Deficiency of hMLH1 and hMSH2 expression is a poor prognostic factor in esophageal squamous cell carcinoma.
BACKGROUND
The human Mut-L-Homologon-1 (MLH1) and Mut-S-Homologon-2 (MSH2) are post replication mismatch repair (MMR) genes.


METHODS
We examined the correlation of the clinical features of 122 patients with esophageal squamous cell carcinoma (ESCC) with the expression of MLH1 and MSH2 by immunohistochemical analysis.


RESULTS
According to our criteria, 34 and 25 cases did not express MLH1 and MSH2, respectively. Expression of both the MLH1 and MSH2 gene products was observed in 73 (59.8%) cases; loss of MLH1 or MSH2 expression was detected in 35(28.7%) cases. Fourteen (11.5%) cases demonstrated loss of both MLH1 and MSH2 expression in ESCC. Loss of MLH1 and/or MSH2 gene expression significantly correlated with increases in malignancy, as evidenced by increases in the existence of metastatic lymph nodes (P = 0.0056), extensive invasion (P = 0.0007), and poor differentiation (P = 0.0992). The MLH1-negative patients had a significantly poorer prognosis than those in the MLH1-positive group (P = 0.0043). Similar results were observed for MSH2 expression (P = 0.0002). Patients both MLH1 and MSH2 negative exhibited the most poor clinical outcome than other patients (P < 0.0001).


CONCLUSIONS
We conclude that MMR protein expression, detected by immunohistochemistry, is a useful marker providing information necessary to decide appropriate therapeutic strategies in patients with ESCC.
Uehara
Hirofumi
H
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan. h-uehara@med.hokudai.ac.jp
Miyamoto
Masaki
M
Kato
Kentaro
K
Cho
Yasushi
Y
Kurokawa
Takanori
T
Murakami
Soichi
S
Fukunaga
Akira
A
Ebihara
Yuma
Y
Kaneko
Hiroyuki
H
Hashimoto
Hiroyuki
H
Murakami
Yosihiro
Y
Shichinohe
Toshiaki
T
Kawarada
You
Y
Itoh
Tomoo
T
Okushiba
Shunichi
S
Kondo
Satoshi
S
Katoh
Hiroyuki
H
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D020137:Base Pair Mismatch; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein