Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

Abstract

To identify tumor antigens useful for diagnosis and immunotherapy of patients with pancreatic ductal adenocarcinoma, we applied a SEREX approach with a cDNA library made from 5 pancreatic cancer cell lines and sera obtained from 8 patients with pancreatic cancer, and isolated total 32 genes, including 14 previously characterized genes and 18 genes with unknown functions. Among these isolated antigens, serum IgG antibodies for 2 isolated DNA mismatch repair enzymes, Homo sapiens mutS homolog 2 (hMSH2) and Homo sapiens postmeiotic segregation increased 1 (hPMS1), were detected in patients with pancreatic ductal adenocarcinoma and dermatomyositis (DM), and polymyositis (PM), but not in sera from healthy individuals. Immunohistochemical study demonstrated that hMSH2 and hPMS1 were over-expressed in pancreatic ductal adenocarcinoma compared to normal pancreatic ducts. These results suggested that hMSH2 and hPMS1 may be useful as CD41 helper T cell antigens for immunotherapy of pancreatic cancer patients and that serum IgG antibodies may be useful for diagnosis of patients with pancreatic ductal adenocarcinoma and DM/PM. ' 2005 Wiley-Liss, Inc.Key words: SEREX; tumor antigens; pancreatic cancer; DNA mismatch repair enzyme Early diagnosis and curative treatment are still difficult for pancreatic ductal adenocarcinoma despite of increased incidence rate.

Cancer and myositis: new insights into an old association

“…Further evidence for this model comes from a recent study of antigen expression in pancreatic adenocarcinoma [34 ]. In that study, antibodies to two DNA mismatch repair proteins (polymyositis S1 and MSH2) were found in eight patients with pancreatic adenocarcinoma, and levels of these proteins were noted to be increased in immunohistochemical analysis of affected tissue.…”

Polymorphisms in hMLH1 and risk of early-onset lung cancer in a southeast Chinese population

“…hMLH1 is a common subunit to all three complexes, and its deficiency lead to a sever disease phenotype [12][13][14][15][16][17]. Recent reports have shown that hMLH1 not only physically interacts with other components of MMR but also interacts with other signaling molecules such as BRCA1 [18], PCNA [19], ATM [20], P53 [21,22] and other enzymes such as BLM (DNA helicase) [23], Exo1p [24] and MED1 [25,26].…”

Dermatomyositis associated with malignancy

“…La DM asociada a malignidad es un síndrome paraneoplásico que puede presentarse antes de la enfermedad oncológica, simultáneamente o meses e incluso años después de la misma. Afecta a individuos de grupos etarios de más de 40 años, incrementándose aún más por encima de los 60 años.Los tumores más frecuentemente asociados son el cáncer de ovario, mama, pulmón, colon, útero, estómago y síndromes mieloproliferativos [14][15][16][17][18][19] . Ciertos estudios manifiestan la presencia de antígenos compartidos por células tumorales y musculares, expresando una respuesta inmune contra el musculo y la piel.…”

“…Ciertos estudios manifiestan la presencia de antígenos compartidos por células tumorales y musculares, expresando una respuesta inmune contra el musculo y la piel. El tratamiento de la neoplasia puede mejorar o no las manifestaciones de la DM [14][15][16][17][18][19] . A continuación presentamos tres casos de DM asociados a neoplasias.…”