Detection Of Lymphovascular Invasion Research Articles

The relationship of lymphatic vessel density, lymphovascular invasion, and lymph node metastasis in breast cancer: a systematic review and meta-analysis.

Lymph node status is one of the key parameters used for determining the stage of breast cancer progression. The relationship of lymphatic vessel density (LVD), lymphovascular invasion (LVI), and lymph node metastasis (LNM) has not been clearly demonstrated yet. Databases of PubMed, Embase, and Web of Science were searched from inception up to 25 May 2016. Spearman correlation coefficient (r) and 95% confidence interval (CI) were used to determine the relationship within each group. Based on pre-established inclusion criteria, 28 studies involving 2920 breast cancer patients were included in this study. The r values of LVD-LVI, LVD-LNM, and LVI-LNM were 0.45 (95% CI: 0.31 to 0.57), 0.32 (95% CI: 0.23 to 0.40), and 0.24 (95% CI: 0.19 to 0.28), respectively. Compared with intratumoral LVD, peritumoral LVD showed more robust correlation with LVI (r = 0.53, 95% CI: 0.27 to 0.72) and LNM (r = 0.33, 95% CI: 0.18 to 0.46). The patients in LNM positive group presented with higher LVI detection rate of 45.85%, while in LNM negative group with detection rate of 23.85%. The results describe a triangle relationship between LVD, LVI, and LNM in breast cancer. Both LVD and LVI are indicated to be valuable predictors of LNM occurrence. Compared with intratumoral lymphatic vessels, peritumoral lymphatics might be the main disseminate route for breast tumor cells.

Enhanced detection of lymphovascular invasion in small rectal neuroendocrine tumors using D2-40 and Elastica van Gieson immunohistochemical analysis.

Rectal neuroendocrine tumor (RNET) lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis after endoscopic resection (ER). However, little is known about the frequency of immunohistochemical detection of LVI in RNETs. This study was performed to establish the actual detection of LVI rate in RNETs ≤10 mm and to evaluate associated clinical outcomes. We retrospectively reviewed the records for 98 consecutive patients treated by ER with a total of 102 RNETs ≤10 mm. Tissue sections were labeled with hematoxylin–eosin (HE) stain, the D2‐40 monoclonal antibody to evaluate lymphatic invasion, and Elastica van Gieson (EVG) stain to detect venous invasion. LVI detection rate by HE versus immunohistochemical analysis was compared. Follow‐up findings and clinical outcomes were also evaluated for 91 patients who were followed for ≥12 months. Lymphatic and venous invasion were detected using HE staining alone in 6.9% and 3.9% of patients, respectively, whereas they were detected using D2‐40 and EVG staining in 20.6% and 47.1% of the patients, respectively. Thus, the LVI detection frequency using D2‐40 and EVG staining (56.9%) was significantly higher than with HE (8.8%). Two out of seven patients who required additional surgery had regional lymph node metastases. However, among the 84 patients who were followed up without surgery, no distant metastases or recurrences were detected. Compared with HE staining, immunohistochemical analysis significantly increased the frequency of LVI detection in RNETs ≤10 mm. However, the clinical impact of LVIs detected using immunohistochemical analysis remains unclear. Clarification of the actual role of LVI using immunohistochemical analysis requires a patient long‐term follow‐up and outcomes.

Lymphovascular invasion in more than one-quarter of small rectal neuroendocrine tumors.

AIMTo identify the frequency, clinicopathological risk factors, and prognostic significance of lymphovascular invasion (LVI) in endoscopically resected small rectal neuroendocrine tumors (NETs).METHODSBetween June 2005 and December 2015, 104 cases of endoscopically resected small (≤ 1 cm) rectal NET specimens at Hallym University Sacred Heart Hospital in Korea were retrospectively evaluated. We compared the detected rate of LVI in small rectal NET specimens by two methods: hematoxylin and eosin (H&E) and ancillary immunohistochemical staining (D2-40 and Elastica van Gieson); in addition, LVI detection rate difference between endoscopic procedures were also evaluated. Patient characteristics, prognosis and endoscopic resection results were reviewed by medical charts.RESULTSWe observed LVI rates of 25.0% and 27.9% through H&E and ancillary immunohistochemical staining. The concordance rate between H&E and ancillary studies was 81.7% for detection of LVI, which showed statistically strong agreement between two methods (κ = 0.531, P < 0.001). Two endoscopic methods were studied, including endoscopic submucosal resection with a ligation device and endoscopic submucosal dissection, and no statistically significant difference in the LVI detection rate was detected between the two (26.3% and 26.8%, P = 0.955). LVI was associated with large tumor size (> 5 mm, P = 0.007), tumor grade 2 (P = 0.006). Among those factors, tumor grade 2 was the only independent predictive factor for the presence of LVI (HR = 4.195, 95%CI: 1.321-12.692, P = 0.015). No recurrence was observed over 28.8 mo regardless of the presence of LVI.CONCLUSIONLVI may be present in a high percentage of small rectal NETs, which may not be associated with short-term prognosis.

PD41-06 CLINICAL VALUE OF IMMUNOHISTOCHEMICALLY DETECTED LYMPHOVASCULAR INVASION IN TRANSURETHRAL BLADDER TUMOR RESECTION SPECIMEN FOR BLADDER CANCER STAGING BEFORE RADICAL CYSTECTOMY

You have accessJournal of UrologyBladder Cancer: Staging1 Apr 2015PD41-06 CLINICAL VALUE OF IMMUNOHISTOCHEMICALLY DETECTED LYMPHOVASCULAR INVASION IN TRANSURETHRAL BLADDER TUMOR RESECTION SPECIMEN FOR BLADDER CANCER STAGING BEFORE RADICAL CYSTECTOMY Tatsuo Gondo, Jun Nakashima, Rie Inoue, Takeshi Hashimoto, Yoshio Ohno, Makoto Ohori, Toshitaka Nagao, and Masaaki Tachibana Tatsuo GondoTatsuo Gondo More articles by this author , Jun NakashimaJun Nakashima More articles by this author , Rie InoueRie Inoue More articles by this author , Takeshi HashimotoTakeshi Hashimoto More articles by this author , Yoshio OhnoYoshio Ohno More articles by this author , Makoto OhoriMakoto Ohori More articles by this author , Toshitaka NagaoToshitaka Nagao More articles by this author , and Masaaki TachibanaMasaaki Tachibana More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2414AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It is one of our major concerns to investigate the clinical implication of lymphovascular invasion (LVI) in transurethral resection of bladder tumor (TURBT) specimens (TUR-LVI) in clinical decision making in patients with bladder cancer. Immunohistochemistry (IHC) may improve LVI detection in small TUR specimens. We aimed to investigate the clinical significance of TUR-LVI for bladder cancer staging and compare the clinical values of IHC-detected LVI (IHC-LVI) with HE-detected LVI (HE-LVI). METHODS This study included 157 non-metastatic bladder cancer patients treated with radical cystectomy (RC) at our institution. A single pathologist with expertise in genitourinary malignancies evaluated all TURBT specimens and assessed the venous, lymphatic and lymphovascular invasions in HE and IHC stained specimens. Two IHC markers for lymphatic channels (D2-40) and endothelial cells (CD31) were used to clarify lymphatic (ly) and venous (v) invasions in IHC studies. The univariate and multivariate logistic regression analyses were used to identify preoperative factors correlated with extra-vesical disease (≥pT3) at RC.□ RESULTS Sixty-nine patients (44%) were diagnosed with ≥pT3 disease on RC specimens. HE-LVI was detected in 38 (24%) patients while IHC-LVI in 57 (36%). Twenty-six (46%) of the 57 patients with positive IHC-LVI was determined negative for HE-LVI, while 7 (18%) of the 38 patients with positive HE-LVI was determined negative by IHC. In univariate analyses, clinical T (cT) stage, tumor multifocality, hydronephrosis, and HE-LVI were significantly associated with ≥pT3 disease, but v and ly by both HE and IHC staining and IHC-LVI were not. In multivariate analyses, cT stage (p<0.001), hydronephrosis (p=0.002), and HE-LVI (p=0.025) were significant factors for the prediction of ≥pT3 disease. We developed a nomogram using these variables (Figure) and the area under the curve was 0.79. CONCLUSIONS cT stage, hydronephrosis, and HE-LVI were significant preoperative predictors for ≥pT3 disease at RC. Although IHC could detect more LVI in TURBT samples, it failed to be an independent factor in this setting. Additionally, detailed distinction between v and ly invasion status added no clinical value. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e842 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tatsuo Gondo More articles by this author Jun Nakashima More articles by this author Rie Inoue More articles by this author Takeshi Hashimoto More articles by this author Yoshio Ohno More articles by this author Makoto Ohori More articles by this author Toshitaka Nagao More articles by this author Masaaki Tachibana More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Detection of lymphovascular invasion in urothelial carcinoma of the bladder through D2-40 immunostaining

Lymphovascular invasion (LVI) represents a surrogate marker for micrometastatic urothelial carcinoma of the bladder (UCB). We evaluated whether D2-40 immunhistochemistry (IHC) alters detection of LVI when compared to conventional HE (hematoxylin-eosin) staining of UCB specimens in a blinded fashion. HE- and D2-40-IHC-stained representative sections of 80 patients after radical cystectomy (RC) were re-reviewed. LVI detection rates were recorded and compared after blinded evaluation. LVI was present in 53 patients (66.3%) in HE-stained sections and in 44 patients (55%) in D2-40 stainings. In 13 patients, LVI (16.3%) was found in HE stained sections but not confirmed when IHC was applied (false positive when using IHC as a reference standard). D2-40 IHC identified LVI in 4 additional patients (5%) who were classified as LVI negative in conventional HE staining (false negative). 52 patients (65%) were lymph node negative (pN0), 21 of whom (40.4%) were LVI positive in conventional HE sections and 16 of whom (30.8%) were LVI positive in IHC. In 9 pN0 patients (17.3%), LVI was diagnosed in HE sections but not confirmed by IHC (false positive). D2-40 IHC identified LVI in 4 additional patients (7.7%) who were node negative and classified as LVI negative in conventional HE staining (false negative). In patients who experienced recurrence (n=35) and who were classified as pN0 at the time of RC, HE staining resulted both in false-positive (n=2; 5.7%) and false-negative (n=3; 8.6%) findings. Different detection rates of LVI were observed when using IHC with D2-40 in UCB patients compared to conventional HE staining. The routine use of D2-40 IHC should be considered in clinical trial design to improve risk stratification of pN0 patients after RC.

Analysis of lymphatic and blood vessel invasion biomarkers in T1 esophagogastric adenocarcinomas for improved patient prognostication

Lymphovascular invasion (LVI) in T1 esophagogastric adenocarcinoma may predict risk of recurrence despite definitive treatment with surgery or endoscopic resection. Podoplanin and CD34 are emerging biomarkers of lymphatic and blood vessel invasion, respectively, and could be adopted to refine LVI assessment. A consecutive series of 65 patients with T1 adenocarcinomas diagnosed at Nottingham University Hospitals were investigated. T1 tumors from 43/65 patients who received primary surgery only were suitable for LVI evaluation by hematoxylin and eosin (H&E) staining as well as by CD34 and Podoplanin immunohistochemistry. LVI was correlated to clinicopathological features and recurrence free survival. H&E staining detected LVI in 11.6% (5/43) of T1 tumors. CD34 and Podoplanin immunohistochemistry significantly improved LVI detection to 25.6% (11/43). Compared with LVI by H&E, immunohistochemical evaluation of blood vessel invasion (CD34) or lymphatic vessel invasion (Podoplanin) was significantly associated with higher grade (P = 0.005), submucosal invasion (T1b) (P = 0.018), lymph node positivity (N1) (P = 0.029) and poor recurrence free survival (P = 0.0003). Our study provides evidence that CD34 and Podoplanin immunohistochemistry could improve LVI detection and allow better prognostication of patients and optimum selection of definitive treatment. Larger multicenter studies are required for further validation that could have significant clinical implications.

ERG Immunohistochemistry as an Endothelial Marker for Assessing Lymphovascular Invasion

BackgroundERG, a member of the ETS family of transcription factors, is a highly specific endothelial marker. We investigated whether the use of ERG immunostaining can help pathologists detect lymphovascular invasion (LVI) and decrease interobserver variability in LVI diagnosis.MethodsFifteen cases of surgically resected colorectal cancers with hepatic metastasis were selected and the most representative sections for LVI detection were immunostained with ERG, CD31, and D2-40. Eight pathologists independently evaluated LVI status on hematoxylin and eosin (H&E) and the corresponding immunostained sections and then convened for a consensus meeting. The results were analyzed by kappa (κ) statistics.ResultsThe average rate of LVI positivity was observed in 43% with H&E only, 10% with CD31, 29% with D2-40, and 16% with ERG. Agreement among pathologists was fair for H&E only (κ=0.27), D2-40 (κ=0.21), ERG (κ=0.23), and was moderate for CD31 (κ=0.55). Consensus revealed that ERG nuclear immunoreactivity showed better visual contrast of LVI detection than the other staining, with improved agreement and LVI detection rate (κ=0.65, LVI positivity rate 80%).ConclusionsThe present study demonstrated a superiority with ERG immunostaining and indicated that ERG is a promising panendothelial marker that might help pathologists increase LVI detection and decrease interobserver variability in LVI diagnosis.

Detection of Lymphovascular Invasion by D2-40 (Podoplanin) Immunoexpression in Endometrial Cancer

Lymph node involvement is a major feature in tumor spread of endometrial cancer and predicts prognosis. Therefore, evaluation of lymph vessel invasion (LVI) in tumor tissue as a predictor for lymph node metastasis is of great importance. Immunostaining of D2-40 (podoplanin), a specific marker for lymphatic endothelial cells, might be able to increase the detection rate of LVI compared with conventional hematoxylin-eosin (H-E) staining. The aim of this retrospective study was to analyze the eligibility of D2-40-based LVI evaluation for the prediction of lymph node metastases and patients' outcome. Immunohistochemical staining with D2-40 monoclonal antibodies was performed on paraffin-embedded tissue sections of 182 patients with primary endometrioid adenocarcinoma treated in 1 gynecologic cancer center. Tumors were screened for the presence of LVI. Correlations with clinicopathological features and clinical outcome were assessed. Immunostaining of D2-40 significantly increased the frequency LVI detection compared with conventional H-E staining. Lymph vessel invasion was identified by D2-40 in 53 (29.1%) of 182 tumors compared with 34 (18.3%) of 182 carcinomas by routine H-E staining (P = 0.001). D2-40 LVI was detectable in 81.0% (17/21) of nodal-positive tumors and significantly predicted lymph node metastasis (P = 0.001). Furthermore, D2-40 LVI was an independent prognostic factor for patients overall survival considering tumor stage, lymph node involvement, and tumor differentiation (P < 0.01). D2-40-negative tumors confined to the inner half of the myometrium showed an excellent outcome (5-year overall survival, 97.8%). D2-40-based LVI assessment improves the histopathological detection of lymphovascular invasion in endometrial cancer. Furthermore, LVI is of prognostic value and predicts lymph node metastasis. D2-40 LVI detection might help to select endometrial cancer patients who will benefit from a lymphadenectomy.

Immunohistochemical Assessment of Lymphovascular Invasion in Stage I Colorectal Carcinoma

Several studies have suggested that the presence of occult nodal metastases (micrometastases) is related to adverse clinical course in stage I colorectal carcinoma. Herein we analyzed the correlation between nodal micrometastases and lymphovascular invasion (LVI) or lymphatic vessel density (LVD) in a series of stage I colorectal carcinomas; the cohort included cases characterized or not characterized by disease progression during the follow-up. In these cases, LVI and LVD were evidenced through the immunohistochemical detection of the specific marker for lymphatic vessels, D2-40. LVI was significantly more frequent in colorectal carcinomas characterized by the presence of micrometastases (P<0.0001), high peritumoral LVD (P<0.0001), and disease progression (P<0.0001). The analysis for progression risk indicated that nodal micrometastases and LVI were significant, negative, independent prognostic parameters associated with shorter disease-free survival of stage I colorectal cancer (P=0.0001; P=0.0242). In conclusion, in this study we demonstrated for the first time that LVI is significantly associated with nodal occult metastases in stage I colorectal carcinoma. In the light of its significant, independent, prognostic value in this neoplasia, the detection of LVI may represent a faster and cheaper tool compared with the time-consuming evaluation of micrometastases to select high-risk patients who may benefit from adjuvant systemic treatment. Furthermore, the assessment of LVI may be applied to establish the likelihood of nodal involvement from carcinomas treated with conservative local excision techniques, which provide no regional nodes for histologic examination.

Clinical Relevance of Detection of Lymphovascular Invasion in Primary Melanoma Using Endothelial Markers D2-40 and CD34

Immunohistochemistry (IHC) using endothelial markers may facilitate the detection of lymphovascular invasion (LVI) in primary melanoma; however, the clinical implications of enhanced detection are unknown. We evaluated whether the use of lymphatic endothelial marker D2-40 and panvascular marker CD34 increases LVI positivity relative to routine histology alone and then evaluated the prognostic relevance of LVI detected using these markers in terms of disease-free (DFS) and overall survival (OS). A total of 246 primary melanomas were assessed for LVI using D2-40, CD34, and routine histology. Associations between LVI positivity and clinicopathologic variables, DFS, and OS were compared using univariate and multivariate analyses. The use of endothelial markers increased the rate of LVI positivity (18% using D2-40 and/or CD34 vs. 3% by routine histology, P<0.0001). On univariate analysis, IHC-detected LVI was significantly associated with more adverse clinicopathologic variables (thickness, ulceration, mitoses, and nodular subtype) compared with LVI detected by routine histology (thickness and ulceration only). In a multivariate model controlling for stage, LVI detected using IHC markers remained a significant marker of both reduced DFS [hazard ratio (HR), 2.01; 95% confidence interval (CI): 1.27-3.18; P=0.003] and OS (HR, 2.08; 95% CI: 1.25-3.46; P=0.005). Results show that D2-40 and CD34 increase the detection of LVI in primary melanoma and that cases missed by routine histology have prognostic relevance.

Pathological upstaging detected in radical cystectomy procedures is associated with a significantly worse tumour-specific survival rate for patients with clinical T1 urothelial carcinoma of the urinary bladder

Due to their variable oncological course, clinical stage T1 (cT1) urothelial carcinomas of the bladder (UCBs) are the subject of controversial discussion with regard to indication for radical cystectomy (RC).This study aimed to evaluate the frequency and prognosis of upstaging in patients undergoing RC due to UCB. Clinical and pathological records of 607 patients, having undergone RC for treatment of UCB in cT1N0M0, were summarized in a multi-institutional database. Cancer-specific survival (CSS) and overall survival (OS) rates were calculated. A multivariable prognostic model predicting the possibility of an upstaging in RC specimens was developed based on clinical information. In 210patients (35%) an upstaging (> pT1 and/or pN+) was detected in the RC specimen. Five-year CSS was 86%, 78%, 60%and 34%, respectively, for tumour stages < pT2N0 (n = 397), pT2N0 (n = 78), > pT2N0 (n = 63)and pN+ (n = 69) (p < 0.001). In a multivariable Cox regression model, pN stage, pT stage and lymphovascular invasion (LVI) revealed an independent influence on CSS (OS: pN, pT, age). An upstaging of cT1 tumours was enhanced by the criteria of G3 tumour grading and absent Tis in the transurethral resection of the bladder (TURB)specimen. Detection of LVI in RC specimens was also independently associated with an upstaging and, therefore, is recommended as a relevant prognostic parameter for the histopathological evaluation of TURB specimens. More than one-third of patients with cT1 tumours had an upstaging that was associated with significant prognosis deterioration. Further valid markers are required for an early identification of these patients. LVI represents such a criterion and, therefore, should be evaluated in prospectively designed trials with accurate histopathological assessment of TURB specimens.

Immunohistochemical detection of lymphovascular invasion with D2-40 in melanoma correlates with sentinel lymph node status, metastasis and survival

Immunohistochemical detection of lymphovascular invasion with D2-40 in melanoma correlates with sentinel lymph node status, metastasis and survival

Prognostic relevance of increased detection of lymphovascular invasion in primary melanoma using D2-40 and CD34 compared to routine histology.

8596 Background: Use of immunohistochemistry (IHC) can increase the detection of lymphovascular invasion (LVI) in primary melanoma, but the prognostic relevance of this enhanced detection is unknow...

Detection of Lymphovascular Invasion in Vulvar Cancer by D2-40 (Podoplanin) as a Predictor for Inguinal Lymph Node Metastases

Background: Lymphatic vessel invasion (LVI) plays a major role in the spread of vulvar cancer and predicts regional lymph node metastasis. D2-40, a monoclonal immunohistochemical marker might be able to increase the detection rate of LVI compared to conventional hematoxylin-eosin (HE) staining. The aim of the study was to evaluate the suitability of D2-40 for the prediction of regional lymph node metastases. Patients and Methods: Immunohistochemical staining with D2-40 was performed on formalin-fixed, paraffin-embedded tissue sections of 32 patients with squamous cell carcinoma of the vulva. Slides were screened for the presence of LVI. Correlation with clinico-pathological features including LVI as retrieved by routine HE-stained sections was assessed. Results: Immunostaining with D2-40 significantly (p = 0.019) increased the frequency of detection of lymphatic invasion compared to conventional HE staining. LVI was correctly identified by D2-40 (D2-40+ LVI) in 65.6% of tumor specimens as compared to 40.6% by routine HE staining (HE+ LVI). D2-40+ LVI significantly (p = 0.026) predicted inguinal lymph node metastases. Conclusions: Immunostaining with D2-40 significantly increased the frequency of detection of lymphatic invasion compared to conventional HE staining in squamous cell carcinomas of the vulva. D2-40+ LVI is a strong predictor for inguinal lymph node metastases.

Small Beginnings: Do They Matter? The Importance of Lymphovascular Invasion in Early Breast Cancer

Small Beginnings: Do They Matter? The Importance of Lymphovascular Invasion in Early Breast Cancer

Lymphatic invasion according to D2‐40 immunostaining is a predictor of nodal metastasis in endometrioid adenocarcinoma of the uterine corpus

In endometrioid adenocarcinoma of the uterine corpus, nodal metastasis is related to prognosis. D2-40 immunostaining has recently been used to detect lymphatic invasion, but a study of D2-40 immunostaining for endometrioid adenocarcinoma of the uterine corpus has not been published. Therefore, as a predictor of nodal metastasis in endometrioid adenocarcinoma of the uterine corpus, the detection of lymphatic invasion on D2-40 immunostaining and lymphovascular invasion on HE stain was compared. A total of 104 cases of invasive endometrioid adenocarcinoma of the uterine corpus, in which the tumor was located in the uterus, were examined on immunohistochemistry using D2-40. In 20 cases there was lymphatic invasion according to D2-40 immunostaining, and the lymphatic invasion was well detected on D2-40 immunostaining. Nodal metastasis was present in 11 cases. Both lymphatic invasion on D2-40 immunostaining and lymphovascular invasion on HE stain were statistically correlated with nodal metastasis, but the evaluation of lymphatic invasion on D2-40 immunostaining was more accurate than detection of lymphovascular invasion using HE stain, in the current and previous studies, for the prediction of nodal metastasis. In conclusion, lymphatic invasion demonstrated on D2-40 immunostaining is very useful as a predictor for nodal metastasis in endometrioid adenocarcinoma of uterine corpus.

Detection of lymphatic vessel invasion in early breast cancer by the monoclonal antibody D2–40 (podoplanin)

22042 Background: The purpose of this study was to compare the detection of lymphovascular invasion (LVI) by D2–40 (podoplanin) immunostaining with conventional hematoxylin-eosin (H.E.) staining in early breast cancer. We also aimed to find associations between the detection of D2–40 + LVI and other clinicopathological variables. Methods: Immunohistochemical staining with D2–40 and CD 34 and conventional H.E. staining was performed on consecutive formalin-fixed, paraffin-embedded tissue sections of 254 invasive breast tumors of 247 patients with node negative and node positive early breast cancer. For every tumor, the whole particular section, stained with H.E., CD34 and D2–40 was screened for the presence of lymphatic invasion Correlation with clinico-pathological factors and the eligibility for the prediction of axillary lymph node metastases was assessed. Results: LVI was identified by D2–40 (D2–40+) in 70 out of 254 tumors (28%) as compared to 40 tumors (16%) by routine HE staining (HE+). The increase of LVI detection was significant (p<0.001). Significant correlation was observed between D2–40+ LVI and age, t-stage, nodal status, grading and “triple negative” tumors (ER/PR and HER2neu negative). There was no correlation between D2–40+ LVI and menopausal-status, HER2-status and histological type. Based on multivariate analysis D2–40+ LVI was the strongest predictor for axillary lymph node metastases (OR = 3.489, p=0.0003), followed only by T-stage and grading (OR = 3.167 and 1.953, p=0.0003 and 0.0352). For 5 out of 35 patients (15%) with primary or secondary mastectomy who did not receive adjuvant radio-therapy, management would have changed to postmastectomy radiation in retrospect because of additional detected LVI by D2–40 immunostaining. Conclusions: Immunostaining with the monoclonal antibody D2–40 significantly increased the frequency of detection of lymphatic invasion compared to conventional H.E. staining in early breast cancer. Immunohistochemical detection of LVI by D2–40 might be of value in clinical practice. No significant financial relationships to disclose.

Detection of lymphovascular invasion in early breast cancer by D2-40 (podoplanin): a clinically useful predictor for axillary lymph node metastases

The aim of this study was to investigate the use of D2-40 for the detection of lymphovascular invasion (LVI) in node positive and negative early breast cancer. LVI is associated with axillary lymph node metastases (ALNM) and a long-term prognostic factor. A precise identification of LVI would have a strong clinical impact for breast cancer patients. Immunohistochemical staining with D2-40 and CD34 was performed on formalin-fixed, paraffin-embedded tissue sections of 254 invasive breast tumors of 247 patients with node negative and node positive early breast cancer. All slides were screened for the presence of LVI. Correlation with clinico-pathological factors including LVI as retrieved by routine haematoxylin and eosin (H.E.) stained sections and the eligibility for the prediction of ALNM was assessed. Using the D2-40 antibody for immunostaining, our results demonstrate a significant higher detection (P < 0.001) of LVI as compared with routine H.E.-staining in early breast cancer. LVI was correctly identified by D2-40 (D2-40+) in 70 out of 254 tumors (28%) as compared to 40 tumors (16%) by routine HE staining (HE+). There was a significant correlation between D2-40 + LVI and age, t-stage, nodal status, grading and hormonreceptor-status. Correlation between D2-40 + LVI and menopausal-status, HER2-status and histological type was not significant, while there was a significant correlation of D2-40 and so called "triple negative" tumors (ER/PR and HER2neu-negative). In a multivariate analysis D2-40+ was the strongest predictor for ALNM with an odds ratio of 3.489 and a P-value of P = 0.0003, followed only by T-stage and grading with odds ratios of 3.167 and 1.953 and P-values P = 0.0003 and P = 0.0352. Immunostaining with D2-40 significantly increased the frequency of detection of lymphatic invasion compared to conventional H.E.-staining in early breast cancer. As LVI is a strong predictive and prognostic marker, the monoclonal antibody D2-40 has the potential to play a significant role in pathological routine workup of breast tumors. Further prospective studies are needed to prove the clinical impact of D2-40.