Increased expression of MCM5 is significantly associated with aggressive progression and poor prognosis of oral squamous cell carcinoma.
BACKGROUND
Overexpression of MCM5 protein has been found to be significantly associated with the progression and prognosis of several human cancers.


METHODS
This study used immunohistochemistry to examine the expression of MCM5 protein in 97 specimens of oral squamous cell carcinomas (OSCC), 80 specimens of oral epithelial dysplasia (OED, including 31 mild, 29 moderate, and 20 severe OED samples), and 20 specimens of normal oral mucosa (NOM).


RESULTS
We found that the mean nuclear MCM5 labeling indices (LIs) increased significantly from NOM (15 ± 6%), through mild (25 ± 10%), moderate (34 ± 9%), and severe OED (43 ± 12%), to OSCC samples (61 ± 16%, P < 0.001). A significant correlation was found between the higher mean nuclear MCM5 LI and OSCCs with site at the tongue (P = 0.046), larger tumor size (P = 0.032), positive lymph node metastasis (P = 0.003), more advanced clinical stage (P = 0.002), higher histological grade (P = 0.002), deeper invasion depth (P = 0.0001), and perineural invasion (P = 0.0047). Only nuclear MCM5 LI ≧ 60% was identified as independent unfavorable prognostic factor by multivariate regression analyses (P = 0.049). The Kaplan-Meier curve showed that patients with OSCC with a nuclear MCM5 LI ≧ 60% had a significantly poorer cumulative survival than those with a nuclear MCM5 LI < 60% (log-rank test, P = 0.0062).


CONCLUSIONS
The increased expression of MCM5 protein begins at the oral pre-cancerous stage. The higher expression of MCM5 protein is significantly associated with the aggressive progression and poor prognosis of OSCC.
Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan.
Shang-Yang
SY
Yu
Yi-Ping
YP
Wang
Julia Yu-Fong
JY
Chang
Wei-Ren
WR
Shen
Hsin-Ming
HM
Chen
Chun-Pin
CP
Chiang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000556:secondary; D018797:Cell Cycle Proteins / Q000032:analysis*; D002467:Cell Nucleus / Q000737:chemistry; D004261:DNA Replication; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry; D009062:Mouth Neoplasms / Q000737:chemistry*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000737:chemistry; D011379:Prognosis; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000737:chemistry
D018797:Cell Cycle Proteins; C489423:MCM5 protein, human
MCM5; oral epithelial dysplasia; oral squamous cell carcinoma; prognosis; progression