title: HLA-A, -B, -C expression in colon carcinoma mimics that of the normal colonic mucosa and is prognostically relevant.
abstract: Whether human leukocyte antigen (HLA)-A, -B, -C expression has any predictive value on the prognosis of human malignancies remains controversial. Herein, monoclonal antibodies with preferential reactivity for HLA-A, HLA-B, and HLA-C (HCA2, HC10, and L31) were used to stain an archival collection of 291 formalin-fixed/paraffin-embedded tissues, comprising neoplastic lesions from stages II and III colon carcinoma patients (n=165), and the uninvolved, morphologically normal mucosae from a subset (n=126) of these patients. Marked staining variability was detected not only in the tumors as in previous studies, but also in the normal paired mucosae. HLA-A, -B, -C expression was similar in approximately two thirds of the available 126 normal/neoplastic pairs, confirming in vivo our previous observation that most tumor cells mimic the HLA phenotypes of their normal counterparts. Both up and down-regulation occurred in the remaining third of the pairs, but did not coincide with high and low expression, respectively, conventionally evaluated on the tumor lesion only. Remarkably, a "paired" evaluation, but not high or low expression in the tumor, was predictive of the clinical outcome. Deviations from the expression in the normal paired mucosa (both increases and decreases) of HCA2-reactive class I molecules (possibly HLA-A), and down-regulation of L31-reactive class I molecules (possibly HLA-C), particularly in tumors from stage II patients, correlated with poor 5-year overall and disease-free survival, hazard risk ranging from 2 to 6, approximately. Thus, a paired immunohistochemical comparison reveals a novel immune evasion strategy that may impact on the prognosis of colon carcinoma.
authors.affiliation: Pathology Department, Regina Elena Cancer Institute CRS, Via delle Messi d'Oro 156, 00158 Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Benevolo
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.forename: Giulia
authors.initials: G
authors.lastname: Piperno
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Antonio
authors.initials: A
authors.lastname: Cione
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sibilio
authors.forename: Aline
authors.initials: A
authors.lastname: Martayan
authors.forename: Raffaele Perrone
authors.initials: RP
authors.lastname: Donnorso
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cosimelli
authors.forename: Patrizio
authors.initials: P
authors.lastname: Giacomini
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D003106:Colon / Q000033:anatomy & histology / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I