title: Relapsed Hodgkin's lymphoma: immunostaining patterns in relation to survival.
abstract: Patients with relapsing Hodgkin's lymphoma (HL) have a rather poor prognosis and mechanisms that lead to resistance to therapy are poorly understood. Our aims were to investigate the immunohistochemical staining patterns of Rb (retinoblastoma protein) and the p53 tumour suppressor protein in HL at initial presentation and at relapse in order to elucidate a possible role in disease progression and resistance to therapy. Further to evaluate the presence and prognostic importance of Epstein-Barr virus (EBV) and anaplastic lymphoma kinase (ALK). Eighty-one cases of relapsing HL were reexamined histopathologically and immunostained for the expression of p53, Rb, ALK and CD30. EBV was detected with LMP-1 stainings and in situ hybridisation for EBER. Clinical data were extracted from the Swedish National Health Care Programme for HL. Median follow-up time was six years (range 0-12) from the date of relapse. The majority of cases were positive for p53 and Rb both at presentation and at relapse, though to a different extent. Both an increase and a decrease in the proportion of stained tumour cells were observed. None of our cases was ALK-positive and 44% were EBV-positive. No specific staining pattern was directly correlated to survival. In 12 patients a switch in HL subtype from diagnosis to relapse was observed and the five-year Hodgkin-specific survival (HLS) was statistically significantly inferior, 37 vs 81% (p = 0.002), in those patients. We found a significant relation between the expression of p53 and EBV at diagnosis and relapse, indicating a clonal relationship. We were unable to find any specific staining pattern of p53 or Rb, affecting survival.
authors.affiliation: Department of Genetics and Pathology, University of Uppsala, Sweden. Rose-Marie.Amini@genpat.uu.se
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Amini
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.forename: Peter
authors.initials: P
authors.lastname: Engström
authors.forename: Birger
authors.initials: B
authors.lastname: Christensson
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology; D006801:Humans; D007124:Immunoenzyme Techniques; D017730:Ki-1 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D012367:RNA, Viral / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D012008:Recurrence; D016160:Retinoblastoma Protein / Q000032:analysis*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014763:Viral Matrix Proteins / Q000032:analysis*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D017730:Ki-1 Antigen; D009363:Neoplasm Proteins; D012367:RNA, Viral; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases