Prognostic significance of p27Kip1, Ki-67, and CRTC1-MAML2 fusion transcript in mucoepidermoid carcinoma: a molecular and clinicopathologic study of 101 cases.
OBJECTIVE
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.


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.
Miyabe
Satoru
S
Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Nagoya, Japan.
Okabe
Mitsukuni
M
Nagatsuka
Hitoshi
H
Hasegawa
Yasuhisa
Y
Inagaki
Akira
A
Ijichi
Kei
K
Nagai
Noriyuki
N
Eimoto
Tadaaki
T
Yokoi
Motoo
M
Shimozato
Kazuo
K
Inagaki
Hiroshi
H
D000367:Age Factors; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018277:Carcinoma, Mucoepidermoid / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D012334:RNA, Neoplasm / Q000032:analysis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012737:Sex Factors; D015996:Survival Rate
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C495418:MECT1-MAML2 fusion protein, human; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; D050760:Cyclin-Dependent Kinase Inhibitor p27