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'Increased expression of seprase, a membrane-type serine protease, is associated with lymph node metastasis in human colorectal cancer'.

Seprase is a membrane-bound serine proteinase with gelatinase activity, which may be involved in cancer invasion and metastasis. We examined seprase expression in colorectal cancer specimens obtained from 109 patients. Seprase immunoreactivity was found in cancer cells and adjacent stromal cells. Immunoblotting showed higher levels of seprase protein in colorectal cancer tissue than in normal colorectal tissue. A semiquantitative assessment of the immunohistochemistry results revealed a significant correlation between seprase expression and lymph node metastasis. These results suggested that an abundant expression of seprase in colorectal cancer tissue is associated with lymph node metastasis.

Adult↗

Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model.

Activation of matrix metalloproteinase-2 (MMP-2) is a common event in head and neck squamous cell carcinoma. An OSC-19 cell line, derived from human oral squamous cell carcinoma and known to metastasize to cervical lymph nodes, was implanted into the lingual margin of mice. The effect of marimastat (BB-2516), a broad MMP inhibitor, on the suppression of regional cervical lymph node metastasis was evaluated with an orthotopic implantation nude mice model. Marimastat was given immediately after OSC-19 implantation and continuously administered by an osmotic pump. The mice were divided into three groups by marimastat dose; Group A; 0 mg/kg/day, Group B; 30 mg/kg/day, and Group C; 150 mg/kg/day. Twenty-one days after implantation, primary oral tumors and cervical lymph nodes were resected. Cervical lymph node status was microscopically examined. Activation of MMP-2 in primary oral tumor was examined by gelatin zymography. Both cervical lymph node metastasis and activation of MMP-2 were significantly suppressed in Group C (P < 0.05). Moreover, the Group C mice had a significantly better survival than group A (P = 0.0026). There was a significant difference between Group A and Group C in terms of proliferation of tumor cells by proliferating cell nuclear antigen immunostaining (P = 0.0120). These results suggest a positive role for marimastat in the inhibition of MMP-2 activation and prevention of cervical lymph node metastasis in oral squamous cell carcinoma (OSCC). Improvement of survival in patients with OSCC could be expected using adjuvant therapy with marimastat.

Animals↗

Prediction of cervical lymph node metastasis in squamous cell carcinoma of the tongue/floor of mouth.

BACKGROUND: Cervical lymph node metastasis has a major influence on survival in oral cancer. However, the factors influencing its occurrence are uncertain. Our aim was to improve the prognostic efficiency of the histologic assessment of the primary tumor in predicting metastasis in an individual patient. METHODS: The relationship between selected clinical and histologic features of the primary tumor of tongue/floor of the mouth and the actual metastatic status was investigated in 45 patients. Invasive cell grading was supplemented by histologic measurements of tumor size and assessments of vascular and perineural invasion. RESULTS: Ten histologic features showed significant differences in relation to metastasis. A logistic regression model with two predictor variables (total histologic malignancy score and vascular invasion) classified correctly 39 (87%) of the 45 cases. CONCLUSIONS: Histologic assessment of tumor size and malignancy grade are useful in predicting metastasis. Vascular and perineural invasion are important predictors and should be included in multifactorial malignancy grading schemes. Application of the prognostic index to the biopsy specimen would aid in treatment planning.

Adult↗

[Analysis of the p53 gene status of lymph node metastasis in the head and neck region in occult primary cancer].

BACKGROUND: Lymph node metastasis in the head and neck region with occult primary cancer are a fairly rare tumor entity in head and neck cancer. Tumor biological parameters as well as mechanism and cause for the development of this so called "cancer of unknown primary" (CUP) are not well investigated in head and neck cancer. Mutations of the p53 tumor suppressor gene are the most prevalent genetic alteration of human malignancies and show an incidence of up to 50% in head and neck cancer. For a further tumor biological definition of CUP the p53 status was determined. METHODS: Twenty-three archival formalin fixed paraffined CUP of an occult squamous cell carcinoma of the head and neck region were examined. In all cases a primary cancer was never diagnosed. The DNA extracted from the tumor material was amplified with specific primers for exon 4-9 of the p53 gene and subsequently sequenced. RESULTS: None of the 23 CUP cases showed a mutation or polymorphism in exon 4-9 of the p53 gene. CONCLUSIONS: The total absence of p53 mutations in the so called mutational "hot spots" shows a significant difference to the frequency of primary tumors of the head and neck region. May be this tumor biological characterisation helps to further elucidate the growth behaviour of CUP in the head and neck region and the reason for their development.

Antisense Elements (Genetics)↗

[Three cases of occult thyroid cancer with mediastinal lymph node metastasis manifesting as a mediastinal cyst].

We experienced three cases (one 38-year-old male, 58-year-old and 67-year-old females) whose resected mediastinal cysts proved to be metastatic lymph nodes from occult thyroid cancer. Primary lesions in thyroid gland were detected by echography in all three cases though they were detected in one case out of two by CT, in one out of three by 201T1 scintigraphy, in two out of three by 123I scintigraphy. After these examinations on thyroid gland, operations (one lobectomy, one hemithyroidectomy, one total thyroidectomy) were performed. Primary lesions in thyroid gland were all papillary carcinomas, and ranged 4 x 3 mm to 12 x 10 mm in size. Multiple foci were found in two cases, many intrathyroidal metastases in one case, cervical lymph node metastases in two cases. In cases of mediastinal cyst, thyroid gland should be examined by echography paying attention to the mediastinal lymph node metastasis from occult thyroid cancer. When occult thyroid cancer with mediastinal lymph node metastasis is diagnosed, total thyroidectomy followed by 131I radiation therapy is recommended as the treatment for a primary lesion, because of multiple foci in thyroid gland and intrathyroidal metastases.

Adult↗

A case of breast cancer diagnosed by inguinal lymph node metastasis.

We describe a case of a 58-year-old woman with right inguinal lymph node swelling and a T1 tumor in the right breast. She was referred with an 18-month history of the former complaint and a six-month history of the latter. Excisional biopsy of the inguinal lymph node revealed breast cancer metastasis. Radiographical examination showed no metastases to the lungs, liver or bone. Modified radical mastectomy was performed. Histological examination revealed solid tubular carcinoma, PT2, PM (axillary lymph node metastases 4/16), stage IV. Estrogen and progesterone receptors were negative. Three cycles of postoperative cyclophosphamide, adriamycin and 5-fluorouracil (CAF) chemotherapy were given, and the right inguinal area was irradiated with 40 Gy. The patient complained of swelling in both legs three years after surgery. Computed tomography revealed marked lymph node swellings in the pelvic cavity. She died six months later. Inguinal lymph node metastasis from breast cancer is very rare, although distant lymph node metastasis in the cervix occurs frequently. This case should help clarify how breast cancer metastasizes to distant lymph nodes.

Adenocarcinoma↗

DNA ploidy is closely linked to tumor invasion, lymph node metastasis, and prognosis in clinical gastric cancer.

DNA ploidy microspectrophotometrically determined in 254 patients with gastric carcinoma was investigated from the standpoint of tumor invasion, lymph node metastasis, and prognosis. DNA distribution patterns were grouped into low and high ploidies. The 24.0% frequency in the high ploidy group, at the mucosal stage, increased in proportion to invasion into the deeper layers. There was a high incidence of lymph node metastasis in the high ploidy group, compared with the low ploidy group, in case of invasion beyond the mucosa. Widespread nodal involvement was frequent in the high ploidy group. The 5-year survival rate was 73.7% in patients of high ploidy, with a statistical difference compared to the 90.6% in those of low ploidy (P less than 0.01). In the multivariate analysis of 226 patients undergoing curative surgery, the DNA ploidy proved to be a major independent prognostic factor. These findings indicate a close correlation among DNA ploidy, tumor invasion and nodal involvement, and the significant clinical value of DNA analysis for predicting the prognosis in patients with gastric carcinoma.

Aged↗

[NDPK/nm23 expression and its correlation with lymph node metastasis in human lung cancer].

Using labelled streptavidin-biotin (LSAB) method, we examined the expression of nucleoside diphosphate kinase(NDPK), the product of metastasis suppressor gene nm23, in human lung cancer. Of 88 patients tested, 48 (54.5%) showed positive staining. The positive staining rate was higher in adenocarcinoma (28/42, 66.7%) than in squamous cell carcinoma (20/46, 43.5%; P < 0.05). Higher incidence of positive staining was also found in squamous cell carcinoma without hilar or mediastinal lymph node metastasis (16/27, 59.3%) than in that with hilar or mediastinal lymph node involvement (4/19, 21.1%; P < 0.05). NDPK/nm23 was equally expressed in adenocarcinoma irrespective of lymph node status. In both cell types of carcinoma, expression of NDPK/nm23 was not correlated with tumor cell differentiation, nor was it correlated with the P-TNM staging. Our results suggest that NDPK/nm23 may play different roles in the pathogenesis and metastasis of human pulmonary squamous cell carcinoma and adenocarcinoma. Its expression levels are inversely correlated with lymph node metastasis in squamous cell carcinoma.

Adenocarcinoma↗

Impact of lymph node metastasis in differentiated carcinoma of the thyroid: a matched-pair analysis.

BACKGROUND: Cervical lymph node metastasis in differentiated thyroid carcinoma has mostly been found to have little relationship to prognosis. However, some studies report nodal involvement to be an adverse factor, while others have found it to be favorable. We have undertaken a matched-pair analysis of previously untreated patients, with and without ipsilateral neck metastasis, to examine the significance of nodal spread in patients with otherwise equivalent prognostic factors for differentiated thyroid cancer. METHOD: From a database of 931 patients, treated from 1930 to 1980, we used a computer to match patients with confirmed lateral neck metastasis (N1) to those who were stage NO, and had the following identical prognostic factors: no distant metastasis, age (within 4 years), and tumor size, histology, and intrathyroidal extent. When possible, matches were also made for gender, multifocality, and extent of thyroid surgery. Survival and treatment failures were analyzed, with and without stratification for age. RESULTS: We were able to select 100 N1 patients with corresponding NO patients, sharing the major prognostic risk factors as listed. Overall, there was no difference in survival, although N1 patients more often had recurrence. Mortality increased with age. Analysis at high-risk age (45 years and older) showed significantly more recurrences in N1 patients (p = .008). Twenty-year survival in N1 patients over the age of 45 was lower than that of NO patients. On the other hand, under the age of 45, N1 patients had better survival. These differences, however, did not reach statistical significance. CONCLUSION: Nodal involvement in older patients with thyroid cancer increases the risk of recurrence, although no significant difference in survival is observed in relation to age.

Adenocarcinoma↗

[Influence of the number of lymph node metastasis on survival and significance of postoperative radiotherapy for esophageal carcinoma].

OBJECTIVE: To analyze the influence of the number of lymph node metastasis on survival and prophylactic postoperative radiotherapy after radical resection of thoracic esophageal carcinoma. METHODS: Four hundred and ninety-five patients with thoracic esophageal squamous cell cancer who had undergone radical resection were randomly divided into surgery group alone (S, 275) and surgery plus radiotherapy group (S + R, 220). The patients were classified into three groups: Group A: 234 patients (47.2%) without lymph node involvement; Group B: 146 patients (29.5%) with 1 to 2 involved lymph nodes and Group C: 115 patients (23.2%) with >or= 3 involved lymph nodes. RESULTS: 1. The 5-year survival rate in Groups A, B and C for the same T stage (T3) was 52.6%, 28.8% and 10.9%, respectively (P = 0.0000); the 5-year survival rate in group C was 0% in S group and 19.3% in S + R group (P = 0.0336); 2. In the positive lymph node group, the metastatic rate of intra-thoracic and supraclavicular lymph node was 35.9% and 21.2% in S group and 19.7% and 4.4% in S+R group (P = 0.014 and P = 0.000). In the negative lymph node group, the metastatic rates of intra-thoracic lymph node was 27.8% in S group and 10.3% in S + R group (P = 0.003). The metastatic rate of intra-abdominal lymph node in Groups A, B and C was 3.9%, 9.4% and 17.5%, respectively (P = 0.0000). The occurrence of hematogenous metastasis was most frequent in group C (27.8%) with >or= 3 positive lymph nodes. CONCLUSION: 1. The number of metastatic lymph node is one of the important factors which affects the survival of thoracic esophageal carcinoma. 2. Chemotherapy might be given to the patients with three or more lymph nodes involved who have the possibility of developing hematogenous metastasis. Postoperative radiotherapy can reduce the occurrence of intra-thoracic and supraclavicular lymph node metastasis and improve the survival of patients with three or more lymph nodes involvement.

Adult↗

Vascular endothelial growth factor and lymph node metastasis in primary lung cancer.

The relationship between vascular endothelial growth factor (VEGF) and lymph node metastasis was studied in 90 cases of primary lung cancer without distant metastasis. As a result of quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, the VEGF121 mRNA expression levels in lung cancer tissues with nodal metastasis (n = 35) were higher than in those without nodal metastasis (n = 55). However, no significant difference could be found in VEGF121 mRNA expression levels as stratified by tumour size (T1N0M0 vs T2N0M0). Simultaneously, ten lymph nodes (four node positive and six node negative) together with the corresponding primary lung tumours and adjacent normal lung tissue, were studied for VEGF expression. The VEGF mRNA expression in metastatic lymph nodes was intense in three out of the four cases examined. Further, while VEGF expression levels in metastatic lymph nodes were conspicuously higher than those for the primary site, all its expression levels in non-metastatic nodes were inferior to those of the primary tumours. Except for macrophages, the VEGF antigen was identified mainly in the cytoplasm of metastatic cancer cells and the endothelial cells of blood or lymphatic vessels in lymph nodes. Although the detailed mechanisms and the significance of strong VEGF expressions in metastatic lymph nodes are still unknown, these data are consistent with a model whereby VEGF increases the opportunity for nodal metastasis through neoblood and lymphatic vessels.

Aged↗

The usefulness of MRI and PET imaging for the detection of parametrial involvement and lymph node metastasis in patients with cervical cancer.

OBJECTIVE: The purpose of this study is to elucidate the usefulness of magnetic resonance imaging (MRI) and positron emission tomography (PET) for the detection of parametrial involvement and lymph node metastasis in patients with cervical cancer. METHODS: Thirty-six patients with cervical cancer were retrospectively enrolled. MRI and PET scans were performed for all patients within a week before radical surgery. The criterion for malignancy on MRI was >1 cm short axis diameter of the suspected lymph node. On PET, only fluorodeoxyglucose (FDG) uptake was significantly higher than the background and, if this FDG uptake showed on at least two consecutive axial slices, then the lesion was considered as a malignancy. We compared the extent of tumor on the surgical findings with the FIGO staging, MRI and PET scans. RESULTS: The accuracy of FIGO and MRI staging was 67 and 84.4%, respectively. The accuracy for detecting pelvic lymph node metastasis was better for PET than for MRI (78 versus 67%, respectively). All FDG uptake lymph nodes were confirmed as metastatic lymph nodes by pathological evaluation; this included five lymph nodes <1 cm in diameter. CONCLUSION: MRI provides an improved evaluation of local tumor extension, but PET is more useful for the evaluation of pelvic lymph nodes than MRI; however, PET still misses microscopic disease. Further studies are necessary to evaluate the usefulness of PET/computed tomography (CT) for the accuracy of the disease extension and the cost-effectiveness of MRI, PET or PET/CT in patients with cervical cancer.

Carcinoma, Squamous Cell↗

Expression of Fas ligand in gastric carcinoma relates to lymph node metastasis.

Tumors may escape a host's immune response by means of various mechanisms. The Fas (CD95/APO-1)/Fas ligand (FasL) system is one of the major apoptotic pathways. Recently, it has been reported that tumor cells can express FasL, induce apoptosis in tumor infiltrating lymphocytes, and thus can escape host immune surveillance. In gastric carcinoma, tumor progression by way of the lymphatics is often seen, and lymph node metastasis is a critical factor influencing the recurrence of cancer and its prognosis. We, therefore, investigated the relationship between the expression of FasL and the lymphatic spread of gastric carcinoma. FasL-expression was examined by an immunohistochemical method using 100 surgically resected gastric carcinomas and 55 metastatic lymph nodes. Apoptotic cells among tumor infiltrating T lymphocytes were detected by T lymphocyte staining and the terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) method in a series of sections of metastatic lymph nodes. FasL-expression was detected in 86% of primary lesions and 71% of metastatic lymph nodes. In cases with high levels of FasL-expression, the observed expression of lymph node metastases was significant (p=0.047). Moreover, FasL-positive cases with both primary lesions and metastatic lymph nodes showed also distant lymph node metastasis beyond the regional lymph nodes (p=0.030). Apoptosis among tumor infiltrating T lymphocytes was more frequently seen in FasL-positive lesions (p=0.057). Furthermore, patients with FasL-negative primary lesions tended to exhibit longer survival times than patients with FasL-positive primary lesions. The results suggest tumor escape through the lymphatic pathway via FasL-expression in gastric carcinomas.

Adenocarcinoma↗

Predicting the patient at low risk for lymph node metastasis with localized prostate cancer: an analysis of four statistical models.

PURPOSE: Statistical models using preoperative Prostate-Specific Antigen, Gleason primary grade or score of the biopsy specimen, and clinical stage have been developed to predict those patients with clinically localized prostate cancer at low risk for lymph node metastasis. It has been recommended that these patients do not require pelvic lymph node dissections. Four such models were evaluated to assess their accuracy in identifying this subgroup of patients. METHODS AND MATERIALS: We reviewed the records of 214 patients with clinically localized prostate cancer who underwent pelvic lymph node dissections. Data from these patients were entered into the four models. RESULTS: Lymph node metastasis was detected in 14% of patients. The results showed the following for each of the proposed models respectively: 78, 50, 76, and 42% of the patients were identified as low risk and, hence, would be spared pelvic lymph node dissections. The false negative rates are 13 (7.8%), 5 (4.6%), 14 (8.6%), and 1 (1.1%). Sensitivities are 56.7, 83.3, 53.3, and 96.7%. CONCLUSIONS: While the pelvic lymph node dissection is the most accurate method of detecting occult nodal metastasis, statistical models can identify a cohort of low risk patients that may be spared lymphadenectomy.

Adult↗

Perivascular-submandibular lymph node metastasis in squamous cell carcinoma of the tongue and floor of mouth.

AIMS: The goal of this study was to investigate the incidence of occult metastasis in perivascular lymph node and nodal recurrence in these nodal pads in squamous cell carcinoma (SCC) of the tongue and floor of mouth. METHODS: We performed a prospective analysis of the incidence of an occult metastasis in the perivascular lymph nodes in 55 patients (41 with an oral tongue carcinoma and 14 with a mouth floor carcinoma) who underwent an elective supraomohyoid neck dissection (SOHND) for SCC of the tongue and floor of mouth, from 1997 to 2002. 99 SOHND procedures were performed as follows: 72 in tongue carcinomas and 27 in the mouth floor carcinomas. RESULT: Clinically occult, but pathologically positive perivascular lymph nodes occurred in four of 72 of the tongue carcinomas and two of 27 of the mouth floor carcinomas. The incidence of the regional recurrence at level I was three of 45. CONCLUSIONS: This preliminary report reveals a small incidence of perivascular lymph-node metastases and the infrequent nodal recurrence in this area after SOHND in early-staged tongue and floor of mouth SCC.

Adult↗

Lymph node metastasis in stage I ovarian carcinoma.

One hundred and sixteen cases of stage I ovarian cancer from 6 hospitals in China were investigated for their lymph node metastasis from September, 1982 to April 1991. Of them, 70 had epithelial tumor, 36 malignant germ cell tumor, 8 gonadal stroma, and 2 undifferentiated tumor. Ovarian tumor confined to one ovary (stage Ia) in 89 patients, both ovaries involved (stage IIb) in 6, and documented stage Ic in 21. Systemic lymphadenectomy involving all pelvic groups of node together with aortic lymph node was accomplished in 82 patients. In the remaining 34 patients, pelvic lymph node dissection was performed. The incidence of lymphatic metastasis was 10.3% in this series. Serous cystadenocarcinoma was the most common lesion. All patients were followed up for at least half year. The mortality rate in patients with and without lymph node metastasis was 8.3% and 2.8% respectively. The clinical significance of retroperitoneal lymphadenectomy in early ovarian carcinoma was discussed.

Adolescent↗

Results of radiation therapy in 19 dogs with cutaneous mast cell tumor and regional lymph node metastasis.

The records of 19 dogs with cutaneous mast cell tumor and regional lymph node metastasis (WHO Stage 2) were reviewed to determine the efficacy of radiation therapy in this population. Dogs with grade I (n = 1), grade II (n = 16), and grade III (n = 2) cutaneous mast cell tumor were included in this study. All dogs were treated with a combination of pre-irradiation surgical cytoreduction of the primary tumor, irradiation of the primary tumor and regional lymph node, and oral prednisone. Total radiation dose to the primary tumor and regional lymph node ranged from 48 to 57 Gray (Gy). The medial iliac and hypogastric lymph nodes were irradiated prophylactically in 11 dogs with primary tumor of the pelvic limb and positive ipsilateral popliteal lymph node. Total radiation dose to these lymph nodes ranged from 48 to 57 Gy. For all radiation fields, dose per fraction was 3 Gy, and therapy was administered on a Monday through Friday schedule. Acute and late radiation side effects observed in this study were considered acceptable. The median disease-free survival was 1,240 days (95% confidence interval 256 to 2,391 days). The disease-free survival in dogs with stage 2 mast cell tumor suggests that the combination of surgery, irradiation, and prednisone for the primary tumor along with irradiation of the positive lymph node is effective.

Animals↗

Parasternal lymph node metastasis of malignant peritoneal mesothelioma: report of a case.

We report a case of malignant peritoneal mesothelioma with parasternal lymph node metastasis. The patient was a 34-year-old man who presented with a history of several years of abdominal pain and ascites of unknown origin. Exploratory laparoscopic biopsies yielded histological findings of malignancy, but a final diagnosis was not able to be made. A chest computed tomographic scan done the following year showed a parasternal nodule, and thoracoscopically obtained biopsied material was positive for calretinin. These findings led to a pathological diagnosis of metastasis to the parasternal lymph node from peritoneal mesothelioma.

Adult↗