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Updated: Jul 7, 2026

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Immunohistochemical detection of XIAP in melanoma
Patrick O M Emanuel1, Robert G Phelps, Adarsh Mudgil
1Division of Dermatopathology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Background:
The X-linked inhibitor of apoptosis protein (XIAP) is the most potent of the inhibitor of apoptosis family of eight proteins. High levels of XIAP have been found in melanoma cell lines and are believed to play a role in therapeutic resistance in a number of malignancies. XIAP expression has not been investigated in clinically obtained melanoma tissue samples, nor have studies attempted to correlate XIAP expression with prognostic variables or clinical aggressiveness of melanomas.
Methods:
Sixty-seven patients with primary cutaneous malignant melanoma for whom clinical follow up was available were identified from the records of the Mount Sinai Hospital, comprising 37 thin melanomas (Breslow thickness < 1.0 mm) and 30 thick melanomas (Breslow thickness > 1.0 mm). Archival paraffin sections from primary lesions and corresponding metastases were stained with monoclonal anti-XIAP antibody using routine immunohistochemical methods.
Results:
Six benign intradermal nevi and four in situ melanomas were XIAP negative. 9 of 37 thin melanomas (24%) were XIAP positive. In contrast, 21 of 30 (73%) thick melanomas were XIAP positive, including 3 of 4 ulcerated melanomas that were strongly positive. Over a follow-up period ranging from 6 months to 6 years, 23 melanomas metastasized (22 thick, 1 thin). In total, XIAP was immunohistochemically detected in 17 of 23 metastases (74%). Metastasis occurred in 1 of 9 XIAP-positive thin melanomas; 0 of 28 XIAP-negative thin melanomas; 17 of 22 XIAP-positive thick melanomas, and 5 of 8 XIAP-negative thick melanomas (63%).
Conclusions:
XIAP is immunohistochemically detectable nearly three times more frequently in thick compared with thin melanomas. These results suggest that XIAP elevation may be correlated with increasing melanoma thickness and tumor progression.
Insights
X-linked inhibitor of apoptosis protein (XIAP) is found more often in thicker melanomas. This suggests XIAP may be linked to melanoma progression and thickness.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- X-linked inhibitor of apoptosis protein (XIAP) is a key regulator of cell death.
- Elevated XIAP levels are implicated in therapeutic resistance in various cancers.
- XIAP's role in melanoma progression and its correlation with clinical factors remain underexplored.
Purpose of the Study:
- To investigate XIAP expression in clinically obtained melanoma tissue samples.
- To correlate XIAP expression with melanoma thickness and aggressiveness.
- To determine if XIAP levels can serve as a prognostic marker for melanoma.
Main Methods:
- Immunohistochemical analysis of XIAP expression in 67 primary cutaneous melanoma samples (37 thin, 30 thick).
- Correlation of XIAP expression with Breslow thickness, ulceration, and metastasis.
- Clinical follow-up data collected over 6 months to 6 years.
Main Results:
- XIAP was not detected in benign nevi or in situ melanomas.
- XIAP positivity was significantly higher in thick melanomas (73%) compared to thin melanomas (24%).
- XIAP was detected in 74% of metastases, with a higher rate in thick melanomas.
Conclusions:
- XIAP expression is significantly elevated in thicker melanomas.
- XIAP elevation correlates with increased melanoma thickness and tumor progression.
- XIAP may represent a potential biomarker for melanoma aggressiveness.

