title: Loss of protein expression of hMLH1 and hMSH2 with double primary carcinomas of the stomach and colorectum.
abstract: The frequency of synchronous or metachronous multiple primary carcinomas in patients with gastrointestinal carcinoma or colorectal carcinoma (CRC) has been reported to be approximately 10%. We determined the role of hMSH2 and hMLH1 in double carcinomas with both GC and CRC. Fifty-six patients with synchronous or metachronous colorectal carcinoma with gastric carcinoma (CRC with GC), and 69 patients with CRC alone was included in our study. We investigated their clinicopathological characteristics, family history and immunohistochemical stains of hMSH2 and hMLH1 were compared between the patients with CRC alone and those with both CRC with GC. The defective protein expression of hMSH1 and/or hMLH1 in colorectal carcinomas was significantly higher in patients with both CRC with GC than in those with CRC alone (p < 0.0001). The survival rate in patients with both CRC with GC was significantly lower than that in those with CRC alone (p < 0.01), in addition, the survival rate in patients with defective protein expression of hMSH2 and/or hMLH1 was higher than in those with a positive protein expression of hMSH2 and/or hMLH1 in CRC with GC (p < 0.05). The incidence of defective protein expression of hMSH2 and/or hMLH1 in CRC with GC patients suggests that abnormalities in the function of hMSH2 and hMLH1 may play an important role in carcinogenesis. Our findings indicate that the CRC patients who demonstrate a defective protein expression of hMSH2 and/or hMLH1 have a higher risk of developing secondary carcinoma in the gastrointestinal tract.
authors.affiliation: Department of General Surgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. mayama@hiroshima-med.jrc.or.jp
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Taguchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Kazuya
authors.initials: K
authors.lastname: Endo
authors.forename: Shunji
authors.initials: S
authors.lastname: Kohnoe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okamura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality; D002352:Carrier Proteins / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis*; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: 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