Loss of Cdx2 Expression in Primary Tumors and Lymph Node Metastases is Specific for Mismatch Repair-Deficiency in Colorectal Cancer

This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53.1%) compared to primary tumors (37.5%) and distant metastases (21.4%) ( p = 0.0183 and p = 0.0005). The discordant rate was significantly higher in lymph node metastases/primary tumor pairs (74.6%) than in distant metastases/primary tumor pairs (52.4%) or lymph node metastases/distant metastases pairs (51.6%) ( p = 0.0113 and p = 0.0261) with more gain (86.7%) than loss (61.1%) of microsatellite instability in the discordant lymph node metastases ( p = 0.0024). Displacement loop instability occurred significantly more frequently in lymph node metastases and distant metastases of patients with early colorectal cancer onset age <60 years ( p = 0.0122 and p = 0.0129), was found with a significant high rate in a small cohort of TP53-mutated distant metastases ( p = 0.0418), and was associated with TP53 wild-type status of primary tumors ( p = 0.0009), but did not correlate with KRAS, NRAS, BRAF, or PIK3CA mutations. In conclusion, mitochondrial microsatellite instability and its association with selected clinical and molecular markers are discordant in primary and metastatic colorectal cancer, which could have importance for surveillance and therapeutic strategies.

Download Full-text

Nuclear Factor Kappa B, Matrix Metalloproteinase-1, p53, and Ki-67 Expressions in the Primary Tumors and the Lymph Node Metastases of Colorectal Cancer Cases

Gastroenterology Research and Practice ◽

10.1155/2015/945392 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Ibrahim Meteoglu ◽

Ibrahim Halil Erdogdu ◽

Pars Tuncyurek ◽

Adil Coskun ◽

Nil Culhaci ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Matrix Metalloproteinase ◽

Lymph Node Metastases ◽

Survival Rates ◽

Ki 67 ◽

Primary Tumors ◽

Metastatic Cells ◽

Matrix Metalloproteinase 1 ◽

Node Metastases

Colorectal cancer (CRC) is the third most frequent malignancy. Many factors such as NF-κB, matrix metalloproteinase-1 (MMP-1), p53, and Ki-67 are likely to be involved in its development and progression. Lymph node metastases indicate increased tumor burden and tumor cell heterogeneity and affect both the treatment strategies and the prognosis. In this study, expressions of NF-κB, MMP-1, p53, and Ki-67 were between the primary tumors and lymph node metastases in 110 Dukes’ stage C, CRC cases by immunohistochemical methods, related to patients’ clinical outcomes. NF-κB, p53, and Ki-67 expressions were significantly higher in the metastatic lymph nodes compared to the primary tumor tissues (P=0.04,P=0.04, andP=0.01, resp.). In the metastatic lymph nodes NF-κB expression was correlated with both p53 (r=0.546,P=0.003) and Ki-67 (r=0.586,P=0.0001) expressions. The univariant and multivariant analyses showed that only “pT stage” preserved an independent prognostic significance for recurrence-free survival rates and 5-year overall survival rates (P<0.001for both). Metastatic cells can acquire different biological characteristics compared to their primaries. Elucidation of properties acquired by metastatic cells is important in order to better determine prognosis, reverse drug resistance, and discover new treatment alternatives.

Download Full-text

Multiple peritoneal dissemination of T2 colorectal cancer without lymph node metastases: a case report

Journal of Surgical Case Reports ◽

10.1093/jscr/rjaa118 ◽

2020 ◽

Vol 2020 (7) ◽

Author(s):

Yosuke Namba ◽

Yuzo Hirata ◽

Shoichiro Mukai ◽

Toshihiro Nishida ◽

Syo Ishikawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastases ◽

Peritoneal Dissemination ◽

Abdominal Cavity ◽

Muscularis Propria ◽

Ileocecal Resection ◽

Pathology Report ◽

Ascending Colon ◽

Node Metastases

Abstract Most cases of peritoneal dissemination of colorectal cancers are from T3 or T4 tumors. A 61-year-old woman was admitted for examination of a positive fecal occult blood test. Colonoscopy showed an ascending colon tumor that was diagnosed as an adenocarcinoma with massive submucosal invasion. Imaging modality revealed numerous nodules throughout the abdominal cavity. Peritoneal dissemination of the ascending colon or ovarian cancer and pseudomyxoma peritonei were considered in the preoperative differential diagnoses, and laparoscopic ileocecal resection was performed. Intraperitoneal observation revealed numerous white nodules in the peritoneum, omentum and Douglas fossa. Both the nodules and tumor were diagnosed as mucinous carcinoma based on a pathology report. The tumor invasion depth was limited to muscularis propria, and no regional lymph node metastasis was detected. Peritoneal dissemination of the ascending colon cancer was considered. We report a rare case of multiple peritoneal dissemination of T2 colorectal cancer without lymph node metastases.

Download Full-text

Supraclavicular lymph node metastases from distant primary tumors: Case reports and review of the literature

International Journal of Surgery Case Reports ◽

10.1016/j.ijscr.2021.105720 ◽

2021 ◽

Vol 81 ◽

pp. 105720

Author(s):

Youssef Oukessou ◽

Yassir Hammouda ◽

Khadija El Bouhmadi ◽

Redallah Larbi Abada ◽

Mohamed Roubal ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastases ◽

Case Reports ◽

Review Of The Literature ◽

Supraclavicular Lymph Node ◽

Primary Tumors ◽

Node Metastases

Download Full-text

Outcomes of isolated distant lymph node metastases in colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.84 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 84-84

Author(s):

Vinod Kalapurackal Mathai ◽

Soe Yu Aung ◽

Vanessa Wong ◽

Catherine Dunn ◽

Jeremy David Shapiro ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Lymph Node ◽

Lymph Node Metastases ◽

Locoregional Therapy ◽

Curative Intent ◽

Palliative Intent ◽

Radical Treatment ◽

Node Metastases ◽

Systemic Therapies

84 Background: The optimal management of isolated distant lymph node metastases (IDLNM) in metastatic colorectal cancer (mCRC) is not clearly established. Small case series and prior data from the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry support the use of radical treatment with curative intent (local resection, chemo-radiation or stereotactic radiotherapy), which may lead to better outcomes in mCRC patients with IDLNM. Aims: This study investigates the clinical characteristics and outcomes of mCRC patients with IDLNM treated with systemic therapies plus locoregional therapy with curative intent versus systemic therapies with palliative intent. Methods: Clinical data were collected and reviewed from the TRACC registry, a prospective, comprehensive registry for mCRC from multiple tertiary hospitals across Australia from 01/07/2009 to 30/06/2020. Clinicopathological characteristics, treatment modalities and survival outcomes were analyzed in patients with IDLNM and compared to patients with other organ metastases. Fisher exact test was used for significance tests and Kaplan Meier curves for survival analyses. Results: Of 3408 mCRC patients with a median follow-up of 38.0 months, 93 (2.7%) were found to have IDLNM. Compared to mCRC with other organ metastases, patients with IDLNM were younger (mean age: 62.1 vs 65.6 years, p=0.0200), more likely to have metachronous disease (57.0% vs 38.9%, p=0.0005), be KRAS wild-type (74.6% vs 53.9%, p=0.0012) and BRAF mutant (12.9% vs 6.2%, p=0.0100). There was no overall survival difference between with IDLNM and those with other organ metastases (median OS 27.24 vs 25.92 months, p=0.2300). Twenty-four patients (25.8%) with IDLNM received treatment with curative intent, with a trend towards improved overall survival compared to those with other organ metastases treated with curative intent (73.5 vs 62.7 months, p=0.8200). Amongst mCRC patients with IDLNM, those who received treatment with curative intent had a significantly better overall survival than those treated with palliative intent (73.5months vs 23.2 months, p=0.0070). Conclusions: Our findings suggest that there are differences in the patterns of presentation of IDLNM and other organ metastases. Radical treatment with curative intent options should be considered for mCRC patients with IDLNM where appropriate.

Download Full-text

Improvement of the diagnostic accuracy of lymph node metastases of colorectal cancer in 18F-FDG-PET/CT by optimizing the iteration number for the image reconstruction

Annals of Nuclear Medicine ◽

10.1007/s12149-007-0141-9 ◽

2008 ◽

Vol 22 (6) ◽

pp. 465-473 ◽

Cited By ~ 9

Author(s):

Kazumasa Inoue ◽

Takashi Sato ◽

Hideaki Kitamura ◽

Masaaki Ito ◽

Yoshiyuki Tsunoda ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Diagnostic Accuracy ◽

Lymph Node Metastases ◽

Fdg Pet ◽

Pet Ct ◽

Node Metastases ◽

18F Fdg ◽

Iteration Number ◽

Fdg Pet Ct

Download Full-text

COL16A1 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/vczaw ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Lymphoid Organ ◽

Primary Tumors ◽

Node Metastases ◽

The Brain

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 metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type XVI alpha 1 chain, COL16A1, 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. COL16A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL16A1 in primary tumors of the breast was correlated with patient overall survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL16A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

Download Full-text

COL6A1 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/krvcj ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Lymphoid Organ ◽

Primary Tumors ◽

Node Metastases ◽

The Brain

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 metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type VI alpha 1 chain, COL6A1, 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. COL6A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL6A1 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL6A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

Download Full-text

TSHZ3 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/kxjqn ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Differentially Expressed ◽

Primary Tumors ◽

Node Metastases ◽

The Brain

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 metastasis to the lymph nodes in humans with metastatic breast cancer. We found that teashirt zinc finger homeobox 3, TSHZ3, 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 TSHZ3 was also differentially expressed in brain metastatic tissues. TSHZ3 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TSHZ3 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TSHZ3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

Download Full-text