Differences in survivin location and Bcl-2 expression in CD30+ lymphoproliferative disorders of the skin compared with systemic anaplastic large cell lymphomas: an immunohistochemical study.
BACKGROUND
Cutaneous CD30+ lymphoproliferative disorders (LPDs) are a spectrum of disease associated with a favourable prognosis. Systemic anaplastic large cell lymphoma (ALCL), although morphologically and phenotypically similar, differs in clinical presentation and has a less favourable biological behaviour. Dysregulation of apoptosis, the process regulating cell population by programmed death, can explain the differences among these disorders.


OBJECTIVE
We investigated the expression of two inhibitors of apoptosis, survivin and Bcl-2 protein, in serial skin lesion samples from CD30+ LPDs compared with systemic ALCL.


METHODS
Immunohistochemical analysis with antibodies against anaplastic lymphoma kinase (ALK)-1 protein, survivin and Bcl-2 protein was performed in 10 cutaneous CD30+ LPDs (five lymphomatoid papulosis, five ALCL) and 18 systemic ALCLs. Reverse transcription-polymerase chain reaction studies for ALK and ALK/nucleophosmin were also performed.


RESULTS
Cutaneous CD30+ LPDs shared a heterogeneous expression of cytoplasmic survivin with all systemic ALCLs, and of Bcl-2 with systemic ALK- ALCLs; however, they differ from systemic ALK- ALCLs because they lack nuclear survivin (P = 0.045), and from systemic ALK+ ALCLs by a higher expression of Bcl-2 (P = 0.045) and a lack of ALK-1. Overall, coexpression of Bcl-2 and nuclear survivin in CD30+ LPDs was associated with a less favourable disease survival.


CONCLUSIONS
The different patterns of expression of Bcl-2 and survivin in CD30+ LPDs might have an impact on their different biological and clinical behaviour. Moreover, nuclear localization of survivin, similarly to ALK, may be a useful marker for predicting a systemic form of ALCL with cutaneous presentation.
Goteri
G
G
Department of Neurosciences, Institute of Anatomic Pathology, Ancona, Italy.
Simonetti
O
O
Rupoli
S
S
Piccinini
G
G
Rubini
C
C
Stramazzotti
D
D
Fazioli
F
F
Capomagi
C
C
Leoni
P
P
Offidani
A M
AM
Lo Muzio
L
L
Lomuzio
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins; D017730:Ki-1 Antigen / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis; D008232:Lymphoproliferative Disorders / Q000175:diagnosis*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D012867:Skin; D012878:Skin Neoplasms / Q000175:diagnosis*; D000077022:Survivin
C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D017730:Ki-1 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases