title: p53 and HLA class-I expression are not down-regulated in colorectal cancer liver metastases.
abstract: p53 overexpression occurs in more than 50% of colorectal carcinomas, which makes it an interesting target for immunotherapy. HLA class I expression on tumor cells is required for the presentation of p53 peptides and an effective T-cell mediated-immune response to ensue. To analyze to which extent p53 and HLA-I expression in a primary tumor reflects expression in liver metastases, we investigated p53, HLA-A and HLA-B/C expression in 82 colorectal carcinomas and 143 associated liver metastases of 82 patients. We used the monoclonal antibodies DO-7 (p53), HCA2 (HLA-A) and HC-10 (HLA-B/C) on formalin-fixed, paraffin embedded tissue. The percentage of expressing cells was estimated. P53 was overexpressed in 73% of the colorectal carcinomas and 66% of liver metastases. HLA-A was expressed in 98% and 96% and HLA-B/C in 100% and 94% of colorectal cancers and liver metastases respectively. There were no significant differences between the primary tumors and the liver metastases for each marker. The concordance was also very high in those cases in which more than one metastasis was available. Discordant cases consisted of tumors in which expression of p53 or HLA-A was lost in the liver metastases, whereas it was present in only a few tumor cells in the primary tumor. The combined analysis of p53 and HLA-I expression in liver metastases demonstrated that both molecules were expressed in 63% of the cases. P53 and HLA-I were expressed in the majority of primary tumors and their associated liver metastases. This allows to select patients for p53-immunotherapy on the basis of p53 and HLA-I expression in the primary tumor.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anand G
authors.initials: AG
authors.lastname: Menon
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Connie M
authors.initials: CM
authors.lastname: Janssen-van Rhijn
authors.forename: Rob
authors.initials: R
authors.lastname: Keijzer
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
mesh_terms: D015179:Colorectal Neoplasms / Q000473:pathology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D016159:Tumor Suppressor Protein p53