Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Predictive Significance of Combined Plasmatic Detection of BRAF Mutations and S100B Tumor Marker in Early-Stage Malignant Melanoma

J. Polivka, MA. Gouda, M. Sharif, M. Pesta, H. Huang, I. Treskova, V. Woznica, J. Windrichova, K. Houfkova, R. Kucera, T. Fikrle, J. Ricar, K. Pivovarcikova, O. Topolcan, F. Janku

. 2024 ; 13 (19) : e70313. [pub] -

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc25003978

Grant support
This work was supported by LTAUSA19080 program, INTEREXCELLENCE, INTER-ACTION, Ministry of Education, Youth and Sports of the Czech Republic; by Cooperation Programme, research areas MED/DIAG, MED/ONCO and MED/SURG Charles University; by a grant of the Ministry of Health of the Czech Republic-Conceptual Development of Research Organization (Faculty Hospital in Pilsen-FNPl, 00669806) and by National Institutes of Health through MD Anderson's Cancer Center Support Grant [grant number P30CA016672

BACKGROUND: Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma. METHODS: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre-amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method. RESULTS: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100Bhigh) and ctDNA BRAFV600E (BRAFmut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild-type. Similarly, patients with preoperative and postoperative S100Bhigh and BRAFmut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.). CONCLUSION: We observed the benefit of the estimation of combination of S100B and ctDNA BRAFmut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis. SIGNIFICANCE: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early-stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAFmut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre- and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc25003978
003      
CZ-PrNML
005      
20250206104833.0
007      
ta
008      
250121s2024 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1002/cam4.70313 $2 doi
035    __
$a (PubMed)39387479
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Polivka, Jiri $u Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
245    10
$a Predictive Significance of Combined Plasmatic Detection of BRAF Mutations and S100B Tumor Marker in Early-Stage Malignant Melanoma / $c J. Polivka, MA. Gouda, M. Sharif, M. Pesta, H. Huang, I. Treskova, V. Woznica, J. Windrichova, K. Houfkova, R. Kucera, T. Fikrle, J. Ricar, K. Pivovarcikova, O. Topolcan, F. Janku
520    9_
$a BACKGROUND: Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma. METHODS: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre-amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method. RESULTS: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100Bhigh) and ctDNA BRAFV600E (BRAFmut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild-type. Similarly, patients with preoperative and postoperative S100Bhigh and BRAFmut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.). CONCLUSION: We observed the benefit of the estimation of combination of S100B and ctDNA BRAFmut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis. SIGNIFICANCE: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early-stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAFmut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre- and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage.
650    _2
$a lidé $7 D006801
650    12
$a protoonkogenní proteiny B-Raf $x genetika $x krev $7 D048493
650    12
$a melanom $x genetika $x krev $x patologie $x diagnóza $x chirurgie $7 D008545
650    12
$a S-100 kalcium vázající protein G, podjednotka beta $x krev $x genetika $7 D064568
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé středního věku $7 D008875
650    12
$a nádorové biomarkery $x krev $x genetika $7 D014408
650    12
$a mutace $7 D009154
650    _2
$a senioři $7 D000368
650    12
$a nádory kůže $x krev $x genetika $x patologie $x diagnóza $x chirurgie $7 D012878
650    12
$a lokální recidiva nádoru $x genetika $x krev $7 D009364
650    _2
$a dospělí $7 D000328
650    _2
$a staging nádorů $7 D009367
650    _2
$a prognóza $7 D011379
650    _2
$a tekutá biopsie $x metody $7 D000073890
650    _2
$a senioři nad 80 let $7 D000369
650    _2
$a prediktivní hodnota testů $7 D011237
655    _2
$a časopisecké články $7 D016428
700    1_
$a Gouda, Mohamed A $u Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA $1 https://orcid.org/0000000348296739
700    1_
$a Sharif, Mahyar $u Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic $1 https://orcid.org/0000000212281300
700    1_
$a Pesta, Martin $u Department of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic $1 https://orcid.org/0000000181870566 $7 xx0073915
700    1_
$a Huang, Helen $u Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
700    1_
$a Treskova, Inka $u Department of Plastic Surgery, University Hospital Pilsen, Pilsen, Czech Republic
700    1_
$a Woznica, Vlastimil $u Department of Plastic Surgery, University Hospital Pilsen, Pilsen, Czech Republic
700    1_
$a Windrichova, Jindra $u Department of Immunochemical Diagnostics, University Hospital Pilsen, Pilsen, Czech Republic
700    1_
$a Houfkova, Katerina $u Department of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
700    1_
$a Kucera, Radek $u Department of Immunochemical Diagnostics, University Hospital Pilsen, Pilsen, Czech Republic $u Department of Pharmacology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
700    1_
$a Fikrle, Tomas $u Department of Dermatovenerology, University Hospital Pilsen, Pilsen, Czech Republic
700    1_
$a Ricar, Jan $u Department of Dermatovenerology, University Hospital Pilsen, Pilsen, Czech Republic
700    1_
$a Pivovarcikova, Kristyna $u Department of Pathology, University Hospital Pilsen, Pilsen, Czech Republic
700    1_
$a Topolcan, Ondrej $u Department of Immunochemical Diagnostics, University Hospital Pilsen, Pilsen, Czech Republic
700    1_
$a Janku, Filip $u Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
773    0_
$w MED00181704 $t Cancer medicine $x 2045-7634 $g Roč. 13, č. 19 (2024), s. e70313
856    41
$u https://pubmed.ncbi.nlm.nih.gov/39387479 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20250121 $b ABA008
991    __
$a 20250206104828 $b ABA008
999    __
$a ok $b bmc $g 2263616 $s 1239985
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 13 $c 19 $d e70313 $e - $i 2045-7634 $m Cancer medicine $n Cancer Med $x MED00181704
GRA    __
$p This work was supported by LTAUSA19080 program, INTEREXCELLENCE, INTER-ACTION, Ministry of Education, Youth and Sports of the Czech Republic; by Cooperation Programme, research areas MED/DIAG, MED/ONCO and MED/SURG Charles University; by a grant of the Ministry of Health of the Czech Republic-Conceptual Development of Research Organization (Faculty Hospital in Pilsen-FNPl, 00669806) and by National Institutes of Health through MD Anderson's Cancer Center Support Grant [grant number P30CA016672
LZP    __
$a Pubmed-20250121

Find record

Citation metrics

Archiving options