGF-II using a human neutralizing antibody (m610) suppresses the growth of prostate cancer cells in a human bone environment. Human MDA PCa 2b prostate cancer cells were inoculated into human adult bone implanted into mammary fat pad of nonobese diabetic/severe combined immunodeficient mice or inoculated into mammary fat pad of the mice without human bone implantation. The mice were treated with m610 or a control antibody (m102.4) once weekly for 4 weeks immediately after inoculation with MDA PCa 2b cells. RESULTS: Histomorphologic examination indicated that m610 treatment significantly decreased the MDA PCa 2b tumor area in the human bone compared with the control. Ki-67 immunostaining revealed that the percentage of proliferating cancer cells in the m610-treated bone tumor sections was significantly lower than that in the control. m610 had no effect on MDA PCa 2b tumor growth in the absence of implanted human bone. m610 prevented the in vitro IGF-II-induced proliferation of MDA PCa 2b cells. CONCLUSIONS: Our results indicate that IGF-II plays an important role in the prostate cancer cell growth in human bone, suggesting that targeting it by neutralizing antibodies offers a new therapeutic strategy for bone metastasis from prostate cancer.

Effects of ATP on the intracellular calcium level in the osteoblastic TBR31-2 cell line.

We investigated the effects of extracellular ATP on TBR31-2 cells established from the bone marrow of transgenic mice harboring the temperature-sensitive simian virus (SV) 40 T-antigen gene. These cells showed the capacity to differentiate toward osteoblasts and could be enhanced by bone morphogenetic protein (BMP)-2, an inducer of osteoblasts. The intracellular calcium ion level ([Ca(2+)](i)) in differentiating TBR31-2 cells was measured by fluorescence confocal microscopic imaging using the Ca(2+)-sensitive probe, Calcium Green 1/AM. P2 receptor agonists, such as ATP (1 microM), uridine 5'-triphosphate (1 microM), and ADP (1 microM), significantly increased the [Ca(2+)](i) of TBR31-2 cells in 2-d and 5-d cultures, but a potent P2X receptor agonist, alpha,beta-methylene ATP (10 microM), did not increase [Ca(2+)](i). The increase in [Ca(2+)](i) induced by ATP in the 2-d culture tended to be higher than in the 5-d culture. The increase in [Ca(2+)](i) of both cultures was inhibited by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, a P2 receptor antagonist. However, in an external Ca(2+)-free condition ATP-induced increase in [Ca(2+)](i) was unchanged at either stage. U73122, phospholipase C inhibitor and Thapsigargin, a calcium-pump inhibitor, significantly inhibited the increase in [Ca(2+)](i) at both stages. Reverse transcription-polymerase chain reaction analysis showed that the expression of P2Y receptor mRNA was higher in the 2-d culture than in the 5-d culture. These results indicate that ATP induces the increase in [Ca(2+)](i) from the calcium store through activating P2Y receptors in TBR31-2 cells and that the 2-d culture can respond to ATP more than the 5-d culture due to the higher expression of P2Y receptors. This suggests that the physiological role of ATP in osteoblasts is altered during differentiation.

Grading system for lymph vessel tumor emboli for prediction of the outcome of invasive ductal carcinoma of the breast.

There are no suitable histologic diagnostic clues for determining the true biological malignancy of invasive ductal carcinomas associated with lymph vessel tumor emboli. The purpose of this study was to devise a grading system for lymph vessel tumor emboli in invasive ductal carcinomas that would allow accurate prediction of the outcome of invasive ductal carcinoma patients with lymph vessel invasion. We classified 393 invasive ductal carcinomas into the following 4 grades according to the number of mitotic and apoptotic figures in tumor cells in lymph vessels at 1 high-power field: grade 0, no lymph vessel invasion; grade 1, absence of mitotic and apoptotic figures, presence of any number of mitotic figures and absence of apoptotic figures, or absence of mitotic figures and presence of any number of apoptotic figures; grade 2, 1 to 4 mitotic figures and 1 or more of apoptotic figures, or 1 or more of mitotic figures and 1 to 6 apoptotic figures; and grade 3, more than 4 mitotic figures and more than 6 apoptotic figures. The mortality rate increased with the grade, and the mortality rate of patients with grade 3 lymph vessel tumor emboli was more than 70%. Multivariate analyses with well-known prognostic factors demonstrated that grade 3 lymph vessel tumor emboli significantly increased the hazard rates for tumor recurrence, and tumor death independent of adjuvant therapy status, nodal status, or invasive tumor size. The grading system for lymph vessel tumor emboli is the best histologic grading system for accurately predicting the outcome of patients with invasive ductal carcinoma of the breast.

Dengue hemorrhagic shock and disseminated candidiasis.

Dengue fever, one of the common endemic viral fevers, often presents with fever, rash, and mild liver dysfunction. However, plasma leakage induced by dengue virus infection can lead to dengue hemorrhagic fever and dengue shock syndrome, and it can cause severe complications including liver failure and encephalopathy. Infection of dengue virus with other pathogens is an unusual but serious complication. We report a case of dengue shock syndrome with liver failure and impaired consciousness. The patient developed a disseminated Candida tropicalis infection, which may have been due to translocation of the fungus from the intestine damaged by the dengue virus.

Accurate assessment of lymph vessel tumor emboli in invasive ductal carcinoma of the breast according to tumor areas, and their prognostic significance.

Lymph vessel tumor emboli (LVTEs) within tumors are difficult to distinguish from stroma-invasive tumor foci. The purpose of this study was to evaluate staining of LVTEs with hematoxylin-eosin (HE) and with D2-40 to determine whether LVTEs identified by HE staining alone are D2-40-positive LVTE and whether the presence of LVTE identified by HE or D2-40 staining is an accurate predictor of outcome in 151 patients with invasive ductal carcinoma (IDC) of the breast. We first attempted to identify LVTE in the stroma-invasive tumor area (intratumor area), the advance area, and the nontumor area by HE staining alone, and then LVTE identified by HE staining was confirmed by D2-40 staining. The number of LVTE identified by HE staining and D2-40 staining successively increased from the intratumor area to the nontumor area. Although D2-40 staining detected larger numbers of LVTE than HE staining in all tumor areas, the highest positive predictive value of LVTE was observed in the intratumor area, and the next was in the advance area, and then the nontumor area, and significant correlations were found between the numbers of LVTE stained by HE and D2-40 in the same tumor areas. LVTE identified by HE staining or D2-40 staining in the intratumor area or nontumor area significantly increased the risk for tumor recurrence or death of patients with IDC, independent of hormone receptor status or nodal status. The results of this study demonstrate that the existence of intratumoral LVTE and that the presence of intratumoral LVTE identified by HE staining or D2-40 staining are accurate predictors of the outcome of patients with IDC of the breast.

Correlation between concordance of tracers, order of harvest, and presence of metastases in sentinel lymph nodes with breast cancer.

BACKGROUND: There are various methods for the detection of sentinel lymph nodes (SLNs) in breast cancer by using a combined method with blue dye and radioisotope (RI) tracers. The purpose of the study was to reveal any correlation between concordance of the tracers and the order of harvest with the presence of metastases in SLNs. METHODS: The outcomes were reviewed in 408 cases with stage 0 to II breast cancer; the combined method was used in which blue dye and RI were injected subcutaneously around the tumor. The radioactivity and blue staining in each harvested SLN were checked. RESULTS: In 330 cases (81%), SLNs contained both blue dye and RI tracers (blue-hot cases), and in 42 (10%) and 31 (8%) cases, the SLNs contained only the blue stain (blue-only cases) and only RI (hot-only cases), respectively. The overall metastatic rate was 25% on a patient basis. Blue-only cases had a higher rate (42%) of metastasis than hot-only cases (14%). The rate of nodes containing both blue dye and RI gradually decreased from the first SLNs harvested to the third SLNs harvested. The rate of nodes containing RI only increased with the number harvested, and there was not so much change in the rate of nodes containing blue only. CONCLUSIONS: These data suggest that RI tracer could detect a wide range of SLNs and that the blue dye tracer could efficiently detect SLNs with metastasis. The combined methods compensates for the deficiencies of each method and thus will probably help to prevent missing SLNs.