scholarly journals TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease

2017 ◽  
Vol 102 (6) ◽  
pp. 1898-1907 ◽  
Author(s):  
Miguel Melo ◽  
Adriana Gaspar da Rocha ◽  
Rui Batista ◽  
João Vinagre ◽  
Maria João Martins ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Primary Tumor ◽  
Low Frequency ◽  
Distant Metastases ◽  
Braf Mutations ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Thyroid Carcinomas ◽  
Cancer Metastases ◽  
Node Metastases

Abstract Context Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives To evaluate the frequency of TERT promoter (TERTp), BRAF, and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNMs), and distant metastases. Design and Patients Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTCs; n = 180), including 196 LNMs and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue. Results We found the following mutation frequency in primary PTCs, LNMs, and distant metastases, respectively: TERTp: 12.9%, 10.5%, and 52.4%; BRAF: 44.6%, 41.7%, and 23.8%; and NRAS: 1.2%, 1.3%, and 14.3%. There was a significant concordance between the primary tumor genotype and the corresponding LNM for all the genes, in particular BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTCs, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison with the paired primary tumors. When present in distant metastases, BRAF mutations frequently coexisted with TERTp mutations. Conclusions When the genotype of primary tumors is compared with the genotype of LNMs, the concordance is high for all the genes studied. On the other hand, distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations may play a role in distant metastases.

Genetic profile of advanced thyroid cancers in relation to distant metastasis

2020 ◽  
Vol 27 (5) ◽  
pp. 285-293 ◽  
Author(s):  
Eyun Song ◽  
Dong Eun Song ◽  
Jonghwa Ahn ◽  
Tae Yong Kim ◽  
Won Bae Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Distant Metastasis ◽  
Distant Metastases ◽  
Thyroid Tumors ◽  
Primary Tumors ◽  
Thyroid Cancers ◽  
Histone Methyltransferases ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated

Major clinical challenges exist with differentiated thyroid cancers with distant metastases or rare but aggressive types, such as poorly differentiated thyroid carcinomas and anaplastic thyroid carcinomas. The precise characterization of the mutational profile in these advanced thyroid cancers is crucial. Samples were collected from primary tumors and distant metastases of 64 patients with distant metastases from differentiated thyroid cancer, poorly differentiated thyroid carcinoma, or anaplastic thyroid carcinoma. Targeted next-generation sequencing was performed with 50 known thyroid-cancer-related genes. Of the 82 tissues, 63 were from primary tumors and 19 from distant metastases. The most prevalent mutation observed from the primary tumors was TERT promoter mutation (56%), followed by BRAF (41%) and RAS (24%) mutations. TP3 was altered by 11%. Mutations in histone methyltransferases, SWI/SNF subunit–related genes, and PI3K/AKT/mTOR pathway-related genes were present in 42%, 12%, and 22%, respectively. When the mutational status was analyzed in 15 matched pairs of thyroid tumors and their matched distant metastases and one pair of distant metastases with two distinct sites, the concordance was high. A similar frequency of mutations in TERT promoter (58%) and BRAF (42%) as well as histone methyltransferases (37%), SWI/SNF subunits (10%), and PI3K/AKT/mTOR pathway (26%) were noted. The same main, early and late mutations were practically always present in individual primary tumor–metastasis pairs. Enrichment of TERT promoter, BRAF, and RAS mutations were detected in highly advanced thyroid cancers with distant metastasis. The genetic profiles of primary thyroid tumors and their corresponding distant metastases showed a high concordance.

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 VEGF-C and COX-2 expression in papillary thyroid cancer

2006 ◽  
Vol 13 (2) ◽  
pp. 465-473 ◽  
Author(s):  
Päivi Siironen ◽  
Ari Ristimäki ◽  
Kirsi Narko ◽  
Stig Nordling ◽  
Johanna Louhimo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Papillary Thyroid Cancer ◽  
Distant Metastases ◽  
Papillary Thyroid ◽  
Tissue Samples ◽  
Node Metastases ◽  
Cox 2 ◽  
Factor C ◽  
Endothelial Growth Factor

In papillary thyroid cancer (PTC), age appears to be the most important single prognostic factor. Another characteristic feature is the lack of association between survival and lymph node metastases. Earlier, we found that expression of cyclooxygenase-2 (COX-2) is higher in older PTC patients, in agreement with the finding that older patients have a worse prognosis. Recent findings suggest that COX-2 can up-regulate vascular endothelial growth factor-C (VEGF-C) expression. Here, we investigated whether expression of VEGF-C differs between young and older PTC patients and whether expression of VEGF-C and COX-2 are correlated. Our retrospective study comprised 106 PTC patients selected by age: those under 35 or over 55 at diagnosis. Paraffin-embedded tissue samples were analysed by immunohistochemistry for VEGF-C protein expression. Furthermore, we investigated by quantitative RT-PCR and enzyme immunoassay the relationship between VEGF-C and COX-2 expression in papillary thyroid cancer cells (NPA cells). VEGF-C expression was significantly increased with age. In the tumours from older lymph node-positive (N1) patients, VEGF-C expression was significantly higher than in the tumours from young N1 patients. Moreover, all patients who died of cancer or who developed distant metastases were old, and most tumours from these patients (4 of 5) expressed VEGF-C and had had nodal metastases at the time of primary operation. Immunohistochemically, expression of COX-2 and VEGF-C correlated strongly. In cell culture, this correlation was not so clear, because the COX-2 selective inhibitor, NS-398, did not reduce VEGF-C expression. However, as both COX-2 and VEGF-C were induced by the tumour promoter phorbol 12-myristate 13-acetate (PMA), the same factors may control them both.

scholarly journals Preoperative Serum Thyroglobulin and Its Correlation with the Burden and Extent of Differentiated Thyroid Cancer

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 625
Author(s):  
Hosu Kim ◽  
So Young Park ◽  
Jun-Ho Choe ◽  
Jee Soo Kim ◽  
Soo Yeon Hahn ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Primary Tumor ◽  
Differentiated Thyroid Cancer ◽  
Medical Center ◽  
Distant Metastases ◽  
Predictive Biomarker ◽  
Tumor Burden ◽  
Serum Thyroglobulin ◽  
Preoperative Serum ◽  
Clinical Records

Lymph node metastasis (LNM) in differentiated thyroid cancer (DTC) is usually detected with preoperative ultrasonography; however, this has limited sensitivity for small metastases, and there is currently no predictive biomarker that can help to inform the extent of surgery required. We evaluated whether preoperative serum thyroglobulin levels can predict tumor burden and extent. We retrospectively reviewed the clinical records of 4029 DTC cases diagnosed and treated at a Samsung Medical Center between 1994 and 2016. We reviewed primary tumor size, number and location of LNM, and presence of distant metastases to reveal relationships between tumor burden and extent and preoperative serum thyroglobulin levels. We found a linear association between increasing preoperative thyroglobulin levels, the size of the primary tumor, and the number of LNM (r = 0.34, p < 0.001, r = 0.20, p < 0.001, respectively). Tumor extent also increased with each decile of increasing preoperative thyroglobulin level (r = 0.18, p < 0.001). Preoperative thyroglobulin levels of 13.15 ng/mL, 30.05 ng/mL, and 62.9 ng/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. Our results suggest that preoperative measurement of serum thyroglobulin may help to predict LNM and help to tailor surgery.

scholarly journals Neurotensin Receptor-1 Expression in Human Prostate Cancer: A Pilot Study on Primary Tumors and Lymph Node Metastases

2019 ◽  
Vol 20 (7) ◽  
pp. 1721 ◽  
Author(s):  
Clément Morgat ◽  
Adrien Chastel ◽  
Vincent Molinie ◽  
Romain Schollhammer ◽  
Gaétan Macgrogan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Nodes ◽  
Distant Metastases ◽  
Human Prostate ◽  
Normal Prostate ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph ◽  
Prostate Cancers

Neurotensin and its high-affinity receptor, NTR1, are involved in the growth of various tumors. Few data are available regarding NTR1 expression in normal and tumoral human prostate tissue samples. NTR1 expression was assessed using immunohistochemistry in 12 normal prostate tissues, 11 benign prostatic hyperplasia (BPH), 44 prostate cancers, and 15 related metastatic lymph nodes (one per patient, when available). NTR1-staining was negative in normal prostate and BPH samples. NTR1 was overexpressed in four out of 44 (9.1%) primary tumors. There was no clear association between NTR1 overexpression and age, PSA-values, Gleason score, pT-status, nodal-status, or margin. NTR1 was expressed at a high level of five out of 15 (33.3%) metastatic lymph nodes. NTR1 overexpression was thus more frequent in metastatic lymph nodes than in primary tumors (p = 0.038). In this limited series of samples, NTR1 overexpression was observed in few primary prostate cancers. Upregulation was more frequent in related lymph nodes. The presence of this target in metastatic lymph nodes may open new perspectives for imaging and radionuclide therapy of prostate cancer. Factors driving NTR1 expression in primary prostate cancer and in nodal and distant metastases still need to be characterized.

Clinical outcomes of adjuvant external-beam radiotherapy for differentiated thyroid cancer

2009 ◽  
Vol 48 (03) ◽  
pp. 89-98 ◽  
Author(s):  
M. K. Pixberg ◽  
B. Riemann ◽  
A. Schuck ◽  
A. Heinecke ◽  
K. W. Schmid ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Differentiated Thyroid Cancer ◽  
Regional Lymph Node ◽  
Statistical Significance ◽  
External Beam Radiotherapy ◽  
Distant Metastases ◽  
External Beam ◽  
Node Metastases

Summary Aim: Evaluate the clinical benefit of external beam radiotherapy (RTx) for locally invasive thyroid carcinoma with follicular cell differentiation (DTC). Patients, methods: The Multicentre Study on Differentiated Thyroid Cancer (MSDS) was planned as a prospective multicenter trial on the benefit of adjuvant RTx in locally invasive DTC (pT4; UICC 1997) with or without lymph node metastases and no known distant metastases. All patients were treated with thyroidectomy, 131I-therapy, and TSH-suppression and were randomized to receive additional RTx or not. In 4/2003 the trial became a prospective cohort study after only 45 of then 311 patients had consented to randomization. 351 of 422 patients met the trial's inclusion criteria. Age was 48 ± 12 years (mean ± SD). 25% were men. Tumours were papillary in 90% and follicular in 10%. Of 47 patients randomized or allocated to RTx, 26 actually received RTx. Results: Mean followup was 930 days. In an actual treatment analysis, 96% (25/26) of the RTx-patients reached complete remission (CR) vs. 86% in the non-RTx patients. Recurrences occurred in 0 vs. 3 % of patients: 6 reoperated for regional lymph node metastases, 1 tracheal invasion treated with tracheoplasty, 1 local invasion necessitating laryngectomy, 2 distant metastases (1 lung, 1 lung + bone). Serious chronic RTx toxicity occurred in 1/26 patients. Conclusion: The MSDS trial showed low mortality and recurrence rates and a weak benefit of RTx in terms of local control that did however not reach statistical significance. Routine RTx in locally invasive DTC can no longer be recommended .

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.

Frequency of discordance in programmed death ligand 1 (PD-L1) expression between primary tumors and paired distant metastases in advanced cancers: A systematic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14290-e14290
Author(s):  
Chia Ching Lee ◽  
Ivan Weng Keong Tham ◽  
Char Loo Tan ◽  
Jeffrey Lum ◽  
Jeremy Chee Seong Tey ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Distant Metastases ◽  
P Value ◽  
Significant Heterogeneity ◽  
Chi Square ◽  
Primary Tumors ◽  
Methodologic Quality ◽  
Discordance Rate

e14290 Background: Randomized trials have demonstrated that PD-L1 expression in tumor cells predicts for response to PD-1 or PD-L1 checkpoint inhibitors in advanced cancers. However, the frequency of discordance in PD-L1 expression between primary tumors and paired distant metastases is currently unclear. We aimed to determine the discordance rate of PD-L1 expression between primary tumor and paired distant metastases in advanced cancers. Methods: We searched MEDLINE and EMBASE for eligible studies. We noted the discordance rate (positive-to-negative or vice versa) and performed subgroup analyses based on the PD-L1 expression in primary tumor, locations of primary tumor and distant metastases, positivity thresholds and type of antibody used for testing. We used QUADAS-2 tool to assess the methodologic quality of the included studies. We performed the meta-analysis using the logistic-normal random effects model. Results: We identified 11 eligible studies including 351 cases of lung, colorectal, breast and ovarian cancers. Nine studies were judged to have low risk of bias in their methodological quality. The overall discordance rate in PD-L1 expression between primary tumor and paired distant metastases was 28% (95% confidence interval (CI) = 18-41) with significant heterogeneity among the studies (chi-square test P-value < 0.0001). There was no statistically significant differences in discordance rates between the subgroups: PD-L1-positive (40%, 95% CI = 21-63) vs PD-L1-negative primary tumors (21%, 95% CI = 12-34), lung primary (31%, 95% CI = 14-55) vs colorectal/ breast/ ovarian primary (27%, 95% CI = 19-37), central nervous system metastases (22%, 95% CI = 8-47) vs liver/ lung/ pleural/ peritoneum metastases (34%, 95% CI = 24-46); 1% (23%, 95% CI 16-33) vs 5% positivity threshold (33%, 95% CI 11-68); E1L3N (42%, 95% CI 10-82) vs SP142 antibody (27%, 95% CI 20-36). Conclusions: The discordance in PD-L1 expression between primary tumors and paired distant metastases is close to 30%, which could potentially affect response to immunotherapy. Further works exploring the mechanisms and impact of this discordance are warranted.

Feasibility of multiple immunoexpression assay for immune tumor micrornvironment (I-TME) on matched metastatic and primary renal cell carcinoma (RCC) for patient prognostication and predictiveness to immunotherapy (preliminary analyses of the Meet URO 18 study).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16545-e16545
Author(s):  
Matteo Brunelli ◽  
Sara Elena Rebuzzi ◽  
Valerio Gaetano Vellone ◽  
Marta Sbaraglia ◽  
Gabriele Gaggero ◽  
...  
Keyword(s):  
Nk Cells ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Tissue Expression ◽  
Tissue Level ◽  
Antibody Testing ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Cd8 Cells ◽  
Primary Renal Cell Carcinoma

e16545 Background: The Meet-URO 18 study is ongoing to assess the prognostic role of I-TME in advanced RCC patients treated with ≥second line nivolumab divided into two cohorts according to clinical benefit [progression-free survival ≥ 12 and ≤ 3 months]. We primarily assessed the feasibility of multiple antibody testing related to I-TME on matched metastases and primary tumor. Methods: Immunohistochemical analyses were used for the TME assessment of T-lineage (CD3, CD4, CD8), FOXP-3, granulocytes (CD15), macrophage-lineage (CD68), natural killer (NK)-cells (CD56), tumor cells (TCs) (CD56), B-lineage (CD20) and phosphorylated mTOR (phmTOR). TCs were quantitatively assessed for CD15, CD56 and phmTOR positivity. For T-, B- and CD68 cells within TC nests, the number of immunoreactive cells were counted with a microscopic field of x200 (0.933 mm2). Results: Overall, 42 tumor tissue samples (primary tumors, metastases) were available and for 17 patients both metastatic and primary tumor tissues were assessable for matched analyses. Among these patients, 12 had clear cell, 1 papillary and 4 mucinous tubular and spindle cell histotype according to WHO 2016 classification. Intratumoral T/CD8 cells ranged from 32 to >400 spots (mean 240; >400 in 7 samples) and intratumoral T/CD4 cells from 4 to >400 spots (mean 168; >400 in 5 samples). Nine samples showed absence of phmTOR expression, while 8 ranged from 10% to 90% of positive TCs. We did not observe countable NK-cells, whereas CD56 was visible in 5 samples (mean 55% of positive TCs). Intratumoral CD68 cells ranged from 34 to >400 spots (mean 175, >400 in 3 patients). Agreement of CD15 method of reporting granulocytic presence was high, thus only CD15 neoplastic expression was reported and ranged from 12% to 55% (mean 30%) in 15 patients. TME multiple analysis resulted equally clustered in 8 patients (<20% variability of single immuno-test) whereas the remaining 9 patients showed significant differences as percentage of immuno-tissue expression in at least one of the 5 immuno-indicators (T/CD8-CD4, C15, CD68, CD56, phmTOR). The remaining 8 samples of patients without matched analyses were used to test the feasibility of multiple analyses; among all antibodies exclusion of the CD20 and FOXP-3 final evaluation was needed, due to technical standardization. According to the 5 immuno-indicators, double-triple positive or penta-positive TME indicators may be identified and graded. Conclusions: Providing multiple immunoexpression platforms on a single specimen may be used as routine workflow. Profiling I-TME, especially CD56, CD15 on TCs and CD68 cells and phmTOR, deserves investigation with extensive control groups. A validation cohort will be tested at tissue level and in correlation with peripheral blood markers.

Increased Expression of BRCA2 and RAD51 in Lymph Node Metastases of Canine Mammary Adenocarcinomas

2009 ◽  
Vol 46 (3) ◽  
pp. 416-422 ◽  
Author(s):  
R. Klopfleisch ◽  
A. D. Gruber
Keyword(s):  
Mammary Gland ◽  
Lymph Node ◽  
Mrna Expression ◽  
Lymph Node Metastases ◽  
Geometric Mean ◽  
Experimental Studies ◽  
Normal Mammary Gland ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Node Metastases

The BRCA/RAD51 complex of tumor suppressor genes plays a major role in the DNA damage response. In this explorative study, BRCA1, BRCA2, and RAD51 mRNA expression was quantified in highly defined laser microdissected tissue samples of simple adenomas, adenocarcinomas of the mammary gland, and their lymph node metastases by real-time quantitative reverse transcription polymerase chain reaction. Expression levels in the tumors were normalized to the geometric mean of 3 housekeeping genes and quantified relative to normal mammary epithelium of the same dog. In adenomas, mRNA expression was reduced for BRCA1 (6/10 dogs, 60%), BRCA2 (4/10 dogs, 40%), and RAD51 (4/10, 40%). In adenocarcinomas BRCA1 expression varied with increased expression in 3 of 10 (30%) dogs and no differences in 7 of 10 (70%) dogs when compared with normal mammary gland. BRCA2 and RAD51 were overexpressed in 5 of 10 (50%) and 6 of 10 (60%) of adenocarcinomas, respectively. An overexpression of RAD51 and BRCA2 was found in 8 of 10 (80%) and 5 of 10 (50%) of the lymph node metastases, respectively. Direct comparison of primary tumors and metastases revealed increased mRNA expression of BRCA1 (2/10 dogs, 20%), BRCA2 (2/10 dogs, 20%), and RAD51 (3/10 dogs, 30%) in lymph node metastases. Taken together, the results suggest that RAD51 is upregulated in the majority of lymph node metastases of canine mammary tumors. Further experimental studies are needed to clarify whether these changes in gene expression are a direct carcinogenetic stimulus or a protective response due to genetic instability during tumor progression.

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