Pediatr Blood Cancer 2008;50:430

LETTER TO THE EDITORUnfavorable Outcome in CD15 NegativePediatric Classical Hodgkin Lymphoma

To the Editor: The letter of Barros et al. [1] raises interesting

issues. In our study on pediatric Hodgkin lymphoma (HL), we found

that lack of CD15 expression was independently associated with

poor overall and poor failure-free survival (HL) [2].

Barros et al. reference to the study Petrella et al. [3] inwhich they

have actually reported an unfavorable outcome of CD15 negative

cases. Also, that study was done prior to when the distinction

between classical HL and nodular lymphocyte predominant (LP)

HL was described [4]. The latter is consistently CD15 negative, and

has a significantly favorable outcome [5]. The report of Petrella et al.

includes 11 cases of LP, which could have been either lymphocyte

rich classical HL (one of the four classical HL subtypes) or nodular

LP, and therefore cannot be compared with studies on CD15

negative classical HL. There are only two studies on classical HL

which report CD15 negativity to be an independent prognostic

factor for overall and disease-free/failure-free survival [2,6], while

no prognostic significance is reported bymany studies, possibly due

to the limited number of cases studied. TheGerman study included a

large number of cases and is a good support for our findings, as they

found a significant association between lack of CD15 expression

and higher stages at diagnosis [6]. Other studies might confirm

whether CD15 negative classical HL presents with unfavorable risk

factors that would lead to a poorer survival.

The significant association between CD15 negativity and p53

negativity reported in our paper refers to a total absence of p53

immunostaining, that is, absence of p53 overexpression. The same

association was found between CD15 negativity and low p53

expression, with a cut-off value of 10% (P¼ 0.009; odds ratio 5.4,

95%confidence interval 1.4–22).Wild-type p53 protein is normally

below the detection sensitivity of immunohistochemistry. P53

immunodetection in Reed-Sternberg cells is thought to be the result

of accumulation of a non-functional p53 protein, due to mdm2

binding, rather than p53 mutation [7]. However, Chabay et al. have

shown that p53 is functional as a transcriptional activator in more

than half the pediatric HL cases studied [7]. In any case, the

association between loss of CD15 antigen expression and lack of

p53 overexpression is a purely statistical correlation, which might

be verified in further studies. The significant cut-off value for p53

expression in Reed-Sternberg cells is still to be identified.

Veronique Dinand, MD, PhD*

Department of Pediatrics

All India Institute of Medical Sciences

New Delhi, India

Laxman S. Arya, MD

Cancer Institute

Indraprastha Apollo Hospital

New Delhi, India

Ramesh Dawar, MBBS, DABP, FICP

Department of Pathology

All India Institute of Medical Sciences

New Delhi, India

REFERENCES

1. Barros MHM, Zalcberg LR, Hassan R. Prognostic impact of CD15

expression and proliferative index in the outcome of children with

classical Hodgkin lymphoma. Pediatr Blood Cancer 2007.

2. Dinand V, Malik A, Unni R, et al. Proliferative index and CD15

expression in pediatric classical Hodgkin lymphoma. Pediatr Blood

Cancer 2007: [Epub ahead of print].

3. Petrella T, Michiels R, Collin F, et al. CD15 antigen in Hodgkin’s

disease. Pathol Res Pract 1989;185:886–890.

4. Harris NL, Jaffe ES, Diebold J, et al. TheWorld Health Organization

classification of neoplasms of the hematopoietic and lymphoid

tissues: Report of the Clinical Advisory Committee meeting—Airlie

House, Virginia, November, 1997. Hematol J 2000;1:53–66.

5. Franklin J, Tesch H, HansmannML, et al. Lymphocyte predominant

Hodgkin’s disease: Pathology and clinical implications. Ann Oncol

1998;9:S39–S44.

6. Elenita-Johnson KS, Medeiros J, Khorsan J, et al. P53 expression in

Reed-Sternberg cells does not correlate with gene mutations in

Hodgkin’s disease. Am J Clin Pathol 1996;106:728–738.

7. Chabay P, Pesce P, De Matteo E, et al. No influence of bcl-2,

p53 and p21waf1 protein expression on the outcome of pediatric

Hodgkin lymphomas. J Pediatr Hematol Oncol 2006;28:552–

558.

� 2007 Wiley-Liss, Inc.DOI 10.1002/pbc.21371

——————*Correspondence to: Veronique Dinand, Department of Pediatrics,

Division of Pediatric Oncology, All India Institute of Medical

Sciences, New Delhi 110 029, India. E-mail: verodinand@fastem.com

Received 16 August 2007; Accepted 16 August 2007