Lippincott Williams & Wilkins - NF-κB Expression … · Web viewSupplementary Information NF-κB...

Supplementary Information

NF-κB Expression and Outcomes in Solid Tumors: A Systematic Review and Meta-Analysis

Dang Wu, Pin Wu, Lufeng Zhao, Lijian Huang, Zhigang Zhang, Shuai Zhao and Jian Huang *

Supplementary data：

Figure S1. Subgroup analysis of three-year overall survival (OS) by Nuclear factor-kappaB (NF-κB)

expression in different tumor types.

Figure S2. Subgroup analysis of Nuclear factor-kappaB (NF-κB) expression in different TNM stages

of tumor.

Figure S3. Subgroup analysis of three-year overall survival (OS) by cellular localization of Nuclear

factor-kappaB (NF-κB) expression. 1 = Nuclear expression; 2 = Cytoplasmic expression.

Figure S4. Subgroup analysis of five-year overall survival (OS) by Nuclear factor-kappaB (NF-κB)

expression in different tumor types.

Figure S5. Subgroup analysis of five-year overall survival (OS) by cellular localization of Nuclear

factor-kappaB (NF-κB) expression. 1 = Nuclear expression; 2 = Cytoplasmic expression.

Table S1. Evaluation of human NF-kB by immunohistochemistry (IHC) in the selected studies

References Country Type of cancer Marker NF-kB (+)%

Antibody (Clone)

Method and Cut-off for overexpression

Abdel-Latif, M. M., et al. (2004)

USAEsophageal carcinoma

NF-kB p65-N/Ca 60.82% NRd NR

Annunziata, C. M., et al. (2010)

Norway Ovarian cancerNF-kB p50-N/C

58.06% sc-1190Positive: IHC >25% tumor cells were positive for NF-kB staining.

Balermpas, P., et al. (2013)

GermanyHead and Neck Squamous Cell Carcinoma

NF-kB p65-Nb 33.66% ab31481

Positive: IHC ≥5% tumor cells were positive for NF-kB staining.

Berardi, R., et al. (2012)

Italy Rectal cancerNF-kB p65-N

47.95% NRPositive: IHC ≥1% tumor cells were positive for NF-kB staining.

Chu, D., et al. (2011)

China Colorectal cancer NF-kB p65-N/C

48.85% ab7970 IHC, score ≥5. The extensional standards taken were as follows: (i) number ofpositive stained cell 5%, scored 0; 6%–25%, scored 1; 26%–50%, scored 2; 51%–75%, scored 3; and >75%, scored 4 and (ii) intensity of stain: colorless, scored 0; pallideflavens, scored 1; yellow, scored 2; and brown scored 3. The extensional standards (i) and (ii) weremultiplied and the staining grade wasstratified as absent (0 score), weak (1–4

score), moderate (5–8 score), and strong(9–12 score).Tumors with moderate or strong immunostaining were classified ashaving positive expression.

Darb-Esfahani, S., et al. (2010)

Germany Ovarian cancerNF-kB p65-Cc 55.29% sc8008

IHC, IRS >4. Total cytoplasmic p65 expression was grouped as followed:“negative”, IRS ≤4; “positive”, IRS >4.

Guo, R. X., et al. (2008)

China Ovarian cancerNF-kB p65-N/C

75.00% NRPositive: IHC >50% tumor cells were positive for NF-kB staining.

Hatata, T., et al. (2012)

JapanEsophageal carcinoma

NF-kB p65-N/C

59.42% sc109Positive: IHC ≥10% tumor cells were positive for NF-kB staining.

Huang, C., et al. (2009)

ChinaLaryngeal squamous cell carcinoma

NF-kB p65-N/C


Izzo, J. G., et al. (2007)


NF-kB p65-N

64.23% G96-337Positive: IHC ≥5% tumor cells were positive for NF-kB staining.

Izzo, J. G.,Correa, A. M., et al. (2006)


NF-kB p65-N


Izzo, J. G.,Malhotra, U., et al. (2006)


NF-kB p65-N


Jiang, L. Z., et al. (2011)

ChinaLaryngeal squamous cell carcinoma

NF-kB p65-N/C


Jin, X., et al. (2008)

ChinaNon-small cell lung cancer

NF-kB p65-N/C

46.59% sc109Positive: IHC >5% tumor cells were positive for NF-kB staining.

Kleinberg, L., et al. (2009)

Norway Ovarian cancerNF-kB p65-N/C


Korkolopoulou, P., et al. (2008)

Greece AstrocytomasNF-kB p50-N/C


Kwon, H. C., et al. (2010)

Korea Colorectal cancerNF-kB p65-C


Kwon, H. C., et al. (2012)

Korea Gastric cancerNF-kB p65-C


Lee, B. L., et al. (2005)

Korea Gastric cancerNF-kB p65-N


Levidou, G., et al. (2007)

Greece Gastric cancerNF-kB p50-C


Lewander, A., et al. (2012)-1b Sweden Colorectal cancer

p-NF-kB p65-N


Lewander, A., et al. (2012)-2c Sweden Colorectal cancer

p-NF-kB p65-C

64.04% NR Positive: IHC ≥5% tumor cells were positive for NF-kB staining.

Li, J., et al. (2009)-M1

China Cervical cancerNF-kB p65-N


Li, J., et al. (2009)-M2

China Cervical cancerNF-kB p50-N


Lin, G., et al. (2012)

China Colorectal cancerNF-kB p65-N/C

30.56% NR NR.

Nair, V. S., et al. (2014)

USANon-small-cell lung cancer

NF-kB p65-C

57.19% D14E12Positive: IHC >20% tumor cells were positive for NF-kB staining.

Nariai, Y., et Japan Oral squamous cell NF-kB 52.00% sc8008 Positive: IHC >81% tumor cells were

al. (2011) carcinoma p65-N/C positive for NF-kB staining.O'Neil, B. H., et al. (2011)

USA Rectal cancerNF-kB p50-N

92.06% sc114 IHC, >180 units.

Okera, M., et al. (2011)

USA Prostate cancerNF-kB p65-N/C

52.73%Cat#RB-1638

IHC, score ≥3. A numeric intensity score of 0–3 was assigned to each case (0, no staining; 1+, weak staining; 2+, moderate staining and 3+, strong staining). Staining was also dichotomized into negative and positive. Negative was scored if 0+/1+ and positive was scored if 2+/3+.

Pancione, M., et al. (2009)

Italy Colorectal cancerNF-kB p65-N/C

58.33% sc109

IHC, score ≥3. The intensity was scored as follows: 1 (weak), 2 (moderate), or 3(strong). The percentage of positive cells was scored as follows: 0 (0%), 1 (1%-25%), 2 (26%-50%), 3 (51%-75%), or 4 (76%-100%). The 2 scores were combined to obtain the final one: negative (0-2), weakly positive (3-5), or stronglypositive (6-7).

Park, K. W., et al. (2014)

Korea Gastric cancerNF-kB p65-C


Scartozzi, M., et al. (2007)

Italy Colorectal cancerNF-kB p65-N/C

60.53% NR NR.

Sun, W., et al. (2012)

ChinaNasopharyngeal carcinoma

NF-kB p65-N/C

55.45% sc109 NR.

Voboril, R., et Czech Rectal cancer NF-kB 20.00% NR IHC, Presence of NF-kB staining.

al. (2008) Republic p65-C

Weichert, W., et al. (2007)-1

Germany Pancreatic cancerNF-kB p65-N

45.12% sc8008

IHC, IRS ≥7. Intensity of staining was designated as either not existent (0), weak (1), moderate (2) or strong (3). The number of cells stained was scoredas either no cells stained (0), less than 10% of cells stained (1), 10– 50% of cells stained (2), 50– 80% of cells stained (3) or more than 80% of cells stained (4). The IRS was calculated by multiplication of these two variables.For statistical analysis, cases were grouped as either negative (IRS 0 –6) or positive (IRS 7 –12).

Weichert, W., et al. (2007)-2

Germany Pancreatic cancer NF-kB p65-C

51.22% sc8008 IHC, IRS ≥7. Intensity of staining was designated as either not existent (0), weak (1), moderate (2) or strong (3). The number of cells stained was scoredas either no cells stained (0), less than 10% of cells stained (1), 10– 50% of cells stained (2), 50– 80% of cells stained (3) or more than 80% of cells stained (4). The IRS was calculated by multiplication of these two variables.For statistical analysis, cases were grouped as either negative (IRS 0 –6)

or positive (IRS 7 –12).Wu, W., et al. (2008)

ChinaGallbladder carcinoma

NF-kB p65-N/C


Wu, Z., et al. (2013)

China Cervical cancerNF-kB p65-N/C


Yamanaka, N., et al. (2004)

Japan Gastric cancerNF-kB p65-N

33.33% sc109Positive: IHC >25% tumor cells were positive for NF-kB staining.

Yang, G., et al. (2011)

USA Ovarian cancerNF-kB p65-N

80.56% NR NR.

Yeh, H. C., et al. (2010)

China Urothelial carcinomaNF-kB p65-N

26.67% sc109

IHC, score ≥5. The intensity of cytoplasmic staining was graded by a score of 1 point (weak), 2 points (moderate), and 3 points intense). The percentage of stained cells was rated as 1 point (≤10%), 2 points (11–50%), and 3 points(>50%). Cases with a sum of ntensity points and percentage points of ≥5 were defined as having an overexpression of NF-κB.

Yoon, S. O., et al. (2009)

KoreaMucinous adenocarcinoma

NF-kB-N 40.00% NRPositive: IHC >10% tumor cells were positive for NF-kB staining.

Voboril, R., et al. (2008)

Czech Republic

Rectal cancerNF-kB p65-C

21.74% NR NR

Zhang, D., et al. (2007)


NF-kB p65-N/C


Zhang, J., et al. (2005)

ChinaAdenoid Cystic Carcinoma of Salivary Glands

NF-kB p65-N

35.00% NR

IHC, score ≥4. The intensity of staining was on the following scale: 0, no staining; 1+, mild staining; 2+, moderate staining; 3+, intense staining. The areaof staining was evaluated as follows: 0, no staining of cells in any microscopic fields; 1+, <25% of tissue stained positive; 2+, between 25% and 50% stained positive; 3+, between 50% and 75% stained positive; 4+, >75% stained positive.The minimum score when summed (extension + intensity) was therefore 0 andthe maximum, 7. The combined staining score (extension + intensity) V3 wasconsidered as negative staining (low staining); a score between 4 and 5 wasconsidered as moderate staining; between 6 and 7 was strong staining.

Zhang, Y., et al. (2011)

China Nasopharyngeal carcinoma

NF-kB p65-N

64.29% NR IHC, score ≥4. The score is the sum of the percentage of positive cells (1, lessthan 25% positive cells; 2, 26 to 50% positive cells; and 3, more than 50% positive cells) and the staining intensity (0, negative; 1, weak; 2, moderate; 3,

strong). Sums between 0 and 3 were scored as negative; sums from 4 to 6 werescored as positive.

Zhang, Z., et al. (2006)


NF-kB p50-N/C


Zhou, Q., et al. (2013)

ChinaIntrahepatic Cholangiocarcinoma

NF-kB-N/C

51.52% NR

IHC, score ≥3. First, the intensities of staining were indicated as follows: 0, nostaining; 1, light yellow; 2, brownish yellow; 3, reddish brown. Second, relativenumbers of positive cells were marked as follows: 0, no positive cells; 1, positive cells ≤ 10%; 2, positive cells 11–50%; 3, positive cells 51–75%; 4, positive cells >75%. Finally, all sections were divided into four grades by the product ofintensity scores and percentage scores described above: –, 0–2 points; +, 3–4points; 2+, 6–8 points; 3+, 9–12 points; ≥ 3 points defined as positive.

a. N/C: Nuclear or cytoplasmic expression; b. N,1: Nuclear expression; c. C,2: Cytoplasmic expression; d. NR: No report.

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