Lymph Node Metastasis In Carcinoma Research Articles

An optical photothermal infrared investigation of lymph nodal metastases of oral squamous cell carcinoma

In this study, optical photothermal infrared (O-PTIR) spectroscopy combined with machine learning algorithms were used to evaluate 46 tissue cores of surgically resected cervical lymph nodes, some of which harboured oral squamous cell carcinoma nodal metastasis. The ratios obtained between O-PTIR chemical images at 1252 cm−1 and 1285 cm−1 were able to reveal morphological details from tissue samples that are comparable to the information achieved by a pathologist’s interpretation of optical microscopy of haematoxylin and eosin (H&E) stained samples. Additionally, when used as input data for a hybrid convolutional neural network (CNN) and random forest (RF) analyses, these yielded sensitivities, specificities and precision of 98.6 ± 0.3%, 92 ± 4% and 94 ± 5%, respectively, and an area under receiver operator characteristic (AUC) of 94 ± 2%. Our findings show the potential of O-PTIR technology as a tool to study cancer on tissue samples.

The effectiveness and safety of thermal ablation for thyroid carcinoma lymph node metastasis are affected by the diameter of metastatic lymph nodes: A meta-analysis

BackgroundTo explore the diameter of lymph nodes with metastatic thyroid carcinoma and the effectiveness and safety of thermal ablation. MethodsSeveral databases were searched for literature on the treatment of thyroid carcinoma metastatic lymph nodes by thermal ablation. A subgroup analysis was performed according to the diameter of the metastatic lymph nodes. The measures included pooled estimates of mean volume reduction, pooled proportions of total disappearance and recurrence, and the pooled proportions of overall complications. ResultsThere were 20 studies with 372 patients and 620 metastatic lymph nodes included. Based on the average maximum diameter of the metastatic lymph nodes, they were divided into three groups: A (≤ 10 mm), B (10 < diameter ≤ 20 mm), and C (> 20 mm). The study results indicated a significant decrease in the average volume only in groups A and B. The ratio of tumor disappearance showed that group A had the highest percentage, followed by group B and then group C. The recurrence rates were comparable between groups A and B, but slightly lower than in group C. Moreover, the overall complication rates for the three groups were ranked as follows: group A > group C > group B. ConclusionOverall, thermal ablation is an effective and safe treatment for thyroid cancer metastatic lymph nodes with diameters of 10-20mm.

Prevalence of Tumor Budding and its Significance for Predicting Lymph Node Metastasis in Carcinomas at Tertiary Care Center

Background: “Tumor budding” basically means the presence of clusters of less than 5 malignant cells in the tumor stroma, located ahead of the invasive front of tumor. Various studies have been carried out regarding tumor budding, its significance in tumor metastasis involving head and neck, breast, gastrointestinal tract, pancreas and cervix and is now evolving in cancer reporting templates. We conducted this study in regards to growing importance of tumor budding in cancer metastasis with objectives to find out the prevalence of tumor budding in carcinoma and to know the association of tumor budding with lymph node, perineural and lymphovascular invasion. Methods: All the resected specimen with regional lymph node were examined for presence or absence of tumor buds. It was graded as high/ low grade based on the number of buds. Association of the tumor buds with lymph node metastasis, lymphovascular and perineural invasion was calculated. The study was conducted from January 2019 to January 2020. Purposive sampling was used. Ethical clearance was ensured from the institutional review board before the start of study (IRC 1322/ 018). All surgically resected specimen of carcinomas with regional lymph nodes were included in the study whereas autolysed specimen and patient who refused to give consent were excluded from the study. Result: Total 37 cases of resected specimens of gastrointestinal tract, breast, head and neck were evaluated. The prevalence of tumor budding was 91.9%. In every instance where tumor budding existed, there was an observation of high-grade tumor bud. Tumor budding was strongly associated with lymph node invasion (p = 0.005). Significant value was not observed in the correlation of tumor budding with lymphovascular and perineural invasion. Conclusion: Tumor budding holds an important role in predicting lymph node metastasis in carcinomas, highlighting its importance in the histopathological reports of resected specimen.

A nomogram for predicting lymph node metastasis in early gastric signet ring cell carcinoma

At present, the risk factors for lymph node metastasis in early gastric signet ring cell carcinoma (SRCC) remain unclear. However, it is worth noting that the LNM rate and prognosis of early gastric SRCC are superior to those of other undifferentiated cancers. With advancements in endoscopic technology, the 5-year survival rate following endoscopic treatment of early gastric cancer is comparable to traditional surgery while offering a better quality of life. The objective of this study was to develop a nomogram that can predict lymph node status in early gastric SRCC before surgery, aiding clinicians in selecting the optimal treatment strategy. A research cohort was established by retrospectively collecting data from 183 patients with early gastric SRCC who underwent radical gastrectomy with lymph node dissection at our hospital between January 2014 and June 2022. The predictors of early gastric signet ring cell carcinoma lymph node metastasis were identified in the study cohort using the least absolute selection and shrinkage operator (Lasso) and multivariate regression analysis, and a nomogram was developed. The discrimination, accuracy, and clinical practicability of the nomogram were assessed using receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis. The incidence of lymph node metastasis was 21.9% (40/183) overall. Multivariate logistic regression analysis revealed that tumor size and lymphovascular invasion (LVI) were independent risk factors for lymph node metastasis. Lasso regression analysis demonstrated that tumor size, invasion depth, LVI, E-cadherin expression, dMMR, CA242, NLR, and macroscopic type were associated with lymph node metastasis. The integrated discrimination improvement (IDI) (P = 0.034) and net reclassification index (NRI) (P = 0.023) were significantly improved when dMMR was added to model 1. In addition, the area under curve (AUC) (P = 0.010), IDI (P = 0.001) and NRI (P < 0.001) of the model were significantly improved when type_1 was included. Therefore, we finally included tumor size, invasion depth, dMMR, and macroscopic type to establish a nomogram, which had good discrimination (AUC = 0.757, 95% CI 0.687–0.828) and calibration. Decision curve analysis showed that the nomogram had good clinical performance. We have developed a risk prediction model for early gastric signet ring cell carcinoma that accurately predicts lymph node involvement, providing clinicians with a valuable tool to aid in patient counseling and treatment decision-making.

One Case of Cervical Lymph Node Metastasis was Reported

Objective: To report a case of cervical lymph node metastatic cancer in order to improve the understanding of this disease. Methods: To analyze the clinical features, clinical manifestations and risk factors of a case of cervical lymph node metastasis after operation of gingival squamous cell carcinoma. Results: Clinical features: The patient had a long clinical course and was diagnosed as "right cervical lymph node metastatic carcinoma", which was consistent with squamous cell carcinoma combined with morphology and history. Tissue: The tumor cells grew into nests and infiltrated, and the cell atypia was obvious, with keratinized beads and pathological mitosis. Immunohistochemistry: P63 (+), P40 (+), CK5/6 (+), P16 (-), Ki-67 hot spot index 40%. Conclusion: Cervical lymph is the aggregation area of the whole-body lymph; the whole-body lymph fluid can be drained through this. Pathology combined with immunohistochemical examination is the gold standard of diagnosis. The main treatment is surgical resection, combined with radiotherapy if necessary, and close follow-up after surgery.

PO85: Preliminary Study on the Dose Verification of 125I Seed Implantation for Cervical Lymph Node Metastatic Carcinoma by SPECT/CT

PO85: Preliminary Study on the Dose Verification of 125I Seed Implantation for Cervical Lymph Node Metastatic Carcinoma by SPECT/CT

Study on the expression of CK7, CK20 and other immunohistochemical markers for diagnosis of malignant tumours

Introduction: Cancer is malignant disease, one of the leading cause of deadth at the global level. The determination of origin of tumors is really essential for not only prognosis but also effective treatment orientation for cancerous patients. Objective: Defining histopathological types of malignant epithelial tumors and determining the origin of tumors by CK7, CK20 and other immunohistochemical markers. Patients and methods: A cross-sectional study of 50 patients diagnosed carcinoma and CK7, CK20 and other immunohistochemical markers stain at Hue University of Medicine and Pharmacy Hospital from January, 2020 to December, 2020. Results: The results of histopathological types: lymph node metastatic carcinoma took up the highest percentage (30%), followed by lung cancer, hepatocellular cell carcinoma, gastric cancer and other organs with 28%, 18%, 10% and 2% respectively. The value of expression of CK7, CK20 and other immunohistochemical markers in differentiated diagnosis of the origin of tumors: CK7, CK20 positive 46%, 12% respectively. The combination of expression of CK7 and CK20: the co-expression of CK7 and CK20 with positive and negative was 2%, 44% respectively; the expression of CK7 positive and CK20 negative and vice versa was 44% and 10% respectively. CKAE1/3 with TTF1 (11/19), P63 (7/14), CEA (6/6), Ki-67 (13/2) and CK19 (10/6) had high positive percentage. Conclusion: Lymph node metastatic carcinoma was one of the most popular histopathological type. There was a statistically significant relationship between the expression of CK7 and CK20. The use of CK7, CK20 and other immunohistochemical markers can assist pathologists in determining exactly the origin of malignant tumors. Key words: carcinoma, CK7/CK20, histopathology, immunohistochemistry, metastasis.

Next-generation sequencing in breast pathology: real impact on routine practice over a decade since its introduction.

The diagnosis, histomolecular classes of breast cancers (luminal A, luminal B, HER2-enriched, and basal-like), and accurate prediction of prognosis are commonly determined using morphological and phenotypical analyses in clinical practice worldwide. Therapeutic strategies are mostly based on the disease stage and molecular subclasses of breast cancer. Targeted therapies, such as anti-HER2s, poly-ADP ribose polymerase inhibitors or, to a lesser extent, phosphatidylinositol 3 kinase inhibitors, have substantially improved breast cancer patient prognosis over the past decades. Human epidermal growth factor receptor 2 (HER2) overexpression is widely determined based on immunohistochemistry, while next-generation sequencing (NGS) is currently employed to assess the presence of molecular alterations, including breast cancer gene 1 (BRCA1) and 2 or phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations, which are targets of these new approved therapies. In addition, next-generation sequencing (NGS) can aid the pathologist in challenging situations, such as a diagnostic workup for a metastatic carcinoma in lymph nodes of unknown origin, differential diagnosis of spindle cell tumourtumor in the breast between metaplastic carcinoma, malignant PT and sarcoma, o, as well as determining relatedness between primary breast cancers and recurrences. NGS offers a powerful tool that enables the pathologist to combine morphological analyses together with molecular alterations in challenging diagnostic situations.

Impact of preoperative magnetic resonance imaging on surgery and eligibility for intraoperative radiotherapy in early breast cancer.

We looked at the usefulness of magnetic resonance imaging (MRI) in decision-making and surgical management of patients selected for intraoperative radiotherapy (IORT). We also compared lesion size measurements in different modalities (ultrasound (US), mammogram (MMG), MRI) against pathological size as the gold standard. 63 patients eligible for IORT based on clinical and imaging criteria over a 34-month period were enrolled. All had MMG and US, while 42 had additional preoperative MRI for locoregional preoperative staging. Imaging findings and pathological size concordances were analysed across the three modalities. MRI changed the surgical management of 5 patients (11.9%) whereby breast-conserving surgery (BCS) and IORT was cancelled due to detection of satellite lesion, tumor size exceeding 30mm and detection of axillary nodal metastases. Ten of 42 patients (23.8%) who underwent preoperative MRI were subjected to additional external beam radiotherapy (EBRT); 7 due to lymphovascular invasion (LVI), 2 due to involved margins, and 1 due to axillary lymph node metastatic carcinoma detected in the surgical specimen. Five of 21 (23.8%) patients without prior MRI were subjected to additional EBRT post-surgery; 3 had LVI and 2 had involved margins. The rest underwent BCS and IORT as planned. MRI and MMG show better imaging-pathological size correlation. Significant increase in the mean 'waiting time' were seen in the MRI group (34.1 days) compared to the conventional imaging group (24.4 days). MRI is a useful adjunct to conventional imaging and impacts decision making in IORT. It is also the best imaging modality to determine the actual tumour size.

Assessment of Papillary Thyroid Carcinoma with Ultrasound Examination.

Ultrasound examination of the thyroid is useful for preoperative assessment of thyroid nodules including papillary thyroid carcinoma. The examination mainly is to determine the malignant potential of thyroid nodule(s). There are different systems to predict malignant potential in the thyroid nodules and cervical lymph nodes by ultrasound. Ultrasound is used in conjunction with fine-needle aspiration to diagnosis papillary thyroid carcinoma. It is used as guidance to locate the sites to obtain the samples for diagnosis and research in papillary thyroid carcinoma.

The prognostic role of radiotherapy and radiotherapy target in cervical lymph node metastatic squamous cell carcinoma with unknown primary: a retrospective study.

Aim to analyze the effect of radiotherapy for cervical lymph node metastatic carcinoma with unknown primary (CCUP) and compare the survival benefits between Comprehensive radiotherapy and Involved Field radiotherapy. The patients diagnosed with CCUP between 2009 and 2019 in our institution were analyzed retrospectively. The categorical variables were tested by χ2 test. Kaplan-Meier method was used for survival analysis. Log-rank test and Cox proportional hazards regression were performed with overall survival (OS) and disease-free survival (DFS) as the primary outcome variables. Of 139 patients, 64.7% (90/139) of them received radiotherapy. Of the 90 patients who underwent radiotherapy, 45.6% (41/90) received Involved Field radiotherapy and the rest 49 patients received Comprehensive radiotherapy. The median follow-up of 139 patients is 69months. The 1-year, 3-year, and 5-year OS rates are 87%, 62%, and 39%, respectively, and the DFS rates are 73%, 45%, and 29%, respectively. Multivariate analysis of 139 patients with CCUP shows that differentiation grade, N stage, radiotherapy, and the length of the largest lymph node (DmaxLN) are the independent prognostic factors for both OS and DFS. Subgroup analysis of 90 patients who received radiotherapy shows that the Comprehensive radiotherapy group has a better OS (P < 0.001) and DFS (P < 0.001) compared with Involved Field radiotherapy. Radiotherapy is the independent prognostic factor for CCUP. Comprehensive radiotherapy may be superior to Involved Field radiotherapy in survival benefits.

Comprehensive analysis of metastatic gastric cancer tumour cells using single-cell RNA-seq

Gastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with metastasis. The mechanism of gastric carcinoma lymph node metastasis remains unknown due to traditional bulk-leveled approaches masking the roles of subpopulations. To answer questions concerning metastasis from the gastric carcinoma intratumoural perspective, we performed single-cell level analysis on three gastric cancer patients with primary cancer and paired metastatic lymph node cancer tissues using single-cell RNA-seq (scRNA-seq). The results showed distinct carcinoma profiles from each patient, and diverse microenvironmental subsets were shared across different patients. Clustering data showed significant intratumoural heterogeneity. The results also revealed a subgroup of cells bridging the metastatic group and primary group, implying the transition state of cancer during the metastatic process. In the present study, we obtained a more comprehensive picture of gastric cancer lymph node metastasis, and we discovered some GC lymph node metastasis marker genes (ERBB2, CLDN11 and CDK12), as well as potential gastric cancer evolution-driving genes (FOS and JUN), which provide a basis for the treatment of GC.

Patterns of Neck Node Metastasis in Carcinoma of Oral Cavity

Objectives: To find out the patterns of cervical lymph node metastasis in oral cavity carcinoma. Methods: This is across sectional study which was carried out in the department of Otolaryngology &amp; Head Neck Surgery Dhaka Medical College Hospital (DMCH), Sir Salimullah Medical College Hospital (SSMC), Bangabandhu Sheikh Mujib Medical University (BSMMU) and National Institute of Cancer Research &amp; Hospital (NICRH) from July 2013 to December 2014.Total 96 cases were included in this study. Data were collected by detail history, clinical examination, relevant investigation and result were processed manually and analyzed with the help of SPSS. Results: In this study 72 (75%) patients presented with clinically palpable neck nodes and 24 (25%) presented without neck node. Among 24 cases 7 cases was radiologically positive neck node. Out of 96 cases stage III was the highest (50.96%) followed by stage IV (27.01%), stage II (13.52%) and stage I (8.32%). That is 23 (23.92%) patients present with early stage and 73 (76.18%) patients present in late or advanced stage. Level l was the highest 49 (61.71%), followed by level all 35(44.1%), level lll 10 (12.6%). Conclusion: As cervical lymph node metastasis is a critical event for patients with squamous cell carcinoma of oral cavity, as this is the most reliable predictor of poor treatment outcomes. Thus for appropriate treatment it is very important to know this pattern of metastases. Bangladesh J Otorhinolaryngol; October 2020; 26(2): 102-108

Rate of Occult Neck Nodal Metastasis in Parotid Cancer: A Meta-Analysis.

The risk for occult neck nodal metastasis in carcinoma of the parotid gland is inconclusive. Therefore, addressing a negative neck prophylactically and the extent to do so remain controversial. This systematic review aimed to determine the rate of occult nodal metastasis for each neck level, and consequently, to elucidate the proper extent of elective neck dissection (END). A meta-analysis of all studies that included patients with a diagnosis of parotid malignancies who underwent an END was performed. The risk for occult nodal metastasis was calculated for each neck level separately. The search strategy identified 124 papers from January 1980 to December 2019 in the various databases. Nine retrospective studies (n =548) met the inclusion criteria. The risk for occult neck nodal metastasis ranged from 0.0 to 9.43% with a random-effect model of 2.2% for level 1 (n =459), from 3.4 to 28.38% with a random-effect model of 16.51% for level 2 (n =548), from 0.0 to 21.63% with a random-effect model of 4.23% for level 3 (n =518), from 0.0 to 17.02% with a fixed-effect model of 0.39% for level 4 (n =310), and from 0.0 to 11.63% with a fixed-effect model of 1.7% for level 5 (n =417). The rate of occult neck nodal metastasis in parotid malignancies is low, with neck level 2 the most commonly involved. The results of this meta-analysis prevented the authors from substantiating the appropriate extent of an END in parotid cancer.

The Additional Value of Ultrafast DCE-MRI to DWI-MRI and 18F-FDG-PET to Detect Occult Primary Head and Neck Squamous Cell Carcinoma.

Simple SummaryPatients with cervical lymph node metastasis from squamous cell carcinoma undergo extensive irradiation or surgery of the head and neck with higher treatment morbidity, recurrence rate and lower overall survival than patients with overt primary tumor. In order to enhance treatment efficiency and morbidity reduction, the primary tumor detection accuracy was evaluated by using Ultrafast-Dynamic Contrast-Enhancement (DCE-)MRI in addition to Diffusion-Weighted (DW-)MRI and 18F-FDG-PET/CT imaging. Ultrafast-DCE, with a temporal resolution of 4 s, enabled capturing lesions with increased neoangiogenesis or perfusion compared to normal tissue. The use of Ultra-fast DCE resulted in higher confidence for suspicious locations and high observer agreement. Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and 18F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and 18F-FDG-PET/CT yielded highest sensitivity.To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or 18F-FDG-PET and the combination of modalities for the detection of unknown primary tumor (UPT) in patients presenting with cervical lymph node metastasis from squamous cell carcinoma (SCC). Between 2014–2019, patients with histologically proven cervical lymph node metastasis of UPT SCC were prospectively included and underwent DWI, ultrafast-DCE, and 18F-FDG-PET/CT. Qualitative assessment was performed by two observers per modality. Interobserver agreement was calculated using the proportion specific agreement. Diagnostic accuracy of combined use of DWI, ultrafast-DCE and 18F-FDG-PET/CT was assessed. Twenty-nine patients were included (20 males. [68%], median age 60 years). Nine (31%) primary tumors remained occult. Ultrafast-DCE added reader confidence for suspicious locations (one additional true positive (5%), 2 decisive true malignant (10%). The per-location analysis showed highest specific positive agreement for ultrafast-DCE (77.6%). The per-location rating showed highest sensitivity (95%, 95%CI = 75.1–99.9, YI = 0.814) when either one of all modalities was scored positive, and 97.4% (95%CI = 93.5–99.3, YI = 0.774) specificity when co-detected on all. The per-patient analysis showed highest sensitivity (100%) for 18F-FDG-PET/CT (YI = 0.222) and either DWI or PET (YI = 0.111). Despite highest trends, no significant differences were found. The per-patient analysis showed highest specific positive agreement when co-detected on all modalities (55.6%, 95%CI = 21.2–86.3, YI = 0.456). Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and 18F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and 18F-FDG-PET/CT yielded highest sensitivity.

Correlation of coagulation markers with axillary lymph node metastasis in breast malignancy: a tertiary care centre study in North India

Background: Breast cancer is the most common female cancer worldwide representing nearly a quarter (25%) of all cancers. Search for a marker which can predict lymph node metastasis in clinically negative axilla has been a matter of research for long. The present study is an attempt to evaluate role of coagulation makers with special reference to D-dimer and factor 7 and 8 in patients of carcinoma breast in predicting lymph node metastasis in carcinoma patients.Methods: The study was a prospective study conducted in 50 diagnosed patients of carcinoma breast in whom D dimer levels and factor 7 and 8 levels were measured at the time of commencement of the treatment and at six weeks after surgery.Results: Most of the patients in the study group were in the age group 41-70 (80%) years. 22% patients were of early Breast cancer. The reduction in D-dimer, factor VII and factor VIII value after 6 weeks of surgery were significant (p value 0.0001 for all three).Conclusions: D-dimer and factor VII were found to be an independent predictive factor for lymph node metastatsis, thus providing as a safe, easy, objective and convenient supplement to sentinel node biopsy in assessing metastatic disease in axilla. Combined- with other biomarkers, it may prove to be an alternative to sentinel node biopsy in assessing metastatic disease in axilla. Significant postoperative decrease in D-dimer, factor VII and factor VIII may provide objective criteria to assess completion of surgery.

Relation between the depth of tumor and neck node metastasis in early carcinoma of tongue

Background: Tongue squamous cell carcinoma (TSCC) is one of the aggressive forms of oral cancer with a high recurrence rate. Forty percentages of all TSCC patients have neck metastasis at the time of diagnosis. The status of cervical lymph nodes at presentation is the single most important prognostic factor in TSCC. This study was focused on establishing relation between the tumor depth and neck node metastasis in carcinoma of tongue. Authors accessed the patterns of cervical node metastasis in it.Methods: prospective non-randomised study of 100 patients was carried out. After detail clinical history punch biopsy were taken from the tongue lesion. Biopsy proven cases of early squamous cell carcinoma (T1/T2) with clinically negative neck (cN0) were included in this study. Ultra-sonography of the tongue using 7.5 MHz probe was performed in all cases to know the depth of lesion. Final histopathological findings i.e. pT, pN, differentiation and depth of invasion were compared with pre-operative clinical and radiological findings.Results: Out of 100 patients, 62 were males and 38 were females. Clinically 56 patients were belonged to T2. Ultra-sonography of tumor had high sensitivity and specificity. Node positivity increased with the depth of primary tumor. On histopathological examination, positive node observed in total 25 patients. Number of occult neck node positivity raised with increased size of primary tumor. i.e. 15% and 31% with pT1 and pT2, respectively. Level II was the most common site for cervical node involvement followed by level III.Conclusions: Ultra-sonography was a reliable tool to access the depth of tumor pre-operatively in the cases of tongue carcinoma patients with sensitivity and specificity more than 90%. Node positivity increased with the depth of primary tumor. Tumor thickness is a significant predictor of nodal metastasis and elective neck dissection should be decided accordingly.

Nkx2.8 Inhibits Epithelial-Mesenchymal Transition in Bladder Urothelial Carcinoma via Transcriptional Repression of Twist1.

Epithelial-to-mesenchymal transition (EMT) promotes metastasis, which is the main cause of bladder urothelial carcinoma-related death. Loss of the candidate tumor-suppressor gene Nkx2.8 has been associated with urothelial carcinoma lymph node metastasis. Here, we show that enforced expression of Nkx2.8 is sufficient to inhibit EMT, reduce motility, and blunt invasiveness of urothelial carcinoma cells. Mechanistic investigations showed that Nkx2.8 negatively regulated expression of the EMT inducer Twist1 in urothelial carcinoma cells, at both the level of mRNA and protein accumulation. Nkx2.8 bound directly to the promoter region of this gene and transcriptionally repressed its expression. Twist1 upregulation reversed EMT inhibition by Nkx2.8, restoring the invasive phenotype of urothelial carcinoma cells. In clinical urothelial carcinoma specimens, expression of Nkx2.8 inversely correlated with Twist1 expression, and urothelial carcinoma patients with Nkx2.8 positivity and low Twist1 expression displayed the best prognosis. Our findings highlight the Nkx2.8-Twist1 axis as candidate target for therapeutic intervention in advanced urothelial carcinoma.Significance: These findings highlight a novel EMT signaling axis as a candidate target for therapeutic intervention in advanced urothelial carcinomas. Cancer Res; 78(5); 1241-52. ©2018 AACR.

A Case of Alpha-Fetoprotein-Producing Adenocarcinoma of the Esophagogastric Junction in which Long-Term Survival Was Achieved by Means of Individualized Multidisciplinary Therapy

Carcinoma of the esophagogastric junction (EGJ) is a type of upper digestive cancer that occurs within 2 cm above or below the EGJ regardless of the histological type. Most cases of carcinoma of the EGJ are detected at an advanced stage and thus show a poor prognosis [1, 2]. The most frequent sites of lymph node metastasis in carcinoma of the EGJ differ from carcinomas in other portions of the gastric tract and esophageal cancers, and a thoracic approach is sometimes taken during surgery. For this reason, unusual procedures (including lymph node dissection) and reconstruction methods are frequently required [3–6]. To date, the therapeutic strategy has not been fully established for carcinoma of the EGJ. Alpha-fetoprotein (AFP) is a useful tumor marker for primary hepatocellular carcinoma and yolk sac tumor [7]. Although AFP-producing cancer develops in the stomach, such tumors rarely developed at the EGJ. AFP-producing carcinoma is thought to have a high potential for metastasis, particularly liver metastasis [8–11] and thus show a poor prognosis [10, 12]. We herein report a case of AFP-producing carcinoma of the EGJ in which long-term survival was achieved through multidisciplinary therapy.

NOTCH1 mutations and extracapsular spread in oral squamous cell carcinoma lymph node metastasis

NOTCH1 mutations and extracapsular spread in oral squamous cell carcinoma lymph node metastasis