Deficiency of hMLH1 and hMSH2 expression is a poor prognostic factor in esophageal squamous cell carcinoma
Corresponding Author
Hirofumi Uehara
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. Fax: +81-11-706-7158.Search for more papers by this authorMasaki Miyamoto
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorKentaro Kato
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorYasushi Cho
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorTakanori Kurokawa
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorSoichi Murakami
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorAkira Fukunaga
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorYuma Ebihara
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorHiroyuki Kaneko
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorHiroyuki Hashimoto
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorYosihiro Murakami
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorToshiaki Shichinohe
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorYou Kawarada
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorTomoo Itoh
Department of Pathology, Hokkaido University Hospital, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorShunichi Okushiba
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorSatoshi Kondo
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorHiroyuki Katoh
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorCorresponding Author
Hirofumi Uehara
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. Fax: +81-11-706-7158.Search for more papers by this authorMasaki Miyamoto
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorKentaro Kato
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorYasushi Cho
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorTakanori Kurokawa
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorSoichi Murakami
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorAkira Fukunaga
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorYuma Ebihara
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorHiroyuki Kaneko
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorHiroyuki Hashimoto
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorYosihiro Murakami
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorToshiaki Shichinohe
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorYou Kawarada
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorTomoo Itoh
Department of Pathology, Hokkaido University Hospital, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorShunichi Okushiba
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorSatoshi Kondo
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorHiroyuki Katoh
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan
Search for more papers by this authorAbstract
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.
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