Higher Frequency Of Lymph Node Metastasis Research Articles

Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related mortality worldwide. Mesenchymal-epithelial transition factor (MET) gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor treatment. MET amplification has been reported in CRC, but data are very limited. Investigating pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical practice. To determine the pathological significance of MET amplification in CRC and to propose a feasible screening strategy. A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen Cancer Hospital of Chinese Academy of Medical Sciences were recruited. All patients were without RAS/RAF mutation or microsatellite instability-high. MET amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Correlations between MET aberration and pathological features were detected using the chi-squared test. Progression free survival (PFS) during the two-year follow-up was detected using the Kaplan-Meier method and log rank test. The results of MET FISH and IHC were compared using one-way ANOVA. Polysomy-induced MET amplification was observed in 14.4% of cases, and focal MET amplification was not detected. Polysomy-induced MET amplification was associated with a higher frequency of lymph node metastasis (LNM) (P < 0.001) and higher tumor budding grade (P = 0.02). In the survival analysis, significant difference was detected between patients with amplified- and non-amplified MET in a two-year follow-up after the first diagnosis (P = 0.001). C-MET scores of 0, 1+, 2+, and 3+ were observed in 1.4%, 24.9%, 54.7%, and 19.0% of tumors, respectively. C-MET overexpression correlated with higher frequency of LNM (P = 0.002), but no significant difference of PFS was detected between patients with different protein levels. In terms of concordance between MET FISH and IHC results, MET copy number showed no difference in c-MET IHC 0/1+ (3.35 ± 0.18), 2+ (3.29 ± 0.11) and 3+ (3.58 ± 0.22) cohorts, and the MET-to-CEP7 ratio showed no difference in three groups (1.09 ± 0.02, 1.10 ± 0.01, and 1.09 ± 0.03). In CRC, focal MET amplification was a rare event. Polysomy-induced MET amplification correlated with adverse pathological characteristics and poor prognosis. IHC was a poor screening tool for MET amplification.

Prognostic Factors and Lymph Node Metastasis Patterns of Primary Duodenal Cancer.

The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2-G4, presence of LNM, pT3-4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis-T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3-4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. Histologic grade G2-G4, presence of LNM, pT3-T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis-T1a. Moreover, based on the high frequency of LNM in T3-4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3-4 DC at any site.

BRAF Mutated Tall Cell Papillary Carcinoma Lung Metastasis Following Thyroidectomy

SESSION TITLE: Metastatic and Other Primary Lung Tumors SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: BRAF Mutated Tall Cell Papillary Carcinoma is a rare tumor infrequently presented as lung metastasis. Although Papillary Carcinoma is one of the most frequent Thyroid Cancers, BRAF-Tall Cell Variant carries the worst prognosis. CASE PRESENTATION: A 65-year-old male former 12-pack year smoking history and total thyroidectomy as a child presents for evaluation of hematochezia. He has no prior history of radiation exposure or familial history of thyroid cancer. Supplemental thyroid replacement therapy was started at age 21 due to clinical hypothyroidism. Residual thyroid glandular tissue was not visible on CT scan or ultrasound studies. Abdominal and pelvic computed tomography (CT) scan demonstrated the incidental finding of a 1.2 cm non-calcified lobulated and speculated pulmonary nodule. Positron Emission Test (PET) Scan demonstrated maximum SUV uptake of 11.0 in mediastinal and pretracheal structures. Mediastinoscopy aborted after experiencing intraoperative bleeding complications. Endobronchial Ultrasound Trans-bronchial fine needle aspiration (EBUS-TB FNA) was was non-diagnostic. Exploratory thoracotomy with right middle lobe wedge resection and mediastinal lymph node dissection was performed. Surgical biopsy diagnosed a poorly differentiated tall cell papillary carcinoma, BRAF positive mutation. DISCUSSION: BRAF is a important oncoprotein responsibile for the MAPK-pathway output. Its role suppresses the expression of genes required for iodide incorporation. Due to poor iodide uptake, radioactive iodine is not useful diagnostically or therapeutically in tall cell variant disease. CONCLUSIONS: BRAF-mutated classical or tall-cell-variant papillary thyroid carcinomas have a high frequency of lymph-node metastases and recurrence after thyroidectomy. These associated carcinomas have a poor response to radioiodine therapy due to the high MAPK-pathway output, which is driven by the BRAF V600E oncoprotein. This case demonstrates the difficulty with diagnosis of mediastinal lymphadenopathy and rare presentation of tall cell variant papillary cell carcinoma as lung metastasis. Reference #1: American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Reference #2: Gimm, O., Rath, F. W. and Dralle, H. (1998), Pattern of lymph node metastases in papillary thyroid carcinoma. Br J Surg, 85: 252-254. doi:10.1046/j.1365-2168.1998.00510.x Reference #3: Xing M, Westra WH, Tufano RP, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab 2005;90:6373-9. DISCLOSURE: The following authors have nothing to disclose: Brandon Hooks No Product/Research Disclosure Information

Risk of lymph node metastasis in mixed-type early gastric cancer determined by the extent of the poorly differentiated component.

To predict the rate of lymph node (LN) metastasis in diffuse- and mixed-type early gastric cancers (EGC) for guidelines of the treatment. We reviewed 550 cases of EGC with diffuse- and mixed-type histology. We investigated the clinicopathological factors and histopathological components that influence the probability of LN metastasis, including sex, age, site, gross type, presence of ulceration, tumour size, depth of invasion, perineural invasion, lymphovascular invasion, and LN metastasis status. We reviewed all slides and estimated the proportions of each tumour component; pure diffuse type, mixed-predominantly diffuse type (diffuse > intestinal type), mixed-predominantly intestinal type (intestinal > diffuse type), and mixed diffuse = intestinal type. We calculated the extents of the respective components. LN metastasis was observed in 12.9% (71/550) of early gastric cancers cases [15/288 mucosal EGCs (5.2%) and 56/262 submucosal EGCs (21.4%)]. Of 550 cases, 302 were diffuse-type and 248 were mixed-type EGCs. Of 248 mixed-type EGCs, 163 were mixed-predominantly diffuse type, 82 were mixed-predominantly intestinal type, and 3 were mixed diffuse = intestinal type. Mixed-type cases with predominantly diffuse type histology showed a higher frequency of LN metastasis (20.2%) than cases of pure diffuse type (9.3%) and predominantly intestinal type (12.2%) histology. We measured the dimensions of each component (intestinal and diffuse type) to determine the association of the extent of each component with LN metastasis in mixed-type gastric carcinoma. The total tumour size and the extent of poorly differentiated components was associated with LN metastasis, while that of signet ring cell components was not. We recommend careful identification and quantitative evaluation of mixed-type early gastric cancer components after endoscopic resection to determine the intensity of the treatment.

Is endoscopic submucosal dissection safe for papillary adenocarcinoma of the stomach?

To identify the clinicopathological predictors of lymph node (LN) metastasis and evaluate the outcomes of endoscopic submucosal dissection (ESD) in papillary adenocarcinoma-type early gastric cancers (EGCs). From January 2005 to May 2013, 49 patients who underwent surgical operation and 24 patients who underwent ESD for papillary adenocarcinoma-type EGC were enrolled to identify clinicopathological characteristics and predictive factors of LN metastasis and to evaluate the outcomes of ESD for papillary adenocarcinoma-type EGC. Most papillary adenocarcinoma-type EGCs were located in the lower third of the stomach and had an elevated macroscopic shape. The overall prevalence of LN metastasis was 18.3% (9/49). The presence of lymphovascular invasion was found to be a predictor of LN metastasis (P = 0.016). According to current indication criteria of ESD, 6 and 11 of the 49 patients had absolute and expanded indications for ESD, respectively. Two patients (11.8%) with expanded indication for ESD had LN metastasis. Of the 24 patients who underwent ESD, 13 (54%) achieved out-of-ESD indication, with 9 of those 13 patients undergoing surgical operation due to non-curative resection. The use of ESD should be carefully considered for papillary adenocarcinoma-type EGC with suspected ESD indication after pre-treatment work-up because of the higher frequency of LN metastasis and additional surgeries.

Clinical and Pathological Features and the BRAFV600E Mutation in Patients with Papillary Thyroid Carcinoma with and without Concurrent Hashimoto Thyroiditis

It has been reported that patients with papillary thyroid carcinoma (PTC) have a high incidence of background Hashimoto thyroiditis (HT); however, the linkage of HT to PTC is controversial. Recent studies have shown that the prevalence of activating point mutations in BRAFV600E is much higher (73-86%) in Korea than in Western countries (29-69%), and associated with a poor prognosis in PTC. The purpose of the present study was to investigate the frequency of the BRAFV600E mutation in PTC with and without HT, and to determine clinical and pathological features that were associated with concomitant HT and PTC. Fine-needle aspiration slides from 101 patients with surgically confirmed PTC were studied. The DNA was extracted from the atypical cells that were scraped from slides. It was then analyzed for the BRAFV600E mutation by pyrosequencing. In addition, the presence of background HT in surgical specimens and other clinical and pathological features of the patients were characterized. HT was present in 37 (36.6%) of the patients. The BRAFV600E mutation was present in 27 (72.9%) of patients with HT but was present in 61 (95.3%) of patients without HT ( p#0.01). The inverse correlation of concurrent HT with the BRAFV600E mutation was significant for both males and females ( p < 0.01). The presence of background HT was not associated with tumor size, extrathyroidal invasion, lymph node (LN) metastasis, or tumor stage. The patients were younger in the group without background HT (44.1 +/- 13.2 vs. 49.8 +/- 13.9, p 1/40.05). The BRAFV600E mutation was present in 88 (87.1%) of the 101 patients with PTC. The presence of the BRAFV600E mutation was significantly associated with LN metastasis ( p < 0.02; odds ratio, 6.24; 95% confidence interval, 1.51-25.79). In Korean patients with PTC, the BRAFV600E mutation is associated with a lower frequency of background HT and a high frequency of LN metastasis.

Prognostic factors in maxillary sinus and nasal cavity carcinoma

Aims The aim of the present study is to define prognostic factors, particularly the impact of treatment on paranasal sinus and nasal cavity malignancies. Material and methods Retrospective study of patients with maxillary antrum and nasal fossae malignancies. A maxillectomy classification as performed to treat malignancies in our institution is described. Multivariate analysis of prognostic factors was done using the Cox's model. Results One hundred and nine patients were evaluated. Squamous cell carcinoma was found in 62 cases and in 95 patients the epicentre of the tumour was located in the maxillary antrum. Ten patients were treated with surgery only, 39 patients with surgery and adjuvant radiation therapy, 37 cases received only radiotherapy, and 18 received radiotherapy followed by surgery; in five cases a combination of chemo-radiotherapy was used. Multivariate analysis identified T classification, orbit invasion, N classification, site of origin of tumour in nasal fossae, and no surgical resection as independent prognostic factors ( p=0.0001). Conclusion T4 tumours with orbit invasion present bad prognosis as compared to other T4 tumours. Surgical resection should be included in the treatment strategy. Because of the high frequency of lymph-node metastasis, neck treatment should be considered in T4 tumours.

Merkel cell carcinoma: a diagnostic and therapeutic challenge

Merkel cell carcinoma (cutaneous neuroendocrine carcinoma) is a highly malignant, neuroendocrine skin tumor. It mostly occurs in elderly patients in the sun-exposed skin of the head and neck and the extremities. Merkel cell carcinomas develop as fast-growing dermal tumors. They are characterized by a high frequency of lymph-node metastases (50%) and local recurrences (25-77%). The 5-year survival rate is 30-74%. Histology reveals uniform, round cells with a small cytoplasmic rim expressing cytokeratin 20, neurofilament, synaptophysin, chromogranin, and neuron-specific enolase. Ultrastructurally, 100-200 nm electron dense granules are typical findings. Wide surgical excision, followed by radiotherapy, is the treatment of choice. Regional lymph-node metastases should be treated by radical lymph-node excision and radiotherapy. In advanced metastatic Merkel cell carcinoma, a remission can be achieved by different chemotherapy schedules or the somatostatin analogue octreotide. However, the prognosis remains poor. The current knowledge about this disease and guidelines for effective diagnosis and treatment are given.

Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage.

Expressions of p53 protein and epidermal growth factor receptor (EGFR) were immunohistochemically investigated in 111 patients with papillary thyroid carcinomas (PTC) in order to evaluate their co-expression in relation to lymph node metastases (LNM), tumor size and clinicopathologic stage. In PTC, positive staining for p53 in dewaxed sections was present in nuclei or cytoplasm, or in both, whereas surface linear or cytoplasmic staining for EGFR was observed with varying degrees of extent and intensity. Positive reaction (more than 10% of tumor cells positive) was observed in 65 cases (58. 5%) for p53, and in 87 cases (78.4%) for EGFR. A significant correlation was found between p53 protein and EGFR overexpressions (p<0.01). Notably, p53-positive cases always exhibited positive staining for EGFR. Forty-four patients (39.6%) exhibited concomitant LNM, most of whom had both p53 and EGFR expression in primary foci. Statistical analysis revealed that co-expression of p53 protein and EGFR was significantly correlated with LNM, tumor size and clinicopathologic stage, but no correlation was found between their co-expression and age or sex. Our findings suggest that overexpression of p53 protein or EGFR in PTC tends to be associated with a high frequency of LNM, increased tumor size and advanced clinicopathologic stage, and that co-expression of both p53 protein and EGFR may predispose to growth and progression of PTC. Our findings also suggest that p53 protein and EGFR expressions may be clinicopathologic and prognostic indicators of PTC.

Clinical study on the pattern of lymphnode metastasis in carcinoma of esophagus (an analysis of 200 cases)

To study the pattern of lymphnode metastasis in carcinoma of the esophagus, 200 cases of resected esophageal cancer specimens were carefully examined pathologically. Lymphnode metastasis, its pathway and extent in relation to pathological changes were analyzed. Lymphnode metastasis was mainly regional and extended vertically in both directions. Leaping-over metastasis was another feature. The deeper invasion by the tumor, the higher frequencies of metastasis development, and vice versa. However, leaping-over metastasis was more likely to occur where tumor invasion was less severe. Owing to the high frequency of lymphnode metastasis in the superior mediastinum and the widely spanned leaping-over metastases, an operative approach by three incisions through right thoracotomy with excision of the whole segment of esophagus and anastomosis at cervical region was recommended, in order to dissect lymphnodes in the cervical, thoracic and abdominal regions and to leave less or no metastatic lymphnodes behind.

Identification of cystatin B in human esophageal carcinoma, using differential displays in which the gene expression is related to lymph‐node metastasis

Identification of the genes that are specifically expressed in either tumor or normal tissue is important for understanding cancer biology. Using differential displays, we obtained one gene which was specifically expressed in normal tissue but is only rarely expressed in carcinoma tissue of the human esophagus. The sequence of this gene was identical with cystatin B, known to be one of the cysteine-proteinase inhibitors, mainly inhibiting cathepsin L. There is little information on the clinical significance of cystatin B expression in human esophageal carcinoma. We thus studied the mRNA expression of cystatin B in 45 tumor/normal pair specimens of the esophagus, using the semi-quantitative reverse transcriptase polymerase chain reaction technique. The expression of cystatin B in tumor tissue was found to be markedly decreased compared with that of the corresponding normal tissue. The cases with a tumor/normal ratio of less than 0.5 showed high frequency of lymph-node metastasis and more advanced clinical stage as compared with those whose tumor/normal ratio was equal to or more than 0.5. The decreased expression of cystatin B protein in carcinoma tissue was confirmed by immunohistochemical staining. Our study suggests that reduced expression of cystatin B in esophageal-carcinoma tissue is associated with lymph-node metastasis and may therefore prove to be a useful marker for predicting the biologic aggressiveness of human esophageal carcinoma. Int. J. Cancer (Pred. Oncol.) 79:175–178, 1998.© 1998 Wiley-Liss, Inc.

Identification of cystatin B in human esophageal carcinoma, using differential displays in which the gene expression is related to lymph-node metastasis.

Identification of the genes that are specifically expressed in either tumor or normal tissue is important for understanding cancer biology. Using differential displays, we obtained one gene which was specifically expressed in normal tissue but is only rarely expressed in carcinoma tissue of the human esophagus. The sequence of this gene was identical with cystatin B, known to be one of the cysteine-proteinase inhibitors, mainly inhibiting cathepsin L. There is little information on the clinical significance of cystatin B expression in human esophageal carcinoma. We thus studied the mRNA expression of cystatin B in 45 tumor/normal pair specimens of the esophagus, using the semi-quantitative reverse transcriptase polymerase chain reaction technique. The expression of cystatin B in tumor tissue was found to be markedly decreased compared with that of the corresponding normal tissue. The cases with a tumor/normal ratio of less than 0.5 showed high frequency of lymph-node metastasis and more advanced clinical stage as compared with those whose tumor/normal ratio was equal to or more than 0.5. The decreased expression of cystatin B protein in carcinoma tissue was confirmed by immunohistochemical staining. Our study suggests that reduced expression of cystatin B in esophageal-carcinoma tissue is associated with lymph-node metastasis and may therefore prove to be a useful marker for predicting the biologic aggressiveness of human esophageal carcinoma.