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. 2017 Feb;40(1):39-48.
doi: 10.1016/j.bj.2017.01.004. Epub 2017 Mar 14.

Overexpression of MutL Homolog 1 and MutS Homolog 2 Proteins Have Reversed Prognostic Implications for Stage I-II Colon Cancer Patients

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Free PMC article

Overexpression of MutL Homolog 1 and MutS Homolog 2 Proteins Have Reversed Prognostic Implications for Stage I-II Colon Cancer Patients

Shih-Chiang Huang et al. Biomed J. .
Free PMC article

Abstract

Background: The outcome of colon cancer patients without lymph node metastasis is heterogeneous. Searching for new prognostic markers is warranted.

Methods: One hundred twenty stage I-II colon cancer patients who received complete surgical excision during 1995-2004 were selected for this biomarker study. Immunohistochemical method was used to assess p53, epidermal growth factor receptor, MLH1, and MSH2 status. KRAS mutation was examined by direct sequencing.

Results: Thirty three patients (27.5%) developed metachronous metastasis during follow up. By multivariate analysis, only female gender (p = 0.03), high serum carcinoembryonic antigen (CEA) level (≧5 ng/ml) (p = 0.04), and MLH1 overexpression (p = 0.003) were associated with the metastasis group. The 5-year-survival rate were also significantly lower for female gender (71.7% versus 88.9%, p = 0.025), high CEA level (64.9% versus 92.4%, p < 0.001), and MLH1 overexpression (77.5% versus 94.4%, p = 0.039). In contrast, MSH2 overexpression was associated with better survival, 95.1% versus 75.5% (p = 0.024).

Conclusions: The reversed prognostic implications in the overexpression of MLH1 and MSH2 for stage I-II colon cancer patients is a novel finding and worthy of further confirmation.

Keywords: CEA; Colon cancer; MLH1; MSH2; Mismatch repair.

Figures

Fig. 1
Fig. 1
Immunohistochemical satin for MLH1 protein expression in the colon adenocarcinoma: (A) Intermediate expression (200×), (B) Overexpression (400×), (C) Negative expression (400×); for MSH2 protein expression: (D) Intermediate expression (200×), (E) Overexpression (400×), (F) Negative expression (400×).
Fig. 2
Fig. 2
Kaplan–Meier overall survival curve of the 120 colon adenocarcinoma patients according to different variables: (A) gender, (B) carcinoembryonic antigen (CEA) level, (C) MLH1 expression, and (D) MSH2 expression.
Fig. 3
Fig. 3
Kaplan–Meier overall survival curve of the 120 colon adenocarcinoma patients based on the three different expression levels of A: MLH1 protein, and B: MSH2 protein.

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References

    1. Parkin D.M., Bray F., Ferlay J., Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108. - PubMed
    1. Cunningham D., Atkin W., Lenz H.J., Lynch H.T., Minsky B., Nordlinger B. Colorectal cancer. Lancet. 2010;375:1030–1047. - PubMed
    1. Gertler R., Rosenberg R., Schuster T., Friess H. Defining a high-risk subgroup with colon cancer stages I and II for possible adjuvant therapy. Eur J Cancer. 2009;45:2992–2999. - PubMed
    1. Mroczkowski P., Schmidt U., Sahm M., Gastinger I., Lippert H., Kube R. Prognostic factors assessed for 15,096 patients with colon cancer in stages I and II. World J Surg. 2012;36:1693–1698. - PubMed
    1. Benson A.B., 3rd, Schrag D., Somerfield M.R., Cohen A.M., Figueredo A.T., Flynn P.J. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–3419. - PubMed

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