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Increased expression of integrin beta-4 in papillary thyroid carcinoma with gross lymph node metastasis.

Although the prognosis is generally good for patients with papillary thyroid carcinoma, gross nodal metastasis of carcinoma has a poor prognosis. It is necessary to clarify how carcinoma progresses to gross nodal metastasis in order to establish a cure. The adhesion molecule integrin beta-4 is considered to be related to cell migration and metastasis in many carcinomas. In the present study, we examined integrin beta-4 expression in 65 cases of human papillary thyroid carcinoma using immunohistochemical methods. Expression of integrin beta-4 was found in all papillary carcinomas, but in few normal thyrocytes. Interestingly, integrin beta-4 expression in the carcinomas with gross (> or =3 cm) lymph node metastasis was significantly higher than that in carcinomas with small (<3 cm) or no lymph node metastasis. These results suggest that integrin beta-4 expression in thyroid carcinoma may play a role in the development of gross lymph node metastasis of papillary carcinomas.

Carcinoma, Papillary↗

Hemangioendothelioma of bone. A report of an unusual case with lymph node metastasis.

An unusual case of hemangioendothelioma of bone with regional lymph node metastasis in a 54-year-old woman is reported. The patient died nine weeks after admission of circulatory collapse. Six possibly similar cases were found in reviewing the literature. It is concluded that lymph node metastases from hemangioendothelioma of bone appear to be an extraordinary event and may represent an extremely unfavourable prognostic finding.

Bone Neoplasms↗

Cyclin D1 gene numerical aberration is a predictive marker for occult cervical lymph node metastasis in TNM Stage I and II squamous cell carcinoma of the oral cavity.

BACKGROUND: The management of occult cervical lymph node metastases originating from oral squamous cell carcinomas (OSCCs) remains controversial. The purpose of this study was to evaluate the value of cyclin D1 gene (CCND1) numerical aberrations in predicting the risk of late lymph node metastases. METHODS: Fluorescence in situ hybridization (FISH), using a BAC clone specific for CCND1, was performed on OSCC specimens obtained by fine-needle aspiration (FNA) biopsy from 45 patients with previously untreated TNM Stage I and II (T1-2N0M0) disease who had not undergone elective cervical lymph node dissection. RESULTS: CCND1 numerical aberrations were observed in 15 (33.3%) of the 45 patients and were significantly associated with the mode of invasion of the primary tumor (P = 0.01) and the presence of occult lymph node metastases (P < 0.001). Twelve of these 15 patients (80%) developed late cervical lymph node metastases within 2 years of surgery for primary OSCCs. All patients with cluster-type amplification of CCND1 developed late lymph node metastases. Multivariate analysis showed that only CCND1 numerical aberrations (risk ratio, 8.685%, 95% confidence interval = 2.232-33.802, P = 0.002) independently predicted late cervical lymph node metastasis. CONCLUSIONS: Aberrations in CCND1 numbers appear to be valuable in identifying patients at high risk of late lymph node metastasis in Stage I and II OSCCs. Analysis of CCND1 numerical aberrations using FISH on FNA biopsy specimens may be useful in selecting patients for elective cervical lymph node dissection.

Adult↗

Predictors of nonsentinel lymph node metastasis in breast cancer patients.

BACKGROUND: In order to define a future subset of breast cancer patients in whom the axilla may be staged by sentinel lymph node biopsy alone, the conditions under which nonsentinel axillary lymph node metastases occur must be delineated. METHODS: A prospective database including 212 breast cancer patients who underwent sentinel lymph node biopsy followed by completion axillary dissection at our institution was reviewed. A multivariate, logistic, stepwise regression was performed to evaluate the relationship between nonsentinel lymph node metastasis and patient age, primary tumor size, presence of lymphatic invasion, use of radioisotope to identify the sentinel node and degree of metastasis in the sentinel node. RESULTS: Tumor size greater than 2 cm, lymphatic invasion of the primary tumor, macrometastasis in the sentinel node, and use of radioisotope all positively correlated independently with metastasis in the nonsentinel lymph node (P = 0.0001, P = 0.0483, P = 0.0008, P = 0.0271, respectively). CONCLUSIONS: Predictors of nonsentinel axillary node metastasis exist and are important in defining those patients in whom a sentinel lymph node biopsy alone may not be adequate.

Adult↗

Clinicopathological analysis of early gastric cancer with solitary lymph node metastasis.

BACKGROUND: The sentinel node concept has not yet been established in gastric cancer. METHODS: Fifty-four patients with early gastric cancer who had only one lymph node metastasis were regarded retrospectively as patients with a possible sentinel node metastasis, and the morphological features of these nodes were assessed. The level I nodes in seven patients with a possible skip metastasis at routine haematoxylin and eosin staining were re-examined using cytokeratin (CK) immunostaining. RESULTS: The shape of the gastric cancer lesion could be examined in 53 of the patients; more than one-third (20 of 53) were microfocal type. Concerning the intranodal cancer foci, the marginal sinus type was found in 32 affected nodes, medullary sinus type in 14 and mixed type in seven. Forty-three per cent of suspected sentinel nodes were the largest in size among all nodes from the station. CK immunostaining of seven non-metastatic nodes with haematoxylin and eosin revealed that three were CK positive. CONCLUSION: These findings suggest that possible sentinel nodes detected by conventional means may not always be primary portions of any metastasis. Adoption of sentinel node biopsy in gastric cancer must await the development of improved procedures for diagnosis during surgery.

Humans↗

Comparison of plasma D-dimer and thrombus precursor protein in patients with operable breast cancer as a potential predictor of lymph node metastasis.

Fibrin formation and removal is continuous during the development of malignancy. Plasma D-dimer is indicative of ongoing fibrinolysis, and circulating soluble fibrin polymer [thrombus precursor protein (TpP)] represents thrombogenic activity. We evaluated the relationship between plasma D-dimer and TpP levels with tumor extent and examined the use of these markers as possible predictors of lymph node metastasis in breast cancer. Preoperative plasma levels of D-dimer and TpP were measured in these 120 patients (93 breast cancer, 27 benign breast disease) and 29 healthy controls. Plasma levels of D-dimer in patients with breast cancer were significantly higher than in healthy controls and in those with benign breast disease. Plasma D-dimer levels in patients with breast cancer were found to be significantly increased according to tumor stage. We also observed that plasma levels of D-dimer were higher in patients with lymph node metastasis than in patients without metastasis. In contrast, TpP levels were not significantly different by the tumor stages and lymph node metastasis. In conclusion, increased D-dimer levels in breast cancer may suggest that an ongoing fibrinolysis within breast cancer tissue occurs during tumor progression. Positive D-dimer levels might be useful for identifying metastatic lymph node in patients with operable breast cancer. However, plasma TpP was not found to be a sensitive marker for detecting tumor-associated subclinical coagulopathy.

Adult↗

Relationships among the expression of epidermal growth factor receptor, proliferating cell nuclear antigen labeling index, and lymph node metastasis in gastric cancer.

The expression of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha) and the labeling index of proliferating cell nuclear antigen (PCNA LI) were examined immunohistochemically in 288 gastric cancer patients, and the relationships between these results and the lymph node metastasis were studied. To investigate the relation between the expression of EGFR and PCNA LI, we divided the patients into the following three groups according to the immunohistochemical findings: group A, EGFR (+); group B, EGFR (-), and EGF(+) or TGF alpha(+); group C, EGFR(-), EGF(-) and TGF alpha(-). In the cancers invading submucosal or proper muscle layer, high-PCNA tumors (PCNA LI > or = 70) in both groups A and B had more frequent lymph node metastasis than in the intermediate-(40-69) and low- (< or = 39) PCNA tumors. In the cancers invading subserosal layer or further, the frequency of metastasis in group A was over 78% and was not related to the PCNA range. In group B, metastasis was more frequent in high- and intermediate-PCNA tumors (about 80%) than in low-PCNA tumors (44%). These results suggest that growth regulation by EGFR is related to lymph node metastasis in gastric cancer, and the higher the PCNA LI of cancer cells becomes, the more frequent the occurrence of lymph node metastasis.

Adult↗

[Neoadjuvant chemotherapy for advanced gastric cancer with para-aortic lymph node metastasis].

Neoadjuvant chemotherapy was applied to patients with advanced gastric cancer and confirmed para-aortic lymph node metastasis. Subjects were 7 patients. The response to the neoadjuvant chemotherapy was a PR in 5 cases, MR in 2 cases for the primary lesion and CR in 2 cases PR in 5 cases for the para-aortic lymph node metastasis. The grades of histological response assessed on the resected specimen were Grade 0 in three cases, Grade 1a in one, Grade 1b in one and Grade 2 in two. While there was no significant difference in survival rate between patient groups with and without neoadjuvant chemotherapy, the 2-year survival rate in patients with neoadjuvant chemotherapy was a good 42.9%, compared with 10% in patients groups without neoadjuvant chemotherapy. It is concluded that a better prognosis can be expected for advanced gastric cancer patients with neoadjuvant chemotherapy.

Aged↗

Multivariate analysis of occult lymph node metastasis as a prognostic indicator for patients with squamous cell carcinoma of the oral cavity.

BACKGROUND: The biologic aggressiveness of squamous cell carcinoma of the oral cavity is reflected in its ability to metastasize to regional cervical lymph nodes. Patients with clinically negative cervical lymph nodes are believed to have a good prognosis; however, the prognosis of patients with lymph node metastasis occurring after excision or radiotherapy of the primary tumor is poor. METHODS: Univariate and multivariate analyses for occult lymph node metastasis (ONM) in 172 patients with clinically negative cervical lymph nodes were performed by the authors to elucidate the clinical and histologic tumor risk factors to enhance their ability to predict ONM. A multivariate Cox proportional hazards model and Hayashi's quantification theory type II were used to analyze prognostic factors and to determine the probability of ONM. RESULTS: Using Cox's proportional regression model, the factors linked to cancer specific survival were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes were found in 21.5% of the cases studied (37 of 172 cases). The 5-year cancer specific survival was 94.0% for patients without lymph node metastasis, and 51.0% for patients with ONM (P < 0.0001, log rank test). The most significant predictors for ONM of each of the clinical and histologic factors, in descending order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration, degree of differentiation, number of mitotic figures, and type of growth by means of Hayashi's quantification theory type II. The presence or absence of ONM in 147 of 172 patients (85.5%) was correctly predicted by the score at the point of intersection of the two curves, which was -0.03. Further investigation revealed that 28 of 32 new cases were differentiated accurately by means of this diagnostic system. CONCLUSIONS: The results of the current study suggest that this method of analysis can establish a reliable predictor of ONM, thereby facilitating correct choices for surgical procedures to enhance the survival rates of patients with clinically negative cervical lymph nodes.

Adult↗

[A case of advanced gastric cancer with liver and intra-abdominal lymph node metastasis treated by hypertensive selective chemotherapy with pharmacokinetic modulating chemotherapy].

There have been few effective chemotherapeutic regimens for advanced gastric cancer with liver and intra-abdominal lymph node metastasis. A 78-year-old male patient was admitted to our hospital because of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced gastric cancer in the antrum of the stomach. Histological study of biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Examination by computed tomography and ultrasonography showed swollen paraaortic lymph nodes and liver metastasis. He was diagnosed as having advanced gastric cancer with liver and lymph node metastasis. This patient was treated weekly with an intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by subcutaneously implanted port system placed into the celiac artery. Furthermore, he was administered tegafur/uracil (400 mg/day) 5 days weekly as pharmacokinetic modulating chemotherapy (PMC). After ten courses of treatment with PMC, the liver and lymph node metastases were reduced in size. This therapy was considered to be an effective treatment for advanced gastric cancer with liver and lymph node metastasis. The theoretical purpose of hypertensive chemotherapy used together with injection of angiotensin-II is to increase the delivery of anticancer drug to the target tumor tissue by increasing the blood flow in the tumor. We conclude that this chemotherapy is effective in cases of advanced gastric cancer with liver and lymph node metastasis from the viewpoints of toxicities, antitumor effect and QOL of the patient.

Adenocarcinoma↗

Habitat radiomics predicts occult lymph node metastasis and uncovers immune microenvironment of head and neck cancer.

BACKGROUND: Occult lymph node metastasis (LNM) is a key prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). This study was to establish radiomics models derived from intratumoral, peritumoral, and habitat regions for identifying occult LNM in HNSCC. METHODS: Patients with pathologically confirmed HNSCC from three medical Centers (from March 2014 to April 2024) and The Cancer Genome Atlas (TCGA) were enrolled. Center 1 was split into training (n&#x2009;=&#x2009;330) and internal test sets (n&#x2009;=&#x2009;154), while Center 2 and Center 3 served as the external test set (n&#x2009;=&#x2009;183). Genomic set (n&#x2009;=&#x2009;50) from TCGA and single-cell RNA sequencing set (n&#x2009;=&#x2009;6) from Center 1 were used for biological analysis. We used the intratumoral, peritumoral, and habitat volumes of interest (VOIs) to extract radiomics features, respectively. Based on Logistic Regression (LR), Support Vector Machine (SVM), and Random Forest (RF) classifiers, nine radiomics models were built to confirm the optimal predictive performance. The best-performing model, along with clinical-radiologic data, was combined to develop a hybrid model. The log-rank test was used to evaluate the model's prognostic performance. Additionally, bulk and single-cell RNA sequencing were applied for investigating the biological mechanisms underlying the optimal model. RESULTS: The RF-habitat radiomics model showed the best performance, achieving AUCs of 0.835-0.919 across all datasets. Survival analysis further confirmed the prognostic value of the RF-habitat radiomics model. The RF-habitat radiomics model and the hybrid model notably surpassed the clinical model in predictive performance. Moreover, the RF-habitat radiomics model was associated with the abundance level of exhaustion-associated CD8&#x2009;+&#x2009;T cells, uncovering the immune microenvironment characteristics contributing to occult LNM in HNSCC. CONCLUSIONS: The RF-habitat radiomics model demonstrated excellent performance for predicting occult LNM in HNSCC across three cohorts, providing a non-invasive solution for occult LNM. Furthermore, radiogenomic analysis further revealed the biological associations of the model, primarily related to T cell dysfunction.

Humans↗

Regional lymph node metastasis as a predictor of peritoneal carcinomatosis in patients with Borrmann type IV gastric carcinoma.

OBJECTIVE: Postoperative survival of patients with Borrmann type IV gastric carcinoma is significantly worse than that in patients with other Borrmann types of gastric carcinomas. The most common pattern of recurrence in patients with Borrmann type IV gastric carcinoma is peritoneal metastasis. We examined the predictors of developing peritoneal metastasis. METHODS: We retrospectively analyzed the relationship between peritoneal metastasis and Borrmann type IV gastric carcinoma. We also examined the dependence of the peritoneal metastasis on clinicopathological findings. RESULTS: Borrmann type IV was an independent prognostic factor of survival by multivariate analysis, and regional lymph node metastasis was an independent predictor of peritoneal metastasis in patients with Borrmann type IV gastric carcinoma. CONCLUSION: Because type of lymph node dissection was not associated with developing peritoneal metastasis, early detection of cancer without lymph node metastasis may be the only means of improving survival in patients with Borrmann type IV gastric cancer.

Carcinoma↗

[The risk factors of lymph node metastasis in submucosal invasive gastric carcinoma--assessment of the indication for endoscopic treatment].

Recent advances in endoscopic diagnosis and treatments have increased the number of early gastric carcinomas being treated by endoscopic resection. However, the appropriate criteria for endoscopic resection of gastric carcinomas with submucosal invasion are not completely established. During the past 12 years from 1980 to 1992, 116 lesions in 116 patients were treated by surgical operation for differentiated type submucosal invasive gastric carcinoma. In this study, the risk factors of lymph node metastasis were investigated clinicopathologically. As the result, 1) Heterogeneity of submucosal invasive tumor margin was demonstrated in 19 (16%) of the 116 lesions of which predominant histology was differentiated adenocarcinoma. 2) Lymph node metastasis was demonstrated in 16 (16%) of the 97 lesions of which histology was differentiated type. 3) Significant risk factors of lymph node metastasis was demonstrated in submucosal massive invasion (sm3), papillary adenocarcinoma, INF gamma, lymph vessel involvement (ly(+)), and existence of ulcer (ul(+)). 4) Sm3 and papillary adenocarcinoma (pap) had a higher malignant potential than ly(+), INF gamma, and ul(+) by multivariate analysis using the logistic regression. 5) All lesions with both well differentiated adenocarcinoma (tub1) and sm minimal invasion (sm1) had no lymph node metastasis. These results suggested that the lesions with both well differentiated adenocarcinoma tub1 and sm1, which have no other risk factors such as ly(+), INF gamma, and ul(+), may be considered as the appropriate indication for endoscopic treatment of gastric submucosal carcinoma.

Adenocarcinoma, Papillary↗

Well-Differentiated villoglandular adenocarcinoma of the uterine cervix: a report of 15 cases including two with lymph node metastasis.

Well-differentiated villoglandular adenocarcinoma is a recently described subtype of cervical adenocarcinoma. The tumor of this type is reported to have distinct clinicopathologic features and excellent prognosis. However, lymph node metastases of this tumor have been described in few reports. Fifteen cases of well-differentiated villoglandular adenocarcinoma treated at Maharaj Nakorn Chiang Mai Hospital were retrospectively reviewed for both clinical and histopathological features. All patients underwent radical hysterectomy with pelvic lymphadenectomy. In the cases with lymph node metastasis, adjuvant radiation therapy was also given. The patients ranged in age from 22 to 53 years (mean, 39.3). Fourteen patients were FIGO stage IB and one was stage IIA. All patients had exophytic friable cervical masses. Tumor size known in 14 cases ranged from 1.5 to 4 cm (mean, 2.3). Eleven tumors (73.3%) were confined to the inner third of the cervical stroma with 9 of these (60%) showing only superficial invasion (depth < or = 3 mm). The tumors invaded deeply to the middle third in 3 cases (20.0%), and to the outer third in one (6.7%). Lymphatic invasion was observed in 3 cases, two of them had pelvic lymph node metastasis. Both patients had tumors involving deeper than the inner third of the cervical wall. The follow-up duration ranged from 21 to 144 months (mean, 67.5). Four of thirteen cases without nodal metastasis were lost to follow-up 36 to 59 months after surgery. All patients showed no evidence of disease at the last visit. Presence of lymphatic invasion and deep stromal involvement appeared to be the risk factors for lymph node metastasis of well-differentiated villoglandular adenocarcinoma.

Adenocarcinoma↗

Prognostic significance of Bcl-2, p53 overexpression, and lymph node metastasis in surgically staged endometrial carcinoma.

OBJECTIVE: The purpose of this study was to clarify whether Bcl-2 and p53 have prognostic significance that is independent of lymph node metastasis and other conventional histopathologic factors in endometrial carcinoma. STUDY DESIGN: Immunohistochemistry for Bcl-2 and p53 expression was performed on the frozen sections of 102 cases that were treated with surgery, including pelvic and para-aortic lymphadenectomy. Cox regression analysis was used to determine the prognostic significance. RESULTS: By univariate analysis, both loss of Bcl-2 expression and p53 overexpression were related to patient survival. Lymph node metastasis, p53 overexpression, and nuclear grade were found to be independent prognostic factors (determined by multivariate analysis). The estimated 5-year survival rate of patients with stage III/IV disease without p53 overexpression was 75.7%; the estimated 5-year survival rate for patients with p53 overexpression was only 40.4%. The difference was highly significant (P =.0053). CONCLUSION: Lymph node metastasis, p53 overexpression, and nuclear grade are independent prognostic factors for endometrial carcinoma. Bcl-2 may have little importance in the progression of endometrial carcinoma and is a less potent prognostic factor than is p53. A new treatment strategy is necessary for advanced stage endometrial carcinoma with p53 overexpression.

Adenocarcinoma↗

IV-DSA is a new diagnostic tool for axillary lymph node metastasis in breast cancer patients.

BACKGROUND AND OBJECTIVE: The aim of this study is to know whether intravenous digital subtraction angiography (IV-DSA) is useful to detect axillary lymph node metastasis of breast cancer and to evaluate the anigiogenesis of lymph nodes in the axilla. PATIENTS AND METHODS: Forty three primary breast cancer patients (N0: 26 cases, N1: 5 cases, N2: 2 cases) who underwent IV-DSA between January and November 2000 were included in the study. Infinix CB apparatus (Toshiba, Japan) was used to collect IV-DSA images and when a mass became stained in the axilla, it was considered to be metastatic. The angiogenesis was studied by examining microvessel density (MVD) after lymph node immunostaining for factor VIII. Primary tumor was detected by IV-DSA in all 43 cases. RESULTS: Axillary lymph node metastases were detected by IV-DSA in 34.9% of cases (15/43), and by pathology in 37.2% (16/43). The sensitivity, specificity, and accuracy of the diagnostic method were 75.0% (12/16), 88.9% (24/27), and 83.7% (36/43), respectively. MVD, calculated after immunostaining for factor VIII, was significantly lower in the in metastatic region of lymph nodes identified by DSA (88.5 +/- 35.0) than in metastasis-free lymph nodes (141.1 +/- 34.0, P < 0.0001). CONCLUSIONS: IV-DSA is useful in the diagnosis of axillary lymph node metastasis of breast cancer. Our results suggest that the primary factors involved in the mechanism of DSA display may be different from high/low MVC values.

Angiography, Digital Subtraction↗

Expression of E-cadherin and lymph node metastasis in resected non-small-cell lung cancer.

This study was conducted to clarify the relationship between E-cadherin expression on tumor and lymph node metastasis as well as its prognostic roles in resected non-small-cell lung cancer. Two hundred forty-nine patients, who underwent surgical resection (stage I-IIIA), were examined. Paraffin-embedded sections of the primary tumors in all cases and of the metastatic lymph nodes in stage IIIA disease were stained with a monoclonal antibody against E-cadherin. Decreased expression of E-cadherin correlated with pathologic stage, tumor size, lymph node metastasis, and histological grade. The 5-year survival rate of E-cadherin-negative patients with stage IIIA disease was significantly lower than that of E-cadherin-positive patients. Multivariate analysis in stage IIIA disease indicated that E-cadherin was an independent prognostic factor. In the patients with clinical N0 tumors, the frequency of pathological N2 tumors was significantly higher in cases where the primary tumor was recognized as E-cadherin expression negative than in cases where the primary tumor was recognized as positive. Decreased E-cadherin expression showed correlation with presence of lymph node metastasis in resected non-small-cell lung cancer and with the prognosis of patients with stage IIIA disease.

Journal Article↗