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Prediction of lymph node metastasis based on p53 and nm23-H1 expression in muscle invasive grade III transitional cell carcinoma of bladder.

OBJECTIVE: A surgically positive lymph node in invasive bladder cancer generally implies distant micrometastasis; thus, preoperative identification of lymph node status is important. Various antioncoproteins were evaluated for their accuracy in predicting lymph node metastasis. SUBJECTS AND METHODS: Fifty-seven subjects who had invasive, grade III transitional cell carcinoma at TURB, and then were confirmed to have stage T2, T3a, and T3b tumors after radical cystectomy from 1985 to 1994, were selected. Tissues acquired from transurethral resection were immunostained with tumor suppressor gene p53 (DO7 and PAb 1801) and antimetastatic gene nm23-H1 (NM301). Results of staining and pathological staging were compared with the status of lymph node metastasis. RESULT: Expression of p53 was 42.1% (24/57) for DO7 and 22.8% (13/57) for PAb1801, with DO7 exhibiting superiority over PAb1801. Expression of nm23-H1 was seen in 50.9% (29/57) of cases. Combined analysis of p53 and nm23-H1 expression and nodal status (N stage) was not significant. However, pathological nodal status was statistically significantly correlated with pathological tumor (T) stage and p53 expression. CONCLUSION: A high risk of lymph node metastasis can be predicted when Grade III, muscle invasive tumor and p53 expression are seen from TURB specimens. Lymph node metastasis is correlated with the degree of invasion in Grade III muscle invasive tumors--especially in T3b tumors, where there is highest probability of node involvement.

Adult↗

DNA index as a significant indicator of lymph node metastasis and local recurrence of rectal cancer.

To confirm the prognostic significance of the DNA index (DI) in cases of rectal cancer, the nuclear DNA content of tumor cells was examined in 184 cases of rectal cancer treated with curative surgery, and the incidence of lymph node metastasis and recurrence of the cancer was analyzed. The incidence of lymph node metastasis was 43.9 percent in cases with aneuploidy (DI above 1.5), being statistically different from the 18.0 percent incidence in cases with diploidy (P < 0.001). Although the extent of lymph node metastasis was limited to adjacent lymph nodes in cases with diploidy, distant lymph node metastases were frequent in cases with aneuploidy, especially in those with a DI above 1.5. Furthermore, the incidence of recurrence of cancer, and especially of local recurrence, was significantly higher (P < 0.001) in cases with aneuploidy (DI above 1.5) than in cases with diploidy and aneuploidy (DI below 1.4). These findings indicate the significant value of the DNA index for the prediction of lymph node metastasis and local recurrence in patients with rectal cancer.

Aneuploidy↗

[A comprehensive diagnostic and therapeutic approach to cervical lymph node metastasis from unknown primary site (author's transl)].

Cervical lymph nodes metastasis from unknown primary lesion are rather infrequent but constitute a specific problem. The present study reports the results obtained from a series of fifty patients treated for such lesions from 1964 to 1976. It emphasizes that a comprehensive therapeutic approach is warranted and should combine surgery and radiation on the cervical areas and irradiation of mucosae that may harbour the primary.

Adult↗

DNA ploidy, Ki-67 and p53 as indicators of lymph node metastasis in early gastric carcinoma.

OBJECTIVE: To perform flow cytometric and immunohistochemical analysis of early gastric carcinoma in order to investigate the clinical value of DNA ploidy, Ki-67 and p53 as indicators of lymph node metastasis. STUDY DESIGN: We studied 108 cases of surgically resected early gastric carcinoma, which comprised 21 cases showing positive lymph node metastasis (group A) and 87 cases showing negative lymph node metastasis (group B). RESULTS: Aneuploidy was seen in 16 cases (76.2%) in group A in contrast to 10 cases (11.5%) in group B (P = .0029). The mean value of the Ki-67 labeling rate in all cases was 21.9%, and 15 cases (79.0%) showed a Ki-67 labeling rate of more than 21.9% in group A, while they numbered 31 (37.4%) in group B (P = .0016). Cases with cell positive for p53 protein numbered 15 (75%) in group A, while they numbered 38 (46%) in group B (P = .0460). CONCLUSION: DNA aneuploidy, a high labeling rate of Ki-67 and overexpression of p53 are all useful indicators of lymph node metastasis in patients with early gastric carcinoma.

Aneuploidy↗

Hyperlipidaemia is positively correlated with lymph node metastasis in men with early gastric cancer.

BACKGROUND: Although increased dietary fat or cholesterol has been reported to be a risk factor for the development of certain cancers, the effect of serum lipid levels on tumour metastasis is not clearly understood. METHODS: The association between lymph node metastasis and preoperative serum levels of total cholesterol (TC) and triglyceride (TG) as well as various pathological findings for tumours was examined in 353 patients with early gastric cancer who underwent gastrectomy with classical lymphadenectomy. RESULTS: The rate of lymph node metastasis was significantly higher in patients with early gastric cancer who had hypercholesterolaemia (TC 220 mg/dl or greater) or hypertriglyceridaemia (TG 150 mg/dl or greater). The tendency was more prominent in men, and multivariate analysis showed that hypertriglyceridaemia was an independent risk factor for nodal metastasis in men, in addition to pathological invasion to the submucosal layer or to lymphatic vessels. In contrast, neither hypercholesterolaemia nor hypertriglyceridaemia showed a significant association with nodal status in women with early gastric cancer. CONCLUSION: Raised serum lipid levels might favour the development of lymph node metastasis in men with early-stage gastric cancer. In patients with early gastric cancer serum lipid levels should be checked before operation, and the use of minimal local treatments must be considered carefully in male patients with hyperlipidaemia.

Adult↗

[A case of anaplastic transformation of thyroid carcinoma in the cervical lymph node metastasis].

A case of a well-differentiated thyroid carcinoma with an area of anaplastic transformation in the cervical lymph node metastasis is reported. The combination of postoperative radiotherapy with chemotherapy, followed by total thyroidectomy and left radical neck dissection was undertaken for the cervical lymph node metastasis with anaplastic progression, and the patient is living, well and tumor-free more than two years after surgery. This case suggests that neck dissection is necessary for well-differentiated thyroid carcinoma with lymph nodes metastasis to prevent the development of anaplastic transformation in the future.

Carcinoma, Papillary↗

Accuracy of criteria for predicting recurrence and metastasis in stage II and III gastric cancer patients with lymph node metastasis.

This study assessed the prediction of gastric cancer recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes, and by using criteria that were developed to identify patients with a high risk of recurrence/metastasis. The subjects were 60 patients of stage II or III gastric cancer with lymph node metastasis. Prediction of recurrence based on the detection of ONCs showed a sensitivity of 33.3% (2/6), specificity of 70.0% (7/10), and accuracy of 51.7% in stage II patients, while the sensitivity was 73.5% (25/34), specificity was 100.0% (10/10), and accuracy was 86.8% in stage III patients. Prediction of recurrence based on the presence of at least 2 high-risk criteria had a sensitivity of 33.3% (2/6), specificity of 100.0% (10/10), and accuracy of 66.7% in stage II patients, while the sensitivity was 82.4% (28/34), specificity was 80.0% (8/10), and accuracy was 81.2% in stage III patients. These results suggest that prediction of recurrence/metastasis soon after surgery using ONCs plus the high-risk criteria can increase the specificity in stage II cancer, and can achieve a sensitivity of 80% or more with a high specificity and accuracy in stage III cancer.

Humans↗

Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer.

OBJECTIVE: Non-small cell lung carcinoma (NSCLC) is one of the leading causes of death in the world. Lymph node metastasis is not only an important factor in estimating the extent and the metastatic potential of an NSCLC but also in prognosticating the patient outcome. Preoperative prediction of lymph node metastasis might greatly facilitate the choice of appropriate surgical and medical options in patients with NSCLC. METHODS AND RESULTS: Using a cDNA array, we analyzed the expression profiles of 1,289 genes in 92 cancer tissues of NSCLC (37 squamous cell carcinomas and 55 adenocarcinomas). We divided the patients into two groups (classes) for each of various pathological factors, such as lymph node metastasis and pT-stage. For each pair of classes, we searched for an optimal combination of genes to classify the cases using a sequential forward selection algorithm starting from a gene set that showed significant difference in expression between the classes. We used the leave-one-out error cross-validation on a k-nearest neighbor classifier to sequentially choose the gene. Using the optimized set of genes, it was possible to stratify the patients for lymph node metastasis (pN-stage) and pT-stage at, respectively, 100% (23 genes) and 100% (55 genes) for cases with squamous cell carcinomas and 94% (43 genes) and 92% (35 genes) for those with adenocarcinomas. CONCLUSION: We conclude that expression profiling using feature selection provides a powerful means of stratification (personalization) of NSCLC patients and choice in treatment options, particularly for factors such as lymph node metastasis whose radiological diagnosis is presently incomplete.

Adenocarcinoma↗

Clinical significance of immunohistochemically detectable lymph node metastasis in adenocarcinoma of the ampulla of Vater.

BACKGROUND: The aim of this study was to assess the impact of immunohistochemically identified lymph node metastasis on survival in patients with carcinoma of the ampulla of Vater. METHODS: Three hundred and twenty-six regional lymph nodes dissected from pancreatoduodenectomy specimens from 25 patients with ampulla of Vater carcinoma were immunostained with anticytokeratin antibody (CAM 5.2). The clinicopathological significance of immunohistochemically detectable lymph node metastasis was evaluated and compared with that of other potential prognostic factors. RESULTS: The frequency of lymph node involvement in relation to the total number of dissected lymph nodes increased from 5.5 per cent (18 of 326) using haematoxylin and eosin staining to 9.5 per cent (31 of 326) using cytokeratin immunostaining (P < 0.001). Lymph node involvement was revealed by haematoxylin and eosin staining in eight of 25 patients and by cytokeratin immunostaining in 11 of 25 patients (P = 0.006). Absence of immunohistochemically detectable lymph node metastasis was identified as an independent predictor of improved postoperative survival. CONCLUSION: Immunostaining of dissected lymph nodes adds additional information to data obtained by conventional haematoxylin and eosin staining when determining the prognosis of patients with carcinoma of the ampulla of Vater.

Adenocarcinoma↗

Lymph node metastasis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging versus PET/CT in a rabbit model.

PURPOSE: To prospectively compare the diagnostic accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging and integrated positron emission tomography-computed tomography (PET/CT) for the depiction of lymph node metastasis in an animal model, with histologic findings as the reference standard. MATERIALS AND METHODS: This experiment was approved by the local animal care committee. VX2 carcinoma was implanted into the thighs of 11 rabbits 4 weeks before the imaging study. T2- and T2*-weighted MR examinations were performed 24 hours after USPIO administration, followed by integrated PET/CT. USPIO-enhanced MR imaging and PET/CT analysis for the evaluation of the presence of metastasis in iliac lymph nodes were performed independently by two radiologists and two nuclear medicine physicians, respectively, without histopathologic knowledge. Results were evaluated by using receiver operating characteristic (ROC) analysis, and sensitivities and specificities were compared by using a Z test. RESULTS: Metastases were histopathologically confirmed in 22 of 62 iliac lymph nodes. USPIO-enhanced MR imaging showed a significantly greater area under the ROC curve than did PET/CT (0.984 vs 0.852; P=.023). The respective sensitivity and specificity for the detection of lymph node metastasis were 91% (20 of 22) and 95% (38 of 40) for USPIO-enhanced MR imaging and 64% (14 of 22) and 98% (39 of 40) for PET/CT. In terms of sensitivity, a significant difference was found between USPIO-enhanced MR imaging and PET/CT, particularly for nodal metastasis of less than 5 mm (86% [six of seven] vs 0% [zero of seven]; P=.031), whereas the specificity of the two imaging modalities was similar (P=.226). CONCLUSION: USPIO-enhanced MR imaging results in higher diagnostic accuracy for depicting lymph node metastasis than does PET/CT.

Animals↗

Malignant schwannoma of the esophagus with lymph node metastasis: literature review of schwannoma of the esophagus.

An extremely rare case of malignant schwannoma of the esophagus with lymph node metastasis is reported. A 49-year-old woman was found to have an abnormal shadow on a chest X-ray film taken during an annual checkup. Upper gastrointestinal series showed extrinsic pressure on the middle thoracic esophagus, without a mucosal lesion. An exploratory operation was performed, with a tentative diagnosis of esophageal leiomyoma. The tumor was enucleated with part of the esophageal mucosa, and a few enlarged lymph nodes around the tumor were dissected. The resected tumor was an elastic firm mass, measuring 8.2 x 5.8 x 3.7 cm, and had a smooth surface. Histological examination of the tumor revealed the proliferation of spindle-shaped cells with chromatin-rich nuclei. The nuclei were variable in size and showed remarkable atypia. A paraesophageal lymph node had same findings as the main tumor. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein and neuron-specific enolase. The pathological diagnosis of this tumor was malignant esophageal schwannoma with lymph node metastasis. Esophageal schwannoma is extremely rare. We reviewed the literature on 19 cases of esophageal schwannoma, including that in our patient. The majority of the tumors were benign. Only three cases of schwannoma were malignant, and this is the first reported case of malignant schwannoma with lymph node metastasis.

Female↗

Flow cytometric determination of the DNA content in transitional cell carcinoma of the bladder: predictability of ploidy with regard to pelvic lymph node metastasis.

Flow cytometry was used to evaluate 93 deparaffinized transurethral resection or cystectomy specimens to investigate the predictability of DNA profiles with regard to pelvic lymph node metastasis. The pathological stage and grade were also compared with the status of the pelvic lymph node. The incidence of aneuploidy in the total specimen group was 55 out of 93 (59%). Aneuploidy and pathologic stage were significant risk factors for pelvic lymph node metastasis (p = 0.0091, 0.0008 respectively) but histologic grade was not correlated with pelvic lymph node status (p = 0.7418). Aneuploidy was noted in all of the 11 specimens exhibiting lymph node involvement compared with 44 of the 82 (54%) without lymph node involvement (p = 0.0091). There was no positive pelvic lymph node involvement in patients with diploid tumor compared with 11 of the 55 (20%) patients with aneuploid tumors. In conclusion, the recognition of a DNA aneuploid stemline in a primary transitional cell carcinoma of the bladder is statistically correlated with a greater likelihood of pelvic lymph node metastasis. This suggests that preoperative DNA flow cytometry for primary tumor might be helpful in selecting patients who should be offered additional treatment such as neoadjuvant chemotherapy before definitive treatment or a more conservative approach such as transurethral resection.

Adult↗

[The clinicopathological analysis of lymph node metastasis of gastric cancer].

One hundred-twenty-one cases of curative resection for gastric cancer with lymph node metastasis were analyzed to determine the prognostic value of the nodal stage (n), number of metastatic lymph nodes, maximum diameter of metastatic lymph nodes, micrometastasis of lymph nodes, histological type of lymph node metastasis, extranodular invasion and infiltration into lymphatic vessels around metastatic lymph nodes. In patients with a higher nodal stage the survival rate was lower and the nodal stage was a good prognostic indicator. Inpatients who had 7 or more metastatic lymph nodes or in whom the maximum diameter of the metastatic lymph nodes was over 15 mm or who had not only micrometastasis of lymph nodes, the survival rate was lower. These results suggest that quantitative analysis of metastatic lymph nodes is necessary. In patients who had nudifferentiated type metastatic lesions of lymph nodes, the survival rate was lower than in those with the differentiated type and the difference was larger than for the primary lesion. In patients who had extranodular invasion or infiltration into lymphatic vessels around metastatic lymph nodes, the survival rate was decreased. These results suggest that histopathological analysis of metastatic lymph nodes is necessary.

Humans↗

The management of lymph node metastasis from bladder cancer.

AIM: The presence of pelvic lymph node metastasis from bladder cancer has traditionally been associated with a very poor prognosis. The aim of this paper is to review the literature with regard to the management of patients with nodal disease, particularly gross nodal metastasis and suggest a strategy for management of these patients. METHODS: We performed a literature search in the PubMed database and the reference lists of relevant papers describing the management of locally advanced bladder cancer. FINDINGS: There are no randomised studies relating specifically to the management of nodal metastasis in bladder cancer. It is clear however that a significant number of patients with micrometastatic nodal disease may be cured. Few studies exist which address the management of patients with gross nodal disease and consist of series from a limited number of institutions. In patients with gross nodal disease detected pre-operatively or at the time of surgery, a multimodality approach consisting of surgery, chemotherapy and possibly radiotherapy seems appropriate. The prognosis of such patients relates to the pathological stage of the primary tumour and the degree of lymph node involvement. In addition a good response to neoadjuvant chemotherapy may identify patients who are likely to survive longer. CONCLUSIONS: The prognosis for patients with gross nodal disease from bladder cancer is poor although cure may be possible in a small number of patients. In such cases a multimodality approach is appropriate and management decisions should be made on an individual patient basis.

Combined Modality Therapy↗

Histopathological assessment of lymph node metastasis in patients with gastric cancer.

BACKGROUND/AIMS: Lymph node dissection has been carried out for two decades in Japan, resulting in improved survival of patients with gastric cancer. By analyzing dissected nodes of resected advanced gastric cancers, we intend to determine which parameter(s) are more concerned in node metastasis. PATIENTS AND METHODS: Curative gastrectomy with dissection of lymph nodes was performed for 78 of the 108 patients with advanced gastric cancer. Metastases were found in 171 of 1359 nodes (13%) dissected. In each node, the maximum and minimum diameters were measured, and the ratio of the former to the latter was calculated. RESULTS: The minimum diameter of node was closely related to node metastasis. When the minimum diameter in node metastatic criteria was "3 mm or more", a sensitivity of 81% and specificity of 54% were calculated. In false negative node, signet-ring cell carcinoma (SIG) (33%) and poorly differentiated adenocarcinoma (POR) (22%) were more frequently found as primary lesions. Half or more of these nodes were invaded by only a few carcinoma cells. When the primary lesion is histologically SIG or POR, endoscopic treatment is contraindicated for possible nodes metastasis. CONCLUSIONS: It is impossible to distinguish nodes with micrometastasis from nodes without metastasis. The minimum diameter of node is more important in node metastasis of gastric cancer than the maximum diameter of node or the ratio of both.

Adenocarcinoma↗

Partial regression of primary cutaneous melanoma: is there an association with sub-clinical sentinel lymph node metastasis?

Whether partial regression of a primary melanoma has an adverse impact on prognosis is controversial. As an indirect mechanism of addressing this question we drew a correlation between the histopathological characteristics of 107 cutaneous melanomas and the presence of sub-clinical metastasis in corresponding sentinel lymph nodes. Partial regression of the primary tumor, defined as focal replacement of the lesion by a scar, unrelated to a previous biopsy, was observed in 20 (19%) cases in the group as a whole. Excluding cases in which an accurate Breslow thickness of the primary melanoma could not be established and/or the presence of a capsular nevus was detected in the sentinel node, a total of 97 remained. Seventeen cases (Breslow thickness 0.63-9.7; mean 2.4 mm) showed partial regression and 80 (Breslow thickness 0.25-7.00; mean 1.8 mm) were devoid of regression. Of the 17 cases with regression 5 (29%) had nodal metastasis (by histopathology and/or molecular analysis) and of the 80 cases without regression 23 (29%) had nodal metastasis (by one or both evaluations). Our data reveals no association between partial regression of the primary melanoma and sentinel node involvement by the disease. The Breslow thickness proved to be the only significant independent variable related to nodal metastasis. Of interest, ulceration of the primary lesion was significantly associated with nodal disease on univariate, but not on multivariate, analysis. While acknowledging that the cohort size may lack the statistical power to demonstrate subtle associations, our data supports the known relevance of tumor thickness and ulceration to regional lymph node metastasis and thereby, to outcome of melanoma in its early stages, but fails to support a similar role for partial regression.

Adult↗

Angiogenesis at the site of deepest penetration predicts lymph node metastasis of submucosal colorectal cancer.

PURPOSE: Intratumor microvessel count has been reported as a useful prognostic factor in patients with cancer of various organs. This study was undertaken to clarify the relation between microvessel count and lymph node metastasis in submucosal colorectal cancer. METHODS: Microvessel count was estimated in 254 invasive tumors that had been resected from patients with submucosal colorectal cancer. Immunohistochemistry with antibodies against CD34 was performed on archival specimens, and microvessel counts were estimated based on the average count of three fields (original magnification, x400) in the most vascular area at the site of deepest submucosal penetration. RESULTS: Microvessel count ranged from 10 to 98, with a median of 40. Lesions with high microvessel counts (> or =40) had a significantly higher incidence of lymph node metastasis than those with low microvessel counts (<40; 21.8 percent vs. 6.2 percent). None of the 79 lesions with low microvessel counts and submucosal invasion up to a depth of 1,500 microm had metastasized to the lymph nodes. In multivariate analysis, microvessel count was an independent risk factor for lymph node metastasis in submucosal colorectal cancer (P = 0.0026). CONCLUSION: Microvessel count at the site of deepest submucosal penetration can be one of the most useful predictors for lymph node metastasis. Analysis that combines microvessel count and depth of submucosal invasion may predict the occurrence of lesions without lymph node metastasis.

Adenocarcinoma↗

Tumor cell dissociation score highly correlates with lymph node metastasis in superficial esophageal carcinoma.

BACKGROUND: It is still not clear which parameters are important for predicting the metastatic potential of superficial esophageal squamous cell carcinoma (SESCC). The purpose of the present paper was thus to investigate tumor cell dissociation (TCD) in SESCC as a predictive factor of lymph node metastasis. METHODS: Thirty-three SESCC were classified into four groups based on the depth of tumor invasion. Carcinomas not invading as far as the muscularis mucosa were classified as group A; carcinomas invading to the muscularis mucosa or less than one-third of the upper submucosa were classified as group B; those invading to the middle layer of the submucosa were classified as group C; and those invading one-third of the lower submucosa were classified as group D. The TCD score was calculated by dividing the length of the TCD region by the maximal longitudinal length of the area of invasion into or beyond the lamina propria, and multiplying by 100. E-cadherin expression of the carcinomas was investigated in the TCD area and the successive area of mucosal invasive carcinoma (SAM). RESULTS: The incidence of lymph node metastasis was 0% in group A, 10% in group B, 36.4% in group C and 57.1% in group D. The mean TCD scores (+/-SEM) of SESCC with lymph node metastasis were higher than that without (85.3 +/- 5.7, 16.3 +/- 3.9, respectively; P < 0.001). In group C, the TCD score of cases with lymph node metastases was higher than in those without lymph node metastasis (P < 0.001). E-cadherin expression was significantly reduced in the area of TCD compared with the SAM located over the TCD area (P < 0.001). CONCLUSIONS: The TCD score is an important predictive marker for lymph node metastasis in SESCC. Clinical evaluation of TCD scores in endoscopic mucosal resection (EMR) specimens would enable accurate prediction of lymph node metastasis and extend the indication of EMR treatment for SESCC.

Aged↗