Overexpression of Chromatin Assembly Factor-1/p60 helps to predict the prognosis of melanoma patients

Abstract

BackgroundCutaneous melanoma (CM) is the most lethal form of skin malignancy, which registers a constant increase in incidence worldwide. The identification of molecular alteration(s) involved in its biological aggressiveness represents a major challenge for researchers, considering that existing therapies are ineffective to treat metastasizing cases. The epigenetic control of chromatin dynamics during DNA synthesis, replication, and repair is fundamental for the orderly progression of cell proliferation. The Chromatin Assembly Factor 1 (CAF-1) complex acts as a major regulator of this process; its intermediate (p60) subunit has been recently proposed as a novel proliferation and prognostic marker for several tumors. We aimed to establish if the evaluation of the expression of CAF-1/p60 in primary CM may help define the prevision of outcome of patients.MethodsImmunohistochemistry with anti-CAF-1/p60 was performed on paraffin-embedded tissue sections of 130 cases of primary CM retrieved from the archive files of the Department of Biomorphological and Functional Sciences, Section of Pathology, University "Federico II" of Naples, Italy. Results were compared with histopathological and follow-up data of patients.ResultsCAF-1/p60 was expressed in all CM. A significant statistical association between the overexpression of the protein and the occurrence of skin, node and/or distant metastases (P < 0.05) emerged, independently from histopathological prognostic factors.ConclusionsCAF-1/p60 looks promising as a new prognostic marker for CM and sheds new light on the molecular events associated with photocancerogenesis and melanoma biology.The screening for CAF-1/p60 might contribute to the molecular sub-classification of CM, with improved translational outcomes.

The role of the chromatin assembly complex (CAF-1) and its p60 subunit (CHAF1b) in homeostasis and disease

“…This has been confirmed in studies performed with both brain and skin tissues [82, 83]. However, during malignant tumor development, CHAF1b levels become significantly elevated and may serve as a prognostic marker and predictor of metastasis.…”

“…Patients with elevated CHAF1b levels can be expected to survive an average of 14 months, compared to patients expressing low levels of CHAF1b who can survive an average of 23.5 months with the disease [82]. While CHAF1b is expressed at a very low levels in healthy skin melanocytes, elevated CHAF1b in melanomas correlates to malignant phase: mid expression levels of CHAF1b are found in radial growth phase melanoma, and highest CHAF1b levels are found in vertical growth phase melanomas [83]. Similar patterns are found in salivary gland and prostatic cancer tumors.…”

Prognostic Significance of EDN/RB, HJURP, p60/CAF-1 and PDLI4, Four New Markers in High-Grade Gliomas

“…Mascalo et al showed that there was a gradient of p60/CAF-1 overproduction between benign naevi and malignant melanomas and that the levels of this protein increased significantly between radial (intraepithelial) growth and vertical (invasive) growth in malignant melanomas. These results suggest that p60/CAF-1 levels are likely to give accurate predictions of prognosis in neoplastic processes [16]. CAF-1/p60 expression levels have also been proposed as a new tool for defining the behaviour of carcinomas of the tongue [17], prostate [18] or breast [19].…”

Overexpression of chromatin assembly factor-1/p60 predicts biological behaviour of laryngeal carcinomas

“…The expression of CAF-1/p60 was then rated semi-quantitatively according to an arbitrary scale, as follows: 0 ( < 10% of positive cells); + (10% - < 20%); ++ (20% - < 30%); +++ (> 30% of positive cells) 24 .…”