Relationship between nm23-H1 expression and lymph node metastasis and prognosis in cervical cancer

OBJECTIVE: To investigate the expression of nm23-H1 in cervical carcinoma and its significance. METHODS: Expression of nm23-H1 was examined by immunohistochemical method in 39 cases of adenocarcinoma and 39 cases of squamous cell carcinoma of the uterine cervix. The relationship between expression of nm23-H1 and clinic-pathologic factors and prognosis was analyzed by chi-square test. RESULTS: Positive staining rate of nm23-H1 was 44.6% in adenocarcinoma and 39.2% in squamous cell Carcinoma. The positive staining rate of nm23-H1 in stage I and II adenocarcinoma was 61.1% and 28.6% respectively (P = 0.044); in patients with recurrence nm23-H1 positive rate was lower than that in patients without recurrence (21.5% vs 56%, P = 0.39); in patients with lymph node negative, nm23-H1 positive staining was more than that in patients with lymph node positive (52% vs 28.6%), however, this difference was not statistically significant (P = 0.162). None of 14 cases of lymph node metastasis was strong positive stainig, whereas 7 of 25 without lymph node metastasis were demonstrated to have strong positive staining (P = 0.031). The 5-year survival rate in negative staining group was lower than that in the positive staining group (52.5% vs 82.4%, P = 0.042). In squamous cell carcinoma there was no statistically significant relationship between nm23-H1 expression and clinic-pathologic factors and prognosis. CONCLUSIONS: nm23-H1 expression was associated with biologic behavior in cervical adenocarcinoma.     

nm23 Protein expression in larynx cancer and the relationship with metastasis

The nm23 gene, which encodes nucleoside diphosphate (NDP) kinase, is proposed as a metastatic suppressor gene and has been demonstrated to correlate inversely with metastatic potential in several tumours. To elucidate the role of nm23 in larynx carcinomas, we examined using immunohistochemistry the expression of the nm23 protein in matched sets of primary tumours and metastatic lymph nodes. nm23 Protein was expressed in all the carcinomas as well as in non-neoplastic larynx mucosa. Overexpression of nm23 protein was found in the majority of primary tumours compared with corresponding normal mucosa, while decreased expression was associated with poor differentiation and distant metastasis and/or recurrence. No significant difference in age, sex and stage was found between primary tumours with high and low nm23 protein expression. These results suggest that decreased nm23 protein expression may play a role in metastasis and/or recurrence in larynx cancer and therefore could be used as a prognostic factor.     

Skip mediastinal lymph node metastasis in non-small cell lung cancer

We retrospectively investigated 186 non-small cell lung cancer cases with N2 disease in order to clarify the significance of skip metastasis. Of the 186 patients with N2 disease, negative N1 nodes recognized to be skip metastasis were seen in 62 patients (33%). The incidence of skip metastasis was not statistically different regarding histology, T status, or M status. The incidence of the skip metastatic site consisted of 35 cases (56%) at sites 1, 2 and 3, while 8 cases (13%) were found at sites 8 and 9. Among the patients with right lung cancer, the skip metastatic incidence for site 7 (subcarinal) was higher in patients with either middle lobe or lower lobe cancer than in those with upper lobe cancer (P < 0.05). The 5-year survival rates of all N2 patients in comparison to those with skip metastasis were 22% and 24%, respectively. When the sites of mediastinal lymph nodes were classified as superior, aortic, and inferior, the 5-year survival rates of the patients with superior skip metastasis, aortic metastasis, and inferior metastasis were 23%, 36%, and 15%, respectively. No statistical difference was observed. The 5-year survival rate of the skip N2 patients with only aortic region involvement was 50% (n = 7). However, no statistically significant difference was found between the two groups (P = 0.08). Our results thus suggested that mediastinal involvement for the aortic region alone might have a better prognosis than the others. We thus conclude that a dissection of the complete hilar and mediastinal lymph nodes should be the procedure of choice in standard operations for non-small cell lung cancer because of the high frequency of skip metastasis.     

Mediastinal lymph node metastasis from lung cancer: evaluation with Tl-201 SPECT--comparison with CT

PURPOSE: To assess the usefulness of thallium-201 single photon emission computed tomography (SPECT) in detection of mediastinal lymph node metastasis from lung cancer. MATERIALS AND METHODS: Computed tomography (CT) and Tl-201 SPECT were performed in 113 patients with lung cancer. Surgical staging was performed in all patients, and the results of the two modalities were compared with the pathologic findings in 364 node stations. RESULTS: Cancerous nodes were found in 32.7% of the patients. The sensitivity of CT in detecting mediastinal node metastasis was 62%; specificity was 80%. These rates were higher for Tl-201 SPECT (76% and 92%, respectively). Furthermore, these rates were excellent in patients with enlarged mediastinal nodes at CT (87% and 93%, respectively). However, Tl-201 SPECT had more limited spatial resolution than did CT. CONCLUSION: Tl-201 SPECT is useful in evaluation of mediastinal node metastasis in lung cancer, especially for patients with enlarged nodes at CT.     

Heterogeneous expression of nm23 gene product as a predictor of lymph nodal status in human breast cancer

The nm23 gene was originally identified by differential hybridization of metastatic murine melanoma cell lines. Some experimental studies demonstrated a significantly low metastatic potential of melanoma cell lines transfected with the nm23 gene. In this study, we clarified the relationship between intracellular nm23-immunoreactivity and lymph nodal status of human breast cancer. We analyzed 82 surgically removed breast tumors including 67 invasive carcinomas (ductal, lobular and mucinous carcinomas). The nm23 expression was diffusely positive in the benign tumors and non-invasive carcinomas. Of the invasive ductal carcinomas, lymph node metastasis was found in 67.7% (21/31) of the focally positive/negative cases and in 18.2% (4/22) of the diffusely positive cases (p<0.001). Immunohistochemically, advanced margins of invasive carcinomas with lymph node metastasis were shown to be negative for nm23 expression, while intraductal carcinoma components were positive. This observation suggested that focally positive/negative nm23 expression can be a predictor of lymph node metastasis of invasive ductal breast carcinoma.     

Mediastinal lymph node metastasis from esophageal carcinoma: CT assessment with pathologic correlation

Computed tomographic (CT) scans were performed in 179 patients with esophageal carcinoma to evaluate mediastinal lymph node metastasis. Histopathologic findings were compared with CT findings in a total of 7,218 resected lymph nodes. First, the criterion for lymph node metastasis on CT scans was 10 mm or more in long transverse diameter. The overall sensitivity and positive predictive value (PPV) were 19% (60 of 317 nodes) and 33% (60 of 180 nodes), respectively. Analysis of each of the eight subgroups of mediastinal nodes revealed that the PPV was more than 70% in node Nos. 105, 108, 110, and 112. In other subgroups, however, the PPV was less than 60%. Sensitivity was less than 50% in all eight subgroups. Second, the criterion for metastasis was 10 mm or more in short transverse diameter. The overall sensitivity and PPV were 8% (26 of 317 nodes) and 63% (26 of 41 nodes), respectively. Analysis of subgroups showed that the PPV in No. 106 nodes increased to 92%. In No. 106 nodes, use of a 5 mm criterion in long transverse diameter increased sensitivity to only 55%. Of the 317 histopathologically proven metastatic lymph nodes, 90 nodes (28%) were 10 mm or more in size, 112 (35%) were 5-10 mm, and 115 (36%) were less than 5 mm. Of the 6,901 non-metastatic lymph nodes, 473 nodes (7%) were 10 mm or more in size. Small (less than 5 mm in size) metastatic nodes were present in all eight subgroups. Among No. 107 and 109 nodes, large (10 mm or more in size) nonmetastatic nodes were prominent, resulting in low sensitivity and PPV. We conclude that CT does not provide an accurate assessment of metastatic versus non-metastatic mediastinal lymph nodes in patients with esophageal carcinoma.     

Clinicopathological features of lymph node metastasis in early gastric cancer

From 1979 through 1992, 482 cases with solitary early gastric cancer were resected in the Department of Surgery of the National Kyushu Medical Center Hospital. Among the 482 cases, the incidence of lymph node metastasis was 10.0% (48/482). The features of lymph node metastasis were studied while taking into account the combination of clinicopathological findings of the gastric cancer. Lymph node metastasis was rare in both the differentiated type mucosal cancers and submucosal cancers measuring 20 mm or smaller in size without depression. From these results, for early gastric cancer with the above-mentioned characteristics, either endoscopic therapy or local resection without lymph node dissection is considered to be sufficient treatment to obtain a favorable outcome.     

Regional lymph node classification for lung cancer staging

Recommendations for classifying regional lymph node stations for lung cancer staging have been adopted by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer. The objective was to unify the two systems that have been in common use for the past 10 years; that is, the schema advocated by the AJCC, adapted from the work of Tsuguo Naruke, and the schema advocated by the American Thoracic Society and the North American Lung Cancer Study Group. Anatomic landmarks for 14 hilar, intrapulmonary, and mediastinal lymph node stations are designated. This classification provides for consistent, reproducible, lymph node mapping that is compatible with the international staging system for lung cancer. It is applicable for clinical and surgical-pathologic staging.     

Combined thoracoscopy and mediastinoscopy for the evaluation of mediastinal lymph node metastasis in left upper lobe lung cancer

Cervical mediastinoscopy has an important but limited role in the evaluation of mediastinal adenopathy of the aorticopulmonary window in patients with left lung cancer. Thoracoscopy is another valuable diagnostic procedure in the assessment of mediastinal adenopathy. Combined thoracoscopic and mediastinoscopic evaluation may be more accurate for assessing mediastinal lymph node metastasis in left lung cancer than either procedure alone.     

Prognostic significance and surgical management of lymph node metastasis in gastric cancer

Eight patient case vignettes are presented to illustrate the possible relationship between melanoma and pregnancy. We pose 10 questions regarding the risk and prognosis and answer them based on information in the medical literature. Key conclusions are that there is no evidence that the risk for melanoma is influenced by pregnancy; there is no evidence that abortion in pregnant women diagnosed with melanoma is therapeutic for the mother or necessary to prevent melanoma in the fetus; although as a group, pregnant women diagnosed with melanoma may have a somewhat worse prognosis compared with nonpregnant controls, this difference disappears when patients are matched for factors including age, location and depth of primary, or stage of disease; and there is still a concern that pregnant women may present with more invasive or advanced disease due to hormonal or growth factor effects or delays in diagnosis because changes are attributed to pregnancy.     

NM23 gene product expression does not predict lymph node metastases or survival in young patients with colorectal cancer

PURPOSE: To develop a hepatic artery embolization protocol and investigate its efficacy in a prospective study treating patients with hereditary hemorrhagic telangiectasia and predominant hepatic involvement. MATERIALS AND METHODS: One man and four women with hereditary hemorrhagic telangiectasia presented with symptoms of high-output heart failure, abdominal angina, or severe portal hypertension. The hepatic arteries were embolized in stages in three to five sessions at 1- to 15-week intervals. After peripheral embolization with polyvinyl alcohol particles, proximal arteries were embolized with coils. Computed tomography and assessment of cardiac output were performed before and after therapy and at the end of follow-up (median, 25 months; range, 12-55 months). RESULTS: After embolization, analgesics and antiemetics were necessary for a median of 5 and 2 days, respectively. Other than ischemic cholangitis (one patient), no complications were observed. The mean cardiac output decreased significantly (P < .05) from 14.2 L/min to 8.0 L/min. Symptoms of high-output heart failure, abdominal angina, and portal hypertension resolved in all patients. Seven months after embolization, one patient died of postoperative sepsis after an unsuccessful surgical attempt to create a portacaval shunt. Delayed recurrence of symptoms was not noted in the other patients. CONCLUSION: In symptomatic patients with hereditary hemorrhagic telangiectasia and predominant hepatic involvement, embolization of the hepatic arteries in stages is well tolerated by the patients and results in good clinical improvement at midterm follow-up.     

Clear cell odontogenic carcinoma with lymph node metastasis

Clear cell odontogenic tumors are rare. Review of the literature showed 9 cases with a prominent clear cell component. These lesions have exhibited an aggressive behavior characterized by an infiltrative local growth pattern, recurrence, or metastases. We report a case of an odontogenic tumor that exhibited a biphasic pattern and was characterized by lymph node involvement identical histologically to the primary tumor. We conclude that the presence of a clear cell component in an ameloblastomatous tumor should be viewed as a sign of de-differentiation, and that a malignancy with or without metastases should be considered and ruled out in such cases.     

p-Stat3、VEGF-C和MMP-2在非小细胞肺癌中的表达及其与淋巴结转移的关系

目的:检测非小细胞肺癌组织中磷酸化信号转导和转录激活子-3(p-Stat3)、血管内皮生长因子C(VEGF-C)和基质金属蛋白酶2(MMP-2)的表达情况,探讨p-Stat3与VEGF-C、MMP-2之间,以及这三者与临床病理指标之间的相关性.方法:采用免疫组织化学SP法,检测53例非小细胞肺癌组织和10例正常肺组织中p-Star3、VEGF-C和MMP-2的表达情况,并对p-Star3、VEGF-C和MMP-2的表达情况进行相关性分析.结果:在53例非小细胞肺癌病例中,P-Stat3、VEGF-C和MMP-2的阳性表达率分别为45.2%(24/53)、77.3%(41/53)和58.4%(31/53).其中,p-Stat3的表达在腺癌中最显著,阳性表达率为75%(9/12),且在低分化肺癌组织中的表达明显高于高分化肺癌组织(P<0.01),在有淋巴结转移的肺癌组织中高于无淋巴结转移的肺癌组织(P<0.05),而阳性表达率与患者的年龄、性别和肿瘤的大小无明显相关(P>0.05).VEGF-C和MMP-2在有淋巴结转移的非小细胞肺癌组织中的阳性表达率高于无淋巴结转移的肺癌组织(P<0.05),且VEGF-C、MMP-2的表达与p-Stat3的表达呈正相关(依次为r=0.427和0.345,P均<0.05).结论:在非小细胞肺癌组织中,p-Stat3、VEGF-C和MMP-2表达均上调,高表达的p-Stat3与肺癌的发生、发展及淋巴结转移密切相关,其机制可能与VEGF-C和MMP-2有关.     

Experience with the two-windows method for mediastinal lymph node dissection in lung cancer

A rapid dipstick test for scrub typhus was prospectively evaluated in Chiangrai, northern Thailand. Sera from 162 patients with fever of unclear etiology were tested by a dot blot immunoassay using two different antigen concentrations. Dipsticks coated with lower concentration of antigen lacked sensitivity compared with the indirect immunoperoxidase test. Dipsticks with higher antigen concentration had increased sensitivity that was equivalent to that of the immunoperoxidase test. By increasing the antigen concentration on the dipstick, sensitivity increased from 67% to 100%, positive predictive value increased from 90% to 93%, and negative predictive value rose from 92% to 100%. The specificity of both antigen concentrations was 98%. This study establishes that scrub typhus can be confirmed serologically by use of a dipstick assay and that serodiagnosis can be effectively tailored to a target population.     

A clinical study on the incidence of retroperitoneal lymph node metastasis and its risk factors in ovarian cancer

BACKGROUND: The need to improve therapy regimes, determine prognosis, and study biological properties of tumors extracorporally led to development of different experimental systems. In order to approach the in vivo situation, specific properties of the tumors of origin should be retained by the cells in culture over relatively long periods. However, culture conditions may change expression of cellular antigens. METHODS: Cryosections of a hypopharyngeal carcinoma were compared in this respect with different cultivation systems (2-dimensional monolayers [ML], 3-dimensional multicellular tumor spheroids [MTS] and substrate cultures on Gelita) in regard to expression of cytokeratins (CK) 1, 7, 10, 14, 18 and 19, vimentin, neurofilament (NF) kD200 and 68, ganglioside GD2, oncogene products (P53 mutant and wild), and membrane-associated antigens (HLA-ABC and -DR, epidermal growth factor receptor EGFR). RESULTS: Semiquantitative immunohistochemical methods revealed differences in expression of CK1, 14 and 19, GD2, and P53 mutant between these systems. CONCLUSION: Pronounced expression of markers in MTS compared to original biopsy and monolayer emphasizes the importance of cell-cell contact and 3-dimensionality or metabolic stress. However, weak marker expression within substrate cultures may reflect loose cell-cell contact observed. In these experiments, the antigenic configuration of MTS resembled the one of the original tumor more than the other culture systems: monolayer and growth on substrate. As vimentin and NF are not expressed by healthy epithelial cells of adults, occurrence of intratumoral vimentin and NF could point to derepression of early differentiation antigens.     

Intra-operative diagnosis of N2 lymph node metastasis of gastric cancer

BACKGROUND/AIMS: Limited lymph node dissection for gastric cancer, which is prevalent in Western countries, leaves cancer cells in the second tier of nodes in patients who have metastasis in those nodes. It is, however, difficult to correctly diagnose nodal status during surgery. The present study was, therefore, designed to examine how to detect N2 metastasis intra-operatively. METHODOLOGY: Five hundred and eight patients undergoing extended lymph node dissections for gastric cancer were retrospectively analyzed. Accuracy of the intraoperative diagnosis of node involvement based on macroscopic findings was investigated, according to the N stage and histological type of the tumor. Furthermore, the distributions of N2 metastasis were clarified, according to tumor site. RESULTS: Intra-operative macroscopic findings were frequently assessed as being less severe than histological findings in cases with N2 metastasis (61.9%, 39/63). Intra-operative recognition of N2 metastasis was significantly lower in the cases with undifferentiated adenocarcinoma (28.2%, 11/39) than in those with differentiated adenocarcinoma (56.5%, 13/23). The distributions of N2 metastasis revealed nodes along the left gastric and common hepatic arteries to be the key junctions for lymphatic flow from the middle and lower thirds of the stomach, respectively. CONCLUSIONS: Intra-operative diagnosis of N2 metastasis is difficult to make based on macroscopic findings, especially in undifferentiated tumors. To detect N2 metastasis intra-operatively, the nodes along the left gastric or common hepatic artery should be submitted to frozen section examination for primary tumors located in the middle or lower third of the stomach, respectively.