scholarly journals Mitochondrial DNA alteration in primary and metastatic colorectal cancer: Different frequency and association with selected clinicopathological and molecular markers

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769224 ◽  
Author(s):  
Britta Kleist ◽  
Thuja Meurer ◽  
Micaela Poetsch
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Lymph Node Metastases ◽  
Primary Tumor ◽  
Distant Metastases ◽  
Primary Tumors ◽  
Node Metastases ◽  
Mitochondrial Microsatellite Instability

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.

scholarly journals Clinical significance of proliferation index and E-cadherin expression in colorectal adenocarcinoma

2021 ◽  
pp. 55-55
Author(s):  
Janko Zujovic ◽  
Milena Vuletic ◽  
Miroslav Stojanovic ◽  
Ranko Lazovic ◽  
Nebojsa Djordjevic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Blood Vessel ◽  
Lymph Node Metastases ◽  
Perineural Invasion ◽  
Distant Metastases ◽  
Proliferation Index ◽  
Blood Vessel Invasion ◽  
Node Metastases ◽  
E Cadherin

Introduction/Objective. The aim of this study is to examine the association of E-cadherin expression and high proliferation index (proIDX) with clinical and pathological indicators of colorectal cancer progression. Methods. The biopsy of 72 patients, obtained by resection of colorectal cancer, was routinely processed at the Institute of Pathology of the Clinical Centre of Montenegro, embedded in paraffin and archived. Based on the archived pathohistological reports, two study groups were formed: the first group (n = 72) consisted of operative biopsies of colorectal cancer, and the control group (n = 72) consisted of biopsies of adjacent non-tumor tissue. Routine hematoxylin-eosin and immunohistochemical ABC method with anti-Ki67 and anti-E-cadherin antibodies was applied on. After quantification of the results for statistical tests, the software package SPSS for Windows (19.0) was used. Results. In colorectal carcinoma, we observed a significant association of proIDX with pT stage, lymph and blood vessel invasion, perineural invasion, lymph node metastases and distant metastases, and Astler-Coller stage tumor disease. We also observed that the absence of E-cadherin was significantly associated with pT stage, lymph and blood vessel invasion, perineural invasion with lymph node metastases, distant metastases, with C2 and D Astler-Coller tumor stage. E-cadherin expression is associated with proIDX with a significantly high, negative correlation coefficient. Conclusion. Our results indicate that it is possible to differentiate patients into groups with a higher or lower risk of developing metastatic disease, based on the expression of Ki67 and E-cadherin.

scholarly journals Chromosomal Genotype in Breast Cancer Progression: Comparison of Primary and Secondary Manifestations

2008 ◽  
Vol 30 (1) ◽  
pp. 39-50
Author(s):  
Katrin Friedrich ◽  
Theresa Weber ◽  
Jens Scheithauer ◽  
Wolfdietrich Meyer ◽  
Gunter Haroske ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Progression ◽  
Lymph Node Metastases ◽  
Distant Metastases ◽  
Comparative Genomic ◽  
Breast Cancers ◽  
Primary Tumors ◽  
Local Recurrences ◽  
Node Metastases

The purpose of this study was to compare the chromosomal genotype between breast cancers with and without secondary manifestations and between primary tumors and their secondary manifestations. Eighty six breast cancers, twenty lymph node metastases, ten distant metastases and ten local recurrences were analyzed by comparative genomic hybridization. Tumors with local recurrences showed significant more frequent losses at 2q32 than the tumors without recurrences. Lymph node positive cases showed significant more frequent losses at 9p21 than node negative cases. Lymph node metastases exhibited significant more frequent losses at 7q11, 14q24.3–q31 and 17q22–q24 than their primary tumors. In cases with distant metastases, losses at 5q23 were more frequent than in those without, but not reaching the significance level. The distant metastases showed significant more frequent losses at 5p15, 12q24 and 17q22–q24 than the primary tumors. These results reveal strong evidence that the potential for progression is determined in the primary tumor and that different ways of the development of local recurrences, lymph node and distant metastases exist. After confirmation of the results by interphase FISH on tissue micro arrays, the detection of these specific chromosomal imbalances may contribute to a more individual prediction of prognosis in breast cancer.

scholarly journals CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC

2020 ◽  
Vol 21 (15) ◽  
pp. 5508
Author(s):  
Finn-Ole Paulsen ◽  
Christian Idel ◽  
Julika Ribbat-Idel ◽  
Patrick Kuppler ◽  
Luise Klapper ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastases ◽  
Recurrent Disease ◽  
Regulation Of Gene Expression ◽  
Distant Metastases ◽  
Primary Tumors ◽  
Local Recurrences ◽  
Recurrent Tumors ◽  
Potential Biomarker ◽  
Node Metastases

The Mediator complex is a central integrator of transcription and a hub for the regulation of gene expression. Cyclin dependent kinase (CDK) 19 and its paralog CDK8 are part of its kinase domain and contribute to cancer progression in different cancer entities. STAT1 is an important immune modulator and a downstream substrate of CDK8/CDK19 mediated phosphorylation. So far, little is known about CDK19’s role in head and neck squamous cell carcinoma (HNSCC) progression, its link to STAT1 activity, and related immune modulation. Immunohistochemistry for CDK19, activated pSTAT1, and PD-L1, known to be affected by STAT1, was conducted on samples of 130 primary tumors, 71 local recurrences, 32 lymph node metastases, and 25 distant metastases of HNSCC. Compared to primary tumors, CDK19 is overexpressed in local recurrences and distant metastases as well as in primary tumors that developed local recurrence after initial therapy. Patients with high-CDK19-expressing primary tumors have a significantly shorter disease-free survival. CDK19 expression correlates with pSTAT1 expression in primary tumors associated with recurrent disease, local recurrent tumors, lymph node metastases, and distant metastases. pSTAT1 expression correlates with PD-L1 expression in recurrent tumors. Our findings identify CDK19 as a potential biomarker in HNSCC to predict recurrent disease and support recent developments to target CDK19 and its paralog CDK8 in advanced cancer.

scholarly journals 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

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
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.

scholarly journals Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5763
Author(s):  
Christian Doll ◽  
Carolin Bestendonk ◽  
Kilian Kreutzer ◽  
Konrad Neumann ◽  
Anne Pohrt ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Estrogen Receptor ◽  
Lymph Node ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lymph Node Metastases ◽  
Primary Tumor ◽  
Primary Tumors ◽  
Node Metastases ◽  
Primary Lymph Node

Introduction: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. Material and Methods: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan–Meier method and log-rank test. Results: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27–96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (n = 11; 11/302) or lymph node metastases (n = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (p = 0.012; p = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: p = 0.0013; p < 0.0001; females: p = 0.56; p = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: p < 0.0001; p < 0.0001; females: p = 0.95; p = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα−) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616–11.076; p = 0.003) and RFS (HR = 12.390; 95%CI 4.073–37.693; p < 0.001) in the male cohort. There was a significant difference (p = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (p = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (p = 0.049) higher rate of bone infiltration in ERα-positive patients. Conclusion: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.

scholarly journals Origins of lymphatic and distant metastases in human colorectal cancer

Science ◽  
2017 ◽  
Vol 357 (6346) ◽  
pp. 55-60 ◽  
Author(s):  
Kamila Naxerova ◽  
Johannes G. Reiter ◽  
Elena Brachtel ◽  
Jochen K. Lennerz ◽  
Marc van de Wetering ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Primary Tumor ◽  
Phylogenetic Trees ◽  
Evolutionary Relationship ◽  
Distant Metastases ◽  
Human Colorectal Cancer ◽  
Regional Lymph Nodes ◽  
Primary Tumors

The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer.

18FDG SUV in the primary tumor and lymph node metastases is not predictive for development of distant metastases in high risk head and neck cancer patients

Oral Oncology ◽  
2015 ◽  
Vol 51 (5) ◽  
pp. 536-540 ◽  
Author(s):  
Jasmijn Meeuwis ◽  
Otto S. Hoekstra ◽  
Birgit I. Witte ◽  
Ronald Boellaard ◽  
C. René Leemans ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Lymph Node ◽  
High Risk ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Lymph Node Metastases ◽  
Primary Tumor ◽  
Distant Metastases ◽  
Node Metastases
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