Association of tumor molecular factors with in-transit metastasis in primary cutaneous melanoma.
angiogenesis
bioinformatics
cutaneous metastatic disease
Journal
International journal of dermatology
ISSN: 1365-4632
Titre abrégé: Int J Dermatol
Pays: England
ID NLM: 0243704
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
revised:
19
12
2021
received:
24
10
2021
accepted:
06
02
2022
pubmed:
6
3
2022
medline:
24
8
2022
entrez:
5
3
2022
Statut:
ppublish
Résumé
In-transit metastases (ITM) are a form of locoregional relapse representing intralymphatic metastatic spread and occur in approximately 4-9% of patients with melanoma >1 mm Breslow thickness. Our objective was to evaluate a combination of clinicopathologic risk factors and gene expression biomarkers predictive of ITM risk. We used PCR to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 854 consecutive thin and intermediate thickness primary cutaneous melanomas. The outcome of interest was ITM >90 days after a melanoma diagnosis. Cox proportional hazard models were fit to estimate each clinicopathologic and molecular characteristic's association with the risk of ITM. The 5-year cumulative incidence of ITM was 3.2%. Clinical factors univariately associated with an increased risk of ITM were older age, greater Breslow thickness, greater mitotic rate, lower extremity location, ulceration, and a positive SLN biopsy. Of 108 genes tested, five were significantly upregulated and five significantly downregulated when evaluated in Cox models adjusted for age, Breslow thickness, mitotic rate, and lower extremity location. Among the upregulated genes, the strongest association was observed for interleukin-8 (IL8). A subset of gene expression biomarkers was identified as independently associated with the risk of ITM after adjusting for key covariates. Once sufficiently validated, our results may lead the way to regional therapy trials for a small, selected group of high-risk patients.
Sections du résumé
BACKGROUND
BACKGROUND
In-transit metastases (ITM) are a form of locoregional relapse representing intralymphatic metastatic spread and occur in approximately 4-9% of patients with melanoma >1 mm Breslow thickness. Our objective was to evaluate a combination of clinicopathologic risk factors and gene expression biomarkers predictive of ITM risk.
METHODS
METHODS
We used PCR to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 854 consecutive thin and intermediate thickness primary cutaneous melanomas. The outcome of interest was ITM >90 days after a melanoma diagnosis. Cox proportional hazard models were fit to estimate each clinicopathologic and molecular characteristic's association with the risk of ITM.
RESULTS
RESULTS
The 5-year cumulative incidence of ITM was 3.2%. Clinical factors univariately associated with an increased risk of ITM were older age, greater Breslow thickness, greater mitotic rate, lower extremity location, ulceration, and a positive SLN biopsy. Of 108 genes tested, five were significantly upregulated and five significantly downregulated when evaluated in Cox models adjusted for age, Breslow thickness, mitotic rate, and lower extremity location. Among the upregulated genes, the strongest association was observed for interleukin-8 (IL8).
CONCLUSION
CONCLUSIONS
A subset of gene expression biomarkers was identified as independently associated with the risk of ITM after adjusting for key covariates. Once sufficiently validated, our results may lead the way to regional therapy trials for a small, selected group of high-risk patients.
Identifiants
pubmed: 35246838
doi: 10.1111/ijd.16141
pmc: PMC9391269
mid: NIHMS1794847
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1117-1123Subventions
Organisme : NCI NIH HHS
ID : K08 CA215105
Pays : United States
Organisme : NCI NIH HHS
ID : CA215105
Pays : United States
Organisme : NCI NIH HHS
ID : CA215105
Pays : United States
Informations de copyright
© 2022 the International Society of Dermatology.
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