The Lymph Node Metastasis Histology in Colorectal Cancer -The Clinical Implication of Tubular-Type Carcinoma in Lymph Nodes -

Author(s):  
Shozo Yokoyama ◽  
Takashi Watanabe ◽  
Yoichi Fujita ◽  
Shuichi Matsumura ◽  
Katsuya Ueda ◽  
...  

Abstract Cribriform carcinoma in lymph nodes (LNs) is associated with distant metastasis, recurrence, and survival in node-positive colorectal cancer (CRC) patients. However, the clinical significance of lymph node metastasis histology remains to investigate. A total of 318 consecutive CRC patients who underwent a colectomy or anterior resection between January 2011 and June 2016 were enrolled, of whom 119 (37.4 %) had LN metastasis (LNM). Based on the LNM histology, patients with LNM were categorized into four groups: the group with tubular-type in all LNs (tub), with cribriform in at least one LN (cri), with mucinous-type in all LNs (muc), and with poorly differentiated-type carcinoma in at least one LN (por). We investigated the association among these histological types with the survival of these patients. The prognosis was good in order of muc, tub, cri, and por in node-positive CRC patients. Stage II and stage III tub groups did not have significantly different over-all survival times, but not recurrence-free survival times. Multivariate analyses revealed that all tubular-type carcinoma in LNs was independent predictive factor for longer survival times, clinical complete response and possible metastasectomy Diagnosis of lymph node metastatic histology is an important factor for patient stratification in node-positive CRC.

2003 ◽  
Vol 32 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Tsutomu Tateishi ◽  
Junji Machi ◽  
Ernest J. Feleppa ◽  
Andrew J. Oishi ◽  
Nancy L. Furumoto ◽  
...  

Author(s):  
Hang Du ◽  
Jingling Tang ◽  
Xiaoyun Li ◽  
Xinjun Wang ◽  
Liyun Wu ◽  
...  

Lymph node metastasis indicates a poor prognosis in colorectal cancer. To better understand the underlying mechanisms of lymph node metastasis, we analyzed transcriptome characteristics of the pre-metastatic lymph node, a putative microenvironment favorable for the seeding and proliferation of cancer cells. Thus, we tried to compare and elucidate the transcriptional and immune characteristics of sentinel lymph nodes (SNs) with matched non-sentinel lymph nodes (NSNs) in colorectal cancer patients. In this study, a total of 38 pairs of SNs and NSNs were collected, in which 26 pairs of non-metastatic lymph nodes were subjected to RNA-seq and bioinformatics analysis for the gene expression profiles. There were 16 differentially expressed genes between SNs and NSNs being identified, including 9 upregulated and 7 downregulated genes in SN. Gene Ontology (GO) classification analysis revealed that the differentially expressed genes were mainly involved in leukocyte differentiation, chemokine secretion, and immune system regulation. In the meantime, gene set enrichment analysis (GSEA) showed that immune-related signaling pathways, such as transforming growth factor beta (TGF-β) signaling and tumor necrosis factor alpha (TNF-α)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, were enriched in NSN, while cell proliferation–related signaling pathways were enriched in SN, including MYC signaling and G2M checkpoint signaling. We further identified SIGLEC15 as a top upregulated gene in SN. However, RNAscope assay showed that SIGLEC15 was not largely co-expressed with M2 macrophage marker CD163. We then selected eight pairs of lymph nodes for further cytological studies. Flow cytometry analysis revealed that Siglec-15 was expressed on all myeloid cell subsets. The relative expression of SEGLEC15 (SN/NSN) was correlated with the microsatellite instability (MSI) status in colorectal cancer patients. Further studies found that small interfering ribonucleic acid (siRNA)-mediated silencing of SLGLEC15 can enhance the anti-tumor function of T cells, as indicated by cytokine release analysis. In conclusion, we presented here a first report on the gene expression profiling of the pre-metastatic lymph node in colorectal cancer. The findings in this study suggest that SIGLEC15 plays an important role in SN immunosuppression. SEGLEC15 silencing could be a therapeutic strategy for restoring T cell function in tumor SNs.


2020 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Jinhao Liu ◽  
Zuoxiu Shi ◽  
Yanlei Chen ◽  
...  

Abstract Background: Lymph node metastasis is a major prognostic factor of colorectal cancer and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development, not only enhancing invasiveness, but also promoting lymph node metastasis. The purpose of this study was to investigate the effect of CD163-positive M2 macrophages on lymph node metastasis in colorectal cancer.Methods: Postoperative lymph node tissues were obtained from 120 patients with colorectal cancer who underwent radical surgery in the First Affiliated Hospital of Jinzhou Medical University between December 2019 and May 2020. We detected the expression of the CD163 protein in lymph nodes by immunohistochemistry. Furthermore, the relationship between M2 macrophages identified by this marker and lymph node metastasis were analyzed using the independent sample T-test and Chi-square test.Results: M2 macrophages were increased not only in metastatic lymph nodes, but also in non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in those with micro-metastases.Conclusions: M2 macrophages represent an important factor for the promotion of lymph node metastasis in colorectal cancer, and may be a potential marker for its prediction. This may offer a new target for the comprehensive treatment of colorectal cancer.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Shuiquan Lin ◽  
Yangbo Lv ◽  
Jianguang Xu ◽  
Xinglong Mao ◽  
Zhenhong Chen ◽  
...  

Abstract Background and objectives Lymph node metastasis is a key factor in predicting and determining the prognosis of patients with colorectal cancer (CRC). Sodium channels are highly expressed in a variety of tumors and are closely related to tumor development, metastasis, and invasion. We investigated the relationship between the expressions of different subtypes of Nav channels and lymph node metastasis of CRC. Methods Real-time PCR (RT-qPCR) was carried out to measure the expressions of different sodium channel subtypes, chemokine receptors (CCR2, CCR4, CCR7), and lymphocyte infiltration-related biomarkers (CD3e, CD8a, IL-2RA) in CRC tissues from 97 patients. The expressions of Nav1.5 and Nav1.6 in surgically isolated lymph nodes were detected by immunohistochemistry. Correlation analysis between expressions of different genes and lymph node metastasis was performed by two-tailed t test. Results Nav1.1 and Nav1.6 were highly expressed in CRC tissues and positively correlated with CRC lymph node metastasis. Nav1.6 was also highly expressed in metastatic lymph nodes. Further analysis showed that the high expression of Nav1.6 was closely related to the one of CCR2\CCR4 in tumor lymph node metastasis. Conclusions These results suggested that Nav1.6 might be a novel marker for CRC lymph node metastasis.


2021 ◽  
Vol 21 (2) ◽  
pp. 886-894
Author(s):  
Donghua Wang ◽  
Manyu Chen ◽  
Long Lv ◽  
Yu Chen ◽  
Kui Tian

Colorectal cancer is the third most common cause of cancer-related death in the world because of its poor prognosis and many related complications. In clinical practice, lymph node metastasis is an important index to evaluate the recurrence and survival rate of patients with rectal cancer, it also the main method to determine the treatment plan of patients with rectal cancer. Nano carbon tracer can guide surgeons to clear regional lymph nodes accurately, improve the number of lymph nodes detected, and then improve the accuracy of pathological staging of rectal cancer. It has an important clinical significance in the removal of lymph nodes of middle and low rectal cancer, and provides an important basis for the development of postoperative adjuvant treatment plan. The purpose of this study is to explore the application value of this method in improving the detection rate of lymph nodes in laparoscopic colorectal cancer. According to the research results, the total number of lymphatic gland, the number of small lymphatic gland, the rate of lymph node metastasis, the number of black stained lymphatic gland and the number of lymphatic gland confirmed by pathology in the two groups were better than those in the traditional surgical treatment, which had better application value in the radical operation of colorectal cancer.


2019 ◽  
Author(s):  
Jun Ho Lee ◽  
Ju-Hee Lee ◽  
Byung Kyu Ahn ◽  
Seung Sam Paik ◽  
Hyunsung Kim ◽  
...  

Abstract Background The function of ASXL1 protein in colorectal cancer has not been investigated yet. The purpose of this study was to investigate the clinicopathological and prognostic impact of ASXL1 protein expression on colorectal cancer.Methods We performed immunohistochemical staining of ASXL1 protein using tissue microarrays of 408 colorectal cancers, 46 normal colonic mucosae, 48 adenomas, and 92 metastatic lymph nodes. The intensity of expression was scored as 0–3, and the extent of staining was scored as 0–4, based on the percentage of positive cells. The immunoreactivity score (IRS) was calculated by multiplying the two scores.Results ASXL1 protein expression rates were 89.1% in normal mucosae, 72.9% in tubular adenomas, 44.4% in adenocarcinomas, and 28.3% in metastatic lymph nodes ( p < 0.001). With respect to the IRS cut-off score, the mean tumor size was smaller in the IRS 0–6 group than in the IRS 8–12 group (4.9 ± 2.1 vs. 6.3 ± 2.7 cm, p = 0.002). Lymph node metastasis was more frequent in the IRS 0–6 group than in the IRS 8–12 group (56.3% vs. 33.3%, p = 0.034). Lymphatic invasion was more frequent in the 0–6 group than in the IRS 8–12 group (56.0% vs. 33.3%, p = 0.035). The 5-year disease-free survival rate did not differ between two groups at stage II and stage III.Conclusions ASXL1 protein might act as a tumor suppressor in colorectal cancer. The loss of ASXL1 expression might be associated with metastasis via the lymphatic system to the lymph nodes.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hongxia Li ◽  
Qiwei Yang ◽  
Sibo Huo ◽  
Zhenwu Du ◽  
Fei Wu ◽  
...  

TMEM16A is a recently identified calcium-activated chloride channel (CaCC) and its overexpression contributes to tumorigenesis and progression in several human malignancies. However, little is known about expression of TMEM16A and its clinical significance in colorectal cancer (CRC). TMEM16A mRNA expression was determined by quantitative real time-PCR (qRT-PCR) in 67 CRC tissues and 24 para-carcinoma tissues. TMEM16A protein expression was performed by immunohistochemistry in 80 CRC tissues. The correlation between TMEM16A expression and clinicopathological parameters, and known genes and proteins involved in CRC was analyzed. The results showed that TMEM16A mRNA expression was frequently detected in 51 CRC tissues (76%), whereas TMEM16A protein expression was determined at a relatively lower frequency (26%). TMEM16A mRNA expression in tumor tissues was higher than its expression in normal para-carcinoma tissues (P &lt; 0.05). TMEM16A mRNA expression was significantly correlated with TNM stage (p = 0.039) and status of lymph node metastasis (p = 0.047). In addition, there was a strong positive correlation between TMEM16A mRNA expression and MSH2 protein. More importantly, TMEM16A protein expression was positively associated with KRAS mutation, and negatively correlated with mutant p53 protein. Logistic regression analysis demonstrated that TMEM16A mRNA expression was an important independent predictive factor of lymph node metastasis (OR = 16.38, CI: 1.91–140.27, p = 0.01). TMEM16A mRNA and protein expression was not significantly related with patient survival. Our findings provide original evidence demonstrating TMEM16A mRNA expression can be a novel predictive marker of lymph node metastasis and TMEM16A protein expression may be an important regulator of tumor proliferation and metastasis in CRC.


2020 ◽  
Author(s):  
Kazuya Takabatake ◽  
Tomohiro Arita ◽  
masayoshi Nakanishi ◽  
Yoshiaki Kuriu ◽  
Yasutoshi Murayama ◽  
...  

Abstract Background: The clinical significance of metastasis in inferior mesenteric artery (IMA) lymph node in patients with left-sided colorectal cancer (LCRC) is unclear. The aim of this study was to investigate the impact of IMA lymph node metastasis (IMA-LN (+)) on the prognosis of patients with LCRC. Methods: A total of 292 patients with stage III LCRC and 111 patients with stage IV LCRC who underwent radical resection of the primary tumor between 2005 and 2016 were included. The clinicopathological features and prognosis, which were retrospectively obtained from medical records, were compared regarding IMA-LN (+). Results: IMA-LN (+) was observed in 10 patients with stage III LCRC (2.3%). Moreover. ≥4 metastatic lymph nodes (p = 0.001) and poorly differentiated type (p = 0.049) were more frequently observed in patients with IMA-LN (+) than in patients without IMA lymph node metastasis (IMA-LN (-)) in stage III; IMA-LN (+) patients had significantly worse overall survival (OS) than IMA-LN (-) patients in stage III (p = 0.015). Conversely, there was no significant difference between the OS of stage III IMA-LN (+) and stage IV patients (p = 0.192). Likewise, there was no significant difference between the OS of stage III IMA-LN (+) and stage IV patients with distant metastatic lymph nodes only (n = 12) (p = 0.294). Conclusion: The prognosis of IMA-LN (+) patients was worse than that of IMA-LN (-) patients in stage III LCRC; moreover, it was similar to that of patients with stage IV LCRC.


2021 ◽  
Author(s):  
Tamotsu Sugai ◽  
Noriyuki Yamada ◽  
Mitsumasa Osakabe ◽  
Mai Hashimoto ◽  
Noriyuki Uesugi ◽  
...  

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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