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PubMed1984

Lymphocyte recognition of lymph node high endothelium: adhesive interactions determining entry into lymph nodes.

Our interpretation of these results is that lymphocyte surface HEBF is composed of high endothelial adhesion molecules which mediate cell-cell interactions that result in lymphocyte entry from blood into lymph nodes. The evidence that anti-HEBF antibody does not interfere with lymphocyte entry into PP is intriguing, since migration into this tissue as well as LN, occurs via HEV. This suggests that high endothelial cells differ in LN and PP at least with respect to the specificity of surface molecules involved in lymphocyte adherence. It could be that separate lymphocyte subpopulations express receptors for these two types of high endothelium. If this explanation is correct, then cells negatively selected using this antibody should be capable of binding to HEV of PP but not HEV of LN. However, if receptors for both high endothelial types are present on the same lymphocyte, then it is unlikely that such selection would yield cells exhibiting tissue specificity. Our observations are consistent with previous findings which suggested that high endothelial cells of mouse LN and PP exhibit differences in lymphocyte binding properties. For example, it has been reported that certain murine lymphomas bind to HEV of either peripheral LN or PP and that, to a limited degree, this preference is a property of most B and T cells [Butcher et al, 1980; Stevens et al, 1982]. Thymus and bone marrow cells show only low levels of HEV binding and less than 10% of such cells react with anti-HEBF antibody. During differentiation lymphocytes appear to acquire surface components which mediate high endothelial adhesion and this event is associated with the appearance of surface molecules recognized by anti-HEBF antibody. This suggests that it is the expression of these surface molecules during differentiation which confers high endothelial recognition properties on lymphocytes and that this mechanism plays a role in adhesive interactions leading to entry of both T and B cells into LN.

Animals↗
PubMed1958

Studies on the transfer of lymph node cells. XII. The effect of anti-rabbit-leucocyte serum on the transfer of antigen-incubated lymph node cells.

In earlier studies it was shown that if rabbit lymph node cells were incubated with Shigella-trypsin filtrate and transferred to other, recipient, rabbits, agglutinins to Shigella appeared subsequently in the sera of the recipients. However, if leucocytes from the donor rabbits were injected into the recipients at a suitable interval prior to lymph node cell transfer, agglutinins to Shigella did not appear after cell transfer. In the present study, a number of experiments were done which bear on the immunologic character of this suppressive effect on the transferred cells, the "pre-injection effect." X-irradiation of the recipients before the injection of donor leucocytes led to a decrease in the extent of the pre-injection effect, i.e. to the appearance of higher agglutinin liters, in the recipient animals. It was found possible to transfer the pre-injection effect by cells of rabbit lymph nodes draining sites of injection of rabbit leucocytes. No such effect was obtained with heated aliquots of these cell suspensions or with lymph node cells from sheep-erythrocyte-injected donors. It was also possible to transfer the pre-injection effect passively by serum. Suppression of transferred lymph node cells was observed regularly after injection of serum pooled from groups of rabbits which had been injected with leucocytes pooled from the blood of 60 to 70 rabbits. The active material in anti-leucocyte serum could be precipitated in the globulin fraction of the serum and could be removed by absorption with rabbit lymph node cells. In the course of experiments on the passive transfer of the pre-injection effect by antisera of individual rabbits to leucocytes of individual donor rabbits, evidence was obtained of the existence in the sera of some normal rabbits of antibodies to some of the rabbit leucocyte antigens.

Animals↗
PubMed2001

Micro-metastases in axillary lymph nodes: an increasing classification and treatment dilemma in breast cancer due to the introduction of the sentinel lymph node procedure.

BACKGROUND: Sentinel lymph node (SN) biopsy will increasingly replace axillary lymph node dissection (ALND) for staging in breast cancer. For daily practice, examination of the SN by serial sectioning (SS) and/or immunohistochemistry (IHC) is being promoted. Use of these techniques may result into stage migration due to the increased detection of micro-metastases. The consequence may be overshooting of patients with adjuvant therapy, as the prognostic relevance of (small) micro-metastases and isolated tumor cells is unclear. METHODS: The prognostic impact of micro-metastases is determined by reviewing ALND studies with a follow up of at least 5 years, including more than 100 patients, before the SN era. Furthermore, studies in which conventionally haematoxylin-eosin (H&E) negative SNs are investigated for occult metastases by SS and/or IHC are reviewed. RESULTS: In only one of eight studies, occult metastases were an independent risk factor for reduced survival. The outcome is dependent on the size of the nodal metastasis. IHC and SS as used in the SN procedure indeed induce a shift from pNO to pN1a (according to TNM). CONCLUSION: By the thorough pathologic examination of the SN, isolated tumor cells and micro-metastases are more frequently detected. We propose to classify small micro-metastases (<0.5 mm) in a separate pN1a(min) category (min for minimal) to prevent stage migration. As the prognostic relevance of isolated tumor cells and (small) micrometastases has not been proven, the value of adjuvant therapy can be questioned for patients with otherwise good prognostic factors.

Axilla↗
PubMed1998

Identification of superior markers for polymerase chain reaction detection of breast cancer metastases in sentinel lymph nodes.

Sentinel lymph node biopsy (SLNB) is being evaluated in breast cancer patients to improve detection of metastases and to guide therapy with minimal morbidity. The use of reverse transcription-PCR analysis to increase detection of tumor cells in SLN of breast cancer patients is hampered by the lack of specific markers. In this study, seven markers were evaluated by reverse transcription-PCR for expression in human breast adenocarcinoma lines (BrCa) and in normal nodes from non-cancer patients. Two markers yielded exceptional results; mammaglobin and carcinoembryonic antigen transcripts were detected in 100 and 71% BrCa, respectively, and were absent from all normal lymph nodes. These markers will be used as components of a multimarker panel to evaluate sentinel nodes in an on-going, multicenter clinical trial.

Biomarkers, Tumor↗
PubMed2002

Comparison of accumulated allele loss between primary tumor and lymph node metastasis in stage II non-small cell lung carcinoma: implications for the timing of lymph node metastasis and prognostic value.

Although the Tumor-Node-Metastasis staging of non-small cell lung carcinoma (NSCLC) is the most effective predictor of survival, the clinical outcome of patients at each stage is variable on an individual case basis. We tested the value of incorporating information about the tumor heterogeneity of NSCLC into microsatellite allelotyping in a cohort of 48 node-positive stage II patients (T1N1M0 and T2N1M0). Microsatellite allelotyping involved microdissection of the invasive component of primary tumor and lymph node metastasis at multiple target sites followed by loss of heterozygosity (LOH) analysis at specific regions on chromosomes 1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, and 18q using 16 markers. All microsatellites manifested LOH ranging from 44 to 76% in primary tumor and showed various degree of heterogeneity between primary tumor and lymph node metastasis. LOH on 3p and 5q in the lymph node metastases was associated significantly with shortened survival of the patients (P = 0.033 and 0.004, respectively), whereas no single LOH in the primary tumors showed association with prognosis. For the analysis of the accumulated load of allele loss, fractional allele loss (FAL) was calculated for each sample. The maximal FAL of lymph node metastasis was significantly lower than that of primary tumor (P = 0.0015), possibly reflecting the early lymphatic spread. High maximal FAL of lymph node metastasis was significantly correlated with an adverse outcome (P = 0.012), whereas maximal FAL of primary tumor did not show any prognostic significance (P = 0.552). A composite mutational profile for each patient based on the allelotyping of the primary tumor and lymph node deposits may make a significant contribution to a more accurate prognosis of stage II NSCLC.

Aged↗
PubMed2003

Validity of intraoperative pathological diagnosis of paratracheal lymph node as a strategy for selection of patients for cervical lymph node dissection during esophagectomy.

The aim of this paper is to examine whether intraoperative examination of paratracheal nodes can indicate cervical node dissection and whether this approach is valid. From 1988 to 1997, 76 patients with thoracic esophageal squamous cell carcinoma received esophagectomies with and without cervical lymph node (LN) dissection based on the results of intraoperative pathological diagnosis from selective checking of paratracheal LN. We retrospectively examined the outcomes for the patients and the micro metastasis in the dissected lymph node using cytokeratin staining. Three of the seven patients with cervical LN dissection were detected as having cervical LN metastasis by postoperative hematoxylin-eosin or cytokeratin staining. Five (7%) of the 69 patients without cervical LN dissection had cervical LN recurrence after the operation. Four of the seven patients who were diagnosed as having metastasis or micro metastasis in paratracheal LN by postoperative examination had cervical LN recurrence after the operation. In conclusion, the esophagectomy with and without cervical LN dissection for thoracic esophageal squamous cell carcinoma based on the results of intraoperative pathological diagnosis from selective checking of paratracheal LN was not fully acceptable. The reliability of intraoperative pathological diagnosis of selective checking may improve by increasing the number of checked LN and the detection of micro metastasis.

Aged↗
PubMed2004

Failure in the detection of the sentinel lymph node with a combined technique of radioactive tracer and blue dye in a patient with cancer of the vulva and a single positive lymph node.

BACKGROUND: In early stage vulvar cancer, the sentinel lymph node procedure with a radioactive tracer appears to be a promising new diagnostic tool to predict lymph node status. No detection failures have been published so far in vulvar cancer. We recently experienced failure in the detection of the sentinel lymph node in a patient with a positive lymph node. CASE: A 75-year-old patient with a clinical T2N0M0 squamous cell carcinoma replacing the clitoris underwent a sentinel node procedure. A sentinel node was detected only at one groin. An exploration of the other groin showed a positive lymph node totally replaced by tumor. CONCLUSION: In the case we present, stasis of the lymph flow might be the leading cause of the failure of the sentinel lymph node procedure.

Aged↗
PubMed2004

[Whether VI region lymph nodes belong to primary site of the thyroid carcinoma or lateral cervical lymph node metastases].

OBJECTIVE: To discuss the evaluation of elective neck dissection (END) for the cN(0) patients with papillary thyroid carcinoma (PTC). METHODS: By analyzing the recurrent and metastatic region (thyroid, group VI lymph nodes, lateral neck region, beyond neck) of 139 PTC patients treated secondly in our hospital, group VI lymph nodal metastasis is divided into recurrence of primary site and distinguished from lateral neck lymph nodes. The clinical value of END for cN(0) PTC patients is also retrospectively analyzed. RESULTS: Thyroidal recurrence accounts for 83% (73/88). Level VI metastasis accounts for 76% (67/88), 17 patients have received END and account for 65% (17/26). Metastasis to lateral neck lymph nodes account for 17% (17/98), among these patients, 5 patients have received END and account for 19% (5/26). CONCLUSIONS: For the patients with cN(0) PTC, ipsilateral thyroid lobectomy plus level VI dissection is recommended and lateral END (level II-V) is not supported. For the patients with cN(0) but UB N(+) and/or CT N(+), lateral END (level II-V) is recommended. The necessity of CT examination in the diagnosis and treatment of thyroid cancer should be emphasized.

Adolescent↗
PubMed2007

The expression of retinoic acid receptors in lymph nodes of young children and the effect of all-trans-retinoic acid on the B cells from lymph nodes.

To elucidate the mechanism of vitamin A enhancing the production of antibody, we examined the expression and distribution of retinoic acid receptors mRNA in lymph nodes of young children ( < or = 5 years of age), and investigated the affection of all-trans-retinoic acid on the maturation and activation of the B cells isolated from the lymph nodes and cultured in vitro. Twenty-four normal lymph nodes were collected. By in situ hybridization, we found that all six retinoic acid receptor genes expressed and distributed widely in the lymph nodes, and the levels of mRNA for retinoic acid receptor genes (detected by RT-fluorescent quantitative PCR) were increased with the development of children. In vitro culture, all-trans retinoic acid promoted the maturation and activation of the B cells from the lymph nodes. Thus, promotion on B cells in lymph node may be the important mechanism of vitamin A reinforcing the humoral immunity in young children.

Age Factors↗
PubMed2002

Completion axillary lymph node dissection minimizes the likelihood of false negatives for patients with invasive breast carcinoma and cytokeratin positive only sentinel lymph nodes.

OBJECTIVE: To document the incidence of metastatic disease in complete axillary lymph node dissections (CALND) of patients with invasive carcinoma after a sentinel lymph node (SLN) biopsy, positive only by immunohistochemical staining for cytokeratin (CK-IHC). METHODS: Sections of all SLNs, negative by routine histology, were immunostained and examined for cytokeratin positive cells. Sections of lymph nodes from CALND specimens were interpreted using routine hematoxylin and eosin (H&E) staining. RESULTS: A total of 409 patients (29.6%) had metastatic disease in at least one sentinel lymph node on H&E examination. Of 971 H&E negative patients, 78 (8.0%) were positive only by CK-IHC. Sixty-two of the CK-IHC positive only patients underwent CALND. Nine of these 62 patients (14.5%) had metastases identified in the CALND specimen. CONCLUSIONS: Because 14.5% of patients with invasive breast cancer and SLNs positive only by CK-IHC were found to have H&E positive lymph nodes on CALND, we conclude first, that CK-IHC should be used to evaluate SLNs, and second, that CALND should be considered when SLNs are positive by CK-IHC only. This approach will result in an absolute reduction of the false negative rate (absolute false negative rate reduced by 2.6% in our series).

Adenocarcinoma↗
PubMed2002

The effect of platinum-based combination chemotherapy on the lymph nodes in advanced-stage epithelial ovarian cancer: does it decrease the incidence of lymph node involvement?

This paper aims to determine the impact of platinum-based combination chemotherapy on the lymph nodes in advanced-stage epithelial ovarian carcinoma. From 1997 to 2000, the patients in whom we performed lymphadenectomy before (group A) or after chemotherapy (group B) in the Department of Obstetrics and Gynecology, Akdeniz University School of Medicine were enrolled in this study. A total of 47 cases were included in the study. Twenty five cases had lymphadenectomy during the initial laparatomy and 22 cases during second-look procedures. Lymph node metastasis was detected in 14 (56%) patients in group A and in 10 (45.4%) cases in group B (P > 0.05). Platinum-based combination chemotherapy does not decrease significantly the incidence of involved lymph nodes in advanced-stage epithelial ovarian carcinoma.

Adult↗
PubMed1998

A modified murine local lymph node assay for the differentiation of contact photoallergy from phototoxicity by analysis of cytokine expression in skin-draining lymph node cells.

Since predictive differentiation of photoallergenic from phototoxic reactions, induced by low molecular weight compounds, represents a current problem, we tried to improve the differentiation between the two reactions by using a modified protocol of the local lymph node assay (LLNA). Briefly, groups of female BALB/c mice received compound solution or vehicle alone on the dorsum of both ears on 3 consecutive days. Immediately after compound application indicated groups of mice were exposed to a UVA light-dose of 10 J/cm2. Auricular lymph nodes draining the ear tissue were excised 24 h following the last exposure. Evaluation consisted of assessing lymph node weights and cell counts to monitor organ hyperplasia and in vivo-proliferative events following substance application. Furthermore, we analysed cytokine gene transcription in freshly prepared lymph node cells (LNC) and the cytokine release in vitro by restimulated CD4+ T-cells and antigen presenting cells (APC), both purified from the skin-draining lymph nodes. Both contact (photo) allergenic (oxazolone and tetrachlorosalicylanilide) and phototoxic substances (8-methoxypsoralen and acridine) caused a dose dependent increase in lymph node weights and cell counts pointing to an inflammatory process in the lymph nodes. Analysis of cytokine gene transcription ex vivo and cytokine release in vitro revealed that during the induction phase of contact (photo) allergy CD4+ T-cells produced IL-2 and IFN-gamma as well as IL-4 and IL-10, whereas IL-6 was derived from APC. In contrast, phototoxic reactions caused only an upregulation of IL-2 and IFN-gamma. Furthermore, we demonstrate that the release of IL-4 and IL-10 by CD4+ T-cells was clearly increased, whereas IL-6 and IFN-gamma expression was reduced or not changed following a challenge with contact (photo) allergens revealing an allergy-indicative shift in cytokine expression. In conclusion, our results show that contact photoallergenic reactions could be differentiated from phototoxic events by analysis of LNC cytokine expression patterns.

Animals↗
PubMed2003

Stage migration in breast cancer: surgical decisions concerning isolated tumour cells and micro-metastases in the sentinel lymph node.

AIMS: Sentinel lymph node biopsy has replaced the axillary lymph node dissection (ALND) in primary surgery for breast cancer in many hospitals and is expected to become the standard of care in due time. Since the sentinel lymph node is subjected to more extensive pathologic examination than the lymph nodes in the axillary dissection specimen, more patients are found to be node positive (N+); however many of them contain micro-metastases (<or=2mm). The consequence may be an overshoot of therapy: additional surgery for non-metastatic lymph nodes or systemic adjuvant therapy. METHODS: We examined 34 (out of a series of 38) clinically T1 (cT1) patients who had a SLN biopsy with or without ALND and compared them to a matched historical control group. RESULTS: Twenty-one of 34 (62%) patients showed tumour cells in their SLN's. From these 21 patients in 13 (62%) the SLNs contained isolated tumour cells, of which 10 (77%) were detected only by immunohistochemistry (IHC), in four (19%) the SLNs contained micrometastases, and in four (19%) macrometastases. From 16 patients with isolated tumour cells or micrometastases in the SLN who underwent a regular ALND one had an H&E detected isolated tumour cell in a non-SLN and one patient with isolated tumour cells in the SLN who did not get a regular ALND developed an axillary recurrence 11 months after the primary treatment. On the other hand, three of four (75%) patients with macrometastases in the SLN had pathologically involved non-SLNs. In the majority (70%) of patients of the historical control group no lymph node involvement was seen. The percentage of macrometastases staged as lymph node positive in the control group was the same as in the studied group. CONCLUSION: Most patients with cT1 breast cancer with isolated tumour cells or micrometastases in the SLN will not benefit from additional axillary dissection; 88% had a negative ALND. Since we cannot select the group that will benefit from ALND, this is still indicated in case of isolated tumour cells or micrometastases in the SLN. Since most of the affected SLNs show isolated tumour cells and are classified as pN0(i+), stage migration due to more meticulous pathologic examination does not occur according to the TNM classification. However some patients do not benefit from the introduction of the SLN, due to the high incidence of isolated tumour cells or micrometastases in the SLN. Many more patients than expected still end up with an ALND.

Axilla↗
PubMed1989

Lymph node macrophage heterogeneity: the phenotypic and functional characterization of two distinct populations of macrophages from rat lymph node.

The isolation and characterization of lymph node macrophages (M phi) has shown a hitherto unknown heterogeneity. Two types of M phi were distinguished by morphology, monoclonal antibody staining and functional assays. The type I M phi failed to express surface Ia even when activated, a characteristic which has only previously been reported for splenic marginal zone M phi; despite studies suggesting an antigen presentation role for the M phi, the failure to express surface Ia would seem to eliminate an interaction with T helper cells for the type I M phi in the lymph node. In contrast, the type I M phi, other characteristics of clustering with activated B cells in vitro, the colocalization of the type I M phi and activated B cells in situ, the specific uptake of thymus-independent type 2 antigens and the failure to undergo respiratory burst activity all suggest a M phi-B cell interaction, possibly of a trophic nature. The defective microbicidal activity of the type I M phi may have been compensated for by the type II M phi, which expresses both strong respiratory burst activity and surface Ia expression when freshly isolated. However, unlike the inflammatory M phi the activated phenotype of the type II M phi did not appear to be interferon-gamma dependent because type II M phi could also be isolated from nude rat lymph nodes.

Animals↗
PubMed1983

The migration of lymphocytes across specialized vascular endothelium. VI. The migratory behaviour of thoracic duct lymphocytes retransferred from the lymph nodes, spleen, blood, or lymph of a primary recipient.

Thoracic duct lymphocytes labelled with 51Cr were injected into a primary recipient and then were transferred for a second time from the lymph nodes (cervical and/or mesenteric), spleen, lymph, or blood into a series of final recipients. Measurement of the organ distribution of labelled lymphocytes in the final recipients enabled three main conclusions to be drawn. (1) Lymphocytes that had localized in the spleen, mesenteric lymph nodes (LN), or cervical LN of the first recipient showed no tendency to return in increased numbers to the same organ in the final recipient. (2) Lymphocytes that had recently entered the spleen or LN were temporarily impaired in their ability to reenter LN. This capacity was recharged when the cells returned to the lymph and the blood. (3) Lymphocytes that had been passaged from blood to lymph and collected for up to 4 hr at room temperature entered the LN of a recipient much faster than did nonpassaged thoracic duct lymphocytes collected overnight at 0 degree C. Supplementary experiments indicated that the different migratory behavior of thoracic duct lymphocytes under these two circumstances was mainly a consequence of their handling in vitro during the collecting and the labelling procedures. This functional impairment was not associated with a diminished ability to enter the spleen and bone marrow or to survive in recipients for up to 24 hr.

Animals↗
PubMed2000

Thymus and lymph node cell CD4(+) and CD8(+) marker expression and their angiogenic activity of offspring of salbutamol-treated pregnant C3H mice.

Salbutamol, beta(2)-adrenoceptor agonist is a first choice drug in preterm delivery treatment. The aim of the present study was to determine whether salbutamol can cause any alterations in neonatal immune systems and therefore should be considered in newborn care. The experiments were performed on 4-5- and 6-7-week-old female and male offspring of salbutamol-treated C3H inbred mice. Thymus and lymph node weight, cellularity and lymphatic organs, lymphocytes phenotypes and their angiogenic activity were evaluated. We observed lower thymus weight in 6-7-week-old progeny of salbutamol-treated mothers and in the same time lower thymus cell number in both age groups. Lower lymph node weight was developed in older progeny while cellularity was diminished both in 4-5- and 6-7-week-old offspring of salbutamol-treated mothers. We have not detected any changes in percentage of CD4, CD8, CD3 and CD4CD8 positive lymphocytes in progeny of salbutamol-treated mothers. As far as lymph node lymphocytes phenotype is considered we showed in both age groups lowering of CD4 and CD3 positive cells in experimental groups. In the LIA test (lymphocyte-induced angiogenesis) we showed lower lymph node cell angiogenic activity of salbutamol-treated mothers' progeny in both age groups. In the case of thymus lymphocytes we have not observed any alterations in their angiogenic activity. The differences in histological examination of thymus and lymph nodes were not detected in experimental and control groups.

Adrenergic beta-Agonists↗