Tumor lymphangiogenesis and metastasis to lymph nodes induced by cancer cell expression of podoplanin

The membrane glycoprotein podoplanin is expressed by several types of human cancers and might be associated with their malignant progression. Its exact biological function and molecular targets are unclear, however. Here, we assessed the relevance of tumor cell expression of podoplanin in cancer metastasis to lymph nodes, using a human MCF7 breast carcinoma xenograft model. We found that podoplanin expression promoted tumor cell motility in vitro and, unexpectedly, increased tumor lymphangiogenesis and metastasis to regional lymph nodes in vivo, without promoting primary tumor growth. Importantly, high cancer cell expression levels of podoplanin correlated with lymph node metastasis and reduced survival times in a large cohort of 252 oral squamous cell carcinoma patients. Based on comparative transcriptional profiling of tumor xenografts, we identified endothelin-1, villin-1, and tenascin-C as potential mediators of podoplanin-induced tumor lymphangiogenesis and metastasis. These unexpected findings identify a novel mechanism of tumor lymphangiogenesis and metastasis induced by cancer cell expression of podoplanin, suggesting that reagents designed to interfere with podoplanin function might be developed as therapeutics for patients with advanced cancer.

High CD10 expression in lymph node metastases from surgically treated prostate cancer independently predicts early death

Patients with nodal positive prostate cancers are an important cohort with poorly defined risk factors. CD10 is a cell surface metallopeptidase that has been suggested to play a role in prostate cancer progression. CD10 expression was evaluated in 119 nodal positive prostate cancer patients using tissue microarrays constructed from primary tumors and lymph node metastases. All patients underwent radical prostatectomy and standardized extended lymphadenectomy. They had no neoadjuvant therapy and received deferred androgen deprivation. In the primary tumor, high CD10 expression was significantly associated with earlier death from disease when compared with low CD10 expression (5-year survival 73.7% vs. 91.8%; p = 0.043). In the metastases, a high CD10 expression was significantly associated with larger total size of metastases (median 11.4 vs. 6.5 mm; p = 0.015), earlier death of disease (5-year survival 71.5% vs. 87.3%; p = 0.017), and death of any cause (5-year survival 70.0% vs. 87.2%; p = 0.001) when compared with low CD10 expression. CD10 expression in the metastases added independent prognostic information for overall survival (p = 0.029) after adjustment for Gleason score of the primary tumor, nodal tumor burden, and resection margins. In conclusion, a high CD10 expression in prostate cancer predicts early death. This information is inherent in the primary tumors and in the lymph node metastases and might help to personalize patient management.

High-level cytoplasmic cyclin D1 expression in lymph node metastases from prostate cancer independently predicts early biochemical failure and death in surgically treated patients

To test the prognostic significance of cyclin D1 in nodal-positive prostate cancer.

Absence of ectopic epithelial inclusions in 3,904 axillary lymph nodes examined in sentinel technique

Intraoperative examination of sentinel axillary lymph nodes can be done by imprint cytology, frozen section, or, most recently, by PCR-based amplification of a cytokeratin signal. Using this technique, benign epithelial inclusions, representing mammary tissue displaced along the milk line, will likely generate a positive PCR signal and lead to a false-positive diagnosis of metastatic disease. To better appreciate the incidence of ectopic epithelial inclusions in axillary lymph nodes, we have performed an autopsy study, examining on 100 μm step sections 3,904 lymph nodes obtained from 160 axillary dissections in 80 patients. The median number of lymph nodes per axilla was 23 (15, 6, and 1 in levels 1, 2, and 3, respectively). A total of 30,450 hematoxylin-eosin stained slides were examined, as well as 8,825 slides immunostained with pan-cytokeratin antibodies. Despite this meticulous work-up, not a single epithelial inclusion was found in this study, suggesting that the incidence of such inclusions is much lower than the assumed 5% reported in the literature.

High CD10 expression predicts favorable outcome in surgically treated lymph node-positive bladder cancer patients

CD10 predicts survival in different cancers. The prognostic significance in bladder cancer still has to be documented. One hundred fifty lymph node-positive bladder cancer patients were treated by cystectomy and standardized pelvic lymphadenectomy in curative intent. CD10 expression was evaluated in tissue microarrays (TMAs) constructed from histopathological normal urothelium, primary tumor (tumor center and invasion front), and corresponding lymph node metastases and correlated with tumor characteristics (stage, extracapsular extension, number, and total diameter of metastases) and survival. CD10 expression was successively lost from normal urothelium to primary tumor to metastases (P < .05) and decreased from the tumor center to the invasion front (P < .002). High CD10 expression in tumor center or invasion front (P < .05) but not in the metastases predicted favorable outcome; the prognostic information in the tumor center was independent from tumor stage and lymph node parameters. High CD10 expression level was not associated with specific tumor characteristics. A well-defined sampling strategy for TMAs allows detection of specific biomarker expression patterns and may generate prognostic information inherent in particular tumor areas. The favorable outcome in bladder cancer patients with high CD10 expression might suggest a tumor suppressive function of CD10.

MMP-2 and MMP-9 in lymph-node-positive bladder cancer

Matrix metalloproteinases (MMP), particularly MMP-2 and MMP-9, participate in tumour progression and metastasis in various cancers. Their significance in urothelial cancer of the bladder (UCB) is unclear. Expression analysis of MMP-2 and MMP-9 in tissue microarrays (TMA) constructed of corresponding samples from histopathological normal urothelium, tumour centre and invasion front of primary tumours and lymph-node (LN) metastases might help to elucidate their relevance in UCB.

Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours

Her2, an alias for the protein of v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), might be an attractive therapeutic target in metastasising bladder cancer. Genotype and phenotype of primary tumours and their metastases may differ.

Extracapsular extension but not the tumour burden of lymph node metastases is an independent adverse risk factor in lymph node-positive bladder cancer

To evaluate risk factors in lymph node-positive bladder cancer.

Indocyanine green fluorescence-guided sentinel lymph node biopsy in dermato-oncology

Sentinel lymph node biopsy (SLNB) for cutaneous malignancies usually carried out with radioactive nanocolloids (Tc-99m). The SLNE is controversially discussed internationally. This is especially given to the high false-negative rate up to 44 %. An alternative could be the fluorescent dye indocyanine green (ICG).

Radio-guided surgery: advantages of a new portable γ-camera (Sentinella(®) ) for intraoperative real time imaging and detection of sentinel lymph nodes in cutaneous malignancies

The histological status of the sentinel lymph node (SLN) is one of the most relevant prognostic factors for the overall survival of patients with cutaneous malignancies, independent of tumour depth of the primary tumour.

Advantages of preoperative hybrid SPECT/CT in detection of sentinel lymph nodes in cutaneous head and neck malignancies

There is some controversy around the value of sentinel lymph node excision (SLNE). Especially SLNE of cutaneous head and neck malignancies has been debated intensively, in part because of the complexity of the lymphatic drainage in this region associated with potential high morbidity. In order to improve preoperative three-dimensional mapping of sentinel lymph nodes (SLN), in the head and neck region, by means of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) is gaining significance. Our study seeks to identify the potential medical and economic advantages of preoperative SPECT/CT in direct comparison to standard SLNE without SPECT/CT in patients with cutaneous head and neck malignancies.

Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study

There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage.

Robotic and laparoscopic high extended pelvic lymph node dissection during radical cystectomy: technique and outcomes

With the increasing use of laparoscopic and robotic radical cystectomy (RC), there are perceived concerns about the adequacy of lymph node dissection (LND).

Extended lymph node dissection: bladder, kidney

To present recent advances in the field of lymph node dissection (LND) in the context of bladder cancer, upper urinary tract urothelial carcinoma and renal cell carcinoma with focus on dissection extent.

Lymph node dissection in renal cell carcinoma

Although lymphadenectomy (lymph node dissection [LND]) is currently accepted as the most accurate and reliable staging procedure for the detection of lymph node invasion (LNI), its therapeutic benefit in renal cell carcinoma (RCC) still remains controversial.