Clinical significance and prognostic value of Chromatin Assembly Factor-1 overexpression in human solid tumors

Sophie E Polo (1) , Stamatios E Theocharis (2) , Laure Grandin (3) , Laetitia Gambotti (3) , Guillemette Antoni (3) , Alexia Savignoni (3) , Bernard Asselain (3) , Efstratios Patsouris (4) , Geneviève Almouzni (5)

1 Wellcome Trust/Cancer Research UK Gurdon Institute
2 Department of ForensicMedicine and Toxicology
3 Department of Biostatistics
4 First Department of Pathology
5 DNPG - Dynamique nucléaire et plasticité du génome

Aims: The chromatin assembly factor CAF-1, whose function is critical for maintaining chromatin stability during DNA replication and repair, has been identified as a proliferation marker in breast cancer. Here, we investigate the interest of CAF-1 as a proliferation marker in a wide spectrum of solid tumors, and assess its potential value in predicting clinical outcome. Methods and Results: Using immunocytochemistry on paraffin-embedded tissue sections, we compare CAF-1 labeling index with known proliferation markers Ki-67 and MCMs, and we analyze its association with clinicopathological data and patients' outcome. CAF-1 expression shows a strong positive correlation with Ki-67, routinely used to detect proliferating cells, while it generally displays weaker correlations with MCM markers, known to label cells with replicative potential. CAF-1 expression is significantly associated with histological grade in breast, cervical, endometrial and renal cell carcinomas, and with disease stage in endometrial and renal carcinomas. Furthermore, high expression of CAF-1 is an independent predictor of adverse clinical outcome in renal, endometrial and cervical carcinomas. Conclusions: These data demonstrate that CAF-1 is a proliferation marker in various malignant tumors with prognostic value in renal, endometrial and cervical carcinomas, which supports the relevance of CAF-1 as a clinical marker to monitor cancer progression.

Mots clés: Medicine

Sophie E Polo, Stamatios E Theocharis, Laure Grandin, Laetitia Gambotti, Guillemette Antoni, et al.. Clinical significance and prognostic value of Chromatin Assembly Factor-1 overexpression in human solid tumors. Histopathology, 2010, 57 (5), pp.716. ⟨10.1111/j.1365-2559.2010.03681.x⟩. ⟨hal-00593448⟩