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Combination of MUC1 and MUC4 expression predicts clinical outcome in patients with oral squamous cell carcinoma

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Abstract

Background

Both MUC1 and MUC4 are high molecular weight glycoproteins and are independent indicators of worse prognosis in many human epithelial cancers including oral squamous cell carcinoma (OSCC). However, there has been no investigation of the clinical importance of the co-expression of MUC1 and MUC4 in OSCC. The aim of this study was to evaluate the co-expression profile of MUC1/MUC4 and analyze the prognostic significance in OSCC.

Methods

We examined the expression profile of MUC1 and MUC4 in OSCC tissues from 206 patients using immunohistochemistry. The co-expression profile of MUC1/MUC4 and its prognostic significance in OSCC was statistically analyzed.

Results

MUC1 and MUC4 overexpression were strongly correlated with each other (p < 0.0001) and a combination of both MUC1 and MUC4 expression was a powerful indicator for tumor aggressiveness such as tumor size (p = 0.014), lymph node metastasis (0.0001), tumor stage (p = 0.006), diffuse invasion (p = 0.028), and vascular invasion (p = 0.014). The MUC1/MUC4 double-positive patients showed the poorest overall and disease-free survival. Multivariate analysis revealed that MUC1/MUC4 double-positivity was the strong independent prognostic factor for overall and disease-free survival (p = 0.007 and (p = 0.0019), in addition to regional recurrence (p = 0.0025).

Conclusions

Taken together, these observations indicate that the use of a combination of MUC1/MUC4 can predict outcomes for patients with OSCC. This combination is also a useful marker for predicting regional recurrence. MUC1 and MUC4 may be attractive targets for the selection of treatment methods in OSCC.

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Acknowledgments

The authors thank Mr. Yoshiharu Atsuji and Ms. Yukari Nishimura for their excellent technical assistance. This study was supported in part by Grants-in-Aid for Scientific Research (B) 23390085 to S. Yonezawa; Scientific Research (C) 24590447 to M. Higashi; Scientific Research (B) 23390466 to K. Sugihara and Young Scientists (B) 24792239 to T. Hamada from the Ministry of Education, Science, Sports, Culture and Technology, Japan.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Oral Surgery, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Yoshiaki Kamikawa, Tomofumi Hamada & Kazumasa Sugihara

  2. Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Yuji Kanmura & Kazumasa Sugihara

  3. Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave., Cincinnati, Ohio, 45229, USA

    Norishige Yamada

  4. Department of Biochemistry and Molecular Biology, Buffett Cancer Center, Eppley Cancer Institute, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198-5870, USA

    Muzafar A. Macha & Surinder K. Batra

  5. Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Michiyo Higashi & Suguru Yonezawa

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  1. Yoshiaki Kamikawa
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  8. Suguru Yonezawa
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Corresponding author

Correspondence to Tomofumi Hamada.

Additional information

Y. Kamikawa and Y. Kanmura contributed equally to this work.

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Kamikawa, Y., Kanmura, Y., Hamada, T. et al. Combination of MUC1 and MUC4 expression predicts clinical outcome in patients with oral squamous cell carcinoma. Int J Clin Oncol 20, 298–307 (2015). https://doi.org/10.1007/s10147-014-0710-6

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  • DOI: https://doi.org/10.1007/s10147-014-0710-6

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