Prognostic Significance of p27Kip1, Ki-67, and CRTC1-MAML2 Fusion Transcript in Mucoepidermoid Carcinoma: A Molecular and Clinicopathologic Study of 101 Cases

Purpose

Mucoepidermoid carcinoma (MEC) is the most frequently detected primary malignancy of the salivary gland and is characterized by a marked variation in prognosis. In the present study, we investigated the prognostic significance of p27Kip1, Ki-67, and CRTC1 (also called MECT1, TORC1, and WAMTP1)-MAML2 fusion in MEC.

Materials and Methods

MEC cases (n = 101) were examined for p27Kip1 and Ki-67 expression using immunohistochemistry and for CRTC1-MAML2 fusion transcript using reverse transcriptase-polymerase chain reaction.

Results

p27Kip1, Ki-67, and the CRTC1-MAML2 fusion transcript were expressed in 71, 31, and 34 of the 101 cases, respectively. p27Kip1 and CRTC1-MAML2 fusion were associated with favorable clinicopathologic tumor features and Ki-67 with aggressive clinicopathologic features. Multivariate survival analyses were performed that included the following 10 clinicopathologic factors: age, gender, tumor site, tumor size, nodal metastasis, clinical stage, histologic grade, p27 expression, Ki-67 expression, and CRTC1-MAML2 fusion. For disease-free survival, only p27Kip1 expression was significant as an independent prognostic factor. For overall survival, p27Kip1 expression, CRTC1-MAML2 fusion, and tumor size were significant. In each analysis, p27Kip1 and CRTC1-MAML2 fusion were independent of the clinical stage. Ki-67 expression was not selected in either multivariate analysis.

Conclusions

p27Kip1 and CRTC1-MAML2 fusion were associated with favorable clinicopathologic tumor features, and both were useful in predicting the overall survival of patients with MEC. For disease-free survival, p27Kip1 might be the most useful prognostic factor. In contrast, Ki-67 might not be a very powerful prognostic indicator for either survival point.

⁎ Research Fellow, Department of Pathology, Nagoya City University Graduate School of Medical Sciences and Research Fellow, Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan

† Research Fellow, Department of Pathology, and Lecturer, Department of Oral and Maxillofacial Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

‡ Professor, Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

§ Head, Department of Head and Neck Surgery, Aichi Cancer Center Central Hospital, Nagoya, Japan

¶ Lecturer, Department of Neuro-otolaryngology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

∥ Lecturer, Department of Neuro-otolaryngology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

# Professor Emeritus, Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

⁎⁎ Professor Emeritus, Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

†† Professor, Department of Oral and Maxillofacial Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

‡‡ Professor, Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan

§§ Professor, Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Address correspondence and reprint requests to Dr Inagaki: Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-ku, Nagoya 467-8601, Japan

PII: S0278-2391(09)00311-5

doi:10.1016/j.joms.2009.03.021

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