Development of a tissue array for primary melanoma with long-term follow-up: discovering melanoma cell adhesion molecule as an important prognostic marker.
Refining current prognostic capability is essential for improving the management of melanoma. This study was undertaken to develop a tumor array for the rapid assessment of novel prognostic markers in a series of specimens from melanoma patients with 7- to 10-year follow-up. A melanoma database of 120 patients with archival specimens was created after histopathological review of original specimens. A tissue array was developed allowing 480 biopsy samples from the 120 primary melanoma specimens to be embedded into a single paraffin block. This was sectioned and stained for the adhesion marker melanoma cell adhesion molecule (MCAM); after further review, 76 of the 120 specimens were suitable for further analysis. The slides were assessed by two independent observers without previous knowledge of the clinical outcome for staining positivity and stain intensity. Assessment of association between MCAM and clinicopathological features was carried out using chi-squared analysis, and univariate and Cox multivariate analyses were performed on the data. There was a high correlation between MCAM intensity and both Clark's level and Breslow thickness (Spearman correlation p < 0.001 for both). The data revealed that MACM was a highly specific prognostic marker for survival in univariate analysis (chi2 = 18, p < 0.0001). Subgroup analysis by stratification of the staining intensity revealed a sequentially worsening survival with increasing staining intensity (chi2 = 22.33, p < 0.0001). Multivariate analysis of survival showed MCAM to be an independent prognostic marker more accurate than all other clinicopathological parameters (p < 0.0001), including the Breslow depth. Further analysis within only intermediate-thickness tumors showed MCAM intensity added further refinement to outcome prediction (chi2 = 22.33, p < 0.0001). The tissue array provided a rapid method of analyzing up to 480 specimens within a single paraffin block. This will benefit many areas of plastic surgery research. The identification of adhesion markers revealed a valuable prognostic marker for predicting outcome and a potential target for therapeutic manipulation.
Pacifico
Marc D
MD
RAFT Institute of Plastic Surgery and the Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom.
Grover
Rajiv
R
Richman
Paul I
PI
Daley
Frances M
FM
Buffa
Francesca
F
Wilson
George D
GD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D013194:Staining and Labeling / Q000379:methods; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods*
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules