Frequency of loss of hMLH1 expression in colorectal carcinoma increases with advancing age.
BACKGROUND
The correlation between age at diagnosis and loss of expression of hMLH1 protein in patients with colorectal carcinoma (CRC) has not been evaluated systematically.


METHODS
Immunohistochemistry was performed for hMLH1 protein in tumor samples from 867 patients with CRC. The authors defined tumors arising in the cecum, ascending colon, and transverse colon as right-sided and tumors arising in the descending colon, sigmoid colon, and rectum as left-sided. Patients' gender, tumor location (side), and hMLH1 expression were analyzed by age groups.


RESULTS
The percentage of tumors with hMLH1 expression loss increased significantly with advancing age (P < 0.0001): There were no tumors in patients age < 40 years that manifested loss of hMLH1 expression, compared with 29% of tumors that manifested loss of hMLH1 expression in patients age > 90 years. Loss of hMLH1 expression occurred more often in patients with right-sided tumors (32.7% vs. 5.2% of patients with left-sided tumors; P < 0.0001) and in tumors from female patients (24.3% vs. 11.5% of tumors from male patients; P < 0.0001). There was no evidence of interaction between gender and tumor location.


CONCLUSIONS
Loss of hMLH1 expression in patients with CRC was associated strongly with increasing age. hMLH1 expression loss was more pronounced in tumors from female patients and in tumors that originated on the right side of the colon. Loss of hMLH1 expression in right-sided tumors occurred in nearly 50% of patients age > 90 years. This age-related trend also was observed for males and in tumors that originated in the left colon.
Kakar
Sanjay
S
Department of Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Burgart
Lawrence J
LJ
Thibodeau
Stephen N
SN
Rabe
Kari G
KG
Petersen
Gloria M
GM
Goldberg
Richard M
RM
Lindor
Noralane M
NM
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009687:Nuclear Proteins; D012737:Sex Factors
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1