title: HMSH2 and HMSH6 gene expression profiles in colorectal adenocarcinoma in patients up to 50 years of age.
abstract: Lynch syndrome, previously called hereditary non-polyposis colorectal cancer (HNPCC), is a major mortality threat. It is an autosomal dominant disease which is caused by a germline mutation in the DNA mismatch repair (MMR), especially in patients aged up to 50 years. Such mutation more frequently occurs in the hMSH2 gene (38-40%) and less frequently in the hMSH6 gene (14-16%). These mutations, when associated with the patient's lifestyle, may reveal a considerable variability in the disease manifestations, such as the degrees of penetrance and clinical aggressiveness. The aim of this study is to analyze the expression of DNA MMR genes, and correlate this expression with the clinical and anatomopathological findings of the neoplasia in patients aged between 39 and 49 years. A total of 45 patients were included: (48.9%) males and (51.1%) females, and they all underwent resection of a colorectal adenocarcinoma. The tissue microarray technique was used to analyze the relative and absolute expression of hMSH2 and hMSH6. Amsterdam II criteria for the diagnosis of HNPCC were obtained from the data provided by medical records and interviews with patients. hMSH2 and hMSH6 was expressed in all patients, which correlated between each other (RHO=0.669 and p<0.001) but not to age. There is a positive correlation between the expressions of males (RHO=0.673 and p=0.001) and females (RHO=0.006 and p<0.001). It is possible to evaluate the expression of MMR genes in embedded anatomopathological samples. Gene expressions correlated between each other and to the sex of the patients, but no difference in relation to age.
authors.affiliation: State Civil Servant Hospital (IAMSPE), São Paulo, Brazil. Electronic address: demetriusgermini@hotmail.com.
authors.forename: Demétrius
authors.initials: D
authors.lastname: Germini
authors.affiliation: Oncology/Hematology Discipline, ABC Medical School, Santo André, São Paulo, Brazil; Paulista University, São Paulo, Brazil. Electronic address: flaviagehrke@hotmail.com.
authors.forename: Flávia
authors.initials: F
authors.lastname: Gehrke
authors.affiliation: Oncology/Hematology Discipline, ABC Medical School, Santo André, São Paulo, Brazil. Electronic address: dlira1@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lira
authors.affiliation: Oncology/Hematology Discipline, ABC Medical School, Santo André, São Paulo, Brazil. Electronic address: bcaalves@uol.com.br.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Alves
authors.affiliation: Institute of Chemical and Pharmaceutical Sciences, UNIFESP, Diadema, São Paulo, Brazil. Electronic address: lazzalis@uol.com.br.
authors.forename: Lígia
authors.initials: L
authors.lastname: Azzalis
authors.affiliation: Oncology/Hematology Discipline, ABC Medical School, Santo André, São Paulo, Brazil. Electronic address: matheusmpontoperez@gmail.com.
authors.forename: Matheus
authors.initials: M
authors.lastname: Perez
authors.affiliation: Oncology/Hematology Discipline, ABC Medical School, Santo André, São Paulo, Brazil; Institute of Chemical and Pharmaceutical Sciences, UNIFESP, Diadema, São Paulo, Brazil. Electronic address: profferfonseca@gmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Fonseca
authors.affiliation: State Civil Servant Hospital (IAMSPE), São Paulo, Brazil; Oncology/Hematology Discipline, ABC Medical School, Santo André, São Paulo, Brazil. Electronic address: jaqueswaisberg@uol.com.br.
authors.forename: Jaques
authors.initials: J
authors.lastname: Waisberg
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein
keywords: Colorectal adenocarcinoma; DNA mismatch repair; Lynch syndrome; hMSH2; hMSH6: hereditary non-polyposis colorectal cancer