Microdissection-Based Allelotyping: A Novel Technique to Determine the Temporal Sequence and Biological Aggressiveness of Colorectal Cancer

2006 ◽  
Vol 72 (5) ◽  
pp. 445-453 ◽  
Author(s):  
T. Clark Gamblin ◽  
Sydney D. Finkelstein ◽  
Neil Upsal ◽  
Jonathan D. Kaye ◽  
David Blumberg
Keyword(s):  
Colorectal Cancer ◽  
Primary Tumor ◽  
Temporal Sequence ◽  
Allelic Loss ◽  
Fixed Tissue ◽  
Tumor Spread ◽  
Primary Tumors ◽  
Mutational Change ◽  
Mutational Profiling ◽  
Metastatic Sites

Pathologic staging in colorectal adenocarcinoma (CA) is based on the concept that the timing of metastatic tumor spread is directly related to the depth of the primary tumor invasion. To evaluate the temporal sequence of CA metastasis, we performed microdissection mutational profiling at multiple microscopic sites of primary and metastatic CA specimens. Twenty-one cases of CA were selected from fixed-tissue archives. Primary tumors were microdissected at the deepest point of invasion. Comparative mutational profiling for different genomic loci [1p36(CCM = cutaneous malignant melanoma], 3p26(OGGI = 8 oxoguanine DNA glycosylase), 5q23 (APC, MCC = mutated in colorectal cancer), 9p21(p16/CDKN2A = cyclin-dependent kinase 2A), 10q23(PTEN = phosphatase and tensin homolog [mutated in multiple advanced cancers 1]), 12p12(K-ras-2 point mutation), 17p13(TP53), 18q25(DCC= deleted in colorectal cancer) was carried out on each microdissected tissue target using microsatellite loss of heterozygosity determination or DNA sequencing. All primary and metastatic sites of CA manifested acquired mutational change in 18 to 91 per cent of the genomic markers. In 15/21 (71%) cases, metastatic sites lacked a specific allelic loss seen in the corresponding primary tumor, indicating that the metastasis occurred before maximal depth of primary invasion. This was further supported by discordant mutational profiles between primary and secondary tumors, requiring divergent clonal evolution. This is the first report describing the temporal sequence and significance of sequential mutational acquisition in clinical tissue specimens with potential implications for a new molecular pathology approach to classify human cancer.

scholarly journals Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2148
Author(s):  
Francesco Ardito ◽  
Francesco Razionale ◽  
Lisa Salvatore ◽  
Tonia Cenci ◽  
Maria Vellone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Colorectal Tumor ◽  
Term Survival ◽  
Primary Tumors ◽  
Mutation Status ◽  
Primary Colorectal Tumor ◽  
Kras Mutation Status

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

Predicting biomarkers of hepatic metastasis in Chinese colorectal cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15545-e15545
Author(s):  
Honghua Peng ◽  
Tianhao Mu ◽  
Yaping Sheng ◽  
Yingmei Li ◽  
Peiguo Cao
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Hepatic Metastasis ◽  
Primary Tumor ◽  
Potential Candidate ◽  
Poor Overall Survival ◽  
Primary Tumors ◽  
Distant Spread ◽  
Colorectal Cancer Patients

e15545 Background: Hepatic metastasis is the most common site of distant spread from colorectal cancer. About 15-25% patients with colorectal cancer harbors hepatic metastasis. The molecular mechanism and predicting biomarkers in colorectal cancer are still not fully understood. Methods: 57 Chinese colorectal cancer patients were enrolled in a cohort study. Samples of primary tumor were collected in these patients and underwent whole exome sequencing. Mutation profiles of primary tumors between the patients with metastasis and those without metastasis were analyzed and compared. Results: In the cohort, 54.4% (31/57) patients presented hepatic metastasis at the time of diagnosis, while 45.6% (26/57) did not. The patients were divided into 2 groups—with hepatic metastasis and without hepatic metastasis. The mutation landscape of primary tumor indicated that the Top 3 most frequently mutated genes of both groups were the same and presented mutated TP53, APC, and KRAS. 2. Interestingly, compared with the patients without hepatic metastasis, the patients with hepatic metastasis presented a higher frequency of mutated TCF7L2 (35.5% vs 3.85%) and TRIM77 (16.1% vs 0%). Moreover, in the patients with hepatic metastasis, the patients with TRIM77 mutation in primary tumor showed a worse overall survival (p < 0.0001). Conclusions: TCF7L2 and TRIM77 may be identified as potential candidate predicting biomarkers for hepatic metastasis in colorectal patients. In addition, mutated TRIM 77 predicted a poor overall survival in hepatic metastasis from colorectal cancer.

Impact of M1a and M1b staging in patients (pts) with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3590-3590 ◽  
Author(s):  
Hagen F. Kennecke ◽  
Jason Yu ◽  
Sharlene Gill ◽  
Winson Y. Cheung ◽  
Charles Davic Blanke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Primary Tumors ◽  
7Th Edition ◽  
The Impact

3590 Background: In 2009, pts with M1 colorectal cancer were divided into two subsets for the American Joint Committee on Cancer (AJCC) 7th edition. Pts with metastases (mets) confined to one organ or site at initial diagnosis became stage M1a while multiple sites or peritoneal mets became M1b. The objectives of the study are to evaluate the impact of site of mets and M1a/b staging among pts with M1 colorectal cancer. Methods: All pts referred to the BC Cancer Agency from 1999-2007 with newly diagnosed M1 colon or rectal cancer were included. Demographic, treatment, and outcome data were prospectively collected. The prognostic impact of individual sites of mets was assessed by hazard ratio estimates from univariate Cox models. Multivariable Cox proportional-hazards models were used to determine variables associated with overall survival in the entire cohort and in those undergoing resection of their primary tumor. Results: 2,049 pts with M1 disease were included. Median age was 66 years; 71% had colonic origin; 70% had their primary tumor resected; and 69% received chemotherapy. In univariate analysis, solitary mets were associated with improved survival. In multivariable analysis, M1a/b status still had significant prognostic effect. The effect remained significant in the subgroup analysis of pts with resected primary tumors when histology, T and N stage were included. Conclusions: Pts with solitary mets, including peritoneum, have superior overall survival as compared to those with multiple sites of mets. AJCC 7th edition staging that includes M1a/b provides significant prognostic information and should be considered in clinical practice and trials of pts with M1 disease who otherwise have few prognostic factors. [Table: see text]

FAK expression as a prognostic marker in colorectal cancer: A single institution study of 298 patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 623-623 ◽  
Author(s):  
Lindy Davis ◽  
Felicia Lenzo ◽  
Lourdes Ylagan ◽  
Angela Omilian ◽  
Kristopher Attwood ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Internal Control ◽  
Primary Tumor ◽  
Expression Patterns ◽  
Tumor Stage ◽  
Therapeutic Window ◽  
Single Institution ◽  
Normal Colon ◽  
Primary Tumors

623 Background: Focal adhesion kinase (FAK) is an attractive therapeutic target in solid cancers, but there is no method for patient selection based on FAK expression nor biomarker for therapeutic response. Previous FAK expression studies were not standardized and showed varying correlations. This single-institution study aims to define FAK expression patterns in colorectal cancer (CRC) and correlate with patient outcomes and expression in other solid cancers. Methods: We analyzed 635 samples from 298 patients (pt) with CRC using tissue microarrays (TMAs) stained for FAK and scored 0-3 by a single pathologist. The TMAs contained samples of 298 primary tumors with 290 matching normal tissue and 47 matching metastases. As an internal control, we examined FAK and outcomes in 135 breast cancer pt and 145 melanoma pt. FAK expression and pt outcomes were evaluated using Kruskal-Wallis exact and Wilcoxon signed-rank tests. Results: FAK expression correlated with aggressive phenotype in CRC primaries. Matching normal colon had lower FAK than primaries (Mean FAK 0.61 vs 1.87, p < 0.001). Higher primary tumor FAK was associated with higher tumor stage; the 88 T1-2 primaries had a mean FAK 1.54, compared to FAK 2.06 in the 99 T3-4 tumors (p < 0.001). There was no difference in FAK among Stage II-IV pt, nor between mean FAK in the primaries (1.87) versus metastases (1.73). When FAK was dichotomized as high vs low (high = FAK > 2), high primary tumor FAK was associated with shorter overall survival (OS). Median OS was 91 months (95% CI 73-130) in high FAK (n = 122 pt) vs 155 months (95% CI 124-196) in low FAK (n = 176 pt), p = 0.007. The OS rates at 5 and 10 years in high FAK were 65% and 43%, vs 79% and 61% in low FAK. FAK in CRC metastases did not correlate with OS (p = 0.945). In contrast, when CRC was compared to breast cancer and melanoma, FAK did not show the same correlations in outcome. Conclusions: For the first time, by standardizing FAK quantification, we have identified that FAK expression in the primary correlates with outcome in CRC. These data may have implications in selection of patients for adjuvant therapy. Normal colon and earlier stage CRC had lower FAK expression compared to more advanced stages, suggesting a therapeutic window for FAK as a target.

Impact of primary tumor sidedness on erlotinib efficacy in patients with metastatic colorectal cancer treated with bevacizumab maintenance: Results from the DREAM phase III trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 737-737 ◽  
Author(s):  
Benoist Chibaudel ◽  
Thierry Andre ◽  
Benoit Samson ◽  
Marie-Line Garcia-Larnicol ◽  
Jérôme Dauba ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Primary Tumor ◽  
Phase Iii ◽  
Primary Tumors ◽  
Phase Iii Trial ◽  
Mutational Status

737 Background: Primary tumor sidedness (PTS) could be a predictive maker for treatment efficacy of EGFR inhibitors monoclonal antibodies in patients with wild-type (WT) RAS metastatic colorectal cancer (MCRC), cetuximab having limited efficacy in patients with WT-RAS right-sided tumors. DREAM study demonstrated that adding erlotinib, an oral EGFR tyrosine kinase inhibitor (TKI) to bevacizumab during maintenance therapy improved clinical outcomes (RR, PFS, OS) in patients with MCRC, whatever KRAS status. The aim of this post-hoc analysis is to evaluate the clinical outcomes according to KRAS mutational status and PTS when adding erlotinib to bevacizumab maintenance therapy. Methods: PTS was retrospectively collected in patients from the DREAM phase III trial treated with bevacizumab with or without erlotinib as maintenance therapy for MCRC who have been controlled by induction therapy. The limit for the definition of PTS was splenic flexure, and rectal tumors were considered as left-sided tumors. The primary endpoint was overall survival (OS). Results: Among 452 patients who received maintenance therapy, PTS ascertainment was 84.7% (n = 383) with 265 (71.0%) patients having left-sided primary tumor and 108 (28.9%) having right-sided primary tumors (3 patients had both and tumor location was unknown in 7 patients). Median OS and treatment effect are presented in table 1. Conclusions: The greatest OS benefit of adding erlotinib to bevacizumab maintenance therapy was observed in patients with WT-KRAS and right-sided MCRC, suggesting a clinical impact of the different mechanism of action between EGFR TKI and monoclonal antibodies. Clinical trial information: NCT00265824. [Table: see text]

Prognostic impact of PD-L1 and PD-1 expression by primary tumor location in colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 628-628 ◽  
Author(s):  
Jonna Berntsson ◽  
Anna Larsson ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
Karin Jirstrom
Keyword(s):  
Colorectal Cancer ◽  
Immune Cells ◽  
Primary Tumor ◽  
Tumor Location ◽  
Left Colon ◽  
Prognostic Impact ◽  
Full Cohort ◽  
Primary Tumors ◽  
Primary Tumor Location ◽  
Entire Cohort

628 Background: A plethora of studies report abundant expression of programmed death-ligand 1 (PD-L1) on tumors to be associated with poor outcome in several cancer forms, whereas immune cell-specific expression of PD-L1 has been associated with improved prognosis in colorectal cancer. However, none of these studies have investigated the association with prognosis according to primary tumor location. This study aimed to investigate the clinicopathological correlates and prognostic impact of PD-L1 and its receptor PD-1 in colorectal cancer, with particular reference to the anatomical subsite of the primary tumor. Methods: Immunohistochemical expression of PD-L1 and PD-1 was analysed in tissue microarrays with tumors from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. Results: High PD-L1 expression on tumor-infiltrating immune cells correlated significantly with an improved 5-year OS in univariable and multivariable analysis, adjusted for age, sex, TNM stage, differentiation grade, and vascular invasion, in the full cohort (HR = 0.49; 95 % CI 0.35-0.68), and in primary tumors of the right (HR = 0.43; 95 % CI 0.25-0.74) and the left colon (HR = 0.28; 95 % CI 0.13-0.61), but not in rectal cancer. High tumor-specific PD-L1-expression was not significantly associated with prognosis in neither the full cohort nor according to primary tumor location. High expression of PD-1 on tumor-infiltrating immune cells was significantly associated with an improved 5-year overall survival in the entire cohort (HR = 0.42; 95 % CI 0.21-0.87), but not in subsite analysis according to primary tumor location. Conclusions: This study is, to the best of our knowledge, the first to investigate the prognostic impact of PD-L1 and PD-1 expression according to primary tumor site in colorectal cancer. Dense infiltration of PD-L1+ immune cells was found to be an independent favorable prognostic factor in primary tumors of the right and left colon, but not in the rectum.

scholarly journals Short-term results after minimally invasive and open liver resection for liver metastases of colorectal cancer: a single center experience

2018 ◽  
Vol 46 (6) ◽  
pp. 584-591
Author(s):  
M. G. Efanov ◽  
R. B. Alikhanov ◽  
V. V. Tsvirkun ◽  
I. V. Kazakov ◽  
P. P. Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Minimally Invasive ◽  
Liver Metastases ◽  
Surgical Margin ◽  
Colorectal Metastases ◽  
Single Center ◽  
Open Resection ◽  
Tumor Spread ◽  
Primary Tumors

Rationale: Until now, safety of minimally invasive liver resection (MILR) has not been studied sufficiently.Aim: To assess immediate results of MILR and open type resections in patients with colorectal metastases, performed in the Russian center of surgical hepatology specialized at implementation of minimally invasive techniques.Materials and мethods: This was a retrospective observational case-control study. Patients who underwent surgery for isolated liver metastases of colorectal cancer in a  single center from October 2013 to February 2018 were included into the study.Results: As per December 2017, over 500 resections have been performed in the study center, including 226 MILR. One hundred two patients underwent open resection and MILR for colorectal metastases. From 83 patients enrolled into the study, 51 (61%) had MILR, including 7 robotic MILR. The open resection and MILR groups did not differ in terms of gender, age, ASA score, primary tumors location and stage by the time of primary intervention. There were no between-group differences for factors that determine the tumor spread and influence the resection problems, i.e. the difficulty index of MILR, rate of anatomic resection, resection of complex segments, vascular involvement, size and number of metastases, multiple liver lesions and bilobar metastases. No difference was found for immediate outcomes in terms of frequency of the free surgical margin > 2 mm, rate of the Pringle maneuver implementation, duration of the procedure, blood components transfusion, severe complications (Clavien-Dindo Grade > II), and time in intensive care unit. Compared to open procedures, MILR were associated with significantly less blood loss: 583 (50–3000) mL vs. 308 (0–3300) mL (p = 0.012), respectively, and shorter duration of hospital stay: 10 (4–29) days vs. 9 (4–29) days (р < 0.001), respectively.Conclusion: In a specialized surgical hepatology center, MILR can be performed equally to complex open procedures without changes in the rates and types of complications, but with an improvement of immediate outcomes.

Baseline predictors of survival in metastatic colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14105-e14105
Author(s):  
Anni Ravnsbæk Jensen ◽  
Camilla J S Kronborg
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Palliative Chemotherapy ◽  
Performance Status ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Metastatic Sites ◽  
Resected Primary Tumor ◽  
Metachronous Metastases

e14105 Background: Patients with non-resectable metastatic colorectal cancer can survive several years with palliative chemotherapy and newer biological agents. However, survival varies greatly within this group. The aim of the present study was to identify baseline predictors of overall mortality in an unselected cohort of patients with metastatic colorectal cancer. Methods: Clinical information was collected from patient files in consecutive patients treated with palliative chemotherapy from August 2007 until June 2011. The primary outcome was overall survival. Cox regression analysis was used to examine the effect of predictive variables on time to outcome. The variables analysed were: Gender, age, performance status, primary tumor site (colon or rectum), status of primary tumor (resected or un-resected), metachronous metastases, more than two metastatic sites, liver-only metastases, and low albumin. Results: We included 314 patients (Median age 64.5 IQ (57-70) years, 194 (61.8%) male). Median follow-up for survival was 471 days IQ (257-708). One-year survival was 79%, CI (74-84%). Median overall survival was 676 days, CI (577-750). Following baseline variables were independent predictors of all-cause mortality: Primary tumor site colon HR: 1.49, CI (1.03-2.16), p=0.036, un-resected primary tumor HR 2.92, CI (1.85-4.62), p<0.001, metachronous metastases HR 1.72, CI (1.06-2.79), p=0.027 and more than two metastatic sites HR 3.46, CI (1.71-6.99), p=0.001. Both Performance status and low albumin were statistically significant in the univariate analysis, but not in the multivariate analysis. Conclusions: In daily clinical practice, baseline predictors of mortality in metastatic colorectal cancer were colon as the primary tumor site, un-resected primary tumor, metachronous metastases, and more than two metastatic sites.

scholarly journals PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiao-Li Wei ◽  
Xuan Luo ◽  
Hui Sheng ◽  
Yun Wang ◽  
Dong-Liang Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Checkpoint Inhibitors ◽  
Tissue Microarrays ◽  
Tumor Differentiation ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Expression Cluster

Abstract Background The outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors. This study was aimed to analyze PD-L1 expression and the immune microenvironment status in liver metastases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer. Methods 74 cases of pathologically confirmed colorectal cancer with liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. We evaluated the disparity between primary tumor and liver metastasis in PD-L1 expression, CD4 and CD8 density and analyzed the factors associated with obvious PD-L1 disparity. Results The expression of PD-L1 was positively related to the density of CD4 and CD8 in liver metastases. The expression of PD-L1 in liver metastases was higher than in primary tumors in certain subgroups, including patients with concurrent liver metastases (n = 63, p = 0.05), patients receiving concurrent resection of primary and metastatic tumors (n = 56, p = 0.04). The two subgroups generally reflected those without inconsistent external influences, such as treatment and temporal factors, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified. Furthermore, tumor differentiation [moderate vs. poor: OR = 0.23, 95% CI: 0.03–0.99, p = 0.05)] were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and liver metastases. Conclusions The expression of PD-L1 in liver metastases was higher than in primary tumors in subgroups, reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was significantly related to the tumor differentiation.

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.

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