Histological expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in human primary melanoma.
OBJECTIVE
Tumour necrosis factor-related apoptosis ligand (TRAIL) appears to selectively induce apoptosis in a wide range of cultured malignant cells, including melanoma. This study was designed to attempt to clarify the role of TRAIL in the biology of human melanoma.


METHODS
Tissue sections cut from formalin-fixed, paraffin-embedded tissue blocks of 45 primary cutaneous melanomas were tested for expression of TRAIL using immunohistochemistry. The intensity, pattern of staining and percentage of positively stained tumour cells were evaluated in each melanoma. Breslow thickness, ulcerative state, dermal mitotic rate and the presence of tumour infiltrating lymphocytes were measured/determined in each case. Median follow up for the cohort of patients was 10 months (range 1-18). Survival analysis was conducted using the Kaplan-Meier method. The level of expression of TRAIL was compared with the various histological determinants using the two-tailed Fisher's exact test and the chi2-test.


RESULTS
Overall and disease-free survival were 72 and 48%, respectively, and did not correlate with TRAIL expression. Among the pathological prognostic determinants, only mitotic rate showed a statistically significant correlation with TRAIL expression using the chi2-test (P=0.04).


CONCLUSIONS
We conclude that TRAIL expression in melanoma defines a more aggressive/proliferative phenotype, either through selection of apoptotic resistant cells or by secondary induction of other factors enhancing proliferation of more malignant cells. Analysis of a larger group of patients with longer follow-up is required to determine whether TRAIL expression correlates with survival of patients.
Bron
Luc P
LP
Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia.
Scolyer
Richard A
RA
Thompson
John F
JF
Hersey
Peter
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D008938:Mitosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha