scholarly journals Biology of Nodal Spread in Colon Cancer: Insights from Molecular and Genetic Studies

2018 ◽  
Vol 59 (5-6) ◽  
pp. 361-370 ◽  
Author(s):  
Pridvi Kandagatla ◽  
Lilias H. Maguire ◽  
Karin M. Hardiman

Colorectal cancer (CRC) lymph node metastases are common but their genetics and the mechanism whereby these metastases occur are not well understood. Here we present recent data regarding genetic heterogeneity in primary CRCs and their metastasis. In addition, we explain the different potential models describing the mechanisms of metastasis and the data supporting them. Multiple studies have also revealed a variety of prognostic molecular markers that are associated with lymph node metastasis in CRC. A better understanding of genetic heterogeneity and the mechanisms of metastasis is critical to predicting clinical response and resistance to targeted therapy.

2007 ◽  
Vol 97 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Toshiaki Tanaka ◽  
Toshiaki Watanabe ◽  
Yoshihiro Kazama ◽  
Junichiro Tanaka ◽  
Takamitsu Kanazawa ◽  
...  

2005 ◽  
Vol 71 (4) ◽  
pp. 336-343 ◽  
Author(s):  
Jan-Sing Hsieh ◽  
Shiu-Ru Lin ◽  
Mei-Yin Chang ◽  
Fang-Ming Chen ◽  
Chien-Yu Lu ◽  
...  

Current researches have proposed a genetic model for colorectal cancer (CRC), in which the sequential accumulation of mutations in specific cancer-related genes, including adenomatous polyposis coli (APC), K- ras, and p53, drives the transition from normal epithelium through increasing adenomatous dysplasia to colorectal cancer. To identify patients with an increased risk of tumor recurrence or metastasis and evaluate the prognostic values of APC, K- ras, and p53 gene mutations, we investigated the frequency of these three mutated genes in tumors and sera of CRC patients. APC, K- ras, and p53 gene mutations in primary tumor tissues and their paired preoperative serum samples of 118 CRC patients were detected by using polymerase chain reaction– single strand conformation polymorphism (PCR-SSCP) analysis, followed by direct DNA sequencing of the PCR-amplified genomic DNA. Subsequently, serum molecular markers were analyzed for their correlation with patients’ clinicopathologic features and presence of postoperative recurrence/metastasis. We did not observe any significant difference in the association of APC or K- ras or p53 gene mutations in primary tumors with patients’ demographic data (all were P > 0.05). In contrast, both serum APC and p53 molecular markers were closely correlated with lymph node metastasis and TNM stage (both P < 0.05). Moreover, the serum overall molecular markers (at least one of the three markers) were prominently associated with depth of tumor invasion ( P = 0.033), lymph node metastasis ( P < 0.001), and TNM stage ( P < 0.001). In addition, a significantly higher postoperative metastasis/recurrence rate in patients positive for overall molecular markers compared to those negative for these molecular markers were also demonstrated ( P < 0.001). APC and K- ras molecular markers were more frequently observed in patients with locoregional metastasis (both P < 0.05), while p53 molecular marker was usually detected in the cases of peritoneal metastasis ( P = 0.004). Our findings suggest that serum molecular markers are potentially useful in the determination of colorectal cancer patients harboring gene mutations at high risk of metastasis. Serial analysis is warranted in order to assess their long-term prognostic significance and the therapeutic implications.


2011 ◽  
Vol 96 (3) ◽  
pp. 207-216 ◽  
Author(s):  
Toshiaki Watanabe ◽  
Takashi Kobunai ◽  
Yoko Yamamoto ◽  
Keiji Matsuda ◽  
Soichiro Ishihara ◽  
...  

Abstract In stage III colorectal cancer, patients with N1 stage tumors show poorer outcome than patients with N2 stage tumors. Our objective was to identify genes that are predictive for the presence of lymph node metastasis, and to characterize the aggressiveness of lymph node metastases. Gene expression profiles of colorectal cancer were determined by microarray in training (n  =  116) and test (n  =  25) sets of patients. We identified 40 discriminating probes in patients with and without lymph node metastases. Using these probes, we could predict the presence of lymph node metastasis with an accuracy of 87.1% (training set) and 76.0% (test set). Among discriminating probes, FOXC2 expression was significantly correlated with the degree of lymph node metastasis. FOXC2 was expressed significantly and disparately in patients with N1 and N2 stage tumors as analyzed by real-time reverse transcriptase–polymerase chain reaction. FOXC2 appears to be involved in determining the aggressiveness of lymph node metastasis in colorectal cancer.


2019 ◽  
Vol 47 (2) ◽  
pp. 905-914 ◽  
Author(s):  
Shidong Hu ◽  
Zilong Hu ◽  
Songyan Li ◽  
Changzheng He ◽  
Youjun Wu ◽  
...  

Objective To investigate CUE domain containing 2 ( CUEDC2) expression in colorectal cancer with different invasion and migration abilities. Methods Fresh colon cancer tissues, obtained from patients with or without lymph node metastasis who were treated at the Department of General Surgery, Chinese People's Liberation Army General Hospital, and SW620 and HT29 colorectal cancer cell lines, were analysed for CUEDC2 expression. Results Real-time polymerase chain reaction showed significantly higher CUEDC2 mRNA levels in colon cancer tissue from patients with ( n = 8) versus without ( n = 8) lymph node metastasis, and in SW620 versus HT29 cells. Western blots revealed significantly higher CUEDC2 protein levels in colon cancer tissues from patients with versus without lymph node metastasis, and in SW620 versus HT29 cells. Colorectal cancer tissues from patients with lymph node metastasis showed more intense immunohistochemical staining and moderate staining of cell nuclei and cytoplasm versus less intense/weak staining in tissues from patients without lymph node metastasis. Conclusions CUEDC2 is highly expressed in colorectal cancer tissues and colorectal cancer cell lines with high invasion and migration ability. CUEDC2 may be involved in promoting invasion and metastasis in colorectal cancer.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Seiichiro Eto ◽  
Nobuo Omura ◽  
Tetsuya Shimada ◽  
Teruyuki Takishima ◽  
Hideyuki Takeuchi ◽  
...  

Abstract Background Extended excision of the permeation organ neighborhood is often performed in locally invasive colon cancer, and it is reported to have a survival benefit. In addition, some cases of secondary lymph node metastases in a permeation organ were reported. However, they are reports of synchronous secondary lymph node metastases, not metachronous secondary lymph node metastases. To the best of our knowledge, there are no cases of metachronous secondary lymph node metastases after the resection of a primary colorectal cancer in PubMed. Case presentation The case was a 67-year-old man who underwent colonoscopy because of weight loss. Sigmoid colon cancer with all circumference-related stenosis was found by examination, and the patient was transferred to our hospital for the purpose of scrutiny and treatment. The small intestine ileus caused by the invasion of sigmoid colon cancer developed after the transfer. Laparoscopic high anterior resection and extended excision of small intestine segmental resection was performed after the intestinal tract decompression with a nasal ileus tube. Histopathological analysis revealed a pathological diagnosis of pT4b (ileal submucosal invasion) N0 (0/11) M0 f Stage II, tub2, ly1, v2, PN0. Although adjuvant chemotherapy with capecitabine after the operation was planned for half a year, treatment was suspended in the first course by the patient’s self-judgment. No recurrence was observed for a year after the operation, but metastasis recurrence in the para-aortic lymph node was found by a computed tomography (CT) one and a half years after the operation. 18 F-fluorodeoxyglucose (FDG) positron emission tomography revealed that FDG was accumulated only in the para-aortic lymph node. Laparoscopic metastasis lymphadenectomy was performed due to the diagnosis of metachronous metastasis to the para-aortic lymph node alone. Intraoperative findings revealed that lymph node metastasis occurred in the mesentery of the ileum. No adjuvant treatment was done after the secondary operation, and he is still alive with no recurrence 1 year and 9 months after the operation. Conclusions We report a rare case of a laparoscopic resection of a metachronous secondary lymph node metastasis in the mesentery of the ileum after surgery for sigmoid colon cancer with ileum invasion.


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