Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy.
Aged
Aged, 80 and over
Aminolevulinic Acid
/ analogs & derivatives
Animals
Biomarkers, Tumor
/ metabolism
Carcinoma, Basal Cell
/ drug therapy
Cell Line, Tumor
Drug Resistance, Neoplasm
Female
Humans
Immunohistochemistry
Male
Mice
Middle Aged
Photochemotherapy
Photosensitizing Agents
/ therapeutic use
Retrospective Studies
Skin Neoplasms
/ drug therapy
Tumor Suppressor Protein p53
/ metabolism
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
30
10
2018
accepted:
03
04
2019
entrez:
25
4
2019
pubmed:
25
4
2019
medline:
30
1
2020
Statut:
epublish
Résumé
Methyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality. The aim of this study was to identify potential biomarkers of BCC response to MAL-PDT. Clinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated. The retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01). Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94-159.8). Our finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapy.
Sections du résumé
BACKGROUND
Methyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality.
OBJECTIVE
The aim of this study was to identify potential biomarkers of BCC response to MAL-PDT.
MATERIAL AND METHODS
Clinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated.
RESULTS
The retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01). Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94-159.8).
CONCLUSION
Our finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapy.
Identifiants
pubmed: 31017970
doi: 10.1371/journal.pone.0215537
pii: PONE-D-18-31319
pmc: PMC6481917
doi:
Substances chimiques
Biomarkers, Tumor
0
Photosensitizing Agents
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
methyl 5-aminolevulinate
585NM85KYM
Aminolevulinic Acid
88755TAZ87
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0215537Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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