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Deficiency of hMLH1 and hMSH2 expression is a poor prognostic factor in esophageal squamous cell carcinoma
Author(s) -
Uehara Hirofumi,
Miyamoto Masaki,
Kato Kentaro,
Cho Yasushi,
Kurokawa Takanori,
Murakami Soichi,
Fukunaga Akira,
Ebihara Yuma,
Kaneko Hiroyuki,
Hashimoto Hiroyuki,
Murakami Yosihiro,
Shichinohe Toshiaki,
Kawarada You,
Itoh Tomoo,
Okushiba Shunichi,
Kondo Satoshi,
Katoh Hiroyuki
Publication year - 2005
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20332
Subject(s) - medicine , esophageal squamous cell carcinoma , oncology , basal cell , carcinoma , cancer research , pathology
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). Conclusion 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. J. Surg. Oncol. 2005;92:109–115. © 2005 Wiley‐Liss, Inc.