title: PARP1 expression in mantle cell lymphoma: the utility of PARP1 immunohistochemistry and its relationship with markers of DNA damage.
abstract: Mantle cell lymphoma (MCL) is an aggressive disease with poor overall survival, attributable in part to frequent defects of the DNA repair genes. In such malignancies, additional inhibition of the ubiquitous DNA damage repair protein, poly-ADP ribose polymerase-1 (PARP1) has shown enhanced cytotoxicity (so-called synthetic lethality). We studied PARP1 expression in a series of clinical cases of MCL, with the secondary aim to ascertain the relationship between PARP1 expression and DNA repair gene expression (namely ATM and p53) by immunohistochemical methods. We also examined the relationship between PARP1 expression and the well-established prognostic biomarker Ki-67, in addition to correlating PARP1 expression with the overall survival. From amongst our series of 79 unselected cases of MCL, we detected PARP1 expression in all but two cases with variable intensity. We also noted correlations between PARP1 expression and ATM and p53 expression. As described in previous studies, we identified a significant survival difference on the basis of Ki-67 and p53 expression. When digital H-score analysis of PARP1 expression was performed, there was a distinct survival advantage noted in patients with lower levels of expression. When our biomarker data were assessed by Cox regression, furthermore, the dominant effects of p53 and PARP1 expression were highlighted. Our data support the need for further research into the potential utility of PARP1 as a biomarker in MCL and for the potential direction of future PARP1 inhibitor-targeted therapy studies.
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary/Calgary Laboratory Services, Calgary, AB, Canada.
authors.forename: Etienne
authors.initials: E
authors.lastname: Mahe
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary/Calgary Laboratory Services, Calgary, AB, Canada.
authors.forename: Ariz
authors.initials: A
authors.lastname: Akhter
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary/Calgary Laboratory Services, Calgary, AB, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Le
authors.affiliation: Division of Hematology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Lelsey
authors.initials: L
authors.lastname: Street
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary/Calgary Laboratory Services, Calgary, AB, Canada.
authors.forename: Payam
authors.initials: P
authors.lastname: Pournaziri
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary/Calgary Laboratory Services, Calgary, AB, Canada.
authors.forename: Farid
authors.initials: F
authors.lastname: Kosari
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary/Calgary Laboratory Services, Calgary, AB, Canada.
authors.forename: Meer-Taher
authors.initials: MT
authors.lastname: Shabani-Rad
authors.affiliation: Division of Hematology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Douglas
authors.initials: D
authors.lastname: Stewart
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary/Calgary Laboratory Services, Calgary, AB, Canada.
authors.forename: Adnan
authors.initials: A
authors.lastname: Mansoor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004249:DNA Damage / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D019394:Ki-67 Antigen; D011065:Poly(ADP-ribose) Polymerases
keywords: Ki-67; PARP1; PARP1 inhibitors; digital image analysis; immunohistochemistry; mantle cell lymphoma; tissue microarray; whole slide imaging