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Cytokeratin19-2g2, a novel fragment of cytokeratin19 in serum, indicating a more invasive behavior and worse prognosis in breast cancer patients.

Kong Y, Wang J, Liu W, Chen Q, Yang J, Wei W, Wu M, Yang L, Xie X, Lv N, Guo J, Li L, Gao J, Xie X, Dai S - PLoS ONE (2013)

Bottom Line: However, so far, few markers have been proved clinically useful except CA153.The sensitivities of CK19-2G2 for breast carcinoma are as high as CEA and CA153, and up to 71% in MBC patients.Serum CK19-2G2 levels (≥2 mU/mL) were associated with pathological stages, tumor size (≥2 cm), lymph node involvement, and HER2 status.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, PR China.

ABSTRACT

Background: Various studies have been searching for new tumor biomarkers for breast cancer for years. However, so far, few markers have been proved clinically useful except CA153. Based on knowledge that most adenocarcinomas including breast carcinoma expressed Cytokeratin19, the authors studied CK19-2G2,a novel fragment of cytokeratin19 shedding into serum in breast cancer patients.

Patients and methods: The serum samples of four hundred and seventeen patients including three hundred and three (fifty-four DCIS and two hundred and forty-nine stage I-III) PBC patients and one hundred and fourteen MBC patients, eighty-one healthy controls and twenty-one breast benign disease patients were provided for measurement of CK19-2G2, CEA and CA153.The correlation between clinicopathological characters, prognosis and CK19-2G2 levels was further studied.

Results: The serum CK19-2G2 levels in breast cancer patients were significantly higher than that in healthy and benign controls. For breast cancer patients, CK19-2G2 levels in MBC were significantly higher than that in PBC patients. The sensitivities of CK19-2G2 for breast carcinoma are as high as CEA and CA153, and up to 71% in MBC patients. Serum CK19-2G2 levels (≥2 mU/mL) were associated with pathological stages, tumor size (≥2 cm), lymph node involvement, and HER2 status. Multivariate analysis revealed that high serum CK19-2G2 level was an independent factor for relapse (P = 0.029) and death (P = 0.040) in breast cancer patients.

Conclusion: Serum CK19-2G2 may be an independent indicator for prognosis and a candidate marker for monitoring metastasis in breast cancer.

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Related in: MedlinePlus

The sensitivity of CEA, CA153 and CK19-2G2 for PBC and MBC.(A) CK19-2G2 is superior to CEA and CA153 in stage II and III breast cancer patients and as sensitive as CA153 in MBC patients. The blank bar: CEA; the gray bar: CA153; the black bar: CK19-2G2 (B) The distribution of CK19-2G2 in MBC, PBC and DCIS. Serum CK19-2G2 levels in MBC are higher than those in the PBC and DCIS respectively(MBC vs PBC, P = 0.007; MBC vs DCIS, P = 0.002). Serum CK19-2G2 levels in PBC are higher than those in DCIS (P = 0.012). Error bars are referring to SE(Standard Error). (C) The distribution of CK19-2G2 in breast cancer patients with different stages, lymph nodes status and HER2 status. Patients with positive lymph nodes, stage III and HER2 positive status had higher serum CK19-2G2 levels than those with negative lymph nodes, stage I/II and HER2 negative status. Error bars are referring to SE(Standard Error).
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pone-0057092-g002: The sensitivity of CEA, CA153 and CK19-2G2 for PBC and MBC.(A) CK19-2G2 is superior to CEA and CA153 in stage II and III breast cancer patients and as sensitive as CA153 in MBC patients. The blank bar: CEA; the gray bar: CA153; the black bar: CK19-2G2 (B) The distribution of CK19-2G2 in MBC, PBC and DCIS. Serum CK19-2G2 levels in MBC are higher than those in the PBC and DCIS respectively(MBC vs PBC, P = 0.007; MBC vs DCIS, P = 0.002). Serum CK19-2G2 levels in PBC are higher than those in DCIS (P = 0.012). Error bars are referring to SE(Standard Error). (C) The distribution of CK19-2G2 in breast cancer patients with different stages, lymph nodes status and HER2 status. Patients with positive lymph nodes, stage III and HER2 positive status had higher serum CK19-2G2 levels than those with negative lymph nodes, stage I/II and HER2 negative status. Error bars are referring to SE(Standard Error).

Mentions: According to ER, PR, HER2, Ki67 status, breast cancer was classified into four types in clinical practice: LuminalA, LuminalB, HER2-enriched and Triple negative. We tested the serum CK19-2G2 levels in different type in PBC patients with stage I-III, and found that CK19-2G2 levels in HER2 enriched and Triple negative type were higher than that in LuminalA/B type, however, there was no statistical difference among the three groups (Figure 1B). The serum CK19-9 levels of breast cancer patients with stage III (3.51±11.29 mU/mL) were significantly higher than those with stage II/I (1.27±2.13 mU/mL) (P<0.001) (Figure 2B). When the cutoff value was defined to be 2.0 mU/mL, the percent of abnormal serum CK19-2G2 (sensitivities) for patients with Stage I, II, III and MBC were 5.4%, 11.9%, 29.5% and 71% respectively (Figure 2A).


Cytokeratin19-2g2, a novel fragment of cytokeratin19 in serum, indicating a more invasive behavior and worse prognosis in breast cancer patients.

Kong Y, Wang J, Liu W, Chen Q, Yang J, Wei W, Wu M, Yang L, Xie X, Lv N, Guo J, Li L, Gao J, Xie X, Dai S - PLoS ONE (2013)

The sensitivity of CEA, CA153 and CK19-2G2 for PBC and MBC.(A) CK19-2G2 is superior to CEA and CA153 in stage II and III breast cancer patients and as sensitive as CA153 in MBC patients. The blank bar: CEA; the gray bar: CA153; the black bar: CK19-2G2 (B) The distribution of CK19-2G2 in MBC, PBC and DCIS. Serum CK19-2G2 levels in MBC are higher than those in the PBC and DCIS respectively(MBC vs PBC, P = 0.007; MBC vs DCIS, P = 0.002). Serum CK19-2G2 levels in PBC are higher than those in DCIS (P = 0.012). Error bars are referring to SE(Standard Error). (C) The distribution of CK19-2G2 in breast cancer patients with different stages, lymph nodes status and HER2 status. Patients with positive lymph nodes, stage III and HER2 positive status had higher serum CK19-2G2 levels than those with negative lymph nodes, stage I/II and HER2 negative status. Error bars are referring to SE(Standard Error).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585311&req=5

pone-0057092-g002: The sensitivity of CEA, CA153 and CK19-2G2 for PBC and MBC.(A) CK19-2G2 is superior to CEA and CA153 in stage II and III breast cancer patients and as sensitive as CA153 in MBC patients. The blank bar: CEA; the gray bar: CA153; the black bar: CK19-2G2 (B) The distribution of CK19-2G2 in MBC, PBC and DCIS. Serum CK19-2G2 levels in MBC are higher than those in the PBC and DCIS respectively(MBC vs PBC, P = 0.007; MBC vs DCIS, P = 0.002). Serum CK19-2G2 levels in PBC are higher than those in DCIS (P = 0.012). Error bars are referring to SE(Standard Error). (C) The distribution of CK19-2G2 in breast cancer patients with different stages, lymph nodes status and HER2 status. Patients with positive lymph nodes, stage III and HER2 positive status had higher serum CK19-2G2 levels than those with negative lymph nodes, stage I/II and HER2 negative status. Error bars are referring to SE(Standard Error).
Mentions: According to ER, PR, HER2, Ki67 status, breast cancer was classified into four types in clinical practice: LuminalA, LuminalB, HER2-enriched and Triple negative. We tested the serum CK19-2G2 levels in different type in PBC patients with stage I-III, and found that CK19-2G2 levels in HER2 enriched and Triple negative type were higher than that in LuminalA/B type, however, there was no statistical difference among the three groups (Figure 1B). The serum CK19-9 levels of breast cancer patients with stage III (3.51±11.29 mU/mL) were significantly higher than those with stage II/I (1.27±2.13 mU/mL) (P<0.001) (Figure 2B). When the cutoff value was defined to be 2.0 mU/mL, the percent of abnormal serum CK19-2G2 (sensitivities) for patients with Stage I, II, III and MBC were 5.4%, 11.9%, 29.5% and 71% respectively (Figure 2A).

Bottom Line: However, so far, few markers have been proved clinically useful except CA153.The sensitivities of CK19-2G2 for breast carcinoma are as high as CEA and CA153, and up to 71% in MBC patients.Serum CK19-2G2 levels (≥2 mU/mL) were associated with pathological stages, tumor size (≥2 cm), lymph node involvement, and HER2 status.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, PR China.

ABSTRACT

Background: Various studies have been searching for new tumor biomarkers for breast cancer for years. However, so far, few markers have been proved clinically useful except CA153. Based on knowledge that most adenocarcinomas including breast carcinoma expressed Cytokeratin19, the authors studied CK19-2G2,a novel fragment of cytokeratin19 shedding into serum in breast cancer patients.

Patients and methods: The serum samples of four hundred and seventeen patients including three hundred and three (fifty-four DCIS and two hundred and forty-nine stage I-III) PBC patients and one hundred and fourteen MBC patients, eighty-one healthy controls and twenty-one breast benign disease patients were provided for measurement of CK19-2G2, CEA and CA153.The correlation between clinicopathological characters, prognosis and CK19-2G2 levels was further studied.

Results: The serum CK19-2G2 levels in breast cancer patients were significantly higher than that in healthy and benign controls. For breast cancer patients, CK19-2G2 levels in MBC were significantly higher than that in PBC patients. The sensitivities of CK19-2G2 for breast carcinoma are as high as CEA and CA153, and up to 71% in MBC patients. Serum CK19-2G2 levels (≥2 mU/mL) were associated with pathological stages, tumor size (≥2 cm), lymph node involvement, and HER2 status. Multivariate analysis revealed that high serum CK19-2G2 level was an independent factor for relapse (P = 0.029) and death (P = 0.040) in breast cancer patients.

Conclusion: Serum CK19-2G2 may be an independent indicator for prognosis and a candidate marker for monitoring metastasis in breast cancer.

Show MeSH
Related in: MedlinePlus