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Smad3 and Smad3 Phosphoisoforms Are Prognostic Markers of Gastric Carcinoma

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Abstract

Background

The transforming growth factor-β/Smads signaling pathway plays an important role in tumorigenesis and progression in cancer, and may closely be related to the biological behaviors of some malignant tumors, such as gastric carcinoma. In this study, we investigated the roles of Smad3 and Smad3 phosphoisoforms in the prognosis of gastric carcinoma.

Methods

We investigated the expressions of Smad3, pSmad3C(S423/425), pSmad3L(T179), pSmad3L(S204), and pSmad3L(S213) in tumor tissue microarrays of 442 gastric carcinoma patients who underwent curative surgery using immunohistochemistry and assessed their correlation with clinical outcome.

Results

Positive Smad3 expression was observed in 33.5 % of gastric carcinoma. The rates of positive Smad3 phosphoisoforms expression varied according to the location of phosphorylation within Smad3: pSmad3C(S423/425) 28.5 %, pSmad3L(T179) 5.9 %, pSmad3L(S204) 1.8 %, and pSmad3L(S213) 20.8 %. Positive Smad3 expression was associated with diffuse type (p = 0.003), poorer histologic differentiation (p = 0.005), more frequent lymph node metastasis (p = 0.001), and higher AJCC stage (p = 0.006). Multivariate analyses revealed that Smad3 expression (p = 0.041), pSmad3L(T179) expression (p = 0.011), pSmad3L(S213) expression (p = 0.003), and American Joint Committee on Cancer (AJCC) stage were independent predictors of shorter disease-free survival. Smad3 expression (p = 0.033), pSmad3L(T179) expression (p = 0.012), pSmad3L(S213) expression (p = 0.005), and AJCC stage were also independent predictors of shorter overall survival. pSmad3C(S423/425) expression tended to show favorable influences on both disease-free survival (p = 0.134) and overall survival (p = 0.232).

Conclusions

Smad3, pSmad3L(T179), and pSmad3L(S213) expression might be independent predictors of both shorter disease-free survival and shorter overall survival in gastric carcinoma patients after curative surgery, and might help clinicians identify patients at high risk of recurrence.

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Acknowledgments

This study was supported by a grant from the Korea Healthcare Technology R&D project of the Ministry of Health, Welfare & Family Affairs (A111809).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea

    Seok-Hyung Kim, Soomin Ahn, Jiyeon Hyeon & Cheol-Keun Park

  2. Department of Pathology, Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, Korea

    Kyung-Hee Kim

Authors
  1. Seok-Hyung Kim
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  2. Kyung-Hee Kim
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  3. Soomin Ahn
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  4. Jiyeon Hyeon
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  5. Cheol-Keun Park
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Corresponding author

Correspondence to Cheol-Keun Park.

Additional information

Seok-Hyung Kim and Kyung-Hee Kim contributed equally to this study.

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Kim, SH., Kim, KH., Ahn, S. et al. Smad3 and Smad3 Phosphoisoforms Are Prognostic Markers of Gastric Carcinoma. Dig Dis Sci 58, 989–997 (2013). https://doi.org/10.1007/s10620-012-2470-3

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  • DOI: https://doi.org/10.1007/s10620-012-2470-3

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