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Factors associated with axillary lymph node metastasis from breast carcinoma: descriptive and predictive analyses.

BACKGROUND: Although axillary lymph node metastasis is one of the most important prognostic determinants of breast carcinoma prognoses, the reasons why tumors vary in their capability to produce for axillary metastases remain unclear. METHODS: The authors used data from the nationwide Patient Care Evaluation (PCE) survey of the American College of Surgeons to evaluate the correlations between patient/tumor characteristics and lymph node status, and to explore the use of these factors, which are all known prior to axillary dissection, in predicting lymph node status. The PCE data set contained 18,025 breast carcinoma cases diagnosed in 1990 after exclusion of women older than 79 years or with fewer than 6 lymph nodes examined. RESULTS: In a multivariate logistic regression model, larger tumor size, young age, African American or Hispanic race, outer half tumor location, poor or moderate differentiation, aneuploidy, and infiltrating ductal histology were independently associated with a higher likelihood of one or more positive lymph nodes. Contrary to expectation, cases negative for estrogen receptor (ER) and progesterone receptor (PR) had a lower risk of positive lymph nodes when adjusted for other factors (odds ratio = 0.82; 95% confidence interval: 0.74-0.91) compared with cases positive for both receptors. This model accurately predicted lymph node status in 2 validation data sets (a 50% random sample of 1990 PCE data and 1992 data from the National Cancer Data Base), but was less accurate in a third, older data set (1983 PCE data). However, the percentage of cases (1990 validation set) with predicted probabilities less than 0.05 or greater than 0.95 were only 4.6% and <0.1%, respectively. CONCLUSIONS: The authors concluded that 1) most variation in axillary lymph node metastatic status can be explained by routinely available data, 2) ER and PR status may be involved in the mechanism of this behavior, and 3) the difficulty of using prediction models to avert axillary dissection should not be underestimated.

Adult↗

Sentinel lymph node detection by combined dye-isotope technique and its predictive value for cervical lymph node metastasis in patients with lingual carcinoma.

OBJECTIVES: To investigate the clinical value of combined dye-isotope technique in detecting sentinel lymph node (SLN) and to examine whether the characteristics of SLN accurately predict cervical lymph node metastasis in lingual carcinoma. METHODS: Thirty patients with lingual carcinoma without lymph metastasis were injected with a dose of about 18.5 MBq of (99m)Tc-SC (sulfur colloid), around the tumor tissues before surgery, and lymphoscintigraphy was performed 5, 10, 30, 60 minutes, and 6 hours after injection. In the following day, all patients were injected with isosulfan blue dye around the primary tumor during surgery to trace SLN and underwent standard cervical lymph node dissection after SLN dissection. The pathological results of SLN were compared with standard lymph node dissection for their ability to accurately predict the final pathological status of the cervical lymph nodes. RESULTS: SLN was successfully identified in 100% of the patients. Both positive and negative predictive values of SLN were 100%. The accuracy rate was 100%, and there were no false negatives. CONCLUSIONS: The detection of SLN using combined dye-isotope technique could accurately predict cervical lymph node metastasis in lingual carcinoma.

Adult↗

Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis.

BACKGROUND: -Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits. OBJECTIVE: -To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis. DESIGN: -We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases. RESULTS: -In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases. CONCLUSIONS: -CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.

Adult↗

Importance of lymph vessels in gastric cancer: a prognostic indicator in general and a predictor for lymph node metastasis in early stage cancer.

BACKGROUND: Metastasis to regional lymph nodes (LNs) through lymphatic vessels is common in cancer progression and is an important prognostic factor in many cancers. Recent evidence suggests that tumour lymphangiogenesis promotes lymphatic metastasis. AIMS: To study the role of lymph vessel density (LVD) in gastric cancer and investigate whether LVD is associated with LN metastasis/prognosis. METHODS: Lymphatics of 117 primary human gastric cancer cases were investigated by quantitative immunohistochemical staining for podoplanin. The relation between LVD and LN metastasis and other established clinicopathological parameters was analysed. The relation between LVD and prognosis was also studied. RESULTS: Mean LVD of "hot spots" was 11.6/case. LVD significantly correlated with LN and podoplanin positive lymphatic invasion. High LVD was associated with worse overall survival. In multivariate analysis, positive LVD was a significant independent predictor of overall survival, depth of invasion, and TNM stage. LVD significantly correlated with LN metastasis at surgery and podoplanin positive lymphatic invasion. In multivariate analysis, positive LVD was an independent significant predictor of LN metastasis. CONCLUSIONS: Increased podoplanin expression is significantly associated with LN metastasis, and may play an important role in detecting LN metastasis in gastric cancer. Furthermore, LVD may be a significant prognostic factor in gastric cancer at any stage. In addition, LVD and lymph vessel invasion detected by podoplanin immunohistochemistry are associated with LN metastasis in T1 early gastric cancer. LVD assessment by podoplanin immunohistochemistry may become a useful predictor of LN metastasis in T1 early gastric cancer and may influence the decision making process for additional surgery.

Biomarkers, Tumor↗

[SIMA leakage into stroma and lymph node metastasis in cervical adenocarcinoma].

The relationship of small intestine mucin antigen (SIMA) leakage into stroma and tumor lymph node metastasis was studied by SIMA immunohistochemical stain in the cervical adenocarcinoma of uterus. The results showed that the more SIMA leakage into stroma, the more possibility of lymph node metastasis. There was no difference between the SIMA staining intensity in the primary tumor or metastatic tumor. Mucin leakage into stroma may play an important role in cervical adenocarcinoma metastasis.

Adenocarcinoma↗

[Evaluation of clinical and pathological factors relating to lymph node metastasis in carcinoma of the tongue].

In this paper we adopt various clinical and pathological parameters to evaluate the factors relative to the lymph node metastasis. We are of the view that the TNM classification can not indicate the presence of the lymph node metastasis clearly. When the size of tumor is less than 2.0 cm in diameter there is almost no metastasis. Using computer, we analyse the factors and found that only the depth, pattern of growth and the degree of lymphoid cell infiltration are relative to metastasis. The coincidence is 78.6%.

Adult↗

Cytologic diagnosis of axillary lymph node metastasis in breast cancer.

OBJECTIVE: To compare imprint cytology with histology as a method for rapid intraoperative diagnosis of axillary lymph node metastasis in breast cancer. STUDY DESIGN: We evaluated imprint cytology, comparing it with histopathology. A sample of 635 axillary lymph nodes was studied by imprint cytology using both Giemsa stain and hematoxylin-eosin. The results were compared with each other and with those of histopathologic examination. RESULTS: The Giemsa stain method, as compared to histopathology, had 94% accuracy, 97% sensitivity, 90% specificity and 94% positive prognostic value. The hematoxylin-eosin stain method was less accurate than the Giemsa stain method as compared to histopathology (accuracy 91%, sensitivity 96%, specificity 83% and positive prognostic value 92%). CONCLUSION: These data confirm the value of imprint cytology as a rapid, reliable method of intraoperative assessment of axillary lymph node metastasis in breast cancer. It results in better staging of the disease. It can be used intraoperatively, as an alternative to frozen section, if a pathology laboratory is not available, to exclude stage I patients from further treatment.

Adenocarcinoma↗

Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human oral squamous cell carcinomas: implications for lymph node metastasis.

We measured the production levels of seven different matrix metalloproteinases (MMP-1, 2, 3, 7, 8, 9 and 13) and two tissue inhibitors of metalloproteinases (TIMP-1 and 2) in the homogenates of human oral squamous cell carcinomas and control normal squamous epithelia by the corresponding sandwich enzyme immunoassay systems. The levels of MMP-1, 2, 3, 8, 9, 13 and TIMP-1 were significantly higher in the carcinoma samples than in the control. Among them, only the production level of MMP-2 was significantly higher in the carcinomas with cervical lymph node metastasis than in those without metastasis (P < 0.05). Gelatin zymography demonstrated that activation ratio of the zymogen of MMP-2 (proMMP-2) is significantly higher in the carcinomas with lymph node metastasis than in those without metastasis (P < 0.05) or normal control (P < 0.01). Quantitative RT-PCR for membrane-types 1, 2 and 3 MMPs (MT1, 2 and 3-MMPs), which activate proMMP-2 in vitro, demonstrated that MT1-MMP is predominantly expressed in the carcinoma tissues, and the expression level is significantly higher in the carcinomas with lymph node metastasis than in those without metastasis (P < 0.05) or the control samples (P < 0.05). Although MT2-MMP and MT3-MMP were detected in approximately 30% of the carcinoma cases, their expression levels were extremely lower compared with that of MT1-MMP. There was a direct correlation between the MT1-MMP expression level and proMMP-2 activation ratio (r = 0.62, P < 0.01). In situ hybridization and immunohistochemistry indicated that carcinoma cells and stromal cells adjacent to carcinoma cell nests express MT1-MMP transcripts and protein. MMP-2 and TIMP-2 were also immunolocalized to the carcinoma cells in the carcinoma samples. By in situ zymography, gelatinolytic activity was demonstrated in the carcinoma cell nests and abolished by the treatment with an MMP inhibitor, BB94. These results suggest that among seven different MMPs, the production of proMMP-2 and its activation mediated by MT1-MMP play an important role in the cervical lymph node metastasis of the human oral squamous cell carcinomas.

Base Sequence↗

p53 as a new prognostic factor for lymph node metastasis in penile carcinoma: analysis of 82 patients treated with amputation and bilateral lymphadenectomy.

PURPOSE: Gold standard treatment for invasive penile carcinoma remains amputation and lymphadenectomy. This procedure has high morbidity and new prognostic factors on the incidence of metastasis would help select candidates to lymphadenectomy. Mutations in the p53 gene common in several neoplasms can be related to the prognosis. We studied 82 patients with penile carcinoma staged according to the 1978 TNM system who underwent amputation and bilateral lymphadenectomy to evaluate the prognostic value of immunohistochemical p53 staining in the primary tumor. MATERIALS AND METHODS: Immunoreactivity of p53 was studied with other clinicopathological variables, including patient age, stage, histological grade, tumor thickness, lymphatic and venous embolization, corpora cavernosa, corpus spongiosum and urethral infiltration, and human papillomavirus (HPV) status. We also determined its association with lymph node metastasis, the survival rate and the risk of death. In addition, we studied the association of p53 and HPV DNA with prognosis. All slides were reviewed by 1 pathologist. HPV DNA was detected by polymerase chain reaction using GP5/6+ generic primers. p53 expression was measured by immunohistochemical testing with monoclonal Clone DO-7 mouse anti-human p53 protein antibody (Dako A/S, Glostrup, Denmark). The Cox regression hazards method was used for multifactorial analysis. RESULTS: Nuclear accumulation of p53 was detected in 34 of 82 samples (41.5%). Clinical lymph node N stage (p = 0.045), lymphatic (p <0.001) and venous (p = 0.04) embolization by neoplastic cells, p53 positivity (p = 0.012) and p53 grade (p = 0.004) were significantly associated with lymph node metastasis. Followup was 0.1 to 453 months (mean 88.7). Multivariate analysis revealed that only lymphatic embolization (relative risk 9.4, 95% confidence interval [CI] 2.8 to 31.6) and p53 positivity (relative risk 4.8, 95% CI 1.6 to 14.9) were independent factors for lymph node metastasis. Patients with negative p53 had significantly better 5 and 10-year overall survival than those in whom tumors stained positive for p53 (64.5% and 54.6% versus 30.2% and 26.4%, respectively, p = 0.009). When tumors were p53 positive and HPV DNA positive, overall survival was worse. Multivariate analysis revealed that only age (relative risk 2.9, 95% CI 1.6 to 5.1) and lymph node metastasis (relative risk 3.2, 95% CI 1.8 to 5.8) were independent risk factors for death. CONCLUSIONS: Immunoreactivity of p53 is an independent factor for lymph node metastasis. The association of positive p53 with positive HPV DNA was related to a worse prognosis.

Adult↗

[The mode of lymph node metastasis and post-operative recurrence in transitional cell carcinoma of the upper urinary tract].

We surveyed 34 patients of transitional cell carcinoma of the upper urinary tract treated with nephroureterectomy with excision of a cuff of bladder or combined with regional lymphadenectomy to investigate the mode of lymph node metastasis and post-operative recurrence. In 8 of 14 patients undergoing nephroureterectomy with excision of a cuff of bladder combined with regional lymphadenectomy, lymph node metastasis was histologically confirmed in the neighbouring lymph node, of which 2 patients showed the skipped lymph node metastasis simultaneously. Subsequent bladder cancer developed in 12 out of 34 patients (35.3%) and the primary tumor showed papillary growth in all patients except for one patient which showed non-papillary growth, but with pR1. During the observation period with the mean of 9.4 months, remote metastases in other organs were detected in 6 patients with invasive primary tumor more than pT2.

Aged↗

[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.

Esophageal Neoplasms↗

Risk factors for lymph node metastasis of submucosal invasive differentiated type gastric carcinoma: clinical significance of histological heterogeneity.

BACKGROUND: The use of endoscopic resection for submucosal invasive gastric carcinoma (Sm-ca) with histologically differentiated type has been expected. However, the treatment criteria remain controversial. The purpose of this study was to clarify the relationship between lymph node metastasis and the histologic features of differentiated Sm-ca. METHODS: The clinicopathologic features of 35 patients with node-positive differentiated Sm-ca were compared with those of 221 patients with node-negative differentiated Sm-ca by multivariate analysis with logistic regression. To clarify the metastatic behavior of differentiated Sm-ca, we examined mucin-histochemical expression and immunohistochemical staining, using Ki-67, p53, and c-erbB2. RESULTS: The rate of lymph node metastasis was significantly higher in differentiated Sm-ca with histological heterogeneity (combined differentiated type, with poorly differentiated component) than in that without histological heterogeneity (27% vs 7%; P < 0.001). Multivariate analysis revealed that lymphatic vessel invasion was the most significant determinant (odds ratio, 8.68) for lymph node metastasis. Histological heterogeneity (odds ratio, 3.88) was next, followed by papillary adenocarcinoma (odds ratio, 3.28), and submucosal invasion level (odds ratio, 2.34). The mean value of the Ki-67 labeling index for node-positive differentiated Sm-ca was higher than that of node-negative differentiated Sm-ca (47% vs 39%; P < 0.05). CONCLUSIONS: When the extension of endoscopic surgery to differentiated Sm-ca is considered, this therapeutic technique should be limited to the differentiated type of Sm-ca without histological heterogeneity. The Ki-67 labeling index provides useful information for identifying those patients with a high risk of lymph node metastasis.

Adenocarcinoma, Papillary↗

Prognosis of lymph node metastasis in soft tissue sarcoma.

BACKGROUND: We defined the tumor characteristics and prognosis of patients with regional lymph node metastasis (RLNM) from soft tissue sarcoma. METHODS: All patients with RLNM from soft tissue sarcoma were identified from the Royal Marsden Hospital Sarcoma Unit prospective database from January 1990. RESULTS: A total of 73 (3.4%) of 2127 patients had RLNM. Fifty-seven patients (78.1%) had RLNM as the first site of spread, and 16 patients (21.9%) presented with RLNM and distant metastasis synchronously. The most common histologies were rhabdomyosarcoma, epithelioid sarcoma, and angiosarcoma. There were 9 T1 and 36 T2 tumors, and tumor size was not available in 28 patients. There were 6 grade 1, 16 grade 2, and 51 grade 3 tumors. Forty-two patients presented with RLNM along with the primary tumor. Of the remaining patients, the median time to development of RLNM from diagnosis of the primary tumor was 13.5 months (95% confidence interval [CI], 1-100 months). The 1-year survival for patients with isolated RLNM was 77.49% (95% CI, 62.99%-86.88%), compared with 36.27% (95% CI, 13.32%-60.04%) for patients who presented with RLNM and distant metastasis (P =.005). The 1-year survival for metachronous and synchronous RLNM was 94.44% (95% CI, 66.64%-99.20%) and 67.54% (95% CI, 47.89%-81.12%), respectively (P =.05). CONCLUSIONS: Lymph node metastasis is rare. Patients who present with isolated RLNM have an improved survival compared with patients who present with regional and distant metastasis at diagnosis. Synchronous RLNM with the primary tumor have a poorer outcome than metachronous RLNM in the absence of distant metastasis.

Adolescent↗

A case of pneumocytoma (so-called sclerosing hemangioma) with lymph node metastasis.

A case of "sclerosing hemangioma" (pneumocytoma) of the lung with lymph node metastasis is reported. A 22-year-old Japanese man was found to have a well-defined round lesion in the right lung (S7), which increased in size slightly during a 2-year follow-up period. He underwent right lower lobectomy with a preoperative diagnosis of a benign lung tumor. The pulmonary tumor revealed histological features characteristic of "sclerosing hemangioma" of the lung, in addition to which there were many large polygonal foamy cells, forming tubular or papillary structures. These cells were found by electron microscopy to contain numerous cytoplasmic lamellar bodies and showed a positive reaction with anti-surfactant apoprotein antibody immunohistochemically. Therefore, they were considered to be cells differentiating toward type II pneumocytes. Review of 21 typical "sclerosing hemangiomas" disclosed a few or some such foamy cells in 10 cases. A single hilar lymph node was the site of microscopic metastases, which consisted of "large clear foamy cells" and smaller polygonal or round cells with slightly eosinophilic cytoplasm, both of which were components of the pulmonary "sclerosing hemangioma." This case supports the theory that "sclerosing hemangioma" is a neoplasm of type II pneumocyte lineage. Although it is said to be benign, rare cases apparently show metastatic potential.

Adult↗

[Cervical adenocarcinoma: histologic staging and pelvic lymph node metastasis].

The relationship between histologic staging of cervical adenocarcinoma and pelvic lymph node metastasis was analyzed in 138 patients who had undergone hysterectomy. In AIS, the cervical glands were replaced by cancer. When glandular or solid cancer budding into the stroma was identified in AIS, it was designated Stage Ia adenocarcinoma. Pelvic lymph node metastases were found in cases with Stage Ib-III adenocarcinoma, but not in Stage Ia adenocarcinoma. This suggests that Stage Ia adenocarcinoma might be treated the same as AIS.

Adenocarcinoma↗

Primary cutaneous adenoid cystic carcinoma with regional lymph node metastasis.

Primary cutaneous adenoid cystic carcinoma (PCACC) is a particularly rare variant of sweat gland carcinoma with characteristics of indolent and progressive course and high incidence of perineural invasion and local recurrence. However, regional lymph node metastasis in PCACC is exceedingly rare and its prognostic implication is unknown. Only two previous cases of recurrent scalp PCACC were reported to be associated with cervical lymph node metastases at 42 months and 20 years, respectively, after the initial treatment. We present a case of PCACC occurring in the left parotid region with regional neck lymph node metastasis in a 64-year-old man. Because the occurrence of lymph node metastasis seems to be associated with recurrent PCACC, we suggest that neck dissection may be included in the treatment for recurrent PCACC patients.

Carcinoma, Adenoid Cystic↗

Immunolocalization of anti-placental alkaline phosphatase monoclonal antibody in mice with testicular tumors and lymph node metastasis.

To evaluate the ability of an anti-placental alkaline phosphatase (PLAP) monoclonal antibody (MAb) to localize to PLAP-expressing tumors, we established a model of testicular tumor with metastasis to lymph nodes and liver in severe combined immunodeficient (SCID) mice. 131I-labeled or 125I-labeled MAb was simultaneously administered via the intravenous or lymphatic route, respectively. Preferential accumulation of MAb in PLAP-expressing tumors at primary as well as metastatic sites was demonstrated. The percentage of the injected dose of MAb found in the tumor was generally higher when MAb was administered intravenously. Identical tumor/blood ratios were found with the two routes of administration. These data suggest that intravenous administration of a radiolabeled MAb is superior to lymphatic administration for tumor imaging and radioimmunotherapy.

Alkaline Phosphatase↗

[Detection of mediastinal lymph node metastasis from lung cancer with positron emission tomography (PET) using 11C-methionine].

Twenty-five patients with primary non-small cell lung cancer underwent the positron emission tomography (PET) using 11C-methionine to detect the mediastinal lymph node metastasis. We introduced the positron angiography to recognize precisely the anatomical orientation of the mediastinal lymph nodes. The 11C-uptake of the lymph node was expressed with distribution absorption ratio (DAR). A total 107 lymph nodes were examined. The average DAR in metastatic lymph nodes (n = 28) was 3.89 while that of non-metastatic nodes (n = 79) was 2.38 indicating a significant difference (p < 0.001). The most adequate threshold for detection of metastasis was 3.3 with sensitivity of 100%, and specificity of 87.3% and overall accuracy of 89.7%. Metastasis of squamous cell carcinoma was diagnosed more accurately than that of adenocarcinoma. Thus, PET using 11C-methionine may offer a new method to detect the mediastinal lymph node metastasis from lung cancer.

Adult↗