Immunocytochemical detection of XIAP in body cavity effusions and washes
Maoxin Wu1, Songyang Yuan, Arnold H Szporn
1Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA. Maoxin.Wu@msnyuhealth.org
Insights
X-linked inhibitor of apoptosis (XIAP) is elevated in most malignant effusions, distinguishing them from benign ones. High XIAP expression may indicate therapy resistance and guide treatment with XIAP-blocking drugs.
Area of Science:
- Oncology
- Cell Biology
- Cancer Diagnostics
Background:
- Body cavity effusions can be early indicators of malignancy or relapse.
- Inhibitors of apoptosis proteins (IAPs), including X-linked inhibitor of apoptosis (XIAP), regulate programmed cell death.
- Elevated XIAP expression may contribute to cancer cell survival and resistance to apoptosis-inducing therapies.
Purpose of the Study:
- To survey the expression of XIAP in benign and malignant body cavity effusions and washes.
- To determine if XIAP expression can differentiate malignant from benign effusions.
- To explore the potential of XIAP as a biomarker for therapy resistance.
Main Methods:
- Immunocytochemical analysis of XIAP expression in 116 cell block specimens from effusions and washes.
- Use of monoclonal anti-XIAP antibody and EnVision-Plus reagents for detection.
- Evaluation of staining patterns (particulate cytoplasmic staining considered positive) across various cancer types and benign effusions.
Main Results:
- XIAP positivity was observed in 67% of malignant effusions (54/81), with prevalence varying by cancer origin (e.g., 100% ovarian, 82% lung, 46% breast).
- Benign effusions were largely XIAP-negative (6%), with rare staining in histiocytes.
- Strong XIAP immunostaining effectively distinguished malignant from benign and reactive cell populations.
Conclusions:
- XIAP is frequently expressed in malignant effusions, serving as a potential diagnostic marker.
- Higher XIAP expression, particularly in ovarian and lung cancers, may correlate with increased resistance to apoptosis.
- XIAP staining intensity could help identify patients likely to benefit from XIAP-blocking therapies.
Abstract:
Body cavity effusions may be the first manifestation of malignancy or of recurrence or relapse. We surveyed effusions and washes for expression of X-linked inhibitor of apoptosis (XIAP), a potent constituent of the inhibitor of apoptosis (IAP) family of proteins. IAPs prevent apoptosis by blocking the activation of caspases, thereby preventing caspase-mediated cell degradation. Elevated expression of XIAP could be an underpinning of relapse and/or resistance to apoptosis-inducing cancer therapy. We performed an immunocytochemical survey of XIAP expression in cell blocks from benign and malignant body cavity effusions and washes. In all, 116 alcohol-fixed, formalin postfixed paraffin-embedded cell block specimens from 82 pleural effusions, 22 ascites, 11 pelvic/peritoneal washes and one pericardial effusion were evaluated immunocytochemically with monoclonal anti-XIAP (#610763, BD Biosciences, San Jose, USA) 1:250, 4 degrees C x 72 h, and developed using EnVision-Plus reagents (Dako) and diaminobenzidine as chromagen. Particulate cytoplasmic staining was considered positive. The prevalence of staining for specific malignancies varied with the tissue of origin as follows: ovarian (13/13, 100%); lung (9/11, 82%), breast (6/13, 46%); gastric (4/7, 57%), colon (0/4, 0%), pancreas (2/3, 67%), gallbladder (1/1, 100%), fallopian tube (1/3, 33%), endometrial (6/7, 86%), mesothelioma (4/5, 80%), carcinoma of unknown primary (5/5, 100%) and hematopoietic malignancies (3/9, 33%). Overall, 54 out of 81 (67%) malignant effusions displayed XIAP positivity. Benign effusions (n = 35) were virtually XIAP-negative except for two cases (6%) in which histiocytes showed moderate staining. Weak nonspecific staining was sometimes noted in inflammatory cells or histiocytes. XIAP immunostaining, when strong, allows for ready distinction of malignant from benign and reactive cell populations. Strong XIAP staining was most prevalent in ovarian carcinomas and less prevalent in mammary carcinomas. The degree of XIAP staining of tumor cells may be a means of identifying the most therapy-resistant cases (ie, those with strong XIAP expression), and allow additional triaging to XIAP-blocking drugs presently being developed and clinically tested.
More Related Videos
08:53In Vivo Immunofluorescence Localization for Assessment of Therapeutic and Diagnostic Antibody Biodistribution in Cancer Research
Published on: September 16, 2019
10:55Detection of Anti-MDA5 Autoantibodies Using HeLa Cells and Immunocytochemistry with Light Microscopy
Published on: October 31, 2025
