Drainage of Tumor-Derived DNA into Sentinel Lymph Nodes in Breast Cancer Patients
Circulating tumor DNA (ctDNA) is released from cancer cells by apoptosis or other mechanisms, and as tumor tissue contains both blood and lymphatic vessels, ctDNA can spread to local lymph nodes (LNs). We aimed to detect the tumor-derived free DNA in metastasis-free LNs in patients with breast cance...
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Published in | Pathology oncology research Vol. 25; no. 4; pp. 1635 - 1643 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Dordrecht
Springer Netherlands
01.10.2019
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Circulating tumor DNA (ctDNA) is released from cancer cells by apoptosis or other mechanisms, and as tumor tissue contains both blood and lymphatic vessels, ctDNA can spread to local lymph nodes (LNs). We aimed to detect the tumor-derived free DNA in metastasis-free LNs in patients with breast cancers harboring the
PIK3CA-
H1047R mutation. One hundred twenty-three patients were evaluated and the
PIK3CA-
H1047R mutation was assayed in sentinel LNs (SLNs), non-SLNs without metastasis, and serum by digital PCR. The mutant DNA was more frequent in metastasis-free SLNs (21.6%) than in metastasis-free non-SLNs (8.6%;
P
= 0.038), and patients with mutation-positive SLNs were more likely to be positive for serum mutant DNA. Apoptosis in primary breast tumors was determined by TUNEL assay. The apoptotic index was significantly higher (
P
= 0.003) in patients with mutation-positive SLNs without metastasis (mean, 1.17%) than those with mutation-negative SLNs without metastasis (mean, 0.79%). It was also significantly higher (
P
= 0.006) in those with mutation-positive serum (mean, 1.41%) than in those with mutation-negative serum (mean, 0.86%). Furthermore, fragment size of
PIK3CA-
H1047R mutant DNA in metastatic-free SLN lysate used for the one-step nucleic acid amplification (OSNA) assay was short (<500 bp). These results support the theory that DNA is released from the primary tumor via apoptotic fragmentation. In conclusion, ctDNA is detectable in metastasis-free LNs and significantly more frequent in SLNs from patients with breast tumors harboring a high apoptotic index, consistent with drainage of ctDNA from apoptotic primary tumor cells into SLNs. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1219-4956 1532-2807 |
DOI: | 10.1007/s12253-019-00618-z |