Expression of mitotic checkpoint proteins BUB1B and MAD2L1 in salivary duct carcinomas.
OBJECTIVE
Defects in the mitotic checkpoint lead to aneuploidy and might facilitate tumorigenesis. However, the ploidy status in salivary duct carcinoma (SDC) has been reported to play limited role in prediction of prognosis. Thus, we need more reliable markers to reflect the rapid tumor progression in SDCs. We aimed here to investigate the expression of mitotic checkpoint proteins benzimidazole 1 homolog beta (BUB1B) and mitosis arrest-deficient 2 like 1 (MAD2L1) in SDCs and to determine their possible role as surrogate prognostic markers.


METHODS
We analyzed the clinical courses, pathologic findings and immunohistochemical profiles of mitotic checkpoint proteins (BUB1B and MAD2L1) in 27 pathologically confirmed SDCs. The expression status of BUB1B and MAD2L1 was compared with clinicopathologic factors and other molecular markers, such as TGF-beta, c-erb-B2, androgen receptor, vascular endothelial growth factor, and epidermal growth factor receptor, for prognostic significance.


RESULTS
High BUB1B expression was detected in 25.9% of subjects, and high MAD2L1 expression was in 55.6% of subjects. However, survival analysis revealed that mitotic checkpoint expression did not have prognostic significance in SDCs, nor did the other studied markers. Rather, the clinical variable of N classification at diagnosis (in N+ status, hazard ratio 5.19, 95% CI 1.26-21.32 for disease-free survival and hazard ratio 7.18, 95% CI 1.09-46.99 for overall survival) was strongly associated with survival and prognosis based on the Cox proportional hazard model.


CONCLUSIONS
Mitotic checkpoint proteins appeared to play a limited role in predicting prognosis in SDCs. Further study is required to elucidate the exact role of mitotic checkpoint proteins in SDCs.
Ko
Young Hyeh
YH
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Roh
Ji Hyeon
JH
Son
Young-Ik
YI
Chung
Man Ki
MK
Jang
Jeon Yeob
JY
Byun
Hayoung
H
Baek
Chung-Hwan
CH
Jeong
Han-Sin
HS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000032:analysis*; D002277:Carcinoma / Q000473:pathology* / Q000556:secondary; D018797:Cell Cycle Proteins / Q000032:analysis*; D015331:Cohort Studies; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D064246:Mad2 Proteins; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011944:Receptors, Androgen / Q000032:analysis; D012074:Remission Induction; D012097:Repressor Proteins / Q000032:analysis*; D018987:Salivary Ducts / Q000473:pathology*; D012468:Salivary Gland Neoplasms / Q000473:pathology*; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000032:analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D066246:ErbB Receptors; D064246:Mad2 Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C577697:MAD2L1 protein, human; C467484:VEGFA protein, human; C090464:Bub1 spindle checkpoint protein