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Tissue microarray-based evaluation of Chromatin Assembly Factor-1 (CAF-1)/p60 as tumour prognostic marker.

Mascolo M, Ilardi G, Merolla F, Russo D, Vecchione ML, de Rosa G, Staibano S - Int J Mol Sci (2012)

Bottom Line: We also analysed, for the first time, 30 larynx and 30 skin squamous cell carcinomas.Notably, a high degree of agreement was found between the CAF-1 p60 assessment on TMAs and on routine tissue sections.Our findings confirm the prognostic role of CAF-1 p60 and indicate TMA as a really advantageous method for CAF-1 p60 immunohistochemical screening, allowing savings on both tissue quantity and operator-time.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomorphological and Functional Sciences, Pathology Section, University of Naples "Federico II", Naples 80138, Italy; E-Mails: mmascol@gmail.com (M.M.); gennaro.ilardi@unina.it (G.I.); francesco.merolla@unina.it (F.M.); danielarusso83@yahoo.it (D.R.); marysilvio@alice.it (M.L.V.); gaderosa@unina.it (G.R.).

ABSTRACT
In this study we aimed to confirm the emerging role of Chromatin Assembly Factor 1 (CAF-1 p60) as a new proliferation and prognostic marker for cancer and to test the usefulness of the tissue microarray technique (TMA) for CAF-1 p60 rapid screening in several human malignancies. CAF-1 is a histone chaperone, regulating chromatin dynamics during DNA replication and repair in eukaryotics. TMA is a powerful high-throughput methodology in the study of cancer, allowing simultaneous assessment of different biomarkers within large numbers of tissue specimens. We generated TMA taking 3 mm diameter-core biopsies from oral squamous cell carcinoma, prostate cancer, salivary gland tumours and skin melanoma specimens, which had been previously tested for CAF-1 p60 on routine tissue sections. We also analysed, for the first time, 30 larynx and 30 skin squamous cell carcinomas. CAF-1 p60 resulted over-expressed in both the tissue sections and the TMA specimens, with the highest levels of expression in tumours which were more aggressive and metastasizing. Notably, a high degree of agreement was found between the CAF-1 p60 assessment on TMAs and on routine tissue sections. Our findings confirm the prognostic role of CAF-1 p60 and indicate TMA as a really advantageous method for CAF-1 p60 immunohistochemical screening, allowing savings on both tissue quantity and operator-time.

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Related in: MedlinePlus

Comparison of the percentage of labelled cells on TMA sections and whole-tissue sections (WS) for the CAF-1 p60 antibody. Scatter plots show a tight grouping of points when the percentage of labelled cells on TMA sections is plotted against the WS for the CAF-1 p60 antibody. The added lines are the lines of best fit, R2 values of linear regressions are shown. (a) Oral squamous cell carcinoma (OSCC); (b) prostate cancer (PC); (c) salivary gland tumour (SGT); (d) skin melanoma (SM); (e) laryngeal squamous cell carcinoma (LSCC); (f) skin squamous cell carcinoma (SSCC).
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f3-ijms-13-11044: Comparison of the percentage of labelled cells on TMA sections and whole-tissue sections (WS) for the CAF-1 p60 antibody. Scatter plots show a tight grouping of points when the percentage of labelled cells on TMA sections is plotted against the WS for the CAF-1 p60 antibody. The added lines are the lines of best fit, R2 values of linear regressions are shown. (a) Oral squamous cell carcinoma (OSCC); (b) prostate cancer (PC); (c) salivary gland tumour (SGT); (d) skin melanoma (SM); (e) laryngeal squamous cell carcinoma (LSCC); (f) skin squamous cell carcinoma (SSCC).

Mentions: All the evaluated malignant tumours showed CAF-1 p60 overexpression (Figure 1, Tables 1–7). Representative images of CAF-1 p60 expression in normal tissues are shown in Figure 2. In detail, a moderate expression (++) of CAF-1 p60 was found in 13 Oral Squamous Cells Carcinoma (OSCC) (3 G1, 8 G2, 2 G3), 22 Prostate Cancer (PC) (1 with Gleason score <7, 15 with a Gleason score equal to 7, of which 5 with a primary pattern of 4 and 10 with a primary pattern of 3, and 6 with Gleason score >7), 14 Skin Melanoma (SM) (4 with Breslow vertical phase thickness <1.00 mm, 3 comprised between 1.01 and 2.00, 4 comprised between 2.01 and 4.00 and 3 > 4.00 mm), 22 Salivary Gland Tumour (SGT), of which 1 polymorphous low-grade carcinoma (PLGC), 3 acinic cell carcinomas (AC), 3 adenoid cystic carcinomas (ACC), 11 muco-epidermoid carcinomas (4 low grade, 3 intermediate-grade and 4 high-grade tumours), and 4 cases of carcinoma ex-PA (CXPA) 26 Laryngeal Squamous Cell Carcinoma (LSCC) (6 G1, 6 G2, 14 G3) and 28 Skin Squamous Cell Carcinoma (SSCC) (8 G1, 10 G2, 10 G3); as a high level of expression (+++) was observed in the remaining 17 OSCC (7 G1, 7 G2 and 3 G3), 8 PC (2 with Gleason score <7, 3 with a Gleason score equal to 7, with a primary pattern of 4, and 3 with Gleason score >7), 16 SM (2 with Breslow vertical phase thickness <1.00 mm, 5 comprised between 1.01 and 2.00, 6 comprised between 2.01 and 4.00 and 3 > 4.00 mm), 7 cases of malignant SGT, of which 1 adenoid cystic carcinomas (ACC), 5 muco-epidermoid carcinomas (1 low grade, 3 intermediate-grade and 1 high-grade tumours) and 1 case of CXPA, 4 LSCC (1 G1, 1 G2, 2 G3) and 2 SSCC (1 G2 and 1 G3). The values found on the whole sections of OSCC, PC, SGTs and SM were in agreement with those already reported in the literature [23–26]. The evaluation of the immunohistochemical expression of CAF-1 p60 on TMA sections of the same tumour series gave rise to quite similar results, with an excellent level of agreement for both the intra- and inter-observer evaluation of the expression of CAF-1 p60 on the whole sections and TMAs (K-coefficient: 0.8018 for OSCC; 0.8148 for PC; 0.8018 for SM; 0.8529 for SGT; 0.8696 for LSCC, 0.8076 for SSCC) (Table 8, Figure 3). According to univariate statistical analysis, both on routine whole sections and on TMA, no statistical correlation was found between CAF-1 p60 expression, age and sex of patients (data not shown).


Tissue microarray-based evaluation of Chromatin Assembly Factor-1 (CAF-1)/p60 as tumour prognostic marker.

Mascolo M, Ilardi G, Merolla F, Russo D, Vecchione ML, de Rosa G, Staibano S - Int J Mol Sci (2012)

Comparison of the percentage of labelled cells on TMA sections and whole-tissue sections (WS) for the CAF-1 p60 antibody. Scatter plots show a tight grouping of points when the percentage of labelled cells on TMA sections is plotted against the WS for the CAF-1 p60 antibody. The added lines are the lines of best fit, R2 values of linear regressions are shown. (a) Oral squamous cell carcinoma (OSCC); (b) prostate cancer (PC); (c) salivary gland tumour (SGT); (d) skin melanoma (SM); (e) laryngeal squamous cell carcinoma (LSCC); (f) skin squamous cell carcinoma (SSCC).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472729&req=5

f3-ijms-13-11044: Comparison of the percentage of labelled cells on TMA sections and whole-tissue sections (WS) for the CAF-1 p60 antibody. Scatter plots show a tight grouping of points when the percentage of labelled cells on TMA sections is plotted against the WS for the CAF-1 p60 antibody. The added lines are the lines of best fit, R2 values of linear regressions are shown. (a) Oral squamous cell carcinoma (OSCC); (b) prostate cancer (PC); (c) salivary gland tumour (SGT); (d) skin melanoma (SM); (e) laryngeal squamous cell carcinoma (LSCC); (f) skin squamous cell carcinoma (SSCC).
Mentions: All the evaluated malignant tumours showed CAF-1 p60 overexpression (Figure 1, Tables 1–7). Representative images of CAF-1 p60 expression in normal tissues are shown in Figure 2. In detail, a moderate expression (++) of CAF-1 p60 was found in 13 Oral Squamous Cells Carcinoma (OSCC) (3 G1, 8 G2, 2 G3), 22 Prostate Cancer (PC) (1 with Gleason score <7, 15 with a Gleason score equal to 7, of which 5 with a primary pattern of 4 and 10 with a primary pattern of 3, and 6 with Gleason score >7), 14 Skin Melanoma (SM) (4 with Breslow vertical phase thickness <1.00 mm, 3 comprised between 1.01 and 2.00, 4 comprised between 2.01 and 4.00 and 3 > 4.00 mm), 22 Salivary Gland Tumour (SGT), of which 1 polymorphous low-grade carcinoma (PLGC), 3 acinic cell carcinomas (AC), 3 adenoid cystic carcinomas (ACC), 11 muco-epidermoid carcinomas (4 low grade, 3 intermediate-grade and 4 high-grade tumours), and 4 cases of carcinoma ex-PA (CXPA) 26 Laryngeal Squamous Cell Carcinoma (LSCC) (6 G1, 6 G2, 14 G3) and 28 Skin Squamous Cell Carcinoma (SSCC) (8 G1, 10 G2, 10 G3); as a high level of expression (+++) was observed in the remaining 17 OSCC (7 G1, 7 G2 and 3 G3), 8 PC (2 with Gleason score <7, 3 with a Gleason score equal to 7, with a primary pattern of 4, and 3 with Gleason score >7), 16 SM (2 with Breslow vertical phase thickness <1.00 mm, 5 comprised between 1.01 and 2.00, 6 comprised between 2.01 and 4.00 and 3 > 4.00 mm), 7 cases of malignant SGT, of which 1 adenoid cystic carcinomas (ACC), 5 muco-epidermoid carcinomas (1 low grade, 3 intermediate-grade and 1 high-grade tumours) and 1 case of CXPA, 4 LSCC (1 G1, 1 G2, 2 G3) and 2 SSCC (1 G2 and 1 G3). The values found on the whole sections of OSCC, PC, SGTs and SM were in agreement with those already reported in the literature [23–26]. The evaluation of the immunohistochemical expression of CAF-1 p60 on TMA sections of the same tumour series gave rise to quite similar results, with an excellent level of agreement for both the intra- and inter-observer evaluation of the expression of CAF-1 p60 on the whole sections and TMAs (K-coefficient: 0.8018 for OSCC; 0.8148 for PC; 0.8018 for SM; 0.8529 for SGT; 0.8696 for LSCC, 0.8076 for SSCC) (Table 8, Figure 3). According to univariate statistical analysis, both on routine whole sections and on TMA, no statistical correlation was found between CAF-1 p60 expression, age and sex of patients (data not shown).

Bottom Line: We also analysed, for the first time, 30 larynx and 30 skin squamous cell carcinomas.Notably, a high degree of agreement was found between the CAF-1 p60 assessment on TMAs and on routine tissue sections.Our findings confirm the prognostic role of CAF-1 p60 and indicate TMA as a really advantageous method for CAF-1 p60 immunohistochemical screening, allowing savings on both tissue quantity and operator-time.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomorphological and Functional Sciences, Pathology Section, University of Naples "Federico II", Naples 80138, Italy; E-Mails: mmascol@gmail.com (M.M.); gennaro.ilardi@unina.it (G.I.); francesco.merolla@unina.it (F.M.); danielarusso83@yahoo.it (D.R.); marysilvio@alice.it (M.L.V.); gaderosa@unina.it (G.R.).

ABSTRACT
In this study we aimed to confirm the emerging role of Chromatin Assembly Factor 1 (CAF-1 p60) as a new proliferation and prognostic marker for cancer and to test the usefulness of the tissue microarray technique (TMA) for CAF-1 p60 rapid screening in several human malignancies. CAF-1 is a histone chaperone, regulating chromatin dynamics during DNA replication and repair in eukaryotics. TMA is a powerful high-throughput methodology in the study of cancer, allowing simultaneous assessment of different biomarkers within large numbers of tissue specimens. We generated TMA taking 3 mm diameter-core biopsies from oral squamous cell carcinoma, prostate cancer, salivary gland tumours and skin melanoma specimens, which had been previously tested for CAF-1 p60 on routine tissue sections. We also analysed, for the first time, 30 larynx and 30 skin squamous cell carcinomas. CAF-1 p60 resulted over-expressed in both the tissue sections and the TMA specimens, with the highest levels of expression in tumours which were more aggressive and metastasizing. Notably, a high degree of agreement was found between the CAF-1 p60 assessment on TMAs and on routine tissue sections. Our findings confirm the prognostic role of CAF-1 p60 and indicate TMA as a really advantageous method for CAF-1 p60 immunohistochemical screening, allowing savings on both tissue quantity and operator-time.

Show MeSH
Related in: MedlinePlus