Estrogen and Progesteron Receptor Status in Pediatric and Adolescent Patients with Hodgkin’s Lymphoma.
Authors: Claviez Alexander , Lüders Heike , Dörffel Wolfgang , Schellong Günther , Tiemann Markus 
Published: October 2019

Abstract
For decades it is known that Hodgkin’s lymphoma (HL) is a highly responsive lymphoma to steroid treatment. Little information is available about the distribution of steroid hormone receptors, such as estrogen receptor (ER) and progesterone receptor (PR) in this tumor. Moreover, different sex distribution among the main histological subtypes may be associated with hormonal developmental status. Particularly, in nodular sclerosis HL (NSHL), a shift towards female sex between childhood and adolescence becomes evident. ER and PR status has gained significant impact for diagnostic and therapeutic purposes in some malignant tumors, such as breast and lung cancer.
Therefore, we analysed 366 paraffin-embedded lymph node biopsy specimens from children and adolescents with primary HL by immunohistochemistry using a monoclonal antibody, clone 1D5, against ER and a polyclonal antibody against PR. Immunohistochemical results were compared with clinical findings.
Staining results from 337 patients (92%) included in pediatric multicenter treatment studies HD-90, HD-95 and HD-2002 pilot were evaluable. The study population included 197 boys and 140 girls. 29 patients had nodular lymphocyte predominant HL (NLPHL, 8.6%), 237 patients had NSHL (70.3%), 66 patients had mixed cellularity HL (MCHL, 19.6%), two patients had lymphocyte depleted HL, one patient had lymphocyte-rich classical HL and in two patients the subtype was not classifiable. The median age of the patients was 14.2 years (range, 2.7 to 20.2 years). Localized stages (I/II) were present in 218 patients (64.9%) and 115 patients (34.1%) had B symptoms. Hodgkin and Reed-Sternberg (H&RS) and lymphocytic and histiocytic (L&H) cells depicted a positive nuclear staining for ER in five cases (1.5%) and for PR in four cases (1.2%). Two of these nine patients had NLPHL and seven patients had classical HL. Eight patients (89%) were male. The median age of these patients was 10.4 years (range, 4.9 to 17.5 years). Four patients (44%) had limited disease and B symptoms were present in two patients with receptor positive neoplastic cells. Apart from neoplastic cells, hormone receptor expression was also found in bystander cells, as lymphocytes, monocytes and fibroblasts, but not in granulocytes and endothelial cells. ER and PR positivity in lymphocytes was found in 19.6% and 3.9% of cases, respectively. Monocytes expressed ER and PR in 24.6% and 3.6%, respectively. ER positivity in monocytes was detected in 19.4% of patients with localized disease compared to 33.9% of patients with advanced stages (p=.003). Seven patients had positively stained single fibroblasts.
In conclusion, only less than 2% of patients expressed ER or PR in H&RS or L&H cells. In contrast, bystander cells were positive in up to 25 percent. Unexpectedly, no association of receptor expression with histological subtype, sex and age was found. Particularly, no increased expression of ER and PR in adolescent girls with NSHL was seen. Therefore, other factors may contribute to the distribution of histological subtypes in HL during adolescence. ER expression in monocytes correlated with advanced disease. However, ER and PR status had no prognostic impact on clinical outcome.