scholarly journals Progression of Papillary Thyroid Carcinoma to Anaplastic Carcinoma in Metastatic Lymph Nodes: Solid/Insular Growth and Hobnail Cell Change in Lymph Nodes Are Predictors of Subsequent Anaplastic Transformation

Author(s):  
Toru Odate ◽  
Naoki Oishi ◽  
Masataka Kawai ◽  
Ippei Tahara ◽  
Kunio Mochizuki ◽  
...  

AbstractMost anaplastic thyroid carcinomas (ATCs) arise from papillary thyroid carcinoma (PTC). This process is also called anaplastic transformation, and the morphological harbingers of this phenomenon in nodal recurrence have not been assessed systematically. For this reason, the current study focused on features of 10 PTCs with regional lymph node recurrence that was accompanied with disease progression due to anaplastic transformation in at least one of the nodal recurrences. The findings of additional 19 PTCs which recurred without anaplastic transformation after ≥ 10 years of follow-up served as the control group. There were no clinicopathological differences between the two groups at initial surgery including age, gender, tumor size, lymph node metastasis, distant metastasis, extrathyroidal extension, histologic subtype, and treatment. The median time from the initial thyroid surgery to anaplastic transformation in the nodal recurrence was 106 months (range 6 to 437 months). Mutational analyses showed recurrent PTCs with anaplastic transformation had a high prevalence of BRAFV600E mutation (8/9) and TERT promoter mutation (9/9), both of which were detected in primary tumors. PIK3CAH1047R mutation was detected in one case. No case had RAS mutation. Nineteen recurrent PTCs without anaplastic transformation harbored BRAFV600E mutation and seventeen of these had TERT promoter mutation. Unlike primary tumors with subsequent nodal anaplastic transformation, TERT promoter mutation was only present in the metastatic nodal recurrence from 4 patients without transformation. No patients had neither high-grade features (necrosis and increased mitotic activity) nor solid/insular growth or hobnail cell features in their primary tumors. In the group of patients with transformation, 3 had solid/insular growth in the lymph node metastasis at the time of primary tumor resection (one displaying nuclear features of PTC and solid growth with increased mitotic activity, one with insular component consistent with poorly differentiated carcinoma component, and one displaying nuclear features of PTC and solid growth), and additional 2 patients had solid/insular growth with no high-grade features or poorly differentiated carcinoma component at the time of subsequent nodal recurrence prior to anaplastic transformation. Hobnail cell features were exclusively seen in subsequent metastatic lymph nodes prior to anaplastic transformation. The control group lacked solid/insular growth and hobnail cell features in the metastatic nodal disease. Aberrant p53 expression and loss of TTF-1 featured tumor components with anaplastic transformation. This series identified a subset of recurrent PTCs with TERT promoter mutation was prone to undergo anaplastic transformation, and that solid/insular growth and hobnail cell features were morphological predictors of anaplastic transformation in the nodal recurrence.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22209-e22209
Author(s):  
Lei Zhang ◽  
Chengyu Wu ◽  
Yong Zhang ◽  
Robert M. Hoffman

e22209 Background: Cyclophosphamide pretreatment of mice enhances metastatsis of HT1080 human fibrosarsoma cells (Cancer Res. 68, 516-520, 2008). Methods: HT1080 human fibrosarsoma cells were injected into the footpad or were injected into the epigastric cranialis vein of mice pre-treated with cyclophosphamide (CYC) or a combination of CYC and the herbal mixture LQ. The efficacy was monitored through dynamic subcellular imaging of trafficking of cancer cells in lymph nodes and blood vessels in live mice. Results: LQ significantly inhibited HT1080 spontaneous metastases to local lymph nodes in the foot-pad-injection model. In the control group, 100% of mice had lymph node metastasis, compared to 12.5% of the mice in the LQ treatment group. LQ also significantly inhibited CYC-enhanced experimental metastasis in the epigastric cranialis vein injection model. LQ prolonged the overall survival of mice in the spontaneous-lymph-node metastatic footpad-injection model. Conclusions: The TCM herbal mixture LQ shows promis to inhibit metastasis and will be further tested in other metastatic models.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoxiao Wang ◽  
Cong Li ◽  
Mengjie Fang ◽  
Liwen Zhang ◽  
Lianzhen Zhong ◽  
...  

Abstract Background This study aimed to develope and validate a radiomics nomogram by integrating the quantitative radiomics characteristics of No.3 lymph nodes (LNs) and primary tumors to better predict preoperative lymph node metastasis (LNM) in T1-2 gastric cancer (GC) patients. Methods A total of 159 T1-2 GC patients who had undergone surgery with lymphadenectomy between March 2012 and November 2017 were retrospectively collected and divided into a training cohort (n = 80) and a testing cohort (n = 79). Radiomic features were extracted from both tumor region and No. 3 station LNs based on computed tomography (CT) images per patient. Then, key features were selected using minimum redundancy maximum relevance algorithm and fed into two radiomic signatures, respectively. Meanwhile, the predictive performance of clinical risk factors was studied. Finally, a nomogram was built by merging radiomic signatures and clinical risk factors and evaluated by the area under the receiver operator characteristic curve (AUC) as well as decision curve. Results Two radiomic signatures, reflecting phenotypes of the tumor and LNs respectively, were significantly associated with LN metastasis. A nomogram incorporating two radiomic signatures and CT-reported LN metastasis status showed good discrimination of LN metastasis in both the training cohort (AUC 0.915; 95% confidence interval [CI] 0.832–0.998) and testing cohort (AUC 0.908; 95% CI 0.814–1.000). The decision curve also indicated its potential clinical usefulness. Conclusions The nomogram received favorable predictive accuracy in predicting No.3 LNM in T1-2 GC, and the nomogram showed positive role in predicting LNM in No.4 LNs. The nomogram may be used to predict LNM in T1-2 GC and could assist the choice of therapy.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with lymph node metastasis in humans with metastatic breast cancer. We found that cartilage oligomeric matrix protein, encoded by COMP, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that COMP was also differentially expressed in brain metastatic tissues5. COMP mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of COMP in primary tumors was correlated with patient recurrence-free survival in lymph node negative patients but not in lymph node positive patients. Modulation of COMP expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with lymph node metastasis in humans with metastatic breast cancer. We found that protein tyrosine phosphatase, receptor type C associated protein, encoded by PTPRCAP, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that PTPRCAP was also differentially expressed in brain metastatic tissues5. PTPRCAP mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of PTPRCAP in primary tumors was correlated with patient distant metastasis-free survival in lymph node negative patients but not in lymph node positive patients. Modulation of PTPRCAP expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with lymph node metastasis in humans with metastatic breast cancer. We found that cluster of differentiation 226, encoded by CD226, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that CD226 was also differentially expressed in brain metastatic tissues (5). CD226 mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of CD226 in primary tumors was correlated with patient overall survival in lymph node negative patients but not in lymph node positive patients. Modulation of CD226 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes in humans with metastatic breast cancer.


2020 ◽  
Vol 8 (3) ◽  
pp. e001234
Author(s):  
Dan Kenny ◽  
Vasiliki Lantzaki ◽  
Rodney Ayl ◽  
David Barker

A 10-year-old male neutered cocker spaniel was presented for further investigation of an enlarged sublumbar lymph node, which was cytologically consistent with epithelial cell malignancy. CT revealed marked left medial and internal iliac and mild lumbo-aortic lymphadenomegaly. Surgical extirpation of the lymph nodes was performed, and histopathology was consistent with poorly differentiated carcinoma. Despite the absence of a discernible primary lesion, metastatic apocrine gland anal sac adenocarcinoma (AGASAC) was suspected and chemotherapy was started. Six days after starting chemotherapy, the patient developed acute-onset paraparesis and trembling. MRI revealed a left-sided extradural mass at the level of T11–T13. CT imaging revealed mild enlargement of multiple left sided lumbo-aortic lymph nodes. The dog was euthanised 3 days later due to neurological deterioration. Postmortem examination confirmed a diagnosis of left AGASAC with local lymph node and T11–T13 vertebral canal metastasis.


2021 ◽  
Author(s):  
Kun Xu ◽  
Wenwen Zhang ◽  
Cong Wang ◽  
Longfei Hu ◽  
Runtian Wang ◽  
...  

Abstract The potentially different genetics and epigenetics in the primary tumors and metastases affect the efficacy of treatment in breast cancer patients. Nevertheless, the cellular and molecular mechanisms of breast cancer lymph node metastasis still remain elusive. Here, we employed single-cell RNA sequencing to acquire the transcriptomic profiles of individual cells from primary tumors, negative lymph nodes (NLs) and positive lymph nodes (PLs). We also performed a single-cell assay for transposase-accessible chromatin (ATAC) sequencing (scATAC-seq) of the positive and NL samples to get the chromatin accessibility profile. We identified a novel cell subpopulation with an abnormally high expression level of CXCL14 in the PL of breast cancer patients. Cell trajectory analysis also revealed that CXCL14 was increased expressed in the late pseudo-time. Moreover, based on a tissue microarray of 55 patients and the Oncomine database, we validated that CXCL14 expression was significantly higher in breast cancer patients with lymph node metastasis. Furthermore, scATAC-seq identified several transcription factors that may be potential regulation factors for the lymph node metastasis of breast cancer. Thus, our findings will improve our current understanding of the mechanism for lymph node metastasis, and they are potentially valuable in providing novel prognosis markers for the lymphatic metastasis of breast cancer.


2021 ◽  
Author(s):  
Mairead Paul ◽  
Brandon Weston ◽  
Oliwier Morin

The most diagnosed malignancy in women is breast cancer1. Metastases in people diagnosed with cancer are the main cause of mortality. 2. Patients with breast cancer are predicted to do worse as the number of metastasized axillary lymph nodes increases3. In order to uncover the genes related with metastases in lymph nodes, the early events of the breast cancer metastasis, we mined the published and multiplexed mRNA quantitation datasets4, 5. When lymph node metastasis was compared to original breast tumors by patients diagnosed with breast cancer, we identified substantial differential expression of AXL encoding. The lower expression of AXL in primary tumors is associated with reduced disease-free survival in patients with breast cancer. AXL may be important in mechanisms that underlie lymph node metastasis.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10077-10077
Author(s):  
L. Lessard ◽  
P. Bellon-Gagnon ◽  
M. Alam-Fahmy ◽  
P. Karakiewicz ◽  
A. Mes-Masson ◽  
...  

10077 Background: Pelvic lymph node metastases are associated with a greater risk of prostate cancer recurrence and peripheral metastasis. Unfortunately, markers predictive of lymph node metastasis and/or recurrence after radical prostatectomy are limited and new molecular markers are needed to identify patients at higher risk of progression. NF-kB (p65) is a candidate molecular marker already associated with poor clinical outcomes such as biochemical recurrence and bone metastasis. We have also reported elevated nuclear p65 expression in prostate cancer lymph node metastasis. Pertinent to this issue, we tested whether the nuclear localization of p65 in radical prostatectomy specimens could predict the presence of lymph node metastases. Methods: Following informed consent, 51 patients who underwent radical prostatectomy were included in the study: 20 patients had lymph node metastasis at surgery and 31 patients had no evidence of lymph node metastasis and were used as the control group. All cases in the control group had no biochemical relapse 5 years following radical prostatectomy. NF-kB expression in prostate tumor sections was assessed by immunohistochemistry using a monoclonal NF-kB p65 antibody. The relation between nuclear p65 expression in primary tumors and lymph node metastasis was tested in univariate and multivariate Cox regression models. Results: Primary tumors of metastatic patients had an average of 21.25% of tumor cells with nuclear p65 expression as opposed to 9.42% of tumor cells of control patients (p=0.001). Univariate Cox regression demonstrated a 7.5% increased risk of having lymph node metastases for each percent increase in p65 nuclear staining (p=0.003). In the multivariate model, after controlling for pre-operative PSA (p=0.175), Gleason patterns (p=0.382), pathological stage (p=0.436), extracapsular extension (p=0.243) and seminal vesicle invasion (p=0.016), nuclear p65 was associated with an 8.8% increased risk for lymph node metastases (p=0.024). Conclusion: In univariate and multivariate analyses, p65 nuclear expression was strongly predictive of lymph node invasion. We propose that nuclear NF-kB (p65) may serve as a useful independent molecular marker for stratifying patients at risk for lymph node metastases. No significant financial relationships to disclose.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 757
Author(s):  
Sanaz Samiei ◽  
Renée W. Y. Granzier ◽  
Abdalla Ibrahim ◽  
Sergey Primakov ◽  
Marc B. I. Lobbes ◽  
...  

Radiomics features may contribute to increased diagnostic performance of MRI in the prediction of axillary lymph node metastasis. The objective of the study was to predict preoperative axillary lymph node metastasis in breast cancer using clinical models and radiomics models based on T2-weighted (T2W) dedicated axillary MRI features with node-by-node analysis. From August 2012 until October 2014, all women who had undergone dedicated axillary 3.0T T2W MRI, followed by axillary surgery, were retrospectively identified, and available clinical data were collected. All axillary lymph nodes were manually delineated on the T2W MR images, and quantitative radiomics features were extracted from the delineated regions. Data were partitioned patient-wise to train 100 models using different splits for the training and validation cohorts to account for multiple lymph nodes per patient and class imbalance. Features were selected in the training cohorts using recursive feature elimination with repeated 5-fold cross-validation, followed by the development of random forest models. The performance of the models was assessed using the area under the curve (AUC). A total of 75 women (median age, 61 years; interquartile range, 51–68 years) with 511 axillary lymph nodes were included. On final pathology, 36 (7%) of the lymph nodes had metastasis. A total of 105 original radiomics features were extracted from the T2W MR images. Each cohort split resulted in a different number of lymph nodes in the training cohorts and a different set of selected features. Performance of the 100 clinical and radiomics models showed a wide range of AUC values between 0.41–0.74 and 0.48–0.89 in the training cohorts, respectively, and between 0.30–0.98 and 0.37–0.99 in the validation cohorts, respectively. With these results, it was not possible to obtain a final prediction model. Clinical characteristics and dedicated axillary MRI-based radiomics with node-by-node analysis did not contribute to the prediction of axillary lymph node metastasis in breast cancer based on data where variations in acquisition and reconstruction parameters were not addressed.


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