Development Of Node Metastases Research Articles

Association of LINC00673 Genetic Variants with Progression of Oral Cancer.

Oral squamous cell carcinoma (OSCC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Polymorphisms in the long intergenic noncoding RNA 673 (LINC00673) have been currently connected to the predisposition to various cancer types. The present study attempted to explore the impact of LINC00673 gene polymorphisms on the risk and progression of OSCC. Three LINC00673 single-nucleotide polymorphisms (SNPs), including rs11655237, rs9914618, and rs6501551, were evaluated in 1231 OSCCC cases and 1194 cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of OSCC between the case and control group. However, while assessing the clinicopathological parameters, patients carrying at least one minor allele of rs9914618 (GA and AA; OR, 1.286; 95% CI, 1.008–1.642; p = 0.043) were found to develop lymph node metastasis more often compared to those who are homozygous for the major allele. Further stratification analyses revealed that this genetic correlation with increased risk of lymphatic spread was further fortified in habitual betel quid chewers (OR, 1.534; 95% CI, 1.160–2.028; p = 0.003) or smokers (OR, 1.320; 95% CI, 1.013–1.721; p = 0.040). Moreover, through analyzing the dataset from The Cancer Genome Atlas (TCGA), we found that elevated LINC00673 levels were associated with the development of large tumors in patients with head and neck squamous cell carcinoma and the risk of lymphatic spread in smokers. These data demonstrate a joint effect of LINC00673 rs9914618 with betel nut chewing or smoking on the progression of oral cancer.

Clinicopathological Risk Factors for Contralateral Lymph Node Metastases in Intraoral Squamous Cell Carcinoma: A Study of 331 Cases.

The current study aimed to examine the effects of clinicopathological factors, including the region, midline involvement, T classification, histological grade, and differentiation of the tumor on the rate of contralateral lymph node metastasis for oral squamous cell carcinoma and to assess their effects on survival rates. A total of 331 patients with intraoral squamous cell carcinomas were included. The influence of tumor location, T status, midline involvement, tumor grading, and the infiltration depth of the tumor on the pattern of metastasis was evaluated. Additionally, the effect of contralateral metastases on the prognosis was examined. Metastases of the contralateral side occurred most frequently in squamous cell carcinomas of the palate and floor of the mouth. Furthermore, tumors with a high T status resulted in significantly higher rates of contralateral metastases. Similarly, the midline involvement, tumor grading, existing ipsilateral metastases, and the infiltration depth of the tumor had a highly significant influence on the development of lymph node metastases on the opposite side. Oral squamous cell carcinomas require a patient-specific decision. There is an ongoing need for further prospective studies to confirm the validity of the prognostic factors described herein.

Sentinel Lymph Node Biopsy in High-Risk Cutaneous Squamous Cell Carcinoma: Analysis of a Large Size Retrospective Series.

One of the most important prognostic factors for mortality in cutaneous squamous cell carcinoma (cSCC) is the development of nodal metastasis. There is no consensus regarding which patient with cSCC should be offered sentinel lymph node biopsy (SLNB). This study aimed to establish the rate of positive SLNBs among patients with high-risk cSCCs and to identify which high-risk features are associated with a positive SLNB. Five-year retrospective case series in an academic tertiary care center reviewing 93 SLNBs. Of the 93 SLNBs performed, 5 (5.4%) were positive. Three patients (3/5) had neck dissection and one (1/5) had radiation therapy, with no recurrence at the time of last follow-up. A tumor diameter ≥2 cm, a tumor depth >6 mm or below subcutaneous fat, perineural invasion of nerves with a diameter ≥0.1 mm, moderate or poor histological differentiation, lymphovascular invasion, and immunosuppression were associated with a positive SLNB. All tumors with a positive SLNB were classified as T2b according to the Brigham and Women's Hospital (BWH) tumor staging. Retrospective study and absence of a control group. Sentinel lymph node biopsy can be considered for BWH T2b and T3 tumors. However, more randomized controlled studies are needed.

Oral cancer: changing the aim of the biopsy in the age of precision medicine. A review.

SUMMARYOral cancer is a heterogeneous disease that develops through a complex, multi-step process. Precision medicine should help to better understand its molecular basis, integrate traditional classifications and have a positive impact on cancer management. To apply this information in clinical practice, we need to define its histology and identify biomarkers expressed by the tumour that provide useful information for planning tailored treatment. The most reliable information currently derives from evaluation of biomarkers on post-operative samples. To plan personalised treatment, oncologists need to assess these markers on biopsy samples. We reviewed the recent literature and identified 6 of 184 publications that compared markers measured on biopsy and post-operative samples or assessed their predictivity for the development of lymph node metastases. Data from these studies suggest that markers measured on biopsy samples can provide useful indications for tailoring treatments. However, due to their heterogeneity and low level of evidence, these results need to be confirmed by clinical studies on a large population to standardise and validate biomarkers in biopsies and to assess their reliability in other diagnostic mini-invasive procedures such as radiomics and liquid biopsy.

A subcentimeter duodenal neuroendocrine neoplasm with a liver metastasis upgraded to G3: a case report

BackgroundAlthough duodenal neuroendocrine neoplasms (DuNENs) usually have indolent phenotypes, some DuNENs exhibit aggressive clinical manifestations. Tumor size > 1 cm, lymph node metastasis, and high grade have been associated with poor prognosis. However, preoperative risk evaluation is often difficult, because Ki-67 index on biopsy is frequently underestimated due to the intratumor heterogeneity. Here, we present a case of a subcentimeter DuNEN with a low Ki-67 index on endoscopic biopsy, who developed lymph node metastasis and high-grade liver metastasis.Case presentationThe patient was a 52-year-old female who presented an epigastric pain. Esophagogastroduodenoscopy revealed a duodenal submucosal lesion with a size of 8 mm. The endoscopic biopsy showed DuNEN with a Ki-67 index of 3.3% (G2 categorized by the World Health Organization 2019 classification). We performed an open partial duodenectomy with adjacent lymph node dissection. Pathological examination of the resected specimens revealed a Ki-67 index of 13.5% (G2) in the “hot spot” and lymph node metastasis. A hepatic low-density area detected on preoperative contrast-enhanced computed tomography appeared to be a liver metastasis on postoperative gadoxetic acid-enhanced magnetic resonance imaging. Subsequently, we performed a laparoscopic partial hepatectomy. Pathological examination of the liver specimen showed a metastatic neuroendocrine tumor with a Ki-67 index of 27.5% (NET-G3). The patient has been alive for 14 months since the hepatectomy.ConclusionsThis case shows the possibility of high malignant potential of DuNEN even if the primary lesion is < 1 cm and has a low Ki-67 index on biopsy.

Endoscopic resection of Barrett's adenocarcinoma: Intramucosal and low-risk tumours are not associated with lymph node metastases.

BackgroundSuperficial oesophageal adenocarcinoma can be resected endoscopically, but data to define a curative endoscopic resection are scarce.ObjectiveOur study aimed to assess the risk of lymph node metastasis depending on the depth of invasion and histological features of oesophageal adenocarcinoma.MethodsWe retrospectively included all patients undergoing an endoscopic resection for T1 oesophageal adenocarcinoma among seven expert centres in France in 2004–2016. Mural invasion was defined as either intramucosal or submucosal tumours; the latter were further divided into superficial submucosal (<1000 mm) and deep submucosal (>1000 mm). Absence or presence of lymphovascular invasion and/or poorly differentiated cancer (G3) defined a low‐risk or a high‐risk tumour, respectively. For submucosal tumours, invasion depth and histological features were systematically confirmed after a second dedicated histological assessment (new 2‐mm thick slices) performed by a second pathologist. Occurrence of lymph node metastasis was recorded during the follow‐up from histological or PET CT reports when an invasive procedure was not possible.ResultsIn total, 188 superficial oesophageal adenocarcinomas were included with a median follow‐up of 34 months. No lymph node metastases occurred for intramucosal oesophageal adenocarcinomas (n = 135) even with high‐risk histological features. Among submucosal oesophageal adenocarcinomas, only tumours with lymphovascular invasion or poorly differentiated cancer or with a depth of invasion >1000 μm developed lymph node metastasis tumours (n = 10/53%; 18.9%; hazard ratio 12.04). No metastatic evolution occurred under a 1000‐mm threshold for all low‐risk tumours (0/25), nor under 1200 mm (0/1) and three over this threshold (3/13%, 23.1%).ConclusionIntramucosal and low‐risk tumours with shallow submucosal invasion up to 1200 mm were not associated with lymph node metastasis during follow‐up. In case of high‐risk features and/or deep submucosal invasion, endoscopic resections are not sufficient to eliminate the risk of lymph node metastasis, and surgical oesophagectomy should be carried out. These results must be confirmed by larger prospective series.

DLL3 (delta-like protein 3) expression correlates with stromal desmoplasia and lymph node metastases in medullary thyroid carcinomas.

Medullary thyroid carcinomas (MTC) are rare and aggressive neuroendocrine tumors of the thyroid. About 70% of MTC are sporadic; approximately 50% of those harbor somatic RET mutation. DLL3 is widely expressed in many neuroendocrine tumors and has been evaluated as a potential therapeutic target. Since stromal desmoplasia in sporadic MTC has been identified as a reliable predictor of aggressive behavior and development of lymph node metastases, a possible correlation of DLL3 expression with the presence of stromal desmoplasia was of particular interest. 59 paraffin-embedded samples of sporadic MTC with (44 cases) and without (15 cases) stromal desmoplasia and known lymph node status were included. DLL3 expression was determined by immunohistochemistry; no expression (0%), low expression (1–49%) and high expression (≥50%) were correlated with clinicopathological data. The proportion of DLL3 positivity was significantly correlated with both stromal desmoplasia (P < 0.0001) and lymph node metastases (P < 0.0001). MTC without stromal desmoplasia consistently lack DLL3 expression. This is the first study to focus on MTC regarding DLL3 expression and the relationship to various factors. Our results demonstrate that expression of DLL3 in MTC represents a reliable surrogate marker for stromal desmoplasia and lymph node metastases and might be an indicator for aggressive clinical behavior. DLL3 expression in ≥50% of tumor cells virtually excludes MTC without stromal desmoplasia. DLL3 was discussed as a potential therapeutic target in malignant tumors of other locations with positive immunohistochemical reaction and might therefore be a new therapeutic option in MTC, as well.

Prognostic and Clinicopathological Significance of Circular RNA circ-ITCH Expression in Cancer Patients: A Meta-analysis.

Circular RNAs are a class of RNAs with a covalently closed configuration, and several members of them have been reported to be capable of regulating various biological processes and predicting the outcome of disease. Among them, circular RNA circ-ITCH has been identified to be aberrantly expressed and associated with disease progression in diverse cancers. However, the correlation of circ-ITCH expression with clinicopathological features, as well as the prognosis of cancers, remains inconclusive. Therefore, a meta-analysis was performed to investigate the clinical significance of circ-ITCH in cancers by systematically summarizing all eligible literatures. Up to August 31, 2020, relevant articles were searched in PubMed, Web of Science, Cochrane library, Embase, CNKI, and Wanfang databases. Pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. A total of 1604 patients from 14 studies were included in this meta-analysis. The results showed that cancer patients with low circ-ITCH expression were more susceptible to develop lymph node metastasis (OR = 2.25, 95% CI: 1.67-3.02, p ≤ 0.01), larger tumor size (OR = 3.01, 95% CI: 2.01-4.52, p ≤ 0.01), advanced TNM stage (OR = 2.82, 95% CI: 1.92-4.14, p ≤ 0.01), and poor overall survival (OS) (HR = 2.45, 95% CI: 2.07–2.90, p ≤ 0.01, univariate analysis; HR = 2.69, 95% CI: 1.82-3.96, p ≤ 0.01, multivariate analysis). Thus, low circ-ITCH expression was significantly associated with aggressive clinicopathological features and unfavorable outcome in various cancers. Therefore, circ-ITCH may serve as a molecular therapy target and a prognostic marker in human cancers.

Recurrence after ESD curative resection for early gastric cancer

BackgroundEndoscopic submucosal dissection (ESD) is gaining ground as a minimally invasive treatment for early gastric cancer (EGC) that has a negligible risk of lymph node metastasis. According to the 5th edition of Japanese gastric cancer treatment guidelines, annual or biannual follow-up with endoscopy is recommended, but follow-up with abdominal ultrasonography or computed tomography (CT) for surveillance of metastases is not recommended after the eCuraA resection. However, we experienced a case of lymph node recurrence following ESD resulting in eCuraA.Case presentationA 76-year-old female received ESD for EGC in a previous hospital 4 years ago. Pathological findings were tub1, 30 mm, T1a (M), UL0, Ly0, V0, pHM-, pVM- (eCuraA) according to the 15th edition of Japanese Classification of Gastric Carcinoma. Follow-up esophagogastroduodenoscopy revealed submucosal tumor, which was suspected as a swollen lymph node by CT and endoscopic ultrasound fine-needle aspiration revealed the recurrence of gastric cancer. We performed total gastrectomy with D2 lymph node dissection. Postoperative pathological examination revealed no local recurrent tumor at the ESD site in the stomach. Swollen lymph node was diagnosed as metastasis and lymph node metastasis was limited near the cardia.ConclusionThis case provides valuable information about tumor with a minimum poorly differentiated adenocarcinoma component may develop lymph node metastasis even satisfying the guidelines criteria for curative resection.

Disregulations of PURPL and MiR-338-3p Could Serve As Prognosis Biomarkers for Epithelial Ovarian Cancer.

Objective: The present study aimed to explore the expressions of long noncoding RNA (lncRNA) p53 upregulated regulator of p53 levels (PURPL) in different ovarian tissues, and to evaluate the significance of disregulations of PURPL and microRNA-338-3p (miR-338-3p) in epithelial ovarian cancer (EOC).Methods: The expressions of PURPL in ovarian cancer, the relations between PURPL and the prognosis of ovarian cancer, and the relation between PURPL and miR-338-3p were queried in multiple biomedical databases. Real-time PCR was performed to detect the expressions of PURPL in different ovarian tissues. Logistic regression analysis was used to analyze the risk factors of recurrence and death. Kaplan-Meier analysis was implemented to evaluate the relations between PURPL and miR-338-3p expressions and the survival of ovarian cancer.Results: PURPL could target miR-338-3p, PURPL were upregulated in ovarian cancer tissues, upregulation of PURPL in ovarian cancer was negatively related with the recurrence free survival (RFS) and overall survival (OS), which were indicated by biomedical databases query. Our data showed upregulations of PURPL were noted in ovarian cancer tissues. Higher expressions of PURPL were associated with more advanced FIGO stage and developed lymph node metastasis in epithelial ovarian cancer. Upregulation of PURPL was related with the recurrence (P=0.002, OR=21.482, 95%CI: 3.457~94.251) and death (P=0.004, OR=35.643, 95%CI: 2.453~84.359) of ovarian cancer patient. PURPL expressions were negatively correlated to miR-338-3p expressions in different ovarian tissues (r = -0.968, P<0.0001). Poor RFS (χ2=19.410, P=0.0002) and OS (χ2=17.600, P=0.0005) were found in patients with high level PURPL and low level miR-338-3p expressions.Conclusions: Upregulation of PURPL and downregulation of miR-338-3p were related with the poor RFS and OS of ovarian cancer, which indicated disregulations of PURPL and miR-338-3p could serve as prognosis biomarkers for epithelial ovarian cancer.

Development and Validation of an Immune Microenvironment Based Prognostic Signature and Signal Pathways in Prostate Cancer

Background: The study of the PCa immune microenvironment has brought new opportunities for the clinical diagnosis and treatment of PCa, but the current study has failed to obtain satisfactory results. We aim to develop a generalized, individualized immune prognostic signature that can improve the survival rate of patients. Methods: We collected a total of 591 sample data from the TCGA and GEO cohorts, and evaluated the abundance and distribution of immune cell members in the mixed cell population in the gene expression matrix by CIBERSORT, ESTIMATE, ssGSEA, and other methods. Calculate the TMB value of the mutant gene to evaluate the reliability of PCa for immunotherapy. Besides, the genes related to the immune microenvironment and mutation load of PCa are obtained, and the target genes are obtained by the intersection with the immune-related genes in the ImmPort database. And perform pan-cancer analysis of the target gene to evaluate the immunological commonality and biological pathways in a variety of cancers. Finally, a Western blot experiment was used to explore the mechanism of the target gene in PCa immune microenvironment. Findings: We found that M0, M2, and Mast cell sresting differed significantly between prostate cancer and normal tissue and that patients with low plasma cell abundance were more likely to develop lymph node metastasis. LTF, as a core gene, is closely related to changes in the immune microenvironment of PCa, and its low expression in tumors promotes primary immune deficiency, cancer development, and enrichment in the JAK/STAT signaling pathway. Cell experiments found that LTF overexpression reduces tumor-derived GM-CSF secretion by inhibiting JAK/STAT pathway, achieving the purpose of regulating tumor immune microenvironment and inhibiting PCa cell proliferation and migration. Interpretation: The proposed clinical-immune signature and core gene is the most promising biomarkers for improving the overall survival rate of PCa. It has been verified that overexpression of LTF reduces the secretion of tumor-derived GM-CSF by inhibiting the JAK/STAT pathway. Funding Statement: This study was supported by the Yangtze University School of Medicine and the First Affiliated Hospital of Yangtze University. Declaration of Interests: The authors declare that there is no conflict of interest. Ethics Approval Statement: The data used in our study were obtained from public databases TCGA and GEO, therefore, ethical approval was not required.

Hobnail variant of papillary thyroid carcinoma: a systematic review and meta-analysis

ObjectiveThe hobnail variant of papillary thyroid carcinoma (HVPTC) has emerged as a rare and aggressive variant of papillary thyroid carcinoma (PTC). We aim to determine the prevalence and clinicopathologic factors of HVPTC.MethodsA systematic review of the literature for studies examining HVPTC was performed. Four databases (PubMed, Scopus, OVID, Cochrane library) were queried from inception of databases through March 20th, 2020.ResultsSixteen studies with 124 cases of HVPTC were included. The mean age for all patients was 52.3 years. HVPTC had a prevalence of 1.08% out of all PTC cases, with a mean tumor size of 3.1 cm. In 62% and 50% of cases, lymphovascular invasion and extrathyroidal extension were present, respectively. Follow-up data, with a mean of 49.9 months, revealed a 66% rate of lymph node metastasis and 23% rate of distant metastasis. Tumors with ≥30% hobnail morphology had a 2.6-fold increased odds of developing lymph node metastasis compared with <30% hobnail morphology, however did not differ in rates of distant metastasis. Patients ≥55 years old had a 4.5-fold increased odds of distant metastasis and a 4.7-fold increased odds of lymphovascular invasion over patients <55.ConclusionsHigh rates of locoregional and distant disease as well as high-risk pathological factors reveal the aggressive nature of HVPTC. Diagnostic criteria regarding percentage of hobnail morphology requires further refinement. Further studies are warranted in order to better understand how recognition of this high-risk variant impacts clinical treatment.

IGFBP3 as an indicator of lymph node metastasis and unfavorable prognosis for papillary thyroid carcinoma

Lymph node metastasis (LNM) is a usual event in papillary thyroid carcinoma (PTC) patients, which usually leads to poor prognosis. However, the molecular mechanisms of LNM remain unclear. Thus, we aimed to screen the possible key genes in the progression of LNM in PTC patients and further validate their roles. The study involved two phases: a discovery phase and a validation one. In the former phase, the candidate genes were screened by using bioinformatics methods. In the latter one, the genes were firstly assessed in a cohort from the cancer genome atlas (TCGA) to evaluate the associations of their expressions with clinical features and the prognostic values, and then, they were assessed at protein levels by using an immunohistochemical assay. Consequently, IGHBP3 was selected as the candidate gene, which might be enriched in several metabolism-related pathways and cancer progression-related pathways. High expressions of IGHBP3 have an association with gender, advanced clinical stages, high T stages, and the presence of LNM. Survival analysis indicated that IGHBP3 may affect the prognosis of PTC patients. The use of a tissue chip confirmed the view that IGHBP3 might play a crucial role in the LNM of PTC. In conclusion, IGHBP3 might be involved in the development of LNM in PTC patients. IGHBP3 over-expression might be a novel indicator and a potential target for PTC therapy.

Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients.

Carbonic anhydrase 9 (CA9) plays a vital role in lung cancer progression. The current study explored the effect of CA9 gene polymorphisms and the epidermal growth factor receptor (EGFR) mutations on the clinicopathological characters of lung adenocarcinoma. In this study, three loci of CA9 single nucleotide polymorphism (SNP) (rs2071676 A > G, rs3829078 A > G, and rs1048638 C > A) were genotyped using the TaqMan allelic discrimination method in 193 EGFR wild type individuals and 281 EGFR mutation subjects. After adjusting for age, gender, and cigarette smoking status in logistic regression, all three CA9 SNPs illustrated a non-significant difference for the distribution between the EGFR wild type group and EGFR mutation group. Nevertheless, a significantly lower rate of CA9 SNP rs2071676 AG (adjusted odds ratio (AOR): 0.40, 95% confidence interval (CI): 0.16–0.95, p = 0.039) and AG + GG (AOR: 0.43, 95% CI: 0.18–0.98, p = 0.046) were found in the male population with L858R EGFR mutation compared to men with EGFR wild type. In addition, the CA9 SNP rs2071676 AG + GG genotype were significantly correlated to the lower tumor stage of lung adenocarcinoma in the whole study population (p = 0.044) and EGFR wild type individuals (p = 0.033). For the male population, the presence of CA9 SNP rs2071676 AG + GG genotype was also correlated to a lower tumor stage (p = 0.037) and fewer lymph node invasion (p = 0.003) in those with EGFR wild type. In conclusion, the existence of CA9 SNP rs2071676 is associated with the rate of EGFR L858R mutation in males. Furthermore, the CA9 SNP rs2071676 is correlated to lower tumor stage and lower risk for developing lymph node metastasis in lung adenocarcinoma, mainly in the EGFR wild type.

Prognostic Impact of Perineural Invasion in Cutaneous Squamous Cell Carcinoma: Results of a Prospective Study of 1,399 Tumors

Perineural infiltration (PNI) and desmoplasia are believed to be high-risk factors in the prognosis of squamous cell carcinoma (SCC). In the literature, dependences between PNI, de-differentiation, and desmoplasia remain unclear. The aim of this study was to analyze the respective prognostic impact of these factors in regard to local recurrence and metastasis. Between 2005 and 2015, 1,399 unselected primary SCCs of 1,434 patients were diagnosed. If a patient had multiple tumors, the tumor with the highest risk profile was selected. Histological sections of all tumors with a tumor thickness of ≥6 mm and desmoplastic SCC with a tumor thickness of 2.1-5.9 mm were re-examined for PNI. Median follow-up was 36.5 months. PNI was present exclusively within tumors of the desmoplastic type (14.5%). PNI was present significantly more often in patients developing lymph node metastasis (3% all non-desmoplastic SCC, 17% desmoplastic SCC, and 29% desmoplastic SCC with PNI) and local recurrence (3%, 26%, and 64%) and associated with overall tumor-specific death (4%, 25%, and 54%). Using a multivariate model of disease recurrence, tumor thickness ≥6 mm, tumor horizontal size ≥20 mm, immunosuppression, desmoplasia, and PNI remained significant factors. In conclusion, PNI was found to be an additional marker indicative of an unfavorable prognosis and an independent high-risk factor within the desmoplastic type of SCC.

Retrospective outcome evaluation for dogs with surgically excised, solitary Kiupel high-grade, cutaneous mast cell tumours.

Published outcomes for dogs with specifically high-grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high-grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2-year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow-up 980 days) and 2 dogs were lost to follow-up. Death was considered MCT-related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.

Lymph node metastasis in extremity chondrosarcomas: A series of four cases.

Background:Primary bone sarcomas mainly metastasize through haematogenous route and rarely through lymph nodes due to paucity of lymphatic channels in the bone (1). Nodal spread in chondrosarcoma is extremely rare and there are two reported cases in literature including one previously published by our institute (3, 5).Aims and Objectives:We present a series of chondrosarcoma cases (primary tumour located in the scapula, proximal femur, proximal humerus and pelvis), presenting with lymph node metastasis, treated at our institute. We assessed the oncological outcome of these cases and the impact of nodal metastasis on survival.Materials and Methods:Between January 2006 and December 2015, 243 patients of extremity and pelvic chondrosarcoma were operated at our institute. These cases were retrieved from a prospectively maintained database. Four (1.6%) of these patients developed lymph node metastasis. Clinical and radiological details of these cases were retrieved from electronic medical records and case files. Histopathology of the primary chondrosarcoma lesion and nodal metastasis was reconfirmed by a pathologist specializing in sarcomas.Conclusion:Lymph node metastasis though extremely rare in primary osseous chondrosarcoma, definitely affects their survival adversely. The rarity of the occurrence of lymph node metastasis in primary osseous tumors, especially chondrosarcoma highlights the need for multi institutional studies to pool knowledge and evaluate the prognostic significance and etiopathogenesis of lymph node metastasis in primary bone chondrosarcoma.

EWING SARCOMA: FEATURES OF LYMPHOGENOUS METASTASIS AND PROGNOSTIC FACTORS

Background. Lymphogenous metastasis in Ewing sarcoma is a relatively rare and poorly studied event associated with aggressive clinical course and poor prognosis. Until now, no risk factors for lymphogenous metastasis in patients with Ewing sarcoma are reported.The purpose of the study was to evaluate tumor characteristics as predictors for lymphogenous metastasis and to create a mathematical model for assessing the risk of developing lymph node metastases in patients with Ewing sarcoma.Material and Methods. Clinical characteristics of the tumor were studied in 88 patients with Ewing sarcoma: in 8 patients with lymphogenous metastasis and in 80 patients having no lymphogenous metastasis. The primary tumor in all patients with lymphogenous metastasis was found to have an extraskeletal origin. Morphological and immunohistochemical characteristics of the tumor were studied in 31 patients with Ewing sarcoma: in 8 patients with lymphogenous metastasis and in 23 patients without lymphogenous metastasis.Results. Statistical analysis and comparative evaluation of the characteristics of the immunophenotype and histological pattern of the tumor in the two studied groups showed significant differences regarding several of them: the structure of nuclear crowding (fusion of nuclei), focal hemorrhages, nuclear normochromasia, and positive expression of cytokeratins by tumor cells. The above signs (except for nuclear normochromasia) were the basis for creating a mathematical model capable of predicting the risk of lymphogenous metastases in Ewing sarcoma.Conclusion. The revealed association with lymphogenous metastasis of cytokeratin expression can be considered as indirect confirmation of the pathogenetic significance of the mesenchymal-epithelial transition in the mechanism of lymphogenous metastasis.

P1.09-29 The Characteristics of Lymph Node Metastasis in Patients with Different Oncogenic Driver Mutations Among T1 Non-Small-Cell Lung Cancer

Whether mutation is associated with lymph node metastases remains unknown. We aim to investigate the incidence and distribution of lymph node metastasis in patients with different gene mutations among pathological T1 non-small-cell lung cancers (NSCLC). NSCLC cases resected in our institution between 2016 and 2018 were included. Driver mutation testing was performed in all resected tumor tissues. These patients were grouped by the type of gene mutations. On the basis of protein that mutant-genes encoded involved in the molecular pathway, the genotypes were further classified into four distinct groups: upstream receptor mutant protein (EGFR, HER2 and MET); downstream regulator mutant protein (KRAS and BRAF); fusion mutant protein (ROS1, ALK and RET) and the wild type group. The incidence of lymph node metastasis was compared among different groups. Of the 1,052 patients enrolled, the frequency of positive mutations was 68.0%. The incidence of lymph node metastasis were as follows (Figure 1): wild type (19.3%), ROS1 (72.8%), BRAF (55.5%), ALK (44.7%), HER2 (40%), RET rearrangement (23.1%), KRAS mutation (15.3%), EGFR (15.3%) and MET mutation (0%) (Chi2=43.45, P<0.001). The incidence of lymph node metastasis was significantly higher in fusion mutant protein group (45.1%) compared with others (wild type 19.3%, downstream signaling regulator protein 19.1%, upstream signaling receptor protein 15.3%, all P<0.001). Patients with fusion genes showed higher proportion of vascular invasion and positive lymph node ratio of greater than 0.33 compared to other (all P<0.005). In subgroup based on gender, age and smoking history, fusion mutant group was still observed with the highest proportion of node metastasis. Different genotypes of NSCLC have different propensity to develop lymph node metastasis. Cases of fusion gene mutations had a higher risk and burden of lymph node metastasis than other genotypes, which may indicate that more intensive treatment or surveillance strategies should be applied for these patients.

Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes

Lymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, we show that breast cancer patients frequently have LN metastases that closely resemble distant metastases. In addition, using a microsurgical model, we show how LN metastasis development and dissemination is regulated by the expression of a chromatin modifier, histone deacetylase 11 (HDAC11). Genetic and pharmacologic blockade of HDAC11 decreases LN tumor growth, yet substantially increases migration and distant metastasis formation. Collectively, we reveal a mechanism explaining how HDAC11 plasticity promotes breast cancer growth as well as dissemination from LNs and suggest caution with the use of HDAC inhibitors.